Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Polypharmacy is a risk factor for disease flare in adult patients with ulcerative colitis: a retrospective cohort study.

BACKGROUND/AIMS: Polypharmacy is a common clinical problem with chronic diseases that can be associated with adverse patient outcomes. The present study aimed to determine the prevalence and patient-specific characteristics associated with polypharmacy in an ulcerative colitis (UC) population and to assess the impact of polypharmacy on disease outcomes. METHODS: A retrospective chart review of patients with UC who visited a tertiary medical center outpatient clinic between 2006 and 2011 was performed. Polypharmacy was defined as major ( ≥ 5 non-UC medications) or minor (2-4 non-UC medications). UC medications were excluded in the polypharmacy grouping to minimize the confounding between disease severity and polypharmacy. Outcomes of interest include disease flare, therapy escalation, UC-related hospitalization, and surgery within 5 years of the initial visit. RESULTS: A total of 457 patients with UC were eligible for baseline analysis. Major polypharmacy was identified in 29.8% of patients, and minor polypharmacy was identified in 40.9% of the population. Polypharmacy at baseline was associated with advanced age (P< 0.001), female sex (P= 0.019), functional gastrointestinal (GI) disorders (P< 0.001), and psychiatric disease (P< 0.001). Over 5 years of follow-up, 265 patients remained eligible for analysis. After adjusting for age, sex, functional GI disorders, and psychiatric disease, major polypharmacy was found to be significantly associated with an increased risk of disease flare (odds ratio, 4.00; 95% confidence interval, 1.66-9.62). However, major polypharmacy was not associated with the risk of therapy escalation, hospitalization, or surgery. CONCLUSIONS: Polypharmacy from non-inflammatory bowel disease medications was present in a substantial proportion of adult patients with UC and was associated with an increased risk of disease flare.

The Clinical Anatomy and Imaging Laboratory: Vertical Integration in the Preclerkship Curriculum.

Introduction: As medical schools implement integrated curricula, anatomy education especially has experienced increased pressure to make foundational content clinically relevant. We designed a novel type of integrative anatomy laboratory experience where students could use foundational anatomy concepts in concert with modern imaging/diagnostic techniques to enhance important clinical concepts. Methods: We selected a process called Lesson Study to develop the multidisciplinary Clinical Anatomy and Imaging Laboratory (CAIL) in the cardiovascular and gastrointestinal systems. We utilized soft-embalmed cadavers extensively for their highly realistic tissue appearance and texture, which allowed instructors and students to perform a wide array of procedures in case-based scenarios similar to practicing clinicians. We conducted field observations of participating students, focus-group discussions, and knowledge-based exams to examine efficacy of the CAIL. Results: Approximately 150 first- and second-year students participated in each of the CAIL activities on an annual basis. Most focus-group participants felt the CAIL was a great learning experience. They commented on how the lab provided relevance to anatomy knowledge and helped integrate prior classroom learning more deeply. Instructors noted that students asked more advanced, clinically relevant questions than in a typical anatomy lab. Knowledge improved significantly after the CAIL, although it is unclear if this translates to summative exams. Discussion: The CAIL creates a unique learning experience where students use prior foundational anatomy knowledge in conjunction with modern imaging and diagnostic techniques to reinforce important clinical concepts. We have continued to integrate CAIL experiences into more clinical systems in our medical school curriculum.

Opioid use and misuse in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) may be exposed to opioids over their disease duration. The use of such medications carries significant risk, including intestinal dysmotility and potential for addiction. However, the rates of narcotic use and misuse in patients with UC have not been studied extensively. Functional gastrointestinal disorders (FGID) are prevalent in patients with UC, and have been shown to increase the risk of narcotic use and misuse in patients with Crohn's disease. We hypothesized that patients with UC and a concurrent diagnosis of FGID would have increased rates of both opioid use and misuse in our patient cohort. AIM: To evaluate the prevalence of chronic opioid use and misuse in UC. METHODS: A retrospective chart review of UC patients seen at the University of Virginia Digestive Health Center was performed on all patients evaluated between 2006 and 2011. Patient demographics, medical, surgical, and medication histories were obtained from the electronic medical record. Concomitant diagnosis of FGID was also noted at the time. The electronic prescription monitoring program was accessed to obtain prescription opioid filling histories. Prescription opioid misuse was defined as opioid prescriptions filled from four or more prescribers and four or more different pharmacies in a 12-mo period. RESULTS: A total of 497 patients with UC were included. Patients with UC and FGID were more likely to be female, but no other demographic variables were associated with FGID. Of the UC patients who had FGID, a greater proportion were found to be using opioids chronically (36% with FGID vs 9% without FGID, P < 0.0001) and were misusing prescription opioids (12.8% vs 1.3%, P < 0.001). Multivariate logistic regression demonstrated a significant association with FGID and chronic opioid use (OR = 4.50; 95%CI: 1.91-10.59) and opioid misuse (OR = 5.19; 95%CI 1.04-25.76). Tobacco use (OR 2.53; 95%CI: 1.06-6.08) and anxiety (OR 3.17; 95%CI: 1.08-9.26) were other variables associated with an increased risk of chronic narcotic use. CONCLUSION: FGID was associated with a 4.5-fold increase in chronic opioid use and a 5-fold increased risk of opioid misuse in this patient cohort with UC.

