Psychological stress and hypnosis in ulcerative colitis.

PhDPrevious studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Furthermore, experimental stress has been shown to worsen inflammation in animal models of colitis. Hypnotherapy is effective for functional gastrointestinal (GI) disorders and claimed by some patients to improve ulcerative colitis (UC). Two major hypotheses are tested in this thesis: i) Psychological stress can worsen inflammation via its effects on various systemic and rectal mucosal inflammatory variables in quiescent UC. ii) Relaxation achieved through hypnosis can reduce inflammation via its effects on various systemic and mucosal inflammatory variables in active UC. Patients with UC and healthy controls underwent an experimental stress test, hypnotherapy session or control procedure. Various systemic and, in patients with UC, rectal mucosal inflammatory measures were assessed before and after each procedure. The major findings are as follows: i) In patients with inactive UC, acute experimental stress increased LPS stimulated TNF-a and IL-6 production by whole blood. Stress also increased leukocyte count, Natural Killer (NK) cell count, platelet activation and platelet-leukocyte aggregate (PLA) formation. At the mucosal level, stress increased TNF-a in perimucosal fluid, and mucosal ROM production; it reduced rectal mucosal blood flow (RMBF). ii) In patients with active UC, one session of hypnotherapy reduced serum IL-6 concentration and caused a transient reduction in NK cell numbers. At the mucosal level, hypnotherapy caused a reduction in the concentration in peri-mucosal fluid of Substance P, histamine and IL-13 and reduced RMBF. iii) Chronic stress, as assessed by psychometric questionnaires,d id not affect the response to acute experimental stress. iv) There was no difference between the responses of patients with UC and healthy volunteers to any protocol. In conclusion, stress increased, whilst hypnotherapy reduced various inflammatory measures at both the systemic and mucosal level in patients with UC. These effects might contribute to the reported adverse effects of stress and therapeutic efficacy of hypnotherapy in UC

Between-trial heterogeneity in meta-analyses may be partially explained by reported design characteristics.

OBJECTIVE: We investigated the associations between risk of bias judgments from Cochrane reviews for sequence generation, allocation concealment and blinding, and between-trial heterogeneity. STUDY DESIGN AND SETTING: Bayesian hierarchical models were fitted to binary data from 117 meta-analyses, to estimate the ratio λ by which heterogeneity changes for trials at high/unclear risk of bias compared with trials at low risk of bias. We estimated the proportion of between-trial heterogeneity in each meta-analysis that could be explained by the bias associated with specific design characteristics. RESULTS: Univariable analyses showed that heterogeneity variances were, on average, increased among trials at high/unclear risk of bias for sequence generation (λˆ 1.14, 95% interval: 0.57-2.30) and blinding (λˆ 1.74, 95% interval: 0.85-3.47). Trials at high/unclear risk of bias for allocation concealment were on average less heterogeneous (λˆ 0.75, 95% interval: 0.35-1.61). Multivariable analyses showed that a median of 37% (95% interval: 0-71%) heterogeneity variance could be explained by trials at high/unclear risk of bias for sequence generation, allocation concealment, and/or blinding. All 95% intervals for changes in heterogeneity were wide and included the null of no difference. CONCLUSION: Our interpretation of the results is limited by imprecise estimates. There is some indication that between-trial heterogeneity could be partially explained by reported design characteristics, and hence adjustment for bias could potentially improve accuracy of meta-analysis results

Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study.

Flaws in the design of randomized trials may bias intervention effect estimates and increase between-trial heterogeneity. Empirical evidence suggests that these problems are greatest for subjectively assessed outcomes. For the Risk of Bias in Evidence Synthesis (ROBES) Study, we extracted risk-of-bias judgements (for sequence generation, allocation concealment, blinding, and incomplete data) from a large collection of meta-analyses published in the Cochrane Library (issue 4; April 2011). We categorized outcome measures as mortality, other objective outcome, or subjective outcome, and we estimated associations of bias judgements with intervention effect estimates using Bayesian hierarchical models. Among 2,443 randomized trials in 228 meta-analyses, intervention effect estimates were, on average, exaggerated in trials with high or unclear (versus low) risk-of-bias judgements for sequence generation (ratio of odds ratios (ROR) = 0.91, 95% credible interval (CrI): 0.86, 0.98), allocation concealment (ROR = 0.92, 95% CrI: 0.86, 0.98), and blinding (ROR = 0.87, 95% CrI: 0.80, 0.93). In contrast to previous work, we did not observe consistently different bias for subjective outcomes compared with mortality. However, we found an increase in between-trial heterogeneity associated with lack of blinding in meta-analyses with subjective outcomes. Inconsistency in criteria for risk-of-bias judgements applied by individual reviewers is a likely limitation of routinely collected bias assessments. Inadequate randomization and lack of blinding may lead to exaggeration of intervention effect estimates in randomized trials

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Beyond ‘BRICS’: ten theses on South–South cooperation in the twenty-first century

Grounded in a review of past and present academic South–South cooperation literatures, this article advances ten theses that problematise empirical, theoretical, conceptual and methodological issues essential to discussions of South–South cooperation in the 21st century. This endeavour is motivated by the perceived undermining, especially in the contemporary Anglophone academic South–South cooperation literature, of the emancipatory potential historically associated with South–South cooperation. By drawing on the interventionist South–South cooperation agendas of ‘left’-leaning Latin America-Caribbean governments, the article seeks to establish a dialogue between social science theories and less ‘visible’ analyses from academic (semi)peripheries. The ten theses culminate in an exploration of the potential of South–South cooperation to promote ‘alternative’ development

Community structure in animal social networks

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Psychological stress and hypnosis in ulcerative colitis

Previous studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Furthermore, experimental stress has been shown to worsen inflammation in animal models of colitis. Hypnotherapy is effective for functional gastrointestinal (GI) disorders and claimed by some patients to improve ulcerative colitis (UC). Two major hypotheses are tested in this thesis: i) Psychological stress can worsen inflammation via its effects on various systemic and rectal mucosal inflammatory variables in quiescent UC. ii) Relaxation achieved through hypnosis can reduce inflammation via its effects on various systemic and mucosal inflammatory variables in active UC. Patients with UC and healthy controls underwent an experimental stress test, hypnotherapy session or control procedure. Various systemic and, in patients with UC, rectal mucosal inflammatory measures were assessed before and after each procedure. The major findings are as follows: i) In patients with inactive UC, acute experimental stress increased LPS stimulated TNF-a and IL-6 production by whole blood. Stress also increased leukocyte count, Natural Killer (NK) cell count, platelet activation and platelet-leukocyte aggregate (PLA) formation. At the mucosal level, stress increased TNF-a in perimucosal fluid, and mucosal ROM production; it reduced rectal mucosal blood flow (RMBF). ii) In patients with active UC, one session of hypnotherapy reduced serum IL-6 concentration and caused a transient reduction in NK cell numbers. At the mucosal level, hypnotherapy caused a reduction in the concentration in peri-mucosal fluid of Substance P, histamine and IL-13 and reduced RMBF. iii) Chronic stress, as assessed by psychometric questionnaires,d id not affect the response to acute experimental stress. iv) There was no difference between the responses of patients with UC and healthy volunteers to any protocol. In conclusion, stress increased, whilst hypnotherapy reduced various inflammatory measures at both the systemic and mucosal level in patients with UC. These effects might contribute to the reported adverse effects of stress and therapeutic efficacy of hypnotherapy in UC.EThOS - Electronic Theses Online ServiceGBUnited Kingdo