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.

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.

Pancreatic ductal adenocarcinoma is associated with a unique endocrinopathy distinct from type 2 diabetes mellitus.

INTRODUCTION: The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained. METHODS: In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower ß-cell area and average islet size and density compared to non-T2DM controls (p < 0.05). RESULTS: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and ß/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control). CONCLUSIONS: Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating ß-cell failure in PC can be important for our understanding of pathophysiology of PC.

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.

Clostridium difficile Infection in the Emergency Department.

INTRODUCTION: Clostridioides difficile infection (CDI) is associated with substantial emergency department (ED) and inpatient burden. To date, few studies have evaluated the ED burden of CDI. Using the Nationwide Emergency Department Sample, we evaluated trends in ED use, ED and inpatient charges, admission and mortality rates, length of stay, and independent risk factors for hospital admission and mortality after an ED visit. METHODS: Using Nationwide Emergency Department Sample for 2006 through 2014, we identified all patients with the primary diagnosis of CDI (using diagnostic codes). We determined the trends in ED visits and used survey logistic regression analysis to identify factors associated with hospital admission. RESULTS: Overall, 909,236 ED visits for CDI resulted in 817,935 admissions (90%) to the hospital. The number of visits increased from 76,709 in 2006 to 106,869 in 2014, and the admission rate decreased from 92.4% to 84.4%. ED charges adjusted for inflation went up from US$1433.0 to 2900, a significant rise even accounting for inflation. The overall length of hospital stay decreased from 7 to 5.8 days. Independent predictors of admission after ED visits included smoking, use of alcohol, and presence of multiple comorbidities. Independent risk factors for mortality in admitted patients include increasing age and presence of comorbidities. CONCLUSIONS: Although ED use for CDI increased, rates of hospital admission decreased over 9 years. Identification of predictors of admission and in-hospital mortality will help guide policies and interventions to reduce the burden on health care resources.

Hospital Utilization in Patients With Gastric Cancer and Factors Affecting In-Hospital Mortality, Length of Stay, and Costs.

INTRODUCTION: Although gastric cancer (GC) rates have been declining in the United States, it continues to be a major cause of morbidity. This study examined trends in hospital admissions, in-hospital mortality, length of stay (LOS), and inpatient costs related to GC. In addition, various factors associated with in-hospital mortality, LOS, and inpatient costs were examined. METHODS: National inpatient sample-the largest publicly available all-payer inpatient care database-was interrogated to obtain information about various demographic and hospital-related factors (including those mentioned above) in patients who were primarily admitted for GC between the years 1998 to 2013. These trends were analyzed. Multivariate analysis was also performed to identify risk factors associated with LOS, costs, and mortality. RESULTS: A total of 679,330 hospital discharges with the principal diagnosis of GC were obtained. Hospital stays increased by approximately 340 stays per year (±110; P=0.00079). However, inpatient mortality rate and LOS declined by 0.36% per year (±0.024%; P<0.0001), and 0.11 days per year (±0.01; P<0.0001), respectively. The inpatient charges have increased at the rate of $3241 per year (±133.3; P<0.0001). Differences in mortality rate, LOS, and inpatient costs were affected by multiple factors. CONCLUSIONS: Despite the overall decline in GC incidence, the incidence of hospitalizations per 100,000 US population related to GC did not change significantly. Although LOS and mortality declined, inpatient charges increased over the study period.

Incidence, Admission Rates, and Predictors, and Economic Burden of Adult Emergency Visits for Acute Pancreatitis: Data From the National Emergency Department Sample, 2006 to 2012.

INTRODUCTION: Acute pancreatitis (AP) is the most common gastroenterology-related reason for hospital admission, and a major source of morbidity and mortality in the United States. This study examines the National Emergency Database Sample, a large national database, to analyze trends in emergency department (ED) utilization and costs, risk factors for hospital admission, and associated hospital costs and length of stay (LOS) in patients presenting with AP. METHODS: The National Emergency Database Sample (2006 to 2012) was evaluated for trends in ED visits, ED charges, hospitalization rates, hospital charges, and hospital LOS in patients with primary diagnosis of AP (further subcategorized by age and etiology). A survey logistic-regression model was used to determine factors predictive of hospitalization. RESULTS: A total of 2,193,830 ED visits were analyzed. There was a nonsignificant 5.5% (P=0.07) increase in incidence of ED visits for AP per 10,000 US adults from 2006 to 2012, largely driven by significant increases in ED visits for AP in the 18 to <45 age group (+9.2%; P=0.025), AP associated with alcohol (+15.9%; P=0.001), and AP associated with chronic pancreatitis (+59.5%; P=0.002). Visits for patients aged ≥65 decreased over the time period. Rates of admission and LOS decreased during the time period, while ED and inpatient costs increased (62.1%; P<0.001 and 7.9%; P=0.0011, respectively). Multiple factors were associated with increased risk of hospital admission from the ED, with the strongest predictors being morbid alcohol use [odds ratio (OR), 4.53; P<0.0001], advanced age (age>84 OR, 3.52; P<0.0001), and smoking (OR, 1.75; P<0.0001). CONCLUSIONS: Despite a relative stabilization in the overall incidence of ED visits for AP, continued increases in ED visits and associated costs appear to be driven by younger patients with alcohol-associated and acute on chronic pancreatitis. While rates of hospitalization and LOS are decreasing, associated inflation-adjusted costs are rising. In addition, identified risk factors for hospitalization, such as obesity, alcohol use, and increased age, should be explored in further study for potential use in predictive models and clinical improvement projects.

Incidence, Admission Rates, and Economic Burden of Adult Emergency Visits for Chronic Pancreatitis: Data From the National Emergency Department Sample, 2006 to 2012.

INTRODUCTION: Chronic pancreatitis (CP) is a common reason for emergency department (ED) visits, but little research has examined ED use by patients with CP. MATERIALS AND METHODS: The Nationwide Emergency Department Sample (2006 to 2012) was interrogated to evaluate trends in adult ED visits for a primary diagnosis of CP (International Classification of Disease, 9th revision, Clinical Modification code: 577.1), the rates of subsequent hospital admission, and total charges. A survey logistic regression model was used to determine factors associated with hospitalization from the ED. RESULTS: We identified 253,753 ED visits with a primary diagnosis of CP. No significant trends in annual incidence were noted. However, the ED-to-hospitalization rates decreased by 3% per year (P<0.001) and mean ED charges after adjusting for inflation increased by 11.8% per year (P<0.001). Higher Charlson comorbidity index, current smoker status, alcohol use, and biliary-related CP were associated with hospitalization. In hospitalized patients, length of stay decreased by 2.2% per year (P=0.003) and inpatient charges increased by 2.9% per year (P=0.004). CONCLUSIONS: Patient characteristics associated with higher risk of hospitalization from the ED deserve further attention.

Incidence and Risk Factors