Shail M. Govani

Combination of Thiopurines and Allopurinol: Adverse Events and Clinical Benefit in IBD

BACKGROUND AND AIMS Allopurinol has been presented as a safe and effective adjunct to thiopurine therapy in inflammatory bowel disease (IBD). We aimed to determine the rate of infectious complications and clinical successes with a combination of thiopurine/allopurinol in IBD, and to identify which variables predict 6-thioguanine, 6-methylmercaptopurine, and white blood cell levels. Additionally we aimed to identify which variables predict complications. METHODS A retrospective database search identified patients with inflammatory bowel disease on both thiopurines and allopurinol. Regression modeling was used to identify which variables predicted metabolite levels, white blood cell levels, and complications. RESULTS Twenty-seven subjects were found, with 20 treated intentionally and 7 inadvertently after a concurrent gout diagnosis. Thirteen of 20 patients had a major clinical improvement and 7 of 16 stopped steroids. Five infectious complications occurred. These included 2 cases of shingles, and one each of PCP, EBV, and viral meningitis. Significant predictors of metabolite levels included the dose of thiopurine and allopurinol, age, and BMI. Low white blood cell count levels were associated with increased doses, high BMI, and older age. Despite having only 5 events, there was a difference in absolute lymphocyte count between patients with and without infection (median 200 per mm³ vs 850 per mm³ respectively, p=0.0503). CONCLUSIONS Adjunctive allopurinol therapy in shunting patients produced major clinical improvement in 48% of patients. However, a surprising number of opportunistic infections have occurred. Low absolute lymphocyte count may be a previously unrecognized indicator of risk of opportunistic infections.

The Impact of Bowel Cleansing on Follow-Up Recommendations in Average-Risk Patients With a Normal Colonoscopy

OBJECTIVES:Repeat colonoscopy in 10 years after a normal screening colonoscopy is recommended in an average-risk patient, and it has been proposed by American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and American Society for Gastrointestinal Endoscopy (ASGE) as a quality measure. However, there are little quantitative data about adherence to this recommendation or factors that may improve adherence. Our study quantifies adherence to this recommendation and the impact of suboptimal bowel preparation on adherence.METHODS:In this retrospective database study, endoscopy reports of average-risk individuals ≥50 years old with a normal screening colonoscopy were reviewed. Quality of colon cleansing was recorded using the Aronchick scale as excellent, good, fair, or poor. Main outcome measurements were quality of bowel preparation and recommendation for timing of repeat colonoscopy. Recommendations were considered consistent with guidelines if 10-year follow-up was documented after excellent, good, or fair prep or if ≤1-year follow-up was recommended after poor prep.RESULTS:Among 1,387 eligible patients, recommendations for follow-up colonoscopy inconsistent with guidelines were seen in 332 (23.9%) subjects. By bowel preparation quality, 15.3% of excellent/good, 75% of fair, and 31.6% of poor bowel preparations were assigned recommendations inconsistent with guidelines (P<0.001). Patients with fair (odds ratio=18.0; 95% confidence interval 12.0–28.0) were more likely to have recommendations inconsistent with guidelines compared with patients with excellent/good preps.CONCLUSIONS:Recommendations inconsistent with guidelines for 10-year intervals after a normal colonoscopy occurred in >20% of patients. Minimizing “fair” bowel preparations may be a helpful intervention to improve adherence to these recommendations.

Factors That Predict High Health Care Utilization and Costs for Patients With Inflammatory Bowel Diseases

BACKGROUND & AIMS A subset of patients with inflammatory bowel diseases (IBD) have continuously active inflammation, leading to a high number of complications and high direct health care costs (diagnostic tests, medications, and surgeries) and indirect costs (reduced employment and productivity and fewer opportunities for activities). Identifying these high‐risk patients and providing effective interventions could produce better outcomes and reduce costs. We used prior year data to create IBD risk models to predict IBD‐related hospitalizations, emergency department visits, and high treatment charges (>

Risk Stratification of Emergency Department Patients With Crohn's Disease Could Reduce Computed Tomography Use by Nearly Half

30,000/year) in the subsequent year. METHODS We performed a retrospective study of medical records from all patients with IBD treated at the University of Michigan Hospital from fiscal years 2013–2015. We selected clinical variables from the prior year and tested their abilities to predict 3 adverse outcomes (IBD‐related hospitalizations, emergency department visits, and treatment charges >

Corticosteroid use and complications in a US inflammatory bowel disease cohort

30,000/year) in the subsequent year. Individual patients were only included once in the data set. We created a multivariate model that was based on a 70% randomly selected cohort (1005 patients) and validated the model on the other 30% (425 patients). Logistic regression was used for bivariate and multivariate analyses. RESULTS Factors that predicted high‐cost outcomes included the presence of psychiatric illness, use of corticosteroids, use of narcotics, low levels of hemoglobin, and high numbers of IBD‐related hospitalizations. In the validation cohort, the model predicted IBD‐related hospitalizations, emergency department visits, and high charges in the following year with receiver operating characteristic curve values of 0.751, 0.738, and 0.744, respectively. CONCLUSIONS We identified 5 factors that can effectively identify patients with IBD at high risk for hospitalization, emergency department visits, and high treatment charges in the next year. These patients should be closely monitored and aggressively managed.

