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      Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease: a systematic review utilising Bradford Hill criteria and meta-analysis of prospective cohort studies

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          Abstract

          Background

          Psychological stress is a prevalent factor in inflammatory bowel disease (IBD) with detrimental effects on patients’ quality of life and possibly disease course. Although the aetiology of symptom exacerbation in IBD has been explored, determining any causation between psychological stress and symptom worsening remains challenging and requires a methodologically rigorous approach.

          Aim

          The aim of this systematic review with meta-analysis was to determine a causal relationship between psychological stress and symptom exacerbation in IBD, subsequently utilising Bradford Hill’s criteria (approach never used in this topic area before) to evaluate the likelihood of causal associations.

          Methods

          Medline, EMBASE, CINAHL and PsycInfo were searched for relevant studies up to July 20, 2019. Data extraction and quality appraisal were performed by two independent reviewers. Results of all retained papers were presented as a narrative synthesis. A random-effect meta-analysis was conducted on studies meeting the criteria for meta-analysis. Bradford Hill criteria were applied to assess the causality of the relationship between all psychological factors and symptom exacerbation.

          Results

          The searches yielded 2472 potential articles. Nineteen clinical prospective cohort studies were eligible for the narrative review with five suitable for the meta-analysis. Meta-analysis showed depression, anxiety and perceived stress did not have a statistically significant association with an increased risk of symptom exacerbation. Four of the Bradford Hill criteria were met which indicates that there is weak to moderate evidence of a causal association between all the psychological factors and disease activity. Inconsistent results and a dearth of studies using the same tools for measuring psychological factors suggest the need for more research to be done to facilitate more conclusive findings.

          Conclusions

          This original review utilising Bradford Hill criteria in addition to meta-analysis to evaluate the causality of relationship between psychological factors and symptom exacerbation in IBD provides evidence that psychological factors have a weak to moderate causal involvement in IBD symptom exacerbation. However, when combining this finding with the outcomes of the meta-analysis, we can say that the results were inconclusive . Interventions to reduce the associated psychological impact should be part of the treatment plan for patients with IBD.

          Systematic review registration

          PROSPERO CRD42012003143

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          Most cited references54

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          Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.

          There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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            Causation and causal inference in epidemiology.

            Concepts of cause and causal inference are largely self-taught from early learning experiences. A model of causation that describes causes in terms of sufficient causes and their component causes illuminates important principles such as multi-causality, the dependence of the strength of component causes on the prevalence of complementary component causes, and interaction between component causes. Philosophers agree that causal propositions cannot be proved, and find flaws or practical limitations in all philosophies of causal inference. Hence, the role of logic, belief, and observation in evaluating causal propositions is not settled. Causal inference in epidemiology is better viewed as an exercise in measurement of an effect rather than as a criterion-guided process for deciding whether an effect is present or not.
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              Evidence based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies.

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                Author and article information

                Contributors
                m.schoultz@salford.ac.uk
                michelle.beatie@uhi.ac.uk
                trish.gorely@uhi.ac.uk
                j.leung@uq.edu.au
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                1 August 2020
                1 August 2020
                2020
                : 9
                : 169
                Affiliations
                [1 ]GRID grid.8752.8, ISNI 0000 0004 0460 5971, School of Health and Society, , University of Salford, ; Manchester, UK
                [2 ]GRID grid.23378.3d, ISNI 0000 0001 2189 1357, Centre for Health Sciences, , University of Highlands and Islands, ; Inverness, Scotland, UK
                [3 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Faculty of Health and Behavioural Sciences, , The University of Queensland, ; Brisbane, Australia
                Author information
                http://orcid.org/0000-0003-3780-8110
                Article
                1426
                10.1186/s13643-020-01426-2
                7395978
                32738908
                86459682-c5fd-46f7-8666-44756b525754
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 9 October 2019
                : 10 July 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Public health
                inflammatory bowel disease,crohn’s disease,ulcerative colitis,psychological factors,symptom exacerbation,systematic review,meta-analysis

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