The Relationship Between the Endoscopic Healing Index, Fecal Calprotectin, and Magnetic Resonance Enterography in Crohn's Disease.

INTRODUCTION: The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity. MATERIALS AND METHODS: Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL. RESULTS: A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P=0.002), FCAL >50 µg/g (87% vs. 64%, P<0.001) and FCAL >250 µg/g (90% vs. 75%, P=0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P<0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P=0.35). CONCLUSION: Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions.

A Quality Improvement Initiative Is Associated With Reduced Time to Administer Biologics and Small Molecules and Emergency Room Visits in Inflammatory Bowel Disease.

BACKGROUND: Delays in biologic or small molecule medication administration are associated with increased adverse events, hospitalization, and surgery in inflammatory bowel disease (IBD). We evaluated the impact of a quality improvement (QI) intervention on the time to administration of biologics or small molecules (TABS) in IBD. METHODS: Data were retrospectively extracted for IBD patients prescribed biologics or small molecules from a convenience sample of providers participating in an accredited QI educational intervention (baseline cohort). Subsequent to the intervention, data were prospectively collected from patients prescribed these medications (postintervention cohort). Dates related to steps between a treatment decision to medication administration were collected. The primary outcome compared TABS in baseline and postintervention cohorts. RESULTS: Eighteen physicians provided survey and patient data for 200 patients in each cohort (n=400). The median time to medication administration (TABS) decreased from baseline to postintervention cohorts (30 vs. 26 d, P=0.04). Emergency room visits before medication administration also decreased (25.5% vs. 12.5%, P=0.001). Similar numerical TABS reductions were observed in subgroups limited to physicians providing patients to both cohorts and for individual medications prescribed. Primary contributors to delays included filling prescriptions subsequent to insurance approval and dispensation subsequent to this. CONCLUSIONS: A QI intervention successfully reduced medication administration times (TABS) by accelerating provider-dependent steps. This intervention was associated with reduced emergency room visits. We propose TABS as a quality metric to assess the effective delivery of therapies in IBD. Further evaluation of QI interventions, patient education on prescription drug insurance, and quality metrics are warranted.

Fragmented Care is Prevalent Among Inflammatory Bowel Disease Readmissions and is Associated With Worse Outcomes.

OBJECTIVES: Inflammatory bowel disease (IBD) is a complex chronic disease that often requires a multispeciality approach; thus, IBD patients are prone to care fragmentation. We aim to determine the prevalence of fragmentation among hospitalized IBD patients and identify associated predictors and visit-level outcomes. METHODS: The State Inpatient Databases for New York and Florida were used to identify 90-day readmissions among IBD inpatients from 2009 to 2013. The prevalence of fragmentation, defined as a readmission to a non-index hospital, was reported. Characteristics associated with fragmented care were identified using multivariable logistic regression. Multivariable models were utilized to determine the association between fragmentation and outcomes (in-hospital mortality, readmission length of stay, and inpatient colonoscopy). RESULTS: Among IBD inpatients, 25,241 and 29,033 90-day readmission visits were identified, in New York and Florida, respectively. The prevalence of fragmentation was 26.4% in New York and 32.5% in Florida. Younger age, a non-emergent admission type, public payer or uninsured status, mood disorder, and substance abuse were associated with fragmented care, while female gender and a primary diagnosis of an IBD-related complication had an inverse association. Fragmented inpatient care is associated with a higher likelihood of in-hospital death, higher rates of inpatient colonoscopy, and a longer readmission length of stay. CONCLUSIONS: Over one in four IBD inpatient readmissions are fragmented. Disparities and differences in fragmentation exist and contribute to poor patient outcomes. Additional efforts targeting fragmentation should be made to better coordinate IBD management, reduce healthcare gaps, and promote high-value care.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

BACKGROUND: Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. AIMS: To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. RESULTS: A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. CONCLUSIONS: Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

Prospective evaluation of a simplified narrowband imaging scoring system for a differential diagnosis of colorectal lesions.

