Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. Design: This is a retrospective, multicentre study of patients admitted with ASUC. Methods: CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. Results: CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). Conclusion: CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Cytomegalovirus reactivation in acute severe ulcerative colitis Cytomegalovirus (CMV) is a highly prevalent virus that may result in concominant reactivation in patients with acute severe ulcerative colitis and potentially worsen their outcomes. Our study aims to determine the impact of presence of CMV in patients with acute severe ulcerate colitis requiring hospitalisation and its association with outcomes including risk of surgical resection of colon, length of hospital stay, readmission rate, as well as effect of outcomes amongst those treated with antivirals for CMV. Our results did not find a significant association between detection of CMV on surgical risk, though outcomes including longer hospital stays, higher readmission rate were found. Antiviral use was not associated with lower risk of surgery but was found to prolong time to surgery. Given that our study was based on retrospective data, further prospective studies will be required to examine the benefit of antiviral use in outcomes for those with concominant CMV and acute severe ulcerative colitis. We conclude from our study that while having concomitant CMV with acute severe uclerative colitis may not necessarily increase risk for surgery, patients may still have worse outcomes in other areas therefore the detection of CMV should be considered a significant and clinically relevant result.

Adolescents and young adults communicating with gastroenterologists: variation in inflammatory bowel disease clinical communication.

OBJECTIVES: This study explored the variation in emerging adults' communication with gastroenterologists around the management of inflammatory bowel disease (IBD). METHODS: Nineteen emerging adults with IBD aged 18-25 and seven gastroenterologists participated in the study. Outpatient specialist consultations of consenting participants were audio-recorded and transcribed. Transcribed consultations were analysed in terms of the linguistic structure of the consultations and the gastroenterologist-patient role relationship. RESULTS: Variations in the emerging adults' communication with their gastroenterologists stem partly from variation in their ability, opportunity, or need to contribute to the different phases of the consultation and partly from variations in the gastroenterologists' style of communication. Gastroenterologists differed in the construction of their role relationship with the patient, resulting in variations in employing empowering strategies including eliciting, exploring, and clarifying the patient's concerns, sharing clinical reasoning, and validating the patient experience. Variations were also observed in the length of appointments and the gastroenterologists' assessment and addressing of adherence issues. Techniques used by the gastroenterologist varied (1) from simply confirming adherence, to a comprehensive assessment of the patient's understanding of their management plan and their feedback, and (2) from use of persuasion to values calibration. CONCLUSIONS: Evidence-based consumer interventions and communication guidelines for clinicians are needed to address the identified variations in providing care to emerging adults living with chronic conditions.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

INTRODUCTION: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes. It is unclear whether a combination of multimedia modalities can improve bowel preparation quality, adenoma detection rates and patient-reported measures in those undergoing colonoscopy assessment. METHODS: The DIGICLEAN trial is a prospective, parallel, multicentre, colonoscopist-blinded, randomised controlled trial. The trial will enrol 1294 participants aged 45 years and older who are indicated for a colonoscopy as an outpatient with a positive faecal occult blood test, iron deficiency anaemia or rectal bleeding. Participants will be randomised into the interventional arm, where bowel preparation instructions are delivered via a web-based application which uses scheduled short messaging service, regular patient survey assessment, email and videos; or the control arm, where routine standard written, verbal or emailed instructions are administered. The web-based application will assess patient-reported bloating, constipation and dietary adherence leading up to the colonoscopy. Depending on patient responses, additional aperients may be encouraged digitally in the interventional arm with same instructions made available in written format for the control arm. Patient-reported measures will be collected in both arms the day after the procedure using the validated Newcastle ENDOPREM questionnaire. In some sites, participants will undergo digital pre-anaesthetic screening as well. The co-primary endpoints are the adenoma detection rates and patient-reported measures taken after the colonoscopy. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Western Sydney Local Health District Human Research Ethics Committee (2022/ETH00059). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000747729.

Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease: A case report and review of literature.

BACKGROUND: Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases, including Crohn's disease (CD). CASE SUMMARY: This case report and narrative review demonstrate the potential safety of dual biologic therapy (DBT) in a 45-year-old female with two separate immune-mediated diseases. She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab, and she had been recently diagnosed with CD after presenting with diarrhoea. The CD diagnosis was confirmed radiologically, endoscopically, histologically, and biochemically. The patient received treatment with vedolizumab, a gut-specific inhibitor of the α4ß7 integrin on leukocytes. No adverse reactions were observed for the duration of treatment. The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated. CONCLUSION: DBT may be a safe and effective option for the treatment of refractory disease or multiple immune-mediated diseases. Newer biologics, which have improved safety profiles and gut specificity, may provide promising avenues for treatment. However, caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties, side effects, and efficacy profiles. Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019, but treatment decisions should be made in a multidisciplinary setting. Further research from controlled trials is needed to better understand the safety profile of DBT in CD. The immunopathological mechanisms underlying DBT also remain to be clarified.

Review of exclusive enteral therapy in adult Crohn's disease.