Nonadherence to Biologic Therapies in Inflammatory Bowel Disease.

BACKGROUND: Nonadherence to medications is common with patients with inflammatory bowel disease (IBD). The aim of this study was to assess adherence to biologic medications prescribed for IBD and to identify risk factors for biologic nonadherence. METHODS: This was a single center retrospective cohort study investigating IBD patient adherence to biologic therapies over a 2-year period from September 2014 to September 2016. Specialty pharmacy and infusion center records were obtained and a modified medication possession ratio was calculated. Patient characteristics associated with nonadherence in a univariate model were placed into a multivariate logistic regression to assess independent predictors of nonadherence. RESULTS: Three hundred sixty-five patients met inclusion criteria; 63 patients were on vedolizumab. Three hundred and one patients (82%) had Crohn's disease. The pooled 24-month adherence rate was 66%; adherence to individual biologic therapy included vedolizumab 83%, infliximab 70%, adalimumab 57%, and certolizumab pegol 50%. Facility-administered biologics were independently associated with higher adherence than self-administered biologics (OR 2.39, 95% CI 1.50 - 3.80). Additional risk factors for nonadherence included younger age (OR 1.22, 95% CI 1.01-1.47) and noncommercial insurance (OR 1.78, 95% CI 1.01 - 3.13). CONCLUSIONS: This is the first study to assess adherence to vedolizumab in IBD patients, which was higher than 3 other commonly prescribed biologic medications. Self-administered injections were strongly associated with biologic nonadherence. Younger age and noncommercial insurance also were associated with biologic nonadherence. Modality of administration should be taken into account when selecting a biologic agent for treatment of IBD.

Antitumor Necrosis Factor-α Therapy Is Associated With Reduced Risk of Thromboembolic Events in Hospitalized Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thromboembolic events. The aim of this study was to assess whether treatment with anti-tumor necrosis factor-α (TNF-α) therapy was associated with a decreased risk of thromboembolism. METHODS: We identified IBD patients hospitalized between July 2002 and July 2011 at our institution. Demographic data, medications, indication for hospitalization, and type of thromboembolic event were obtained by chart review. Wald tests were used to calculate an association between clinical characteristics and risk of thromboembolism. A multivariable logistic regression model was used to identify independent risk factors for thromboembolic events. RESULTS: A total of 547 patients (1048 hospitalizations) were identified. Fifty thromboembolic events occurred. Patient-related factors associated with thromboembolism included older age (P<0.0001), chronic kidney disease (P=0.001), diabetes (P=0.009), liver disease (P=0.005), and prior history of thromboembolism (P<0.0001). Acute infection (P=0.009), trauma (P=0.009), prolonged hospitalization (P<0.0001), and lack of thromboembolic prophylaxis (P<0.0001) were also associated with increased risk. Systemic corticosteroids were associated with increased risk of thromboembolism (P=0.003), whereas TNF-α inhibitors were protective (P=0.011). Multivariate regression identified systemic corticosteroid use (OR=4.62, P=0.0004) as associated with an increased risk of thromboembolism. TNF-α inhibitors were associated with a reduced risk of thromboembolism (OR=0.20, P=0.049). CONCLUSIONS: In this cohort of hospitalized IBD patients, TNF-α inhibitor therapy was associated with a reduced risk of thromboembolism, whereas systemic corticosteroid use was associated with an increased risk of thromboembolism.

Narcotic use and misuse in Crohn's disease.