BACKGROUND: Narrowband imaging (NBI) allows characterization of colorectal polyps during endoscopy; however, this is underutilized by most US physicians. The aim of this study was to assess diagnostic performance of an NBI scoring system, based on the NBI international colorectal endoscopic classification, and determine a threshold score yielding the highest negative predictive value (NPV) in the characterization of colorectal neoplasia. METHODS: During colonoscopy, colorectal lesions were scored using the NBI scoring system on a 0-3 scale for NBI findings. All lesions were biopsied or endoscopically removed for pathological examinations. RESULTS: Two hundred and three patients were enrolled, and a total of 156 colorectal lesions were detected in 67 patients. Diagnostic yields under white light mode showed limited diagnostic performance [accuracy 75.6 % (68.9-82.3), sensitivity 69.2 % (58.6-78.3), specificity 84.6 % (73.1-92.0), positive predictive value (PPV) 86.3 % (75.8-92.9), NPV 66.3 % (55.0-76.0)]. Of NBI threshold scores from 1 to 3 for the diagnosis of neoplastic lesion, the score of ≥1 resulted in an accuracy of 88.5 % (83.5-93.5), sensitivity of 97.8 % (91.5-96.6), and specificity of 75.4 % (62.9-84.9), with PPV of 84.8 % (76.1-90.8) and NPV of 96.1 % (85.4-99.3). CONCLUSIONS: The threshold value of ≥1 in this simplified NBI scoring system yielded the highest sensitivity and NPV for non-adenomatous colorectal polyps. This scoring system is simple to apply and is superior to white light endoscopy.

Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (ß-coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

Factors Associated with the Success of In Vitro Fertilization in Women with Inflammatory Bowel Disease.

BACKGROUND: It is unknown whether certain factors are associated with the success of in vitro fertilization (IVF) in women with inflammatory bowel disease (IBD). AIM: This study assessed whether certain characteristics are associated with greater success of live birth following IVF. METHODS: In a cohort study of 8684 women with IBD seen at two tertiary care centers, we identified 121 women with IBD who underwent IVF. We assessed the effect of numerous factors on likelihood of achieving live birth after IVF. RESULTS: Seventy-one patients with ulcerative colitis (UC) and 49 patients with Crohn's disease (CD) were analyzed. Patients with UC who achieved a live birth were younger (p = 0.03), had a shorter duration of disease (p = 0.01), and were more likely to be in remission (p = 0.03) versus those who did not achieve live birth. Patients with CD who achieved live birth were younger (p < 0.001), had lower body mass index (BMI) (p = 0.02), and had lower cycle day 3 follicle-stimulating hormone levels (p = 0.02). There was no difference in likelihood of achieving live birth among patients in remission and those with mild or unknown disease status (p = 0.69), though most CD patients (79.5 %) were in remission. Prior surgery was not associated with live birth in patients with UC (p = 0.31) or CD (p = 0.62). CONCLUSIONS: As in the general infertility population, younger patients and those with lower BMI were more likely to achieve live birth. History of surgery was not associated with live birth among IBD patients. This is important information for practitioners counseling IBD patients.

In Vitro Fertilization in Women With Inflammatory Bowel Disease Is as Successful as in Women From the General Infertility Population.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population. METHODS: We conducted a matched retrospective cohort study of female patients with IBD who underwent IVF from 1998 through 2011 at 2 tertiary care centers. Patients were matched 4:1 to those without IBD (controls). The primary outcome was the cumulative rate of live births after up to 6 cycles of IVF. Secondary outcomes included the proportion of patients who became pregnant and the rate of live births for each cycle. RESULTS: Forty-nine patients with Crohn's disease (CD), 71 patients with ulcerative colitis (UC), 1 patient with IBD-unclassified, and 470 controls underwent IVF during the study period. The cumulative rate of live births was 53% for controls, 69% for patients with UC (P = .08 compared with controls), and 57% for patients with CD (P = .87 compared with controls). The incidence of pregnancy after the first cycle of IVF was similar among controls (40.9%), patients with UC (49.3%; P = .18), and patients with CD (42.9%; P = .79). Similarly, the incidence of live births after the first cycle of IVF was similar among controls (30.2%), patients with UC (33.8%; P = .54), and patients with CD (30.6%; P = .95). CONCLUSIONS: Based on a matched cohort study, infertile women with IBD achieve a rate of live births after IVF that is comparable with those of infertile women without IBD.

In Vitro Fertilization Is Successful in Women With Ulcerative Colitis and Ileal Pouch Anal Anastomosis.

