Head‐to‐head trials in inflammatory bowel disease Radford‐Smith, Graham
Journal of gastroenterology and hepatology,
April 2021, 2021-Apr, 2021-04-00, 20210401, Volume:
36, Issue:
S1
Journal Article
Peer reviewed
Open access
Article Note: Declaration of conflict of interest Dr Graham Radford-Smith has received research support from Janssen and is an advisory board member for Takeda, Janssen, Pfizer, Abbvie, and Ferring. ...Byline: Graham Radford-Smith
LINKED CONTENT
This article is linked to Okabayashi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16865 and https://doi.org/10.1111/apt.16925
Background
Thiopurine‐related adverse events such as leukopenia, liver dysfunction and pancreatitis are associated with variants in the NUDT15 gene. Loss‐of‐function (low or no enzyme activity) ...alleles are more common in Asian and Hispanic populations. The prevalence of these variants in the Australian inflammatory bowel disease (IBD) population has not yet been reported.
Aim
To evaluate the presence of NUDT15 loss‐of‐function alleles *2,*3,*9 in the Australian IBD population.
Methods
The NUDT15 screening cohort included 423 IBD patients from Brisbane, Australia. Study patients were recruited by: (i) retrospective review of clinical charts for thiopurine‐related severe adverse events; (ii) pathology data (white blood cell (WBC) and neutrophil counts). NUDT15 genotyping was performed using polymerase chain reaction (PCR)‐high‐resolution melt (HRM), TaqMan genotyping and Sanger sequencing.
Results
NUDT15 mutation R139C (allele *3) was identified in 8 of 423 (1.9%) IBD patients. Seven of eight patients were R139C heterozygous (C/T) and one patient was R139C homozygous (T/T). One of the C/T group and the T/T patient developed thiopurine‐induced myelosuppression (TIM) within 60 days of dosing. One patient in the C/T group developed TIM after 60 days of thiopurine dosing. The remaining five patients in the C/T group did not show TIM; however, other thiopurine‐related events could not be ruled out and therefore careful monitoring over a long period is recommended.
Conclusions
This is the first study to report the frequency of NUDT15 haplotypes *2,*3,*9 in an Australian IBD population. The most common variant detected was the R139C mutation. PCR and Sanger sequencing are efficient and cost‐effective approaches for NUDT15 genotyping.
Background
Inflammatory bowel disease (IBD) patients living in regional or remote Queensland are often disadvantaged by limited access to IBD specialist care. Telehealth clinics could potentially ...address this disparity and improve patient outcomes.
Aim
We report the impact of the Royal Brisbane and Women's Hospital (RBWH) IBD telehealth clinics from March 2011 to December 2017, including patient satisfaction and healthcare activity.
Methods
Patient satisfaction surveys were collected prospectively between March 2011 and March 2012. Healthcare activity was assessed through occasions of service (OOS), number of enrolled patients on biologics and IBD related admissions to RBWH.
Results
Overall, 3764 OOS were completed including 576 new patient and 3188 follow‐up visits. Mean age at first telehealth visit was 44 years (range: 16–87 years). The IBD telehealth clinics were well accepted with 99% of the first 153 patients surveyed choosing to continue with telehealth and 94% rated the telehealth experience as very good or excellent. The net number of patients under active review increased from 125 patients in 2011 to 345 patients in 2017. Enrolled patients on biologics also increased from 9 patients in 2011 to 63 patients in 2017. There was an initial dip in annual IBD related admissions to RBWH in 2011 but these have progressively increased over time although the average length of inpatient stay annually has remained stable.
Conclusion
The RBWH IBD telehealth clinics have shown that telemedicine is well received and can be used successfully to deliver IBD specialist care to patients living in regional or remote areas.
