Automated electronic health record-based application for sedation triage in routine colonoscopy.

BACKGROUND AND AIMS: Nearly all routine endoscopy procedures are performed using moderate sedation (MS) or monitored anesthesia care (MAC). In this article, we describe how we improved decision-making and decreased practitioners' cognitive burden for choosing between MAC and MS by using patient data in an automated application within the electronic health record (EHR). METHODS: In our practice, we choose between MS or MAC for routine GI procedures according to written anesthesia-use guidelines and practitioner preferences. To expedite our decision-making for MS versus MAC, we developed an Excel (Microsoft Corp, Redmond, Wash, USA)-based tool from patient demographic characteristics, comorbid conditions, and medication use extracted from the EHR. The data points from Excel were then implemented in the automated application in the EHR to predict the type of sedation for GI procedures. RESULTS: Before use of the new application, nurses spent an average of 4 minutes and gastroenterology practitioners spent 5 minutes reviewing the EHR to determine the appropriate sedation (MS or MAC). After the application was implemented, the use of MS substantially increased. Time spent reviewing the EHR was reduced to 2 minutes. The rate of adverse events for MS (.5%) versus MAC (.6%) was comparable and low overall. CONCLUSIONS: The EHR-based application, which automates and standardizes determination of sedation type, is a highly beneficial tool that eliminates subjectivity in decision-making, thus allowing for appropriate use of MAC. Adverse event rates and sedation failure did not increase with use of the application. With the increased use of MS over MAC, healthcare costs for the more-expensive MAC sedation should also decrease.

Incidence and predictors of 30-day hospital readmissions for liver cirrhosis: insights from the United States National Readmissions Database.

BACKGROUND: Cirrhosis is associated with substantial inpatient morbidity and mortality. This study aimed to determine the trends in 30-day hospital readmission rates among patients with cirrhosis and identify factors associated with these readmissions. METHODS: We conducted a retrospective analysis of data retrieved from the Nationwide Readmissions Database to determine trends in 30-day readmission for patients discharged with a diagnosis of cirrhosis in 2010 through 2014. Multivariate logistic regression analysis was used to identify predictors of readmission. RESULTS: Among 303,346 patients identified from the database, the 30-day readmission rate for patients with a discharge diagnosis of cirrhosis was 31.4% (n=95,298). The trends in the readmission rates remained steady during the study period. On multivariate analysis, female sex, age 45 years or older, esophagogastroduodenoscopy (EGD) during admission, and disposition to a short-term care facility or skilled nursing facility protected against readmissions. In contrast, coverage by Medicaid insurance, admission during a weekend, nonalcoholic cause of cirrhosis, and history of hepatic encephalopathy and ascites were associated with readmission. CONCLUSIONS: We found an exceptionally high 30-day readmission rate in patients with cirrhosis, although it remained stable during the study period. This study identified some modifiable factors such as disposition to a short-term care facility or skilled nursing facility and patients' attendance of alcohol rehabilitation facilities that could decrease the likelihood of readmission and could inform local and national healthcare policymakers.

Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study.

BACKGROUND: The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time. METHODS: From a cohort of 128 subjects (Cohort A) with CT scans done 3-36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort). RESULTS: CTs were abnormal in 16% and 85% at 24-36 and 3-6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (-12.8); CTS II: Low density mass confined to pancreas (-9.5), CTS III: Peri-pancreatic infiltration (-5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04). CONCLUSION: Starting 12-18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.

Early detection of pancreatic cancer.

PURPOSE OF REVIEW: Pancreatic cancer is the third leading cause of cancer death and with a dismal 5-year survival of 10%. Poor survival of pancreatic cancer is mostly due to its presentation and diagnosis at a late stage. The present article aims to update clinicians with recent progress in the field of early detection of pancreatic cancer. RECENT FINDINGS: Pancreatic cancer screening is not recommended in the general population due to its low prevalence. In this review, we discuss high-risk groups for pancreatic cancer, including inherited predisposition to pancreatic cancer, new-onset diabetes, mucinous pancreatic cyst, and chronic pancreatitis. We discuss methods of enrichment of high-risk groups with clinical models using electronic health records and biomarkers. We also discuss improvements in imaging modalities and emerging role of machine learning and artificial intelligence in the field of imaging and biomarker to aid in early identification of pancreatic cancer. SUMMARY: There are still vast challenges in the field of early detection of pancreatic cancer. We need to develop noninvasive prediagnostic validated biomarkers for longitudinal surveillance of high-risk individuals and imaging modalities that can identify pancreatic cancer early.

