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.

Systematic review: medical therapy for fibrostenosing Crohn's disease.

BACKGROUND: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). AIM: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. RESULTS: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). CONCLUSIONS: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Safety of drugs used for the treatment of Crohn's disease.

INTRODUCTION: Medications in treating Crohn's disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn's disease in adult patients. AREAS COVERED: The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on 'trial' and 'real-world' data for the biologic agents. Safety in pregnancy and the elderly are also presented. EXPERT OPINION: Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.

A Global Survey of Gastroenterologists' Travel Advice to Patients with Inflammatory Bowel Disease on Immunosuppressive Agents and Management of Those Visiting Tuberculosis-Endemic Areas.

BACKGROUND: With increasing use of biological therapies and immunosuppressive agents, patients with inflammatory bowel disease[IBD] have improved clinical outcome and international travel in this group is becoming common. Adequate pre-travel advice is important. We aim to determine the proportion of gastroenterologists who provided pre-travel advice, and to assess their management strategies for patients on biological therapies visiting tuberculosis[TB]-endemic areas. METHODS: A 57-question survey was distributed to IBD physicians in 23 countries. We collected physicians' demographics, and using a standardized Likert scale, assessed physicians' agreement with stated treatment choices. RESULTS: A total of 305 gastroenterologists met inclusion criteria. Overall, 52% would discuss travel-related issues: travellers' diarrhoea [TD], travel-specific vaccines, medical care and health insurance abroad, and TB. They were more likely to advise patients not to travel to TB-endemic area if on both anti-tumour necrosis factor [TNF] and azathioprine, than if on vedolizumab and azathioprine [47% vs 17.6%, p < 0.01]. More IBD physicians agreed with vedolizumab monotherapy vs anti-TNF monotherapy [29.9% vs 23%, p < 0.01]. Two-thirds would continue all IBD treatments and not cease any medications. Chest X-ray and interferon-gamma-release assay were the preferred methods to assess for active and latent TB infection. Knowledge on vaccines among IBD physicians was inadequate (survey mean [SD] scores 10.76 [±6.8]). However, they were more familiar with the societal guidelines on management of venous thromboembolism and TD (mean scores 14.9 [±5.3] and 11.9 [±3.9] respectively). CONCLUSION: Half of IBD specialists would provide pre-travel advice to IBD patients and two-thirds would advise continuing all IBD medications even when travelling to TB-endemic areas. More education on vaccinations would be particularly helpful for IBD physicians.

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease.

BACKGROUND: Vedolizumab (VDZ), an α4ß7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously. AIM: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing. MATERIALS AND METHODS: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected. RESULTS: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size. CONCLUSION: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.

α-Methyldopa-induced hepatitis during the postpartum period.

A 34-year-old woman, with a history of pre-eclampsia, was diagnosed with α-methyldopa-induced hepatotoxicity, after she presented with severe jaundice and hepatitis 8 weeks following delivery. Laboratory investigations and liver biopsy ruled out other causes of hepatitis. She continued to improve clinically after cessation of α-methyldopa, and was discharged 10 days after admission. This case report emphasises that it may not be possible to predict which patients may develop α-methyldopa-induced hepatitis, hence regular monitoring of liver function tests during treatment should be implemented.

Instituting surveillance guidelines and adverse outcomes in preeclampsia.

OBJECTIVE: To assess the incidence of combined adverse maternal and perinatal outcomes in women with preeclampsia before and after introducing standardized assessment and surveillance. METHODS: This study was a preintervention (retrospective) compared with a postintervention (prospective) cohort comparison in a single-tertiary, perinatal unit that included women admitted to hospital with preeclampsia. We interrogated an existing retrospective 24-month database and then introduced the guidelines, assessing the incidence of the combined adverse maternal and perinatal outcomes for 41 months (September 2003 through February 2007). Tests of organ (dys)function were performed at least as often as on the day of admission, admission day +1, every Monday and Thursday, day of delivery, and delivery day +1. All data were checked for errors. The combined maternal outcome was maternal death or one or more of hepatic failure, hematoma, or rupture, Glasgow coma score of less than 13, stroke, at least two seizures, cortical blindness, need for positive inotrope support, myocardial infarction, infusion of any third antihypertensive, renal dialysis, renal transplantation, at least 50% FIO(2) for greater than 1 hour, intubation, or transfusion of at least 10 units of blood products. The combined perinatal outcome was perinatal or infant mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, grade III/IV intraventricular hemorrhage, cystic periventricular leukomalacia, or stage 3-5 retinopathy of prematurity. RESULTS: Two hundred ninety-five and 405 women were in the preintervention and postintervention cohorts, respectively. The incidence of adverse maternal outcome fell (5.1% to 0.7%; Fisher P<.001; odds ratio 0.14, 95% confidence interval 0.04-0.49). Perinatal outcomes did not change. CONCLUSION: Standardized surveillance of women with preeclampsia was associated with reduced maternal risk.