5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC), comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intrapatient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the timing of medical interventions according to the host circadian rhythms in order to optimize drug response and minimize toxicity, and is one explanation for the large variability in response to medications. The long-term objective of our research is to establish the hypothesis that is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g] on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity (Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.

This is a prospective observational cohort study that will create a patient registry by collecting data on patients who receive REBYOTA to prevent recurrence of Clostridioides difficile infection (CDI). The registry will include data about CDI episodes, CDI related symptoms, healthcare resource utilization (i.e., hospitalizations and re-admissions) and this data will be collected up to 6-months after receiving REBYOTA™.

While blood clots after major cancer surgery are common and harmful to patients, the medications available to decrease blood clot risk are seldom used despite the recommendation of multiple professional medical societies. The reasons why these medications are seldom prescribed is not well understood. We aim to characterize barriers and facilitators to extended blood clot prophylaxis guideline adherence as perceived by stakeholders via interviews with a diverse group of patients and surgeons at hospitals within the MUSC Health system that routinely perform cancer surgery. These findings will inform educational interventions to improve the use of guideline concordant care and mitigate observed disparities in cancer care.

While blood clots after major cancer surgery are common and harmful to patients, the medications available to decrease blood clot risk are seldom used despite the recommendation of multiple professional medical societies. The reasons why these medications are seldom prescribed is not well understood. We aim to characterize barriers and facilitators to extended blood clot prophylaxis guideline adherence as perceived by stakeholders via interviews with a diverse group of patients and surgeons at hospitals within the MUSC Health system that routinely perform cancer surgery. These findings will inform educational interventions to improve the use of guideline concordant care and mitigate observed disparities in cancer care.

While blood clots after major cancer surgery are common and harmful to patients, the medications available to decrease blood clot risk are seldom used despite the recommendation of multiple professional medical societies. The reasons why these medications are seldom prescribed is not well understood. We aim to characterize barriers and facilitators to extended blood clot prophylaxis guideline adherence as perceived by stakeholders via interviews with a diverse group of patients and surgeons at hospitals within the MUSC Health system that routinely perform cancer surgery. These findings will inform educational interventions to improve the use of guideline concordant care and mitigate observed disparities in cancer care.