Legalization of Cannabis Does Not Reduce Opioid Prescribing in Patients With Inflammatory Bowel Disease: A Difference-in-Difference Analysis.

INTRODUCTION: Cannabis may provide inflammatory bowel disease (IBD) patients with an alternative to opioids for pain. METHODS: We conducted a difference-in-difference analysis using MarketScan. Changes over time in rates of opioid prescribing were compared in states with legalized cannabis to those without. RESULTS: We identified 6,240 patients with IBD in states with legalized cannabis and 79,272 patients with IBD in states without legalized cannabis. The rate of opioid prescribing decreased over time in both groups and were not significantly different (attributed differential = 0.34, confidence interval -13.02 to 13.70, P = 0.96). DISCUSSION: Opioid prescribing decreased from 2009 to 2016 among patients with IBD in both states with legalized and state without legalized cannabis, similar to what has been observed nationally across a variety of diseases. Cannabis legalization was not associated with a lower rate of opioid prescribing for patients with IBD.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Morning light treatment for inflammatory bowel disease: a clinical trial.

BACKGROUND: Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD. METHODS: We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex. DISCUSSION: Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.

Racial Disparity in Esophageal Squamous Cell Carcinoma Treatment and Survival in the United States.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) has a higher incidence and prevalence than esophageal adenocarcinoma among Black individuals in the United States. Black individuals have lower ESCC survival. These racial disparities have not been thoroughly investigated. We examined the disparity in treatment and survival stratified by ESCC stage at diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with ESCC between 2000 and 2019. The identified cohort was divided into subgroups by race. Patient and cancer characteristics, treatment received, and survival rates were compared across the racial subgroups. RESULTS: A total of 23,768 patients with ESCC were identified. Compared with White individuals, Black individuals were younger and had more distant disease during diagnosis (distant disease: 26.7% vs 23.8%, P < 0.001). Black individuals had lower age-standardized 5-year survival for localized (survival % [95% confidence interval]: 19.3% [16-22.8] vs 27.6% [25.1-30.2]), regional (14.3% [12-16.7] vs 21.1% [19.6-22.7]), and distant (2.9% [1.9-4.1] vs 6.5% [5.5-7.5]) disease. Black individuals were less likely to receive chemotherapy (54.7% vs 57.5%, P = 0.001), radiation (58.5% vs 60.4%, P = 0.03), and surgery (11.4% vs 16.3%, P < 0.0001). DISCUSSION: Black individuals with ESCC have a lower survival rate than White individuals. This could be related to presenting at a later stage but also disparities in which treatments they receive even among individuals with the same stage of disease. To what extent these disparities in receipt of treatment is due to structural racism, social determinants of health, implicit bias, or patient preferences deserves further study.

Characteristics of Facilities With Early and Rapid Ustekinumab Adoption for Patients With Inflammatory Bowel Disease.

INTRODUCTION: To examine which facility characteristics, including teamwork, are associated with early or rapid inflammatory bowel disease-related ustekinumab adoption. METHODS: We examined the association between ustekinumab adoption and the characteristics of 130 Veterans Affairs facilities. RESULTS: Mean ustekinumab adoption increased by 3.9% from 2016 to 2018 and was higher in urban compared with rural facilities (ß = 0.03, P = 0.033) and among facilities with more teamwork (ß = 0.11, P = 0.041). Compared with nonearly adopters, early adopters were more likely be high-volume facilities (46% vs 19%, P = 0.001). DISCUSSION: Facility variation in medication adoption provides an opportunity for improving inflammatory bowel disease care through targeted dissemination strategies to improve medication uptake.

In-hospital management of inflammatory bowel disease.

PURPOSE OF REVIEW: The management of hospitalized patients with inflammatory bowel disease (IBD) is complex. Despite considerable therapeutic advancements in outpatient ulcerative colitis and Crohn's disease management, the in-hospital management continues to lag with suboptimal outcomes. The purpose of this review is to provide a brief overview of our approach to managing patients hospitalized with acute severe ulcerative colitis (ASUC) and Crohn's disease-related complications, followed by a summary of emerging evidence for new management approaches. RECENT FINDINGS: ASUC has seen the emergence of well validated prognostic models for colectomy as well as the development of novel treatment strategies such as accelerated infliximab dosing, Janus kinase inhibitor therapy, and sequential therapy, yet the rate of colectomy for steroid-refractory ASUC has not meaningfully improved. Crohn's disease has seen the development of better diagnostic tools, early Crohn's disease-related complication stratification and identification, as well as better surgical techniques, yet the rates of hospitalization and development of Crohn's disease-related complications remain high. SUMMARY: Significant progress has been made in the in-hospital IBD management; however, both the management of ASUC and hospitalized Crohn's disease remain a challenge with suboptimal outcomes. Critical knowledge gaps still exist, and dedicated studies in hospitalized patients with IBD are needed to address them.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