BACKGROUND: The rate of narcotic misuse in the inflammatory bowel disease population is not well studied. The primary aim of this study was to determine in Crohn's disease (CD) whether a concurrent functional gastrointestinal disorder (FGID) was associated with increased rates of chronic narcotic use. Second, we aimed to identify potential risk factors for narcotic misuse. METHODS: A retrospective chart review of patients with CD followed at the University of Virginia's Gastroenterology Clinic from 2006 to 2011 was performed. The prescription monitoring program was accessed to confirm narcotic prescription filling histories. Narcotic misuse was defined as narcotic prescriptions filled from 4 or more prescribers and at 4 or more different pharmacies. RESULTS: Nine hundred thirty-one patients with CD were included in the study cohort. Eighty-seven (9.3%) patients were identified as having a concurrent FGID, and 192 (20%) were taking chronic narcotics. Patients with FGID were more likely to be taking chronic narcotics (44% versus 18%, P < 0.001). Thirty-seven percent (32/87) of patients with an FGID were misusing narcotics, compared with 9.6% (81/844) (P < 0.0001). Multivariate logistic regression demonstrated a significant association of misuse in patients with a concurrent FGID (odds ratio = 3.33, 95% confidence interval, 1.87-5.93). CONCLUSIONS: Twenty percent of patients with CD were using chronic narcotics with higher rates in those with FGID. Using the prescription monitoring program, a significant proportion of patients with CD with an FGID were misusing narcotics. We would recommend screening for narcotic misuse in patients with CD with a concomitant FGID and consider using prescription monitoring programs to identify others at risk for misuse.

Profile of ustekinumab and its potential in patients with moderate-to-severe Crohn's disease.

The advent of anti-tumor necrosis factor (TNF)-α therapy has been a major advance in the medical management of Crohn's disease (CD). However, a significant proportion of patients with CD do not respond adequately to treatment with these agents. Primary and secondary nonresponse to anti-TNFα therapy represents a common clinical challenge, and highlights the need for the development of additional medication options for CD. The proinflammatory cytokines interleukin (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and serve as a potential target for additional biologic therapies. Monoclonal antibodies targeting IL-12/23 have shown efficacy in animal models of colitis, and are currently being studied in Phase III clinical trials of CD. This review focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody, which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and describes the current efficacy and safety data for ustekinumab in patients with CD.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage.

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.

Accelerated infliximab infusions for inflammatory bowel disease improve effectiveness.

AIM: To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease (IBD). METHODS: Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min. Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions. To be eligible for the study, patients needed a minimum of four prior infusions. An initial infusion of 90-min was given to each patient; those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits. Any patient having significant infusion reactions would be reverted to the standard 120-min protocol. A change in a patient's dose mandated a single 120-min infusion before accelerated infusions could be administered again. RESULTS: The University of Virginia Medical Center's Institutional Review Board approved this study. Fifty IBD patients treated with infliximab 5 mg/kg, 7.5 mg/kg and 10 mg/kg were offered accelerated infusions. Forty-six patients consented to participate in the study. Nineteen (41.3%) were female, five (10.9%) were African American and nine (19.6%) had ulcerative colitis. The mean age was 42.6 years old. Patients under age 18 were excluded. Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine, three were taking 6-mercaptopurine and one was taking methotrexate. One of the 46 study patients used corticosteroid therapy for his IBD. Seventeen of the patients used prophylactic medications prior to receiving infusions; six patients received corticosteroids as pre-medication. Four patients had a history of distant transfusion reactions to infliximab. These reactions included shortness of breath, chest tightness, flushing, pruritus and urticaria. These patients all took prophylactic medications before receiving infusions. 46 patients (27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions. No infusion reactions were reported. There were no adverse events, including drug-related infections. None of the patients developed cancer of any type during the study timeframe. Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632 ($116 965 vs $63 333, P = 0.001). One hundred and eighteen hours were saved in the administration of the accelerated infusions (17 160 min vs 10 080 min, P = 0.001). In the study population, overweight females [body mass index (BMI) > 25.00 kg/m(2)] were found to have statistically higher BMIs than overweight males (mean BMI 35.07 ± 2.66 kg/m(2) vs 30.08 ± 0.99 kg/m(2), P = 0.05), finding which is of significance since obesity was described as being one of the risk factors for Crohn's disease. CONCLUSION: We are the first US group to report substantial cost savings, increased safety and patient satisfaction associated with accelerated infliximab infusion.

