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Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. A low level of serum bilirubin, an endogenous antioxidant, has been associated with increased risk for Crohn's disease (CD), but no study has tested another common IBD ulcerative colitis (UC). Bilirubin is metabolized in the liver by uridine glucuronosyltransferase 1A1 (UGT1A1) exclusively. Genetic variants cause functional changes in UGT1A1 which result in hyperbilirubinemia, which can be toxic to tissues if untreated and results in a characteristic jaundiced appearance. Approximately 10% of the Caucasian population is homozygous for the microsatellite polymorphism UGT1A1*28, which results in increased total serum bilirubin levels due to reduced transcriptional efficiency of UGT1A1 and an overall 70% reduction in UGT1A1 enzymatic activity. The aim of this study was to examine whether bilirubin levels are associated with the risk for ulcerative colitis (UC). Using the Informatics for Integrating Biology and the Bedside (i2b2), a large case-control population was identified from a single tertiary care center, Penn State Hershey Medical Center (PSU). Similarly, a validation cohort was identified at Virginia Commonwealth University Medical Center. Logistic regression analysis was performed to determine the risk of developing UC with lower concentrations of serum bilirubin. From the PSU cohort, a subset of terminal ileum tissue was obtained at the time of surgical resection to analyze UGT1A1 gene expression (which encodes the enzyme responsible for bilirubin metabolism). Similar to CD patients, UC patients also demonstrated reduced levels of total serum bilirubin. Upon segregating serum bilirubin levels into quartiles, risk of UC increased with reduced concentrations of serum bilirubin. These results were confirmed in our validation cohort. UGT1A1 gene expression was up-regulated in the terminal ileum of a subset of UC patients. Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. One potential explanation for these lower bilirubin levels may be up-regulation of UGT1A1 gene expression, which encodes the only enzyme involved in conjugating bilirubin. Therapeutics that reduce oxidative stress may be beneficial for these patients.
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Digital Health Apps in the Clinical Care of Inflammatory Bowel Disease: Scoping Review
Background Digital health is poised to transform health care and redefine personalized health. As Internet and mobile phone usage increases, as technology develops new ways to collect data, and as clinical guidelines change, all areas of medicine face new challenges and opportunities. Inflammatory bowel disease (IBD) is one of many chronic diseases that may benefit from these advances in digital health. This review intends to lay a foundation for clinicians and technologists to understand future directions and opportunities together. Objective This review covers mobile health apps that have been used in IBD, how they have fit into a clinical care framework, and the challenges that clinicians and technologists face in approaching future opportunities. Methods We searched PubMed, Scopus, and ClinicalTrials.gov to identify mobile apps that have been studied and were published in the literature from January 1, 2010, to April 19, 2019. The search terms were (“mobile health” OR “eHealth” OR “digital health” OR “smart phone” OR “mobile app” OR “mobile applications” OR “mHealth” OR “smartphones”) AND (“IBD” OR “Inflammatory bowel disease” OR “Crohn's Disease” (CD) OR “Ulcerative Colitis” (UC) OR “UC” OR “CD”), followed by further analysis of citations from the results. We searched the Apple iTunes app store to identify a limited selection of commercial apps to include for discussion. Results A total of 68 articles met the inclusion criteria. A total of 11 digital health apps were identified in the literature and 4 commercial apps were selected to be described in this review. While most apps have some educational component, the majority of apps focus on eliciting patient-reported outcomes related to disease activity, and a few are for treatment management. Significant benefits have been seen in trials relating to education, quality of life, quality of care, treatment adherence, and medication management. No studies have reported a negative impact on any of the above. There are mixed results in terms of effects on office visits and follow-up. Conclusions While studies have shown that digital health can fit into, complement, and improve the standard clinical care of patients with IBD, there is a need for further validation and improvement, from both a clinical and patient perspective. Exploring new research methods, like microrandomized trials, may allow for more implementation of technology and rapid advancement of knowledge. New technologies that can objectively and seamlessly capture remote data, as well as complement the clinical shift from symptom-based to inflammation-based care, will help the clinical and health technology communities to understand the full potential of digital health in the care of IBD and other chronic illnesses.
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- Award ID(s):
- 1700832
- PAR ID:
- 10348249
- Date Published:
- Journal Name:
- Journal of Medical Internet Research
- Volume:
- 21
- Issue:
- 8
- ISSN:
- 1438-8871
- Page Range / eLocation ID:
- e14630
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.2196/14630
