Active Inflammatory Bowel Disease Is Associated with Short Sleep Duration via Objective Measures.

INTRODUCTION: Poor sleep quality has been associated with inflammatory bowel disease (IBD) activity, although studies incorporating actigraphy suggest that the perception of sleep differs rather than objective difference in sleep quality. Short sleep duration has been associated with increased pro-inflammatory cytokines that have been implicated in the pathogenesis of IBD. METHODS: An observational study incorporated home-based polysomnography that was conducted within twelve weeks of an objective assessment of IBD activity such as calprotectin, colonoscopy, or MRI. Participants completed a survey on subjective measures of sleep quality, clinical IBD activity, depression, and anxiety. Polysomnography results were normalized by standardized results for a healthy population matched by gender and age. RESULTS: Twenty participants were included in the final analysis. Those with objective evidence of active IBD had shorter stage 2 sleep duration, leading to shorter NREM sleep and total sleep time. Sleep latency was also longer in those with active IBD, leading to worse sleep efficiency-despite no difference in time available for sleep between the two groups. These changes persisted after normalization of polysomnography results by health population age and gender matched norms. Depression scores correlated with sleep latency and stage 2 sleep duration and were associated with objectively active IBD. CONCLUSIONS: Objectively confirmed active IBD was associated with shorter sleep duration. Observed sleep changes may, in part, relate to coexistent depression. Further research should consider the utility of changes in sleep duration and quality as a means of longitudinally assessing objective IBD activity.

Latent profiles of fatigue in inflammatory bowel disease.

INTRODUCTION: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. METHODS: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. RESULTS: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. CONCLUSION: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Insomnia is common in inflammatory bowel disease (IBD) and is associated with mental health conditions as well as IBD activity.

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.

Simple Novel Screening Tool for Obstructive Sleep Apnea in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) has been associated with an increased risk of obstructive sleep apnea (OSA). We aimed to examine the associations of obstructive sleep apnea, sleepiness, and IBD-related data and comorbidities, with the aim of developing a screening tool for sleep apnea in this population. Methods: An online survey of adults with IBD was administered which included measures of assessment of the risk of OSA, and measures of IBD activity, IBD-related disability, anxiety, and depression. Logistic regression was performed to investigate the associations between the risk of OSA and IBD data, medications, demographics, and mental health conditions. Further models were built for an outcome of severe daytime sleepiness and a combined outcome of risk of OSA and at least mild daytime sleepiness. A simple score was constructed for the purpose of screening for OSA. Results: There were 670 responses to the online questionnaire. The median age was 41 years, the majority had Crohn's disease (57%), the median disease duration was 11.9 years, and approximately half were on biologics (50.5%). Moderate-high risk of OSA was demonstrated in 22.6% of the cohort. A multivariate regression model for moderate-high risk of OSA included increasing age, obesity, smoking, and abdominal pain subscore. For a combined outcome of moderate-high risk of OSA and at least mild daytime sleepiness, a multivariate model included abdominal pain, age, smoking, obesity, and clinically significant depression. A simple score was constructed for screening for OSA utilizing age, obesity, IBD activity, and smoking status with an area under the receiver-operating curve of 0.77. A score >2 had a sensitivity of 89% and a specificity of 56% for moderate-high risk of OSA and could be utilized for screening for OSA in the IBD clinic. Conclusions: Over one-fifth of an IBD cohort met significantly high-risk criteria for OSA to warrant referral for a diagnostic sleep study. The risk of OSA was associated with abdominal pain, along with more traditional risk factors such as smoking, increasing age, and obesity. Consideration should be given for screening for OSA in IBD patients utilizing a novel screening tool that utilizes parameters typically available in IBD clinic.

Examining the influence of inflammatory bowel disease medications on sleep quality.

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.

Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Proactive Metabolite Testing in Patients on Thiopurine May Yield Long-Term Clinical Benefits in Inflammatory Bowel Disease.

BACKGROUND: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP). TDM of thiopurines involves measurement and interpretation of metabolites 6-TGN and 6-MMPR. AIMS: This study aimed to assess long-cterm outcomes of patients on thiopurines following therapeutic drug monitoring. METHODS: A multicenter retrospective observational study of outcomes post thiopurine TDM was conducted. Demographics, disease characteristics, physician global assessment, IBD therapy at baseline TDM and again at 12 months were collected. Clinical outcomes were analyzed according to TDM result, and indication for TDM including proactive and other indications. RESULTS: The study included 541 patients. Only 39% of patients had appropriate dosing of thiopurines. AZA/6MP TDM informed a management change in 61.9%, and enabled 88.8% of the cohort to continue AZA/6MP following TDM. At 12 months following TDM the majority (74.1%) of the cohort remained on AZA/6MP. Clinical remission was higher at 12-months following thiopurines TDM (68%) compared to baseline (37%), including proactive TDM. Post TDM, 13.0% of patients were identified as shunters and commenced on thiopurine-allopurinol co-therapy. CONCLUSION: Thiopurine TDM resulted in a change in management for the majority of patients. Post TDM significantly more patients were in remission. TDM allowed the identification of non-adherence and shunters who, without intervention, would not reach therapeutic drug levels. Proactive TDM allowed identification and management of inappropriate dosing, and was associated with increased levels of clinical remission.