Anti-adhesion therapies and the rule of 3 for rare events

BACKGROUND & AIMS Computed tomography (CT) is a useful tool for assessing disease activity and excluding complications in patients with Crohns disease (CD). However, excessive radiation increases risk for malignancy. We aimed to identify automatable algorithms with high negative predictive values for significant CT findings in patients with CD who present at the emergency department. METHODS We conducted a retrospective review of a tertiary centers medical records to identify adults diagnosed with CD who presented from 2000 through 2011. Logistic regression was used to model complications (perforations, abscesses, or other serious findings) and inflammation. RESULTS There were 1095 visits made by 613 individuals that included a CT scan within 24 hours of arrival. The average number of CT scans was 1.8 (range, 1-31). Complications of CD were observed in 16.8% of CT scans, inflammation in 54.5%, and new/worse findings in 67.2%. On the basis of 10-fold cross-validation, the area under the receiver operating characteristic curve value for the complications model was 0.80 (95% confidence interval, 0.74-0.86) and for the inflammation model was 0.71 (95% confidence interval, 0.68-0.74). Scanning only patients with model-predicted complications would reduce scans by 43.0%, with a miss rate of 0.8% (4 of 491). CONCLUSIONS Patients presenting to the emergency department with CD are frequently assessed by CT. However, no significant findings are observed in 32.8%, and only 17% have complications from CD. We created models to identify patients not likely to have significant findings from CT with high negative predictive values; these could aid physicians in avoiding CT scans for many patients. Studies are needed to validate these models beyond a single center.

Increased ultraviolet light exposure is associated with reduced risk of inpatient surgery among patients with Crohn's disease.

Background and Aims Corticosteroids are effective for the short-term treatment of inflammatory bowel disease (IBD). Long-term use, however, is associated with significant adverse effects. To define the: (1) frequency and duration of corticosteroid use, (2) frequency of escalation to corticosteroid-sparing therapy, (3) rate of complications related to corticosteroid use, (4) rate of appropriate bone density measurements (dual energy X-ray absorptiometry [DEXA] scans), and (5) factors associated with escalation and DEXA scans. Methods Retrospective review of Veterans Health Administration (VHA) data from 2002–2010. Results Of the 30,456 Veterans with IBD, 32% required at least one course of corticosteroids during the study time period, and 17% of the steroid users had a prolonged course. Among these patients, only 26.2% underwent escalation of therapy. Patients visiting a gastroenterology (GI) physician were significantly more likely to receive corticosteroid-sparing medications. Factors associated with corticosteroid-sparing medications included younger age (OR = 0.96 per year,95%CI:0.95, 0.97), male gender (OR = 2.00,95%CI:1.16,3.46), GI visit during the corticosteroid evaluation period (OR = 8.01,95%CI:5.85,10.95) and the use of continuous corticosteroids vs. intermittent corticosteroids (OR = 2.28,95%CI:1.33,3.90). Rates of complications per 1000 person-years after IBD diagnosis were higher among corticosteroid users (venous thromboembolism [VTE] 9.0%; fragility fracture 2.6%; Infections 54.3) than non-corticosteroid users (VTE 4.9%; fragility fracture 1.9%; Infections 26.9). DEXA scan utilization rates among corticosteroid users were only 7.8%. Conclusions Prolonged corticosteroid therapy for the treatment of IBD is common and is associated with significant harm to patients. Patients with prolonged use of corticosteroids for IBD should be referred to gastroenterology early and universal efforts to improve the delivery of high quality care should be undertaken.

Spironolactone and colitis: increased mortality in rodents and in humans.

During the open-label trial of natalizumab for Crohns disease, an isolated case of progressive multifocal leukoencephalopathy (PML) was found. This prompted a more careful review by regulators, physicians, and the pharmaceutical industry. A new gut-specific monoclonal antibody, vedolizumab, has been shown to be effective in inflammatory bowel disease, and in continued trials no patients have developed PML. Given the mortality of PML and lack of effective treatments, patients may remain concerned that PML is a possible risk factor. So, going forward, how do we quantify the risk of this serious adverse event? This review details how we define the maximum risk when no (or very few) events have occurred with an easy-to-use equation.

Prevalence and risk factors for heterotopic gastric mucosa of the upper esophagus among men undergoing routine screening colonoscopy

BACKGROUND AND AIMS Due to the formation of strictures and fistulas, patients with Crohns disease (CD) frequently need surgery. Vitamin D has been found to play a role in the degree of inflammation. We aimed to study the effect of UV exposure on the need for inpatient surgery in patients with CD. METHODS The national inpatient sample, the largest database of hospitalizations from the USA, was used to conduct a retrospective study of patients hospitalized from 2004-2011 with CD by ICD-9CM code 555. Surgery was characterized as any intestinal surgery or fistula repair. An average state UV exposure was calculated for each hospitalization. Multivariate logistic regression was used to calculate the effect of UV exposure on surgery accounting for important covariates. RESULTS There were 481712 hospitalizations with a primary diagnosis of CD. Of these hospitalizations, 67751 included a relevant surgical procedure code. Mean UV exposure was statistically lower in the group undergoing surgery (4.3 units versus 4.4 units, p = 0.001). The ratio of hospitalizations per UV exposure tertile for CD was statistically different compared with all hospitalizations (p < 0.001). In univariate analysis, increased UV exposure was associated with a lower risk of inpatient surgery with an OR of 0.90 per unit (95% CI 0.84-0.96, p = 0.001). Accounting for age, gender, race/ethnicity, season, income, hospital setting, and Charlson-Deyo comorbidities, the effect of UV exposure remained protective for inpatient surgery (OR 0.91, 95% CI: 0.84-0.98, p = 0.01). CONCLUSIONS Increased UV exposure is associated with a reduced risk of inpatient surgery among patients with CD. Further studies of vitamin Ds role in CD are necessary.

Intestinal Dilation and Platelet: Albumin Ratio Are Predictors of Surgery in Stricturing Small Bowel Crohn's Disease

Background: Crohns disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation. Methods: In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF‐&bgr;)‐stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation‐induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results: Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n = 390 deaths, P < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51–2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50–2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82–2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use. Conclusions: We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2‐fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S. (Inflamm Bowel Dis 2011;)