Why are we performing fewer cholecystectomies for mild acute biliary pancreatitis? Trends and predictors of cholecystectomy from the National Readmissions Database (2010-2014).

BACKGROUND: Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis (MABP) during the index admission because it is associated with better outcomes. In this study, we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day readmission. METHODS: Using diagnostic codes and the National Readmissions Database, we identified patients admitted with MABP between 2010 and 2014. Differences in cholecystectomy rates were computed on the basis of various characteristics. We conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same admission. RESULTS: We identified 255,695 unique index MABP cases (41.3% male) and the 30-day readmission rate was 12.6%. Overall, 43.8% underwent cholecystectomy and 25% underwent endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy. We observed a decreasing trend in both procedures during the study period (P < 0.001). In multivariate analysis, odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy (odds ratio, 0.78; 95% confidence interval, 0.74-0.84) or cholecystectomy (odds ratio, 0.37; 95% confidence interval, 0.35-0.39). CONCLUSIONS: For patients with MABP, cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day readmission. Despite this benefit and national guidelines recommending cholecystectomy during the index MABP admission, the rate of cholecystectomies performed nationally decreased during the study period. Further research is needed to understand the implications and reasons underlying this deviation from guidelines.

Acute pancreatitis associated with intravenous administration of propofol: evaluation of causality in a systematic review of the literature.

Acute pancreatitis (AP) associated with intravenous administration of propofol has been described with unknown causal relation. We therefore assessed this causality in a systematic review. Multiple databases were searched on 16 August 2017; studies were appraised and selected by two reviewers based on a priori criteria. Propofol causality was evaluated with the Naranjo scale and Badalov classification. We identified 18 studies from 11 countries with a total of 21 patients, and the majority had adequate methodological quality. The median age was 35 years (range, 4-77) and 10 (48%) were males. Overall, propofol was administrated in 8 patients as sedative along with induction/maintenance of anesthesia in 13 patients; median dose was 200 mg, with intermediate latency (1-30 days) in 14 (67%). Serum triglycerides were >1000 mg/dL in four patients. Severe AP was observed in four patients (19%). AP recurrence occurred in one out of two patients who underwent rechallenge. Mortality related to AP was 3/21(14%). Propofol was the probable cause of AP according to the Naranjo scale in 19 patients (89%). Propofol-induced AP has a probable causal relation and evidence supports Badalov class Ib. Hypertriglyceridemia is not the only mechanism by which propofol illicit AP. Propofol-induced AP was severe in 19% of patients with a mortality rate related to AP of 14%. Future research is needed to delineate whether this risk is higher if combined with other procedures that portend inherent risk of pancreatitis such as endoscopic retrograde cholangiopancreatography.

CD4+ CD25+ FOXP3+ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn's disease.

BACKGROUND: Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker. METHODS: The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients. RESULTS: Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%. CONCLUSION: Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

Incidence and Predictors of Readmissions in Acute Pancreatitis: A Nationwide Analysis.

OBJECTIVES: Acute pancreatitis (AP) is a common cause for hospitalization, and readmission is common, with variable associated risk factors for readmission. Here, we assessed the incidence and risk factors for readmission in AP in a large national database. METHODS: We analyzed data from the National Readmission Database during the year 2013. Index admissions with a primary discharge diagnosis of AP using the International Classification of Diseases, Ninth Revision, Clinical Modification were identified from January to November to identify 30-day readmission rates. Demographic, hospital, and clinical diagnoses were included in multivariate regression analysis to identify readmission risk factors. RESULTS: We identified 243,816 index AP discharges with 39,623 (16.2%) readmitted within 30 days. The most common reason for readmission was recurrent AP (41.5%). Increased odds of all-cause readmission were associated with younger age, nonhome discharge, increasing Charlson Comorbidity Index, and increased length of stay. Cholecystectomy during index admission was associated with reduced all-cause and recurrent AP readmissions (odds ratios of 0.5, and 0.35, respectively). CONCLUSIONS: Readmission for AP is common, most often due to recurrent AP. Multiple factors, including cholecystectomy, during index admission, are associated with significantly reduced odds of all-cause and recurrent AP readmissions.

Evaluating clinical, dietary, and psychological risk factors for relapse of ulcerative colitis in clinical, endoscopic, and histological remission.

