Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 µg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 µg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 µg/mL, interquartile rate [IQR], 12.3-18.5 µg/mL versus 15.9 µg/mL, IQR, 10.1-22.7 µg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Is the European Crohn's and Colitis organisation (ECCO) e-guide an acceptable and feasible tool for increasing gastroenterologists' guideline adherence? A mixed methods evaluation.

BACKGROUND AND AIMS: Management of inflammatory bowel disease is constantly evolving, increasing the importance for gastroenterologists to keep up to date with guidelines. Traditional implementation strategies have had only small positive impacts on clinical practice. eHealth strategies such as the European Crohn's and Colitis Organisation e-guide may be beneficial for clinician decision making in keeping with guidelines. The aim of this study was to evaluate the feasibility and acceptability of the e-guide. METHODS: A mixed methods approach was used to evaluate feasibility and acceptability. Cognitive (think-aloud) interviews were conducted with Australian gastroenterologists while using the e-guide. Two clinical scenarios were developed to allow evaluation of various aspects of the e-guide. Content analysis was applied to the qualitative interview data and descriptive analysis to the quantitative and observational data. RESULTS: Seventeen participants completed the study. Data saturation were reached. The ECCO e-guide was largely feasible and acceptable, as demonstrated by most clinical questions answered correctly, 87% reaching the answer within 3 min, and most feeling it was useful, would be beneficial to their practice and would use it again. Issues raised included difficulties with website navigation, layout of the e-guide and difficulties with access (network firewalls, paid subscription required). CONCLUSIONS: The ECCO e-guide is largely acceptable and feasible for gastroenterologists to use. Aspects of the e-guide could be modified to improve user experience. This study highlights the importance of engaging end-users in the development and evaluation of clinician educational tools.

Integration of mental health and quality of life screening tools in an inflammatory bowel disease-specific electronic medical record (Crohn Colitis Care): process and early outcomes.

Psychological problems are prevalent in people with inflammatory bowel diseases but are not routinely addressed. To improve recognition, three psychological screening tools were integrated into clinical management software (Crohn Colitis Care). In the first 6 months, completion rates varied between participating sites, and approximately 23-34% of respondents scored in moderate or higher ranges for psychological distress. Evaluation of the clinical utility of the module to improve patient outcomes is recommended.

Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas.

BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 µg/mL; adalimumab 9.1 vs 6.2 µg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 µg/mL; P < .05; adalimumab 9.8 vs 6.2 µg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.

Safety, satisfaction and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

BACKGROUND: Infliximab remains a mainstay for the treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and healthcare providers. AIMS: To assess the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. METHODS: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions: over 30 min if receiving a standard dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. RESULTS: Fifty-two patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with a standard dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild and self-limiting. None required drug cessation. Patient satisfaction was improved with shortened infusion time as compared with the patients' previous experiences (P = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (±4.9) to 7.9 mg/L (±4.1) (P = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per patient per year for standard and dose-intensified infliximab respectively. CONCLUSION: Accelerated infliximab infusions for standard and dose-intensified regimens seem to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations.

Development and Feasibility of a Web-Based Decision Aid for Patients With Ulcerative Colitis: Qualitative Pilot Study.

BACKGROUND: Shared decision making (SDM) is becoming an important part of ulcerative colitis (UC) management because of the increasing complexity of available treatment choices and their trade-offs. The use of decision aids (DA) may be effective in increasing patients' participation in UC management but their uptake has been limited due to high attrition rates and lack of a participatory approach to their design and implementation. OBJECTIVE: The primary aim of this study is to explore the perspectives of Australian patients and their clinicians regarding the feasibility and acceptability of myAID, a web-based DA, in informing treatment decisions in UC. The secondary aim is to use the findings of this pilot study to inform the design of a cluster randomized clinical trial (CRCT) to assess the efficacy of the DA compared with usual care. METHODS: myAID, a DA was designed and developed using a participatory approach by a multidisciplinary team of clinicians, patients, and nonmedical volunteers. A qualitative pilot study to evaluate the DA, involving patients with UC facing new treatment decisions and inflammatory bowel disease clinicians, was undertaken. RESULTS: A total of 11 patients with UC and 15 clinicians provided feedback on myAID. Themes explored included the following: Acceptability and usability of myAID-myAID was found to be acceptable by the majority of clinicians as a tool to facilitate SDM, uptake was thought to vary depending on clinicians' approaches to patient education and practice, potential to overcome time restrictions associated with outpatient clinics was identified, presentation of unbiased information enabling patients to digest information at their own pace was noted, and potential to provoke anxiety among patients with a new diagnosis or mild disease was raised; Perceived role and usefulness of myAID-discordance was observed between patients who prioritized voicing preferences and clinicians who prioritized treatment adherence, and myAID facilitated early discussion of medical versus surgical treatment options; Target population and timing of use-greatest benefit was perceived at the time of initiating or changing treatment and following commencement of immunosuppressive therapy; and Potential concerns and areas for improvement-some perceived that use of myAID may precipitate anxiety by increasing decisional conflict and impact the therapeutic relationship between patient and the clinician and may increase resource requirements. CONCLUSIONS: These preliminary findings suggest that patients and clinicians consider myAID as a feasible and acceptable tool to facilitate SDM for UC management. These pilot data have informed a participatory approach to the design of a CRCT, which will evaluate the clinical efficacy of myAID compared with usual care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617001246370; http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617001246370.

