Recommendations for Broadening Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials.

BACKGROUND: Clinical trial recruitment for patients with inflammatory bowel disease (IBD) has become more challenging over time. We aimed to develop recommendations for broadening IBD clinical trial eligibility to improve the inclusion of a more representative patient population in a more efficient timeline. METHODS: We applied the RAND/UCLA Appropriateness Method focused on broadening IBD clinical trial eligibility. A literature review was performed for 7 domains, each representing a different area related to trial recruitment. Based on these domains, 32 statements were developed. A questionnaire was sent to IBD specialists to anonymously vote on each statement with regards to its appropriateness and feasibility. After the first round of voting, participants met for a moderated discussion to review all statements. At the end of the discussion a second round of anonymous voting led to the final recommendations. RESULTS: The final round of voting resulted in 26 statements. All were rated as feasible and 25 of 26 rated as appropriate. Recommendations generally are to be more inclusive of complicated disease phenotypes, more liberal around safety criteria, to recognize the importance of non-invasive imaging and biomarkers, to minimize the washout period and to not enforce a minimum or maximum number of prior medications, to allow a recently recorded colonoscopy to count as a baseline study, and to be less restrictive of age. CONCLUSION: Recommendations to broaden clinical trial eligibility were found to be both appropriate and feasible with a high degree of agreement amongst an international group of IBD specialists.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

BACKGROUND AND AIMS: The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. APPROACH AND RESULTS: In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. CONCLUSIONS: Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.

Exposure to harmful housing conditions is common in children admitted to Wellington Hospital.

AIM: To measure the prevalence of exposure to potentially modifiable risk factors in the homes of children hospitalised in Wellington. METHODS: Parents/caregivers of all children admitted to Wellington Public Hospital during a two-week period in July 2012 completed a standardised questionnaire in a face-to-face interview. The questionnaire collected sociodemographic, health and housing condition data. RESULTS: We interviewed parents/caregivers of 106 children, of whom 72% were aged 0-4 years. Respiratory conditions were the most common cause of admission. One third of parents noticed dampness and mould in their house, 50% stated that their house was colder than they preferred during the past month, 20% lived in uninsulated houses, 20% lived in overcrowded houses, and 38% were exposed to second hand smoke (SHS). Compared to New Zealand European (NZE) children, the odds ratios (OR) for Pacific children living in cold and overcrowded houses and being exposed to SHS were 14.0 (95%CI 3.0-66.0), 10.8 (95%CI 2.6-44.1) and 16.0 (95%CI 4.8-55.5) respectively. OR for Maori children living in cold and overcrowded houses and being exposed to SHS were 3.0 (95%CI 1.0-9.0), 6.8 (95%CI 1.6-30.1) and 8.0 (95%CI 2.5-28.6) respectively, compared to NZE children. The OR for children from deprived neighbourhoods (NZDep2006 areas 7-10) living in cold and overcrowded houses and being exposed to SHS were 4.1 (95%CI 1.8-9.6), 5.7 (95%CI 1.9-17.0) and 4.1 (95%CI 1.6-9.6) respectively. CONCLUSIONS: Among children admitted to Wellington Hospital there is a high prevalence of exposure to cold, damp and overcrowded houses and many children are exposed to SHS. Maori and Pacific children and children living in socioeconomically deprived areas are more likely than others to be exposed to these potential risk factors for childhood hospitalisation. This audit of child admissions could be repeated to provide surveillance of modifiable risk factors. A shortened version of the questionnaire could be used to screen children to identify those with harmful exposures in their home environment, provided suitable intervention programmes can be established.