BACKGROUND AND AIM: The literature on possible factors that could trigger a relapse in patients with ulcerative colitis (UC) in clinical, endoscopic, and histological remission on long-term follow up is scarce. To determine the relapse rate in patients with UC in clinical, endoscopic, and histological remission and identify factors that may influence the risk of relapse. METHODS: Patients with UC in clinical, endoscopic, and histological remission were enrolled between January and July 2010 and followed up for 1 year to determine the effect of clinical, dietary, and psychological factors on relapse. Information regarding factors that may affect relapse such as infection, antibiotic, or non-steroidal anti-inflammatory drugs (NSAIDs) use and any other factor that the patient felt important and compliance with medications was obtained. RESULTS: Ninety-seven patients (59 males, mean age 39 ± 11.9 years) were followed up for a mean duration of 9 ± 2.3 months. Eighteen (18.6%) relapsed with the median time to relapse being 3.5 months. On univariate analysis, more relapsers had significantly higher NSAIDs use within 15 days of relapse, respiratory tract infection within 4 weeks, use of steroids more than once in past, higher consumption of calcium, riboflavin, and vitamin A, and lower consumption of sugars. On multivariate analysis, NSAIDs use (HR [95% CI]: 6.41 [1.88-21.9]) and intake of vitamin A (HR [95% CI]: 1.008 [1.000-1.016]) were statistically significant predictors of relapse. CONCLUSION: With a relapse rate of 18.6% over a follow up of 9 months in patients with UC in clinical, endoscopic, and histological remission, independent predictors of relapse were history of NSAIDs use within 15 days of relapse and higher intake of vitamin A.

Short-Term Clinical Response to Corticosteroids Can Predict Long-Term Natural History of Ulcerative Colitis: Prospective Study Experience.

BACKGROUND: Long-term outcome and natural history of steroid response in adult ulcerative colitis patients based on short-term response is largely unknown. AIM: To evaluate whether short-term clinical response at 30  days after steroid initiation for moderate to severe disease can predict long-term outcome. METHODS: This prospective observational study recruited 161 patients who received oral/intravenous steroid therapy at our institution from April 2005 to July 2009. Short-term response at 30 days and long-term response at the end of first and third years were measured. Risk factors for long-term outcome at 1 and 3 years were analyzed by multivariate regression model. RESULTS: At the end of 30 days, 90 patients (55.9%) had complete response, 47 (29.2%) partial response, and 24 (14.9%) did not respond at all. At the end of first year, 53/90 (60%) complete responders (at 30 days) maintained steroid-free remission when compared to 17/71 (23.9%, p < 0.001) partial/no responders. Similar result was observed at the end of third year (74.7 vs 55.1%, p = 0.017). On multivariable analysis, short-term outcome at 30 days was a predictor of outcome at the end of one year (RR 4.1, 95% CI 2.2-8.5) and 3 years (RR 2.1, 95% CI 1.02-4.5). CONCLUSIONS: Short-term response to steroids is a strong predictor of long-term outcome at 1 and 3 years in active ulcerative colitis patients.

Long-Term Disease Course and Pregnancy Outcomes in Women with Inflammatory Bowel Disease: An Indian Cohort Study.

BACKGROUND: The literature on interaction between pregnancy and inflammatory bowel disease (IBD) is inconsistent, and there are no reports on this aspect from Asia. This study evaluated the impact both IBD and pregnancy have on each other in a large cohort of Indian patients. METHODS: In total, 514 females with ulcerative colitis (UC) or Crohn's disease (CD) aged between 18 and 45 years attending IBD clinic, at our institute, from July 2004 to July 2013 were screened, and patients with data on pregnancy status were included (n = 406). Pregnancies were categorized as either before, after or coinciding with disease onset. Long-term disease course was ascertained from prospectively maintained records. Pregnancy and fetal outcomes were recorded from antenatal records or individual interviews. RESULTS: Of 406 patients (UC: 336, CD: 70), 310 became pregnant (UC: 256, CD: 54), with a total of 597 pregnancies (UC: 524, CD: 73). More UC patients with pregnancies were in long-term remission than non-pregnant patients (56.7 vs. 43.4 %, p = 0.04). Long-term remission was less frequent in UC patients in whom pregnancy coincided with disease onset than patients with pregnancies before and after/pregnancy after the disease onset (41.4 vs. 62.5 %, p = 0.023). Pregnancies after the disease onset were associated with more cesarean sections and adverse fetal outcomes than pregnancies before disease onset in both UC and CD patients. CONCLUSIONS: Long-term disease course in UC patients was better in pregnant as compared to non-pregnant patients. Among pregnant UC patients, disease course was worst when pregnancy coincided with disease onset. Pregnancy and fetal outcomes were worse in pregnancy after disease onset than pregnancy before disease onset.