Practical management of inflammatory bowel disease patients during the COVID-19 pandemic: expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS-CoV-2 manifests with a severe acute respiratory illness and currently there is insufficient data regarding the virulence of COVID-19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease patients in the context of the COVID-19 pandemic in the Australasian setting.

Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection.

BACKGROUND & AIMS: Little is known about in utero exposure to and postnatal clearance of anti-tumor necrosis factor (anti-TNF) agents in neonates. We investigated the concentrations of adalimumab and infliximab in umbilical cord blood of newborns and rates of clearance after birth, and how these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life. METHODS: We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36 received adalimumab and 44 received infliximab; 39 received concomitant thiopurines during pregnancy. Data were collected from medical records on disease activity and treatment before, during, and after pregnancy. Concentrations of anti-TNF agents were measured in blood samples from women at delivery and in umbilical cords, and in infants for every 3 months until the drug was no longer detected. RESULTS: The time from last exposure to anti-TNF agent during pregnancy correlated inversely with the concentration of the drugs in the umbilical cord (adalimumab: r = -0.64, P = .0003; infliximab: r = -0.77, P < .0001) and in mothers at time of birth (adalimumab, r = -0.80; infliximab, r = -0.80; P < .0001 for both). The median ratio of infant:mother drug concentration at birth was 1.21 for adalimumab (95% confidence interval [CI], 0.94-1.49) and 1.97 for infliximab (95% CI, 1.50-2.43). The mean time to drug clearance in infants was 4.0 months for adalimumab (95% CI, 2.9-5.0) and 7.3 months for infliximab (95% CI, 6.2-8.3; P < .0001). Drugs were not detected in infants after 12 months of age. Bacterial infections developed in 4 infants (5%) and viral infections developed in 16 (20%), all with benign courses. The relative risk for infection was 2.7 in infants whose mothers received the combination of an anti-TNF agent and thiopurine, compared with anti-TNF monotherapy (95% CI, 1.09-6.78; P = .02). CONCLUSIONS: In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during pregnancy increased the relative risk for infant infections almost 3-fold compared with anti-TNF monotherapy. Live vaccines therefore should be avoided for up to 1 year unless drug clearance is documented, and pregnant women should be educated on the risks of anti-TNF use.

The need for better preventative strategies for inflammatory bowel disease patients at risk of herpes zoster virus.

BACKGROUND: Immunosuppressed inflammatory bowel disease (IBD) patients have an increased risk of herpes zoster virus (HZV) infection. The existing live-attenuated HZV vaccine is contraindicated in some of these patients and can only be used with caution in others. AIMS: To describe characteristics of IBD patients suffering HZV to enable implementation of risk mitigation strategies for those at highest risk. METHODS: Gastroenterologists completed a proforma for IBD patients who experienced HZV infection: IBD phenotype, details of HZV infection, immunosuppression and any change to treatment upon diagnosis of HZV. RESULTS: A total of 30 cases was identified: Crohn disease (CD) (n = 25) and ulcerative colitis (n = 5). In total, 80% (20/25) of the CD patients had penetrating, stricturing or perianal disease. Time from commencement of immunosuppression to HZV infection was highly variable (range: 3 months to over 10 years). A total of 90% (27/30) of patients was on at least one immunosuppressive therapy; of those, one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A total of 89% (24/27) of immunosupressed patients was on a thiopurine (monotherapy; 6/27) or in combination (18/27). Complications of HZV occurred in 27% (8/30) of patients. CONCLUSION: Our series is consistent with existing epidemiological analysis that identified more severe IBD and the use of multiple immunosuppressive therapies as risk factors for HZV. If the promise of an investigational subunit HZV vaccine is realised in immunocompromised patients, better protection may be possible in the future. Thiopurine medications were the most commonly used immunosuppressant in this series. Age and duration of immunosuppressive therapy do not appear to predict HZV infection.