Racial disparities in cholecystectomy rates during hospitalizations for acute gallstone pancreatitis: a national survey.

BACKGROUND: Practice guidelines advocate performing cholecystectomy for acute gallstone pancreatitis during the same hospitalization stay. Our objectives were to determine nationwide rates of adherence to these guidelines in the United States and whether this varied with race and ethnicity. METHODS: We queried the Nationwide Inpatient Sample (NIS) to identify admissions for acute gallstone pancreatitis between 1998 and 2003. We calculated overall and race-specific proportions of patients who underwent cholecystectomy or endoscopic retrograde cholangiopancreatography (ERCP) prior to discharge. We used multivariate analysis to determine racial effects while adjusting for age, comorbidity, health insurance payer, and hospital factors. RESULTS: The overall rate of cholecystectomy was 51% and that of either cholecystectomy or ERCP was 62%. Cholecystectomy rates were lower among African Americans (AAs) and Asians compared to Whites (44% and 43%, respectively, vs 50%, P < 0.001). After multivariate adjustment, the odds of cholecystectomy was lower in AAs (OR 0.68, 95% CI 0.63-0.73) and Asians/Pacific Islanders (OR 0.75, 95% CI 0.65-0.87) relative to Whites, while rates were modestly higher among Hispanics (OR 1.12, 95% CI 1.03-1.22). AAs were less likely to receive ERCP than Whites (OR 0.71, 95% CI 0.65-0.78). In contrast, Asians/Pacific Islanders (OR 1.40, 95% CI 1.16-1.69) and Hispanics (OR 1.19, 95% CI 1.09-1.29) were more likely to receive ERCP than Whites. CONCLUSIONS: Despite practice guidelines, about only half of admissions for gallstone pancreatitis receive cholecystectomy during the same hospitalization, and cholecystectomy rates vary substantially by race. These findings raise concerns regarding suboptimal healthcare delivery.

Community-based health preferences for proctocolectomy: a race comparison.

Our objective was to determine whether there are dominating racial differences in patient preferences for surgery that may explain the disparities in proctocolectomy utilization between African Americans (AA) and whites. We used the time trade-off technique to measure health preferences for undergoing ileal pouch anal anastomosis (IPAA) and ileostomy among a community sample of 23 white and 16 AA participants who were unaffected by colorectal disease. Our results show that African Americans were similar to whites with respect to baseline quality of life and comorbidities. There were no differences in health utility ratings for IPAA between AA and whites (0.49 +/- 0.34 vs 0.51 +/- 0.31, P = 0.95). The health preference for ileostomy among AA (0.52 +/- 0.32) was also similar to that in whites (0.54 +/- 0.32). We conclude that patient preferences for proctocolectomy are unlikely to be a dominant contributing factor to racial disparities in total proctocolectomy for diseases of the colon.

Rising hospitalization rates for inflammatory bowel disease in the United States between 1998 and 2004.

BACKGROUND: Recent epidemiological studies suggest that the prevalences of Crohn's disease (CD) and ulcerative colitis (UC) are increasing in the United States. We sought to determine whether nationwide rates of inflammatory bowel disease (IBD) hospitalizations have increased in response to temporal trends in prevalence. METHODS: We identified all admissions with a primary diagnosis of CD or UC, or 1 of their complications in the Nationwide Inpatient Sample between 1998 and 2004. National estimates of hospitalization rates and rates of surgery were determined using the U.S. Census population as the denominator. RESULTS: There were an estimated 359,124 and 214,498 admissions for CD and UC, respectively. The overall hospitalization rate for CD was 18.0 per 100,000 and that for UC was 10.8 per 100,000. There was a 4.3% annual relative increase in hospitalization rate for CD (P < 0.0001) and a 3.0% annual increase for UC (P < 0.0001). Surgery rates were 3.4 bowel resections per 100,000 for CD and 1.2 colectomies per 100,000 for UC and remained stable. There were no temporal patterns for average length of stay for CD (5.8 days) or for UC (6.8 days). The national estimate of total inpatient charges attributable to CD increased from $762 million to $1,330 million between 1998 and 2004, and that for UC increased from $592 million to $945 million. CONCLUSIONS: Hospitalization rates for IBD, particularly CD, have increased within a 7-year period, incurring a substantial rise in inflation-adjusted economic burden. The findings reinforce the need for effective treatment strategies to reduce IBD complications.