Trends and Outcomes of Pulmonary Arterial Hypertension-Related Hospitalizations in the United States: Analysis of the Nationwide Inpatient Sample Database From 2001 Through 2012.

IMPORTANCE: Recent trends and outcomes of pulmonary arterial hypertension (PAH)-related hospitalization in adults in the United States are unknown. OBJECTIVE: To examine the characteristics of PAH-related hospitalizations. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the National Inpatient Sample database for all adult patients (≥18 years old) with PAH as the principal discharge diagnosis from January 1, 2001, through December 31, 2012. MAIN OUTCOMES AND MEASURES: We analyzed the temporal trends in hospitalization rate, hospital charges, in-hospital mortality, length of hospitalization, and comorbidities pertaining to PAH-related hospitalizations. We also evaluated the predictors of in-hospital mortality and length of hospitalizations. RESULTS: The number of PAH-related hospitalizations per year in adults decreased significantly from 2001 through 2012 (3177 vs 1345, P for trend <.001). However, the mean hospital charge per admission increased 2.7-fold from 2001 through 2012 ($29 507 vs $79 607, P for trend <.001). There was a significant increase in each of these associated comorbid conditions: diabetes (4.6%-7.8%), hypertension (5.1%-17.1%), coronary artery disease (15.6%-22.3%), chronic obstructive pulmonary disease (14.4%-20.1%), anemia (12.4%-20.4%), cardiac dysrhythmias (21.7%-29.0%), congestive heart failure (40.7%-56.1%), acute (5.9%-20.1%) or chronic kidney disease (1.1%-16.4%), fluid and electrolyte imbalance (18.9%-35.3%), pneumonia (4.4%-6.3%), cardiogenic shock (0.5%-1.5%), and acute respiratory failure (4.3%-20.8%) from 2001 through 2012. The length of hospitalization increased (mean [SE], 7.0 [0.5] days in 2001 vs 7.6 [0.6] days in 2012, P for trend = .009), but in-patient mortality remained unchanged (7.8% [1.1%] in 2001 vs 6.3% [1.7%] in 2012, P for trend = .54). Admission to a teaching hospital (ß coefficient for length of hospitalization, 2.0; 95% CI, 1.3-1.6; odds ratio [OR] for mortality, 1.5; 95% CI, 1.1-2.1), cardiac dysrhythmias (ß coefficient, 1.8; 95% CI, 1.1-2.6; OR, 1.8; 95% CI, 1.4-2.4), acute kidney injury (ß coefficient, 5.0; 95% CI, 3.9-6.1; OR, 2.3; 95% CI, 1.7-3.2), acute cerebrovascular accident (ß coefficient, 6.6; 95% CI, 1.9-11.3; OR, 6.7; 95% CI, 2.1-21.1), and acute respiratory failure (ß coefficient, 6.2; 95% CI, 5.1-7.4; OR, 5.6; 95% CI, 4.2-7.5) were associated with increased length of hospitalization and in-hospital mortality. Congestive heart failure (OR, 1.7; 95% CI, 1.3-2.2), cardiogenic shock (OR, 5.4; 95% CI, 2.7-10.9), and fluid and electrolyte imbalance (OR, 1.9; 95% CI, 1.5-2.4) were associated with increased in-hospital mortality but not length of hospitalization. CONCLUSIONS AND RELEVANCE: Analyses of temporal changes in PAH care reveal a significant decrease in PAH-related hospitalizations in the United States, but hospital charges have increased substantially and are increasingly being borne by Medicare. In-hospital mortality remains unchanged, but length of hospitalization has increased. This study should help identify the characteristics of patients with PAH that are associated with increased risk of in-hospital mortality and longer length of hospitalization.

Genome-wide gene expression analysis for target genes to differentiate patients with intestinal tuberculosis and Crohn's disease and discriminative value of FOXP3 mRNA expression.