Dietary Emulsifier Exposure in People With Inflammatory Bowel Disease Compared With Healthy Controls: Is There a Cause for Concern?

BACKGROUND: Emulsifiers are implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined emulsifier intake in people with existing IBD. We aimed to describe the frequency of exposure to 6 selected emulsifiers in a contemporary cohort of people with IBD and compare intake with healthy controls (HCs). METHODS: Baseline food records from participants in an Australian prospective cohort study examining the microbiome of IBD patients and HCs were analyzed. Exposure to inflammatory emulsifiers polysorbate-80 (P80); carboxymethylcellulose (CMC); carrageenan; xanthan gum (XG); lecithin (soy and sunflower) and mono- and diglycerides of fatty acids (MDGs) were determined by examining ingredient lists. Frequency of emulsifier exposure between groups (IBD vs HC, Crohn's disease [CD] vs ulcerative colitis [UC], IBD children vs adults, active disease vs remission) was examined after controlling for confounders. RESULTS: Records from 367 participants were analyzed (n = 176 IBD, of which there were 101 CD, 75 UC, and 191 HC patients). In total, 5022 unique food items were examined, with 18% containing 1 or more emulsifier of interest. Inflammatory bowel disease participants had significantly higher total daily emulsifier exposure compared with HCs (2.7 ±â€…1.8 vs 2.3 ±â€…1.6, P = .02). In IBD participants, emulsifiers with the highest daily exposure were MDGs (1.2 ±â€…0.93), lecithin (0.85 ±â€…0.93), and XG (0.38 ±â€…0.42). There were no recorded exposures to P80. CONCLUSIONS: Inflammatory bowel disease participants were exposed to more emulsifiers than HCs. Intake of inflammatory emulsifiers were low or nonexistent, suggesting their presence in the food supply are not as common as frequently stated.

Clinician Adherence to Inflammatory Bowel Disease Guidelines: Results of a Qualitative Study of Barriers and Enablers.

Background: With the evolving inflammatory bowel disease (IBD) management landscape, it is critical that gastroenterologists keep up to date with the clinical practice guidelines (CPGs). Several studies in IBD have documented suboptimal adherence to CPGs. We aimed to gain an in-depth understanding of guideline adherence barriers reported by gastroenterologists and determine how evidence-based education can best be delivered. Methods: Interviews were conducted with a purposive sample of gastroenterologists' representative of the current workforce. Questions focused on previously identified problematic areas and shaped by the theoretical domains framework, a theory-informed approach to understanding clinician behavior, to assess all determinants of behavior. Questions explored perceived barriers to adherence and clinicians' preferred content and modes of delivery for an educational intervention. Interviews were conducted by a single interviewer and qualitative analysis performed. Results: A total of 20 interviews were conducted before data saturation was achieved (male = 12, work in a metropolitan area = 17). Five dominant subthemes for barriers to adherence emerged: negative experiences impacting future decisions, time constraints, long guidelines are impractical, unfamiliar with guideline specifics and prescribing restrictions. Adherence enablers were identified including features that improved the usability of CPGs. Computer- or smart phone-based educational interventions were preferred. Conclusions: This study identified several barriers and enablers for IBD guideline adherence and gained insight into how gastroenterologists prefer to receive evidence-based education. These results will inform the development of a targeted intervention to improve IBD guideline adherence. Improving guideline adherence is expected to facilitate standardized IBD care, ultimately leading to improved patient outcomes.

Health Communication Research Informs Inflammatory Bowel Disease Practice and Research: A Narrative Review.