The inflammatory bowel diseases (IBDs) are a group of heterogeneous disorders characterized by acute and chronic inflammatory changes in the small or large bowel, or in both. Increasing incidence and ...prevalence figures for IBD both in the developed and developing world indicate that environmental factors are at least as significant in IBD as genetic susceptibility. Of these, diet and the host microbiota are likely to play important but as yet poorly defined roles. The major constituents of a standard "Western" diet may contribute to, or protect against, intestinal inflammation via several mechanisms. These include the effects of insulin resistance and short-chain fatty acids such as butyrate, modification of intestinal permeability, the antiinflammatory role of polyunsaturated fatty acids, and the effect of sulfur compounds from protein on host microbiota. This detailed review critically assesses the evidence for the role of diet in the development of IBD and examines the evidence for obesity as a contributing factor to IBD pathogenesis. Particular attention is focused on methodological issues including suitability of cases and controls, confounders such as smoking, and total energy expenditure.
There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on ...dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes.
There is convincing preclinical evidence demonstrating the effect of the gut microbiota in altering brain mechanisms supporting threat processing. However, there remains a large gap in understanding how microbiota consortia engenders variability in neural dynamics underpinning human threat processing. Our study supports distinct interactions between microbial abundance patterns—reflected across different taxonomic scales—with neural dynamics supporting threat learning and threat updating processes in healthy individuals.
Aim
Previous research has shown that individuals with inflammatory bowel disease avoid specific food items, such as fibre rich foods, in order to manage symptoms. Dietary fibre and the traditional ...Mediterranean diet are both associated with reduced mucosal and systemic inflammation, gut barrier integrity, and microbiota diversity. There is limited data on the diet composition of individuals with inflammatory bowel disease. The aim of this study was to evaluate how it compares to the traditional Mediterranean diet and national dietary guidelines.
Methods
Outpatients with inflammatory bowel disease were recruited to the study between February and August 2019. Demographic and medical information was obtained for consenting participants. All participants completed a dietary assessment of usual intake (24‐h diet recall and 17‐point ready reckoner) from which a Mediterranean diet adherence score was calculated. Dietary intake of core food groups was compared to the recommended number of serves outlined in the Australian Guide to Healthy Eating.
Results
100 participants were recruited. The mean Mediterranean diet adherence score was 5.1 ± 1.3 (maximum 14 points), 4% of participants scored ≥9 (commonly agreed criteria for Mediterranean diet adherence). Participants also consumed considerably less grains and vegetables than national dietary guidelines recommendations.
Conclusions
The diet of outpatients with inflammatory bowel disease did not align with Mediterranean diet characteristics. Participants consumed significantly less grains and vegetables than national guidelines, suggesting a low fibre intake. These findings suggest that dietary interventions focusing on improving the diet of individuals with inflammatory bowel disease to align with Mediterranean diet characteristics are warranted.
Background
Functional gut disorders (FGD) are common. Diagnosis is symptom based, although symptoms may be indistinguishable from inflammatory bowel disease. As a result of this, investigations are ...common, diagnostic yield is low. A streamlined novel model of care may reduce costly investigations.
Aim
To compare a new model of care for patients with low‐risk gastrointestinal symptoms to a matched historical cohort.
Methods
Data were prospectively collected over 12 months. General practitioner referrals for low‐risk abdominal symptoms were triaged to a new multidisciplinary clinic structure utilising intestinal ultrasound. Outcomes were compared to the historical model in the preceding 12 months. Duration of care (time from referral to discharge), number of contact episodes and investigations ordered were reviewed.
Results
Thirty‐seven patients meeting strict inclusion criteria completed their care. Compared with the historical cohort, colonoscopies reduced from 0.7 to 0.05 per patient (P < 0.0001). Gastroenterology consults reduced from 1.5 to 1.2 (P = 0.303) and dietitian review increased from 0.8 to 1.5 (P < 0.0001). Total contact episodes reduced from 3.2 to 1.8 (P < 0.0001). Duration of care reduced from a median of 252 days to 130 days (interquartile ranges (IQR) 287 and 69, respectively; P < 0.0001). Time from first consultation to discharge reduced from 125 to 42 days (IQR 188 and 63; P < 0.0001).
Conclusion
This multidisciplinary approach to care of low‐risk abdominal symptoms significantly reduced contact episodes, time in care and invasive investigations. It decreased costly gastroenterology consultation and increased allied health exposure. It demonstrates improved health service outcomes.
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