BACKGROUND AND AIMS: Crohn's disease (CD) and intestinal tuberculosis (ITB) are both chronic granulomatous conditions with similar phenotypic presentations. Hence, there is need for a biomarker to differentiate between both these two diseases. This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls. To evaluate the role of T regulatory cells, forkhead box P3 (FOXP3) mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls. METHODS: Paired samples, including serum and colonic biopsies, were taken from 33 study subjects (CD, ITB and controls), and total RNA was extracted. Human whole genome gene expression microarray analysis was performed using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three groups in duplicates. Real-time PCR for FOXP3 mRNA expression was analyzed in serum samples and colonic biopsy samples (4-CD, 5-ITB, 4-controls). RESULTS: In CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold downregulation of 91 and 256 genes, respectively. Peroxisome proliferators via the PPARγ pathway were most significantly downregulated (P < 0.005) in CD. Additionally, the IL4/5/6 signaling pathways and Toll-like receptor signaling pathway were identified as significantly differentially regulated (P < 0.005) at > 2-fold change. In ITB, the complement activation pathway, specifically the classical pathway, was the most significantly upregulated. FOXP3 mRNA expression was significantly elevated in colonic biopsies obtained from ITB patients as compared with CD cases (4.70 ± 2.21 vs 1.48 ± 0.31, P = 0.016). CONCLUSIONS: FOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between ITB and CD. Upregulation of the complement activation pathway in ITB suggests that pathogenetic mechanisms for ITB are similar to those of pulmonary tuberculosis. In CD, downregulation of PPARγ was seen in colonic tissue, suggesting that restoration of PPARγ-dependent anti-microbial barrier function may be a therapeutic target.

VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial.

BACKGROUND: The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated. OBJECTIVE: To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC. METHODS: A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks. RESULTS: Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups. CONCLUSIONS: The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC. TRIAL REGISTRATION NUMBER: The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. "CTRI/2008/091/000086" (registered on: 23/06/2008).

Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis.

BACKGROUND: Adalimumab is used in an attempt to maintain remission for Ulcerative colitis. This study was to evaluate the efficacy and adverse events of adalimumab compared with placebo in inducing remission of Ulcerative colitis. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID, BIOSIS, CNKI, and Google were searched. All randomized trials comparing adalimumab with placebo in inducing remission of moderate-to-severe ulcerative colitis were included. RESULTS: Two randomized controlled trials with a total of 754 participants met the inclusion criteria. The pooled risk ratio (RR) of clinical remission was 1.85 (95% confidence interval (CI) 1.26 to 2.72) following adalimumab treatment. RR of clinical response was 1.40 (95% CI 1.19 to 1.65) while that of mucosal healing was 1.23 (95% CI 1.03 to 1.47). RR of any adverse events was 1.00 (95% CI 0.93 to 1.09). CONCLUSION: Compared with placebo, administration of adalimumab may increase the proportion of patients with moderate-to-severe ulcerative colitis attaining clinical remission, clinical response and mucosal healing. Adalimumab is also tolerated well in these patients.

A meta-analysis on efficacy and safety: single-balloon vs. double-balloon enteroscopy.

BACKGROUND AND AIM: Double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are new techniques capable of providing deep enteroscopy. Results of individual studies comparing these techniques have not been able to identify a superior strategy. Our aim was to systematically pool all available studies to compare the efficacy and safety of DBE with SBE for evaluation of the small bowel. METHODS: Databases were searched, including PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The main outcome measures were complete small-bowel visualization, diagnostic yield, therapeutic yield, and complication rate. Statistical analysis was performed using Review Manager (RevMan version 5.2). Meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. We used the χ(2) and I(2) test to assess heterogeneity between trials. Results were expressed as risk ratios (RR) or mean differences with 95% confidence intervals (CI). RESULTS: Four prospective, randomized, controlled trials with a total of 375 patients were identified. DBE was superior to SBE for visualization of the entire small bowel [pooled RR = 0.37 (95% CI: 0.19-0.73; P = 0.004)]. DBE and SBE were similar in ability to provide diagnosis [pooled RR = 0.95 (95% CI: 0.77-1.17; P = 0.62)]. There was no significant difference between DBE and SBE in therapeutic yield [pooled RR = 0.78 (95% CI: 0.59-1.04; P = 0.09)] and complication rate [pooled RR = 1.08 (95% CI: 0.28-4.22); P = 0.91]. CONCLUSIONS: DBE was superior to SBE with regard to complete small bowel visualization. DBE was similar to SBE with regard to diagnostic yield, ability to provide treatment and complication rate, but these results should be interpreted with caution as they is based on very few studies and the overall quality of the evidence was rated as low to moderate, due to the small sample size.

Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial.

AIM: Minimal hepatic encephalopathy (MHE) impairs daily functioning and health-related quality of life in chronic liver disease (CLD). Lactulose is the standard treatment but has side-effects. Probiotics have an encouraging role in MHE. The aim of the present study was to test whether probiotics are non-inferior to lactulose in improving MHE. METHODS: Patients with CLD (n = 227) were screened for MHE using neuropsychometric tests (number connection tests A and B [or figure connection tests A and B]) and/or neurophysiological test (P-300 auditory event-related potential), and 120 (53%) were diagnosed with MHE by abnormal tests. MHE patients were randomized to lactulose (30-60 mL/day) or probiotic (four capsules of VSL#3; total of 450 billion CFU/day) for 2 months. Response was defined as normalization of tests. Serum ammonia was measured by commercial kit. RESULTS: Of 120 patients randomized, 40 in the lactulose arm and 33 in the probiotic arm completed 2 months of intervention. MHE improved in 25 (62.5%) patients taking lactulose and 23 (69.7%) taking probiotics. The effect size of difference of improvement in MHE between lactulose and probiotic was 0.072 per per-protocol analysis and 0.040 as per intention to treat analysis (within -20% of non-inferiority margin). Serum ammonia was comparable between groups at baseline and 2 months; it decreased in patients in whom MHE improved, while increased in patients with no improvement in MHE. CONCLUSION: The probiotic VSL#3 was non-inferior to the standard therapy, lactulose in the treatment of MHE. Improvement in MHE correlated with reduction of ammonia levels.

Comparative efficacy of pharmacologic interventions in preventing relapse of Crohn's disease after surgery: a systematic review and network meta-analysis.

BACKGROUND & AIMS: There are several drugs that might decrease the risk of relapse of Crohn's disease (CD) after surgery, but it is unclear whether one is superior to others. We estimated the comparative efficacy of different pharmacologic interventions for postoperative prophylaxis of CD, through a network meta-analysis of randomized controlled trials. METHODS: We conducted a systematic search of the literature through March 2014. We identified randomized controlled trials that compared the abilities of mesalamine, antibiotics, budesonide, immunomodulators, anti-tumor necrosis factor α (anti-TNF) (started within 3 months of surgery), and/or placebo or no intervention to prevent clinical and/or endoscopic relapse of CD in adults after surgical resection. We used Bayesian network meta-analysis to combine direct and indirect evidence and estimate the relative effects of treatment. RESULTS: We identified 21 trials comprising 2006 participants comparing 7 treatment strategies. In a network meta-analysis, compared with placebo, mesalamine (relative risk [RR], 0.60; 95% credible interval [CrI], 0.37-0.88), antibiotics (RR, 0.26; 95% CrI, 0.08-0.61), immunomodulator monotherapy (RR, 0.36; 95% CrI, 0.17-0.63), immunomodulator with antibiotics (RR, 0.11; 95% CrI, 0.02-0.51), and anti-TNF monotherapy (RR, 0.04; 95% CrI, 0.00-0.14), but not budesonide (RR, 0.93; 95% CrI, 0.40-1.84), reduced the risk of clinical relapse. Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CrI, 0.15-0.92), immunomodulator monotherapy (RR, 0.33; 95% CrI, 0.13-0.68), immunomodulator with antibiotics (RR, 0.16; 95% CrI, 0.04-0.48), and anti-TNF monotherapy (RR, 0.01; 95% CrI, 0.00-0.05), but neither mesalamine (RR, 0.67; 95% CrI, 0.39-1.08) nor budesonide (RR, 0.86; 95% CrI, 0.61-1.22), reduced the risk of endoscopic relapse. Anti-TNF monotherapy was the most effective pharmacologic intervention for postoperative prophylaxis, with large effect sizes relative to all other strategies (clinical relapse: RR, 0.02-0.20; endoscopic relapse: RR, 0.005-0.04). CONCLUSIONS: Based on Bayesian network meta-analysis combining direct and indirect treatment comparisons, anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.

Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis.

OBJECTIVE: To study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD). PATIENTS AND METHODS: We conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach. RESULTS: We identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%). CONCLUSION: On the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.