Background: In the absence of targeted empirical evidence on effective clinical communication in inflammatory bowel disease (IBD), a broad overview of existing evidence on effective communication in healthcare and available recommendations for communication in telehealth is provided and mapped onto IBD research and practice. Methods: A narrative literature review was conducted using Pubmed and Scopus databases and snowballing literature search. Results: Evidence-based relationship building strategies include communicating emotions, acknowledging and addressing patients' hesitancy, and ensuring continued support. A particular recommendation regarding telehealth interaction is to avoid long stretches of talk. Effective informational strategies include facilitating and supporting information exchange and considering patients' preferences in decision-making. In teleconsultations, clinicians should ask direct questions about patients' emotional state, clarify their understanding of patients' concerns and check patients' understanding, address at least one patient-reported outcome when discussing the recommended treatment, and shorten the consultation where possible. Strategies for maximizing effective clinical communication in the spoken communicative mode include using infographics and simple language, and assessing adherence at the beginning of the consultation. For teleconsultations, clinicians are advised to allow patients to explain the reason for their call at the beginning of the teleconsultation, probe additional concerns early and before ending the teleconsultation, and be mindful of technical issues such as voice delays. Conclusions: Use of question prompt lists, decision aids, micro-lessons, and communication training interventions for clinicians could be beneficial in IBD care. Further research into the implementation of such interventions as well as clinical communication concerns specific to IBD is warranted.

Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review.

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference -1.16 (-1.50, -0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

Colonic Epstein-Barr Virus-Associated Mucocutaneous Ulcer Associated With Ulcerative Colitis.

Epstein-Barr virus-associated mucocutaneous ulcer is a rare lymphoproliferative disorder that occurs in immunosuppressed states that can develop in the gastrointestinal tract and mimic inflammatory bowel disease or other malignancies. We present the case of a 61-year-old man who presented with concurrent acute severe ulcerative colitis and colonic Epstein-Barr virus-associated mucocutaneous ulcer requiring rituximab therapy and a subtotal colectomy.

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.

An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Ulcerative colitis [UC] is a major form of inflammatory bowel disease globally. Phenotypic heterogeneity is defined by several variables including age of onset and disease extent. The genetics of disease severity remains poorly understood. To further investigate this, we performed a genome wide association [GWA] study using an extremes of phenotype strategy. METHODS: We conducted GWA analyses in 311 patients with medically refractory UC [MRUC], 287 with non-medically refractory UC [non-MRUC] and 583 controls. Odds ratios [ORs] were calculated for known risk variants comparing MRUC and non-MRUC, and controls. RESULTS: MRUC-control analysis had the greatest yield of genome-wide significant single nucleotide polymorphisms [SNPs] [2018], including lead SNP = rs111838972 [OR = 1.82, p = 6.28 × 10-9] near MMEL1 and a locus in the human leukocyte antigen [HLA] region [lead SNP = rs144717024, OR = 12.23, p = 1.7 × 10-19]. ORs for the lead SNPs were significantly higher in MRUC compared to non-MRUC [p < 9.0 × 10-6]. No SNPs reached significance in the non-MRUC-control analysis (top SNP, rs7680780 [OR 2.70, p = 5.56 × 10-8). We replicate findings for rs4151651 in the Complement Factor B [CFB] gene and demonstrate significant changes in CFB gene expression in active UC. Detailed HLA analyses support the strong associations with MHC II genes, particularly HLA-DQA1, HLA-DQB1 and HLA-DRB1 in MRUC. CONCLUSIONS: Our MRUC subgroup replicates multiple known UC risk variants in contrast to non-MRUC and demonstrates significant differences in effect sizes compared to those published. Non-MRUC cases demonstrate lower ORs similar to those published. Additional risk and prognostic loci may be identified by targeted recruitment of individuals with severe disease.

Colorectal cancer screening practise is influenced by ethnicity of medical practitioner and patient.