BACKGROUND: Exclusive enteral nutrition (EEN) is a potentially effective but underused therapy for Crohn's disease (CD) in adults. It is first-line induction treatment for paediatric patients but remains a second-line or third-line therapy in adults. OBJECTIVE: To analyse the evidence for EEN in adult patients with CD, and summarise this in a narrative review. METHODS: In April/May 2020 and July 2021, a literature search was performed using the Medical Subject Headings (MeSH) terms: 'Crohn's disease', 'CD', 'inflammatory bowel disease', 'IBD', 'exclusive enteral nutrition', 'enteral nutrition', 'EEN', in PubMed, Scopus, Cochrane. Additional studies were obtained from references of search result articles as well as general reading. Studies with adult patients with CD treated with EEN were selected. 79 articles of relevance were found. Where data in adults were lacking, data from paediatric studies as extrapolated with care. RESULTS: EEN in adult patients been shown to improve clinical, biomarker, endoscopic and radiologic measures of disease activity. EEN avoids the potential adverse effects of recurrent corticosteroids for induction such as metabolic derangements and opportunistic infections. EEN has also demonstrated benefits among adult patients with fistulising and stricturing CD. It may avoid surgery in such patients. Preoperative EEN has also been shown to reduce postoperative complications and recurrence. There appears to be benefits in combing EEN with antitumour necrosis factor agents, however, benefits of combination therapy with other biologics are less clear. A major drawback of EEN therapy in adults has been poor compliance. More palatable polymeric formulations improved patient education and dietitian support may overcome this. Evidence in adults is limited to small studies, often with suboptimal control arms and lack of blinding. Larger scale studies with improved study design are needed to confirm these beneficial effects. CONCLUSION: Despite limitations in evidence EEN should be considered in treating adults with CD.

Early thiopurine maintenance is associated with reduced proximal disease progression and colectomy rate in ulcerative colitis.

BACKGROUND: Thiopurines effectively maintain remission in ulcerative colitis patients. Whether early initiation of thiopurines after ulcerative colitis diagnosis decreases proximal disease progression and colectomy rates is not known. METHODS: We conducted a cohort study of ulcerative colitis subjects recruited from 1970 to 2009. Early thiopurine maintenance was defined as commencement of azathioprine or mercaptopurine within 5 years of diagnosis and maintenance for at least 6 months. Propensity score matching was conducted to correct for confounders influencing early thiopurine introduction. Outcomes of interest were colectomy rate and endoscopic proximal disease extension. RESULTS: 982 consecutive ulcerative colitis subjects (12 879 patient-years) were recruited with 116 requiring colectomy. Thiopurines initiation and maintenance increased over time with median time to thiopurine commencement decreasing from 23 years in the first decade to 2 years in the last decade (P < 0.0001). Multivariate analysis showed that early thiopurine maintenance significantly decreased the need for colectomy [hazard ratio, 0.13; 95% confidence interval (CI):0.03-0.55; P = 0.006]. The number of subjects needed to be treated to reduce one colectomy at 5 and 10 years was 18 (95% CI, 16- 36) and 12 (95% CI, 11-25). After propensity score matching, early thiopurine maintenance was significantly associated with decreased colectomy (hazard ratio, 0.10; 95% CI, 0.03-0.43; P = 0.002) and proximal progression of disease extent (hazard ratio, 0.26; 95% CI, 0.10-0.78; P = 0.015). CONCLUSION: Early thiopurine maintenance for >6 months is significantly associated with reduced colectomy and proximal progression of disease extent in ulcerative colitis.

Depression, anxiety and stress among patients with inflammatory bowel disease during the COVID-19 pandemic: Australian national survey.

BACKGROUND: The global COVID-19 pandemic has impacted on the mental health of individuals, particularly those with chronic illnesses. We aimed to quantify stress, anxiety and depression among individuals with Inflammatory bowel disease (IBD) in Australia during the pandemic. METHODS: An electronic survey was made available to IBD patients Australia-wide from 17 June to 12 July 2020. Respondents with an underlying diagnosis of IBD and over 18 years of age were included. A validated questionnaire (Depression, Anxiety, Stress Score-21, DASS21) was used to assess depression, anxiety and stress. Data on potential predictors of depression, anxiety and stress were collected. RESULTS: 352 participated in the survey across Australia. 60.5% of respondents fulfilled DASS criteria for at least moderate depression, anxiety or stress. 45% reported a pre-existing diagnosis of depression and/or anxiety. Over 2/3 of these respondents reported worsening of their pre-existing depression/anxiety due to the current pandemic. Of those without a pre-existing diagnosis of anxiety or depression, high rates of at least moderate to severe depression (34.9%), anxiety (32.0%) and stress (29.7%) were noted. Younger age (OR 0.96, 95% CI 0.94 to 0.98, p<0.001), lack of access to an IBD nurse (OR 1.81, 95% CI 1.03 to 3.19, p=0.04) and lack of education on reducing infection risk (OR 1.99, 95% CI 1.13 to 3.50, p=0.017) were associated with significant stress, anxiety and/or depression. CONCLUSION: High prevalence of undiagnosed depression, anxiety and stress was identified among respondents. Improved access to IBD nurse support and greater attention to education are modifiable factors that may reduce depression, anxiety and/or stress among patients with IBD during the pandemic.