Systematic review and meta-analysis of sleep quality in inactive inflammatory bowel disease.

Poor sleep in people with inflammatory bowel disease (IBD) has been demonstrated to be prevalent and has been associated with disease activity. This meta-analysis aimed to assess the prevalence of poor sleep in inactive IBD and in controls by considering cohort and cross-sectional studies. Electronic databases were searched for publications from inception to 1 November 2021. Poor sleep and IBD activity were defined according to self-reported subjective sleep measures. A random effects model was used to determine the standardized mean difference between poor sleep in inactive IBD and healthy controls. Publication bias was assessed by funnel plot and Egger's test. Five hundred and nineteen studies were screened with 9 studies included in the meta-analysis incorporating a total of 729 people with IBD and 508 controls. A random effects model showed a standardized mean difference with poor sleep being more frequent in those with inactive IBD than controls with moderate effect size (Hedge's g 0.41, CI [0.22-0.59]) and no significant heterogeneity. There was no publication bias evident. Poor sleep is more common in individuals with inactive IBD than healthy controls. Further studies should consider potential mechanisms to explain this result, including the role of subclinical inflammation and psychosocial factors that may influence sleep quality in people with IBD.

A systematic review and meta-analysis of the prevalence of poor sleep in inflammatory bowel disease.

Study Objectives: Poor sleep-in people with inflammatory bowel disease (IBD) has been associated with worse quality of life, along with anxiety, depression, and fatigue. This meta-analysis aimed to determine the pooled prevalence of poor sleep-in IBD. Methods: Electronic databases were searched for publications from inception to November 1st 2021. Poor sleep was defined according to subjective sleep measures. A random effects model was used to determine the pooled prevalence of poor sleep-in people with IBD. Heterogeneity was investigated through subgroup analysis and meta-regression. Publication bias was assessed by funnel plot and Egger's test. Results: 519 Studies were screened with 36 studies included in the meta-analysis incorporating a total of 24 209 people with IBD. Pooled prevalence of poor sleep-in IBD was 56%, 95% CI (51-61%) with significant heterogeneity. The prevalence did not differ based on the definition of poor sleep. Meta-regression was significant for increased prevalence of poor sleep with increase in age and increased of prevalence of poor sleep with objective IBD activity but not subjective IBD activity, depression, or disease duration. Conclusions: Poor sleep is common in people with IBD. Further research is warranted to investigate if improving sleep quality in people with IBD will improve IBD activity and quality of life.

Corticosteroid exposure prior to admission and predicting need for rescue therapy in acute severe ulcerative colitis.

BACKGROUND: Steroid exposure has been associated with poorer outcomes following colectomy in acute severe ulcerative colitis (ASUC). AIM: To examine the effect of prolonged oral corticosteroid therapy immediately prior to admission on the likelihood of requiring rescue therapy along with predictors of intravenous corticosteroid failure on Day 1 of admission. METHODS: A retrospective case note and electronic record review was conducted at a tertiary inflammatory bowel disease referral centre of admissions for ASUC meeting Truelove and Witts criteria from 2013 to 2019.The data was analysed for the effect of pre-admission steroid exposure on need for rescue therapy and for predictors of intravenous corticosteroid failure. RESULTS: Ninety-two admissions were identified for ASUC meeting Truelove and Witts criteria. Over 1 week of steroid therapy prior to admission was associated with need for rescue therapy and trended to significance for colectomy at admission and at 12 months. A generalised linear model was constructed with multivariate regression significant for over 1 week of steroid therapy prior to admission, endoscopic Mayo score and albumin. The area under the receiver operator curve for this model was 0.86. CONCLUSION: Prolonged steroid use prior to ASUC admission is a significant predictor of need for rescue therapy. A generalised linear model incorporating steroid prior to admission, endoscopic Mayo score and albumin was highly accurate at predicting failure of corticosteroid. Consideration should be given for commencement of rescue therapy prior to Day 3, especially in those with prolonged steroid prior to admission.

Inpatient usage of faecal calprotectin in a tertiary hospital.

BACKGROUND: Faecal calprotectin (FCP) is a highly sensitive non-invasive marker of intestinal inflammation that has evidence-based roles in outpatient diagnosis and management of inflammatory bowel disease. AIMS: To examine indications for FCP in a tertiary inpatient population and its role in inpatient management and subsequent investigations. METHODS: An electronic database was used to identify all patients over the age of 18 years who had FCP performed during a hospital admission over a 3-year period from March 2016 to the end of March 2019. Electronic records and case notes were reviewed with follow up to March 2020, seeking indication for testing, healthcare units requesting, and subsequent investigations and treatment resulting from FCP. RESULTS: Over a 3-year period, 111 FCP inpatient results were identified. There were three changes in management based on the FCP result that led to further investigations that did not lead to any clinically significant pathology. There was no observable difference in the number of colonoscopies performed based on FCP level. The numerical FCP value was associated with clinically significant findings on colonoscopy. Negative predictive value of FCP level (≤50 µg/g) for clinically significant finding on colonoscopy was 64%. CONCLUSION: Non-guideline-based hospital inpatient usage of FCP rarely changes inpatient management and had no observable difference in the usage of subsequent diagnostic colonoscopy. Regardless, the FCP level remained a strong predictor of clinically significant pathology on colonoscopy.

