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Objectives: Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling. Design: Online questionnaire circulated via three tertiary IBD centres and Crohn’s Colitis Australia. Methods: Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated. Results: There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn’s disease and ulcerative colitis demonstrated a good fit. In Crohn’s disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn’s disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis. Conclusion: In Crohn’s disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn’s disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority.

Background/Aims Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability. Methods An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn’s Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn’s disease and ulcerative colitis were considered. Results In a cohort of 670 respondents the median age was 41 years (range, 32–70 years), with the majority female (78.4%), the majority had Crohn’s disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn’s disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety. Conclusions Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.

Background and study aims: Colonoscopy with inhaled methoxyflurane (Penthrox) is well tolerated in unselected subjects and is not associated with respiratory depression. The aim of this prospective study was to compare the feasibility, safety, and post-procedural outcomes of portable methoxyflurane used as an analgesic agent during colonoscopy with those of anesthesia-assisted deep sedation (AADS) in subjects with morbid obesity and/or obstructive sleep apnea (OSA). Patients and methods: The outcomes of 140 patients with morbid obesity/OSA who underwent colonoscopy with either Penthrox inhalation (n = 85; 46 men, 39 women; mean age 57.2 ± 1.1 years) or AADS (n = 55; 27 men, 28 women; mean age, 54.9 ± 1.1 years) were prospectively assessed. Results: All Penthrox-assisted colonoscopies were successful, without any requirement for additional intravenous sedation. Compared with AADS, Penthrox was associated with a shorter total procedural time (24 ± 1 vs. 52 ± 1 minutes, P

Abstract Background and Aim Inflammatory bowel disease (IBD) can disrupt sleep, leading to poor sleep quality. This may in part be due to the symptoms of IBD and the influence of pro‐inflammatory cytokines on sleep. This study aimed to investigate the potential influence of IBD medications on sleep quality. Methods An online survey of adults with IBD was conducted, which included measures of sleep quality, IBD activity, anxiety, depression, and physical activity. Logistic regression was used to investigate possible associations between IBD medications (corticosteroids, immunomodulators, biologics, aminosalicyate) and outcome of poor sleep. A generalized linear model was built for outcome of sleep quality score. Results There were 544 participants included in the final analysis, median age of 42, and 61% with Crohn's disease. Increased odds of poor sleep were seen in those taking opioids, medications for anxiety or depression, corticosteroids, vitamin D, methotrexate, and infliximab. A multivariate model was built incorporating demographic and IBD variables with opioids present in the final model and associated with increased odds of poor sleep. This was in addition to medications for sleep, depression, anxiety, IBD activity, and body weight. In a multivariate generalized linear model, opioids and methotrexate were associated with worse sleep quality scores. Conclusions Opioids were associated with increased odds of poor sleep independent of other factors. This provides further support for avoiding these medications in people with IBD. Infliximab was associated with increased body weight and consequently increased odds of poor sleep.

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.