BACKGROUND AND AIM: Colorectal cancer (CRC) screening improves survival and requires appropriate recommendation by general practitioners (GPs). Screening practises may be influenced by barriers related to ethnicity and training. METHODS: A mail survey assessed GPs' practises and the barriers towards CRC screening. The association of screening practises and demography, including GP ethnicity, medical training and practise characteristics, were evaluated. RESULTS: Of 212 GPs (median age 54 years, 73% men, 27% Caucasian, 38% foreign graduates), 87% agreed that fecal occult blood test (FOBT) screening improved survival in the average-risk patient. Considerable variations existed in the starting age (40-49 years: 31%; 50 years: 65%) and frequency (1-2 years: 77%; 3-5 years: 22%) of screening. FOBT was used for indications other than screening: anemia (59%), altered bowel habits (54%), abdominal pain (24%), and rectal bleeding (23%), and these were significantly more frequent in Asian GPs independent of medical training. GPs were less likely to recommend screening to immigrants, and most reported that immigrants were less likely to participate. More Asian and Middle Eastern GPs reported a major barrier with FOBT inaccuracy compared with Caucasian GPs (22% vs 9%, P = 0.03; and 27% vs 9%, P = 0.03, respectively). CONCLUSIONS: Considerable differences existed in GPs' CRC screening practises. Indications for use of FOBT and the subsequent investigation of a positive FOBT also varied according to GPs' ethnicity, independent of medical training. Patient's ethnicity and associated language and cultural barriers may affect screening uptake, which may negatively affect the health of immigrants. Resources and culture-specific interventions are recommended to improve overall screening participation.

Timing of Live Attenuated Vaccination in Infants Exposed to Infliximab or Adalimumab in Utero: A Prospective Cohort Study in 107 Children.

BACKGROUND AND AIMS: For infants exposed in utero to anti-tumour necrosis factor-α [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy. METHODS: We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included. RESULTS: Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n = 25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n = 3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/. CONCLUSIONS: Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.

Ulcerative Colitis Narrative findings: Australian survey data comparing patient and physician disease management views.

BACKGROUND AND AIM: The Global Ulcerative Colitis (UC) Narrative Survey aimed to evaluate the impact of UC, perceptions of UC burden, and management approaches. Here, we present data from patients and physicians in Australia. METHODS: Surveys, fielded by The Harris Poll, were completed by 215 patients with UC and 90 physicians, between August 2017 and February 2018. Surveys included questions on disease characteristics, impact on life, communication with physicians, and patient knowledge of UC. Results are presented descriptively from all respondents (with no imputation for missing data). RESULTS: Based on medication history, 84% of patients had moderate to severe UC. Diagnostic delay was on average 1.9 (SD 5.0) years and 48% of patients had waited ≥1 year for diagnosis. Nearly two-thirds (65%) of patients considered themselves to be in remission, with 97% also reporting a flare in the past year. The majority (92%) of patients were satisfied with their UC medication and, if their treatment made them feel "good enough," many (75%) would not consider an alternative. Most (90%) patients were satisfied with communication with their physician; however, only 48% felt comfortable raising emotional concerns. Both patients and physicians desired more time during routine appointments. Patients had gaps in their knowledge of UC, which physicians mostly recognized. CONCLUSIONS: The Australian survey results highlighted the diagnostic delay and burden of UC patients' experience, gaps in patients' knowledge of UC, and challenges in patient-physician communication. Compared with the overall Global UC Narrative Survey, patients in Australia reported a high burden of disease.

The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study.

BACKGROUND: This retrospective cohort study investigated the economic impact of implementing a nurse-led inflammatory bowel disease (IBD) advice-line and virtual clinic on the Australian healthcare system. The advice line is a telephone and email service managed by IBD specialist nurses. The virtual clinic is a planned, formal communication between the gastroenterologist and the specialist IBD nurse the result of which is communicated to the patient electronically. METHODS: Advice line telephone calls and virtual clinic consultations registered between 1 June 2015 and 1 June 2016 were reviewed and analyzed in terms of outcome: avoidance of general practitioner (GP) consultation, IBD outpatient consultation, emergency department (ED) presentation, or hospital admission. Cost-benefit analysis was conducted to estimate financial savings. RESULTS: During the study period, 220 calls were received through the advice line and 1017 virtual clinic consultations occurred. The advice line resulted in the avoidance of 53 GP visits, 159 IBD outpatient department visits, six ED presentations, and one hospital admission. The virtual clinic resulted in the avoidance of four GP visits, 954 IBD outpatient department visits, and 58 ED presentations. This led to an estimated annual cost saving of AUD 169 376.80, with the annual costs incurred estimated to be $58 713. Thus, the annual net benefit of implementing the advice line and the virtual clinic was estimated to be $110 663.80. CONCLUSION: Specialized-IBD-nurse-led advice line and virtual clinic improves IBD patients' access to services and reduces healthcare costs. This highlights the importance of a proactive multidisciplinary approach in optimizing the care of patients with IBD.