Ocrelizumab-induced inflammatory bowel disease-like illness characterized by esophagitis and colitis.

Ocrelizumab is an intravenous anti-CD20 monoclonal antibody, approved for use in primary progressive multiple sclerosis due to its selective depletion of B-lymphocytes. Herein we describe the case of a 56-year-old female who developed odynophagia and bloody diarrhea following treatment with ocrelizumab. This was characterized endoscopically by ulcerations in the esophagus and colon. The patient was treated with high-dose intravenous glucocorticoids with good clinical response.

Medication adherence and complementary therapy usage in inflammatory bowel disease patients during the coronavirus disease 2019 pandemic.

BACKGROUND AND AIM: Medication nonadherence is common in patients with inflammatory bowel disease (IBD) and has been associated with worse outcomes. The coronavirus disease 2019 (COVID-19) pandemic led to significant consumer and medical concern regarding the possible risks of immunosuppressive medications during the pandemic. This study aimed to examine medication adherence and complementary and alternative medicine (CAM) usage during the COVID-19 pandemic. METHODS: An online survey was sent to patients from two tertiary IBD units. The survey included medication nonadherence attributed to the COVID-19 pandemic, complementary therapy, and IBD medication use. Validated measures of IBD disease activity, medication adherence, and beliefs about medicines were obtained. RESULTS: Of 262 respondents (median age of 46, 58% female) 14 (5%) patients reported self-initiated missed doses or dose reduction of IBD medications directly attributed to the COVID-19 pandemic. Positive associations with medication nonadherence included current corticosteroid requirement (P = 0.022), higher disease activity scores (P = 0.026), and higher concern about medicines score (P = 0.04). CAM usage was common, aimed at treating mental health in most cases, and infrequently attributed to the COVID-19 pandemic. CONCLUSIONS: Even in the setting of low COVID-19 prevalence, the pandemic reduced IBD medication adherence in 1 in 20 patients. This reduced adherence was co-associated with increased disease activity and corticosteroid use. Understanding the underlying beliefs driving suboptimal IBD medication adherence is critical to prevent avoidable adverse IBD outcomes.

Level of UV Exposure, Skin Type, and Age Are More Important than Thiopurine Use for Keratinocyte Carcinoma Development in IBD Patients.

BACKGROUND: Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. METHODS: Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. RESULTS: A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61 years old versus less than 30 years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). CONCLUSION: Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.

Limited uptake of ulcerative colitis "treat-to-target" recommendations in real-world practice.

BACKGROUND AND AIMS: A "treat-to-target" approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges. METHODS: A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated gastroenterologists' perceptions of treat to target in UC. Statistical analysis included logistic regression and Fisher's exact tests. RESULTS: Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤ 1), and 16% in concordant clinical, endoscopic, and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, P < 0.001; OR 3.3, 95% CI 1.1-12.5, P = 0.04, respectively). Clinicians used C-reactive protein more often than endoscopy as a biomarker for disease activity (75% vs 47%, P < 0.001). In the survey, 45/61 gastroenterologists responded, with significant disparity between clinician estimates of targets achieved in practice and real-world data (P < 0.001 for clinical and endoscopic remission). CONCLUSIONS: Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.

Doctor communication quality and Friends' attitudes influence complementary medicine use in inflammatory bowel disease.

AIM: To examine the frequency of regular complementary and alternative therapy (CAM) use in three Australian cohorts of contrasting care setting and geography, and identify independent attitudinal and psychological predictors of CAM use across all cohorts. METHODS: A cross sectional questionnaire was administered to inflammatory bowel disease (IBD) patients in 3 separate cohorts which differed by geographical region and care setting. Demographics and frequency of regular CAM use were assessed, along with attitudes towards IBD medication and psychological parameters such as anxiety, depression, personality traits and quality of life (QOL), and compared across cohorts. Independent attitudinal and psychological predictors of CAM use were determined using binary logistic regression analysis. RESULTS: In 473 respondents (mean age 50.3 years, 60.2% female) regular CAM use was reported by 45.4%, and did not vary between cohorts. Only 54.1% of users disclosed CAM use to their doctor. Independent predictors of CAM use which confirm those reported previously were: covert conventional medication dose reduction (P < 0.001), seeking psychological treatment (P < 0.001), adverse effects of conventional medication (P = 0.043), and higher QOL (P < 0.001). Newly identified predictors were CAM use by family or friends (P < 0.001), dissatisfaction with patient-doctor communication (P < 0.001), and lower depression scores (P < 0.001). CONCLUSION: In addition to previously identified predictors of CAM use, these data show that physician attention to communication and the patient-doctor relationship is important as these factors influence CAM use. Patient reluctance to discuss CAM with physicians may promote greater reliance on social contacts to influence CAM decisions.