BACKGROUND: Women with ulcerative colitis (UC), who require ileal pouch anal anastomosis (IPAA), have up to a threefold increased incidence of infertility. To better counsel patients who require colectomy, we examined the success rates of in vitro fertilization (IVF) among women who have undergone IPAA. METHODS: This was a retrospective cohort study conducted at the Brigham and Women's Hospital and Beth Israel Deaconess Medical Center. Female patients with UC were identified via ICD-9 codes and cross-referenced with those presenting for IVF from 1998 through 2011. UC patients with IPAA were compared with the following two unexposed groups that underwent IVF: (1) patients with UC, who had not undergone IPAA, and (2) patients without inflammatory bowel disease (IBD). The primary outcome was the cumulative live birth rate. Secondary outcomes included number of oocytes retrieved, proportion of patients who underwent embryo transfer, pregnancy rate, and live birth rate at first cycle. RESULTS: There were 22 patients with UC and IPAA, 49 patients with UC and without IPAA, and 470 patients without IBD. The cumulative live birth rate after six cycles in the UC and IPAA groups was 64% (95% confidence interval (CI): 44-83%). This rate did not differ from the cumulative live birth rate in the UC without IPAA group (71%, 95% CI: 59-83%; P=0.63) or the group without IBD (53%, 95% CI: 48-57%; P=0.57). CONCLUSIONS: This study demonstrates that in our cohort, women who undergo IPAA achieve live births following IVF at comparable rates to women with UC without IPAA and to women without IBD.

Increased mortality and length of stay among patients with inflammatory bowel disease and hospital-acquired infections.

BACKGROUND & AIMS: Hospitalized patients with inflammatory bowel disease (IBD) could be at increased risk for hospital-acquired infections (HAIs). By using HAI outcome data from Pennsylvania, we examined the influence of HAIs on in-patient mortality and length of stay (LOS) in the hospital among patients with IBD. METHODS: Data were generated by linking the Clinical Research Databases from CareFusion (formerly MediQual), which includes all acute care hospitals in Pennsylvania, with publicly reported HAI data from Pennsylvania. The study population included all patients discharged in 2004 with International Classification of Diseases, 9th Clinical Modification codes of 555.x or 556.x (2324 IBD cases from 161 hospitals). Controls were selected using risk-score matching with a 5:1 ratio. Mortality and LOS end points were estimated and corroborated with regression methods. RESULTS: Among the IBD patients studied, there were 20 deaths and 22 reported cases of HAI. The mortality from HAI among patients with IBD was 13.6%, compared with 0.9% among controls (P = .0146, Fisher exact test). The odds ratio for mortality was 17.2 (95% confidence interval, 1.7-174.3). The median LOS for patients with IBD and HAI was 22 days, versus 6 days for controls (P < .001, Wilcoxon). Of the 22 cases with HAIs, 15 were urinary tract infections, 5 were blood stream infections, and 2 were from multiple sources. CONCLUSIONS: Results from a population-based data set indicate that mortality and LOS are increased among IBD patients who develop HAIs. A majority of the HAIs were from urinary sources. Although HAIs are low-frequency events, increased vigilance to avoid HAI among patients with IBD could improve outcomes.

Differential regulation of peripheral leukocyte genes in patients with active Crohn's disease and Crohn's disease in remission.

GOALS: Assessment of disease severity is a frequent challenge in the management of Crohn's disease. Noninvasive, accurate markers for monitoring disease activity are urgently required. Specific gene expression patterns and molecular biomarkers associated with active Crohn's disease could serve as such markers, thereby providing a novel approach to disease activity monitoring. BACKGROUND: Gene expression profiling in circulating leukocytes has shown promise in several medical conditions and blood may provide an easily accessible surrogate tissue for using gene expression profiling to assess activity of Crohn's disease. STUDY: In this study, we compared genome-wide transcription profiles of circulating leukocytes in patients with active and quiescent Crohn's disease. RESULTS: We observed complex changes in blood gene expression patterns in active Crohn's disease: genes of various functional categories were differentially regulated between active and inactive Crohn's disease. We specifically identified a number of inflammatory molecules overexpressed or underexpressed in active Crohn's disease and validated a subset of these genes by real-time reverse transcription-polymerase chain reaction. CONCLUSIONS: The genes differentially regulated in peripheral leukocytes represent potential new biomarkers for assessing the activity of Crohn's disease.