BACKGROUND: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. RESULTS: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. CONCLUSION: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

A Care Coordination Intervention Improves Symptoms But Not Charges in High-Risk Patients With Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with substantial symptom burden, variability in clinical outcomes, and high direct costs. We sought to determine if a care coordination-based strategy was effective at improving patient symptom burden and reducing healthcare costs for patients with IBD in the top quintile of predicted healthcare utilization and costs. METHODS: We performed a randomized controlled trial to evaluate the efficacy of a patient-tailored multicomponent care coordination intervention composed of proactive symptom monitoring and care coordinator-triggered algorithms. Enrolled patients with IBD were randomized to usual care or to our care coordination intervention over a 9-month period (April 2019 to January 2020). Primary outcomes included change in patient symptom scores throughout the intervention and IBD-related charges at 12 months. RESULTS: Eligible IBD patients in the top quintile for predicted healthcare utilization and expenditures were identified. A total of 205 patients were enrolled and randomized to our intervention (n = 100) or to usual care (n = 105). Patients in the care coordinator arm demonstrated an improvement in symptoms scores compared with usual care (coefficient, -0.68, 95% confidence interval, -1.18 to -0.18; P = .008) without a significant difference in median annual IBD-related healthcare charges ($10,094 vs $9080; P = .322). CONCLUSIONS: In this first randomized controlled trial of a patient-tailored care coordination intervention, composed of proactive symptom monitoring and care coordinator-triggered algorithms, we observed an improvement in patient symptom scores but not in healthcare charges. Care coordination programs may represent an effective value-based approach to improve symptoms scores without added direct costs in a subgroup of high-risk patients with IBD. (ClinicalTrials.gov, Number: NCT04796571).

Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review.

BACKGROUND AND AIMS: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. METHODS: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). RESULTS: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. CONCLUSIONS: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.

Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study.

BACKGROUND & AIMS: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC. METHODS: A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes. RESULTS: Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10-0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02-0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21-2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls. CONCLUSIONS: Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.

Association of Household Pets, Common Dietary Factors, and Lifestyle Factors with Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI. AIMS: We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI. METHODS: We surveyed subjects aged 18-90 over a 14-month period using a retrospective case-control design. Subjects with CDI were matched by gender and age to patients who tested negative and had no prior history of CDI. A web-based survey was provided to subjects by mail or assisted by phone. Conditional logistic regression was used to assess for associations between CDI and the various risk factors. RESULTS: 205 CDI positive and 205 CDI negative subjects (response rate of 50.2%) were included. After matching for age and sex, living with a cat or dog was not associated with negative CDI testing. Exploratory multivariable modeling identified an unexpected association between positive CDI testing and high meat intake (OR 2.13, 95% CI 1.21-3.77) as well as between positive CDI testing and cat allergies (OR 1.88, 95% CI 1.02-3.46). CONCLUSION: Living with a cat or dog was not associated with negative CDI testing. Several novel risk factors for CDI have been identified including high meat intake and cat allergies.

Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. AIMS: To characterize the impact of HS on disease severity and liver injury in COVID-19. METHODS: We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. RESULTS: In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. CONCLUSIONS: HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.

Use of Accelerated Induction Strategy of Infliximab for Ulcerative Colitis in Hospitalized Patients at a Tertiary Care Center.

BACKGROUND: Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy. AIM: To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC. METHODS: We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics. RESULTS: From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction. CONCLUSIONS: In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

Efficacy of Induction Therapy With High-Intensity Tofacitinib in 4 Patients With Acute Severe Ulcerative Colitis.

As many as 25% of patients diagnosed with ulcerative colitis are hospitalized with an episode of acute severe ulcerative colitis (ASUC).1 The standard of care for patients hospitalized with ASUC relies on rapid induction with intravenous (IV) corticosteroids. Up to 30% of patients do not respond to corticosteroids alone.2 Rescue therapy with infliximab or cyclosporine has been shown to reduce rates of colectomy to 20% by 90 days.3,4 This still represents a significant rate of treatment failure, which leads to an unplanned and irreversible surgery. In recent years, increasing numbers of patients admitted with ASUC have already failed infliximab therapy, highlighting the need for additional treatment options for these patients. Tofacitinib is a rapidly acting, oral, small-molecule Janus kinase inhibitor that was recently approved by the Food and Drug Administration for treatment of ulcerative colitis.5 We present the first reported use of off-label, high-intensity tofacitinib in 4 patients admitted to our institution with ASUC predicted to fail medical management.

Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS. METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement. RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low. DISCUSSION: Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.