Medication non-adherence in inflammatory bowel diseases is associated with disability.

BACKGROUND/AIMS: Medication non-adherence is common in inflammatory bowel diseases (IBD). The short-term consequences of non-adherence include increased disease relapse but the long-term impact upon patients in terms of daily functional impairment are less well characterized. Identifying negative outcomes, such as disability, may encourage adherence. METHODS: Consecutive ambulatory IBD subjects completed the Medication Adherence Rating Scale (MARS; non-adherence defined as ≤16), Inflammatory Bowel Diseases Disability Index (IBD-DI; disability: <3.5) and Beliefs about Medicines Questionnaire (high necessity/concerns: ≥16). The primary outcome was the association between medication non-adherence and disability. Secondary outcomes were the predictors of these outcomes. RESULTS: A total of 173 subjects on IBD maintenance medications were recruited (98 Crohn's disease, 75 ulcerative colitis: median IBD-DI, -5.0; interquartile range [IQR], -14.0 to 4.0 and median MARS, 19.0; IQR, 18 to 20) of whom 24% were non-adherent. Disability correlated significantly with medication non-adherence (r=0.38, P<0.0001). Median IBD-DI for non-adherers was significantly lower than adherers (-16.0 vs. -2.0, P<0.0001). Predictors of disability included female sex (P=0.002), previous hospitalization (P=0.023), management in a referral hospital clinic (P=0.008) and medication concerns (P<0.0001). Non-adherence was independently associated with difficulty managing bowel movements (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.50-9.16, P=0.005), rectal bleeding (OR, 2.69; 95% CI, 1.14-6.36; P=0.024) and arthralgia/arthritis (OR, 2.56; 95% CI, 1.11-5.92; P=0.028). CONCLUSIONS: Medication non-adherence was associated with significantly increased disability in IBD. Female gender, higher disease severity and medication concerns were additional predictors of disability.

Therapeutic drug monitoring of anti-tumour necrosis factor-α agents in inflammatory bowel disease.

INTRODUCTION: Anti-TNFα therapy has revolutionised treatment of inflammatory bowel disease, however primary non-response and secondary loss of response are a significant problem. Therapeutic drug monitoring (TDM) has recently emerged as a means of optimising use of anti-TNFα agents. Areas covered: TDM of anti-TNFα agents can guide clinical decisions during treatment failure events, prevent treatment failure events, and potentially result in significant healthcare cost saving. TDM for anti-TNFα agent involves measurement of drug levels and anti-drug antibodies, and can be performed reactively or proactively. Reactive TDM reserves testing for treatment failure events, while proactive TDM also consists of periodic TDM for patients responding to anti-TNFα therapy to allow treatment optimisation. Generation of anti-drug antibodies is recognised as one important mechanism of treatment failure and adverse events. Expert opinion: Evidence strongly supports TDM at time of treatment failure, while studies employing proactive TDM have demonstrated conflicting results. TDM can also help better select patients likely to remain in clinical remission on anti-TNFα treatment interruption. Currently TDM is used to optimise anti-TNFα treatment, but it is not used by most clinicians to prevent adverse reactions to anti-TNFα agents.

Hygiene Hypothesis: Is the Evidence the Same All Over the World?

BACKGROUND: The hygiene hypothesis refers to where modern living conditions are responsible for the increasing incidences of immune-related diseases including the development of inflammatory bowel diseases (IBD). Improved hygiene may result in decreased enteric microbiota diversity and dysbiosis, which may be responsible for the development of IBD. KEY MESSAGES: The rising incidence of IBD is well documented in developing regions of the world, in accordance with the hygiene hypothesis. What is unknown, however, is whether the hygiene hypothesis is applicable all over the world. Hygiene cannot be easily measured and proxy markers need to be used. These include regional data such as a country's gross domestic product or an individual's affluence or exposure to infection risk factors. A comparative case-control study of Caucasian Australian IBD subjects versus migrants from the Middle East to Australia identified that environmental risk factors are different in the 2 populations. Among Australian Caucasians, hygiene-related environmental risk factors are no longer relevant in the development of IBD. Given the country's high affluence, there has been high hygienic standard for several generations. However, migrants from less affluent countries exposed to hygiene-related environmental factors are at increased risks of developing IBD, especially in the second generation migrants born in the affluent country. Divergent risk factors include the use of antibiotics in childhood increasing the risk of IBD in developed societies but being a risk factor for developing IBD in migrants. In India, risk factors associated with infections were found to be positively associated with the development of ulcerative colitis, rather than protective. CONCLUSIONS: The hygiene hypothesis is not applicable to all populations worldwide, being most relevant in societies undergoing increasing affluence or following migration from less to more affluent countries. This review examines data from around the world that link the hygiene hypothesis with the development of IBD and in particular the divergent results arising from data from affluent countries versus less-affluent countries.