Esophageal motility in nonacid reflux compared with acid reflux.

Esophageal motility has been well studied in gastroesophageal reflux disease (GERD) and acid reflux, but not in nonacid reflux. Consecutive patients who had both 24-h multichannel intraluminal impedance-pH (MII-pH) and esophageal motility tests for suspected GERD were studied. Patients were grouped into nonacid refluxers, acid refluxers, and nonrefluxers based on positive symptom correlation and objective findings of acid reflux. Of 96 patients enrolled, 21 patients (22%) were nonacid refluxers, 44 patients (46%) were acid refluxers, and 31 patients (32%) had no objective evidence of reflux. Normal motility was recorded in 86% of nonacid refluxers, 71% of acid refluxers, and 60% of nonrefluxers. Ineffective esophageal motility was seen in 24% of acid refluxers, and 5% of nonacid refluxers (P = 0.11). Symptomatic nonacid reflux events comprised 22% of patients studied for GERD symptoms by MII-pH. Esophageal motility in nonacid reflux is normal 86% of the time.

The Use of Actigraphy Differentiates Sleep Disturbances in Active and Inactive Crohn's Disease.

BACKGROUND: Sleep disturbances (SDs) are commonly reported in patients with Crohn's disease (CD). Several survey instruments assessing subjective measures of insufficient sleep have identified SDs in subjects with CD. However, there are limited data on objective measures of SDs in these patients as they relate to disease activity. In this prospective cross-sectional study, we compared objective estimates of sleep obtained using multiday wrist actigraphy in individuals with CD with varying disease activity. METHODS: Eighty patients with a diagnosis of CD were recruited to take part in the study. Participants were stratified by disease activity into remission, mild disease, and moderate to severe disease groups using the Harvey-Bradshaw Index and C-reactive protein levels. Participants were excluded on the basis of significant comorbidity (Charlson Comorbidity Index ≥3), a known history of a sleep disorder, or the concomitant use of systemic corticosteroids. Participants completed surveys, including the PROMIS-SD Short Form 8a, the Epworth Sleepiness Scale, and the Women's Health Initiative Insomnia Rating scale, and were provided with an accelerometer that estimated sleep-wake patterns over 7 days. Comparisons of actigraphic sleep parameters were performed between disease activity groups. Multivariate logistic regression analyses were performed using covariates determined a priori to have an association with sleep disturbance in CD through a review of the literature. RESULTS: Of the 80 participants enrolled in the study, 72 completed 5 days of actigraphy data: 28 subjects in remission, 22 subjects with mild disease activity, and 22 subjects with moderate to severe disease activity. Self-reported sleep characteristics assessed by questionnaires were similar between groups. By actigraphy, individuals with moderate to severe CD spent a significantly longer time awake after falling asleep compared with subjects with remissive disease or compared with subjects with mild disease (65.8 minutes vs 44.3 minutes and 49.1 minutes, respectively; each P < 0.05). Individuals with moderate to severe CD had significantly lower sleep efficiency compared with those with remissive CD (86.6% vs 89.9%; P = 0.03). In the multivariate analyses, moderate to severe CD disease activity was significantly associated with an increased amount of fragmented sleep (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.23-11.32; P = 0.02; WASO ≥ 60 minutes). Moreover, the use of controlled substances was associated with poor sleep efficiency (OR, 3.86; 95% CI, 1.01-14.7; P = 0.04; SE ≤ 85.5%). CONCLUSIONS: This is the first study to objectively quantify disturbed sleep using wrist actigraphy in adults with CD with varying disease activity. Wrist actigraphy may serve as a useful modality for discerning SD in subjects with active vs remissive disease that is not evident with questionnaires alone. Although we determined that disease severity is a significant factor that leads to SDs in CD, larger studies using these objective measures may help determine the contribution of other factors.

Inflammatory bowel disease readmissions are associated with utilization and comorbidity.

OBJECTIVES: Hospital care accounts for up to one-third of the cost of inflammatory bowel disease (IBD) management. A select group of patients with IBD is responsible for a large proportion of this utilization, demonstrating the burden of frequent hospitalizations. We aim to better understand the burden of 30-day readmissions among patients with IBD using a national hospital database. STUDY DESIGN: Retrospective cohort study of state-specific inpatient databases. METHODS: The State Inpatient Databases for New York and Florida were used to identify patients with IBD hospitalized between 2009 and 2013. The prevalence of 30-day IBD-specific readmission was determined. The association between 30-day readmission and visit outcomes, specifically length of stay and a composite of comorbid conditions (venous thromboembolism, pneumonia, sepsis, Clostridium difficile infection, enteral and parenteral nutrition, and blood transfusion), was analyzed using multivariable logistic regression. RESULTS: Patients with IBD accounted for 35,514 and 39,506 inpatient stays in New York and Florida, respectively. Of these stays, 13.7% to 16.2% resulted in a 30-day readmission. On multivariable analysis, 30-day readmissions were associated with a longer length of stay than index hospitalizations by 1.00 day (adjusted regression coefficient, 1.00; 95% CI, 0.73-1.26) and a higher likelihood of having a comorbid condition (adjusted odds ratio, 1.83; 95% CI, 1.68-1.99) in New York. Similar associations were confirmed in Florida. CONCLUSIONS: Nearly 1 in 7 hospitalizations of patients with IBD lead to a 30-day readmission. These IBD-specific readmissions are associated with increased utilization and comorbidity. Patients at risk for readmission need to be targeted to improve outcomes and IBD care quality.

Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND/AIMS: Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in prelung transplant IPF patients. METHODS: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes. RESULTS: Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380). CONCLUSION: Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients.

The Impact of Opioid Epidemic Trends on Hospitalised Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Opioid use disorder [OUD] has become a public health crisis among patients with chronic disease. Inflammatory bowel disease [IBD] patients are at high risk for OUD because they suffer from chronic relapsing-remitting pain. We aimed to describe the prevalence and trends in OUD-related diagnoses among hospitalised IBD patients. METHODS: A retrospective study was performed using weighted Nationwide Inpatient Sample data from 2005 to 2014. Adult IBD hospital visits and OUD-related diagnoses were identified using a previously published schema. Annual diagnoses were calculated. Characteristics associated with OUD were assessed using multivariable logistic regression. Associations between OUD and length of stay were assessed overall and separately for surgical and non-surgical stays. RESULTS: In all, 2.2% of 2585174 weighted discharges with any diagnosis of IBD also had an OUD-related diagnosis, with an 8.8% average annual increase. In multivariable analysis, Crohn's disease, public payer or no insurance, and psychiatric comorbidities were associated with a higher likelihood of OUD, whereas a primary diagnosis of an IBD-related complication was associated with a lower likelihood. An OUD-related diagnosis was associated with 0.84 days (95% confidence interval [CI] 0.71, 0.97] increased length of stay overall, 2.79 days [95% CI 1.44, 4.14] for surgical stays, and 0.71 days [95% CI 0.59, 0.82] for non-surgical stays. CONCLUSIONS: OUD-related diagnoses are increasing among IBD patients and are associated with increased length of stay. With a rising prevalence, it is important to screen and diagnose OUD in IBD and refer patients for evidence-based treatment to address unmet patient needs and reduce health care utilisation.

Chemoprophylaxis of colorectal cancer in inflammatory bowel disease: current concepts.

Ulcerative colitis and Crohn's disease both confer an increased risk of developing colorectal cancer. The use of 5-aminosalicylate as a remission-inducing agent has been long accepted. Its use as a potential chemoprophylactic agent has been proposed and is used by some practitioners. This review examines the most recent data on 5-aminosalicylate as a chemoprophylactic drug as well as ursodeoxycholic acid, folic acid, azathioprine, and 6-mercaptopurine.

Use of antibiotics in the treatment of inflammatory bowel disease.

An increasing amount of evidence suggests that enteric flora may have a role in the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD appear to have an altered composition of luminal bacteria that may provide the stimulus for the chronic inflammation characterizing IBD. The suspected role of bacteria in the pathogenesis of IBD provides the rationale for using agents, such as antibiotics, that alter the intestinal flora. However, there remains much uncertainty about the optimal use of antibiotics in the treatment of Crohn's disease, ulcerative colitis, and pouchitis. This article reviews the literature and presents a clinical model for the use of antibiotics in IBD.

5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine.

BACKGROUND: Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). METHODS: A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. RESULTS: Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. CONCLUSIONS: We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.

A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.

BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.