Citations

AbstractBackgroundThere are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online.MethodsParticipants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in‐depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together.Key ResultsThe proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%–39.7% vs. 41.2%; 95% CI 40.8%–41.6%,p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid‐induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p < 0.05) were more prevalent in the UK. Cyclic vomiting, functional constipation, unspecified functional bowel disorder, and proctalgia fugax (p < 0.05) were more prevalent in the other 25 countries. Diet in the UK population consisted of higher consumption of meat and milk (p < 0.001), and lower consumption of rice, fruit, eggs, tofu, pasta, vegetables/legumes, and fish (p < 0.001).Conclusions and InferencesThe prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries.

Significance Statement Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression. Background Changes in log urinary albumin-to-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown. Methods Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2 , or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination. Results Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were −0.41 (95% Bayesian Credible Interval, −0.64 to −0.17) per 1 ml/min per 1.73 m 2 per year for the treatment effect on GFR slope and −0.06 (95% Bayesian Credible Interval, −0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up. Conclusions In Phase 2 trials of CKD with sample sizes of 100–200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.

Abstract Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. Results: Although the standard approach did not identify significant signals, the eQTL set–based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set–based genetic association approach. Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set–based genetic association approach as an alternative method for TWAS analysis.

Background: We present an innovative care model for telehealth by creating a video conference group telemedicine program for patients with chronic disease and discuss findings from a post-program survey that was instrumental in understanding the response to telemedicine in a group setting. Methods: All patients who attended the group telemedicine program had a diagnosis of Hypermobile Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorder and were requested to complete survey responses at the close of the program. Surveys were completed anonymously and electronically by REDCap. Elements of the Press Ganey, Consumer Assessment of Healthcare Providers and Systems, and Utah Telehealth Network patient satisfaction surveys were modified to construct the survey. Results: A total of 102 patients completed the post-telehealth program survey between August 20, 2021, and February 11, 2022. Around 93.1% stated that they gained a better understanding of the chronic condition, 88.3% stated that the program gave them the tools to improve, and 76.5% indicated the program addressed their specific needs. Approximately 92.1% found it easy to interact with the program facilitator and 79.4% found it easy to interact with program members. Around 93.1% said they would recommend the program to others. Discussion: We created a group telemedicine program for a complex chronic medical condition. The foundation of knowledge provided by the telemedicine program allowed more time during face-to-face encounters for individual assessment of the patient, and increased access to care. Overall, the program has improved the treatment process by reducing treatment burden and empowering patients with self-management skills to help reach our fundamental treatment goal of improving quality of life.

e13631 Background: Colorectal cancer (CRC) screening disruptions have been observed with the COVID-19 pandemic, putting patients at risk for more advanced-stage disease at the time of diagnosis. We estimated the impact of increased use of stool-based tests for screening during the COVID-19 pandemic on near-term clinical outcomes in a simulated United States (US) population. Methods: A previously developed budget impact model was adapted to assess the impact of increasing use of multi-target stool DNA [mt-sDNA] or fecal immunochemical [FIT] tests to offset the COVID-19 related disruption in colonoscopy screening. Adults, ages 50 – 75 years, at average risk for CRC were included over a 3-year time horizon (2020 – 2023) to explore the impact of increased screening for CRC using mt-sDNA or FIT, from the perspective of a US payer. Compared to the base case (S0; 85% colonoscopy and 15% non-invasive tests), the estimated number of missed CRCs and advanced adenomas (AAs) were determined for four COVID-19-affected screening scenarios: S1, 9 months of CRC screening at 50% capacity, followed by 21 months at 75% capacity; S2, S1 followed by increasing stool-based testing by an average of 10% over 3-years; S3, 18 months of CRC screening at 50% capacity, followed by 12 months of 75% capacity; and S4, S3 followed by increasing stool-based testing by an average of 13% over 3-years. Results: Increasing the proportional use of mt-sDNA, the detection of AAs improved by 6.0% (Scenario 2 versus 1) to 8.4% (Scenario 4 versus 3) and the number of missed CRCs decreased by 15.1% to 17.3% respectively. Increasing FIT utilization improved the detection of AAs by 3.3% (Scenario 2 versus 1) to 4.6% (Scenario 4 versus 3) and the number of missed CRCs decreased by 12.9% (Scenario 2 versus 1) to 14.9% (Scenario 4 versus 3). Across all scenarios, the number of AAs detected was higher for mt-sDNA than for FIT, and the number of missed CRCs was lower for mt-sDNA than for FIT. Conclusions: Using home-based stool tests for average-risk CRC screening can mitigate the consequences of reduced colonoscopy screening resulting from the COVID-19 pandemic. Use of mt-sDNA led to fewer missed CRCs and more AAs detected, compared to FIT.

AbstractBackgroundGuidelines include several options for average‐risk colorectal cancer (CRC) screening that vary in aspects such as invasiveness, recommended frequency, and precision. Thus, patient and provider preferences can help identify an appropriate screening strategy. This study elicited CRC screening preferences of physicians and individuals at average risk for CRC (IAR).MethodsIAR aged 45–75 years and licensed physicians (primary care or gastroenterology) completed an online discrete choice experiment (DCE). Participants were recruited from representative access panels in the US. Within the DCE, participants traded off preferences between screening type, screening frequency, true‐positive, true‐negative, and adenoma true positive (physicians only). A mixed logit model was used to obtain predicted choice probabilities for colonoscopy, multi‐target stool DNA (mt‐sDNA), fecal immunochemical test (FIT), and methylated septin 9 (mSEPT9) blood test.ResultsPreferences of IAR and physicians were affected by screening precision and screening type. IAR also valued more regular screening. Physicians preferred colonoscopy (96.8%) over mt‐sDNA (2.8%; p < 0.001), FIT (0.3%; p < 0.001) and mSEPT9 blood test (0.1%; p < 0.01). IAR preferred mt‐sDNA (38.8%) over colonoscopy (32.5%; p < 0.001), FIT (19.2%; p < 0.001), and mSEPT9 blood test (9.4%; p < 0.001). IAR naïve to screening preferred non‐invasive screening (p < 0.001), while the opposite was found for those who previously underwent colonoscopy or sigmoidoscopy.ConclusionsWhile physicians overwhelmingly preferred colonoscopy, preferences of IAR were heterogenous, with mt‐sDNA being most frequently preferred on average. Offering choices in addition to colonoscopy could improve CRC screening uptake among IAR.This study used a discrete choice experiment in the US to elicit preferences of physicians and individuals at average risk for colorectal cancer screening modalities and their characteristics.