Lower Risk of Recurrence with a Higher Induction Dose of Mesalazine and Longer Duration of Treatment in Ulcerative Colitis: Results from the Dutch, Non-Interventional, IMPACT Study

Background & Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes.Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity.Results: In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of >= 4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on >= 4 g/day had a significantly lower chance of recurrence versus those on 2-6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p= 4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-= 4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions.

Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.GMK is supported by a Clinical Lecturer Starter Grant from the Academy of Medical Sciences, UK (grant no. 80354) and a Gosling Fellowship from the Royal College of Psychiatrists, UK (2015). GMK also received funding support from the Wellcome Trust 094790/Z/10/Z). PBJ acknowledges grant sup port from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0606-1335, Cambridge Biomedical Research Centre and CLAHRC East of England). RD has received grants from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health (grants R01 NS073939; R01 NS074999).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/mp.2016.16

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions

Migration study on the island of Schouwen-Duiveland 1975

Motives to migrate to and from Schouwen-Duiveland ( island in the province of Zeeland ) / housing situation. Background variables: basic characteristics/ residence/ housing situation/ household characteristics/ place of work/ occupation/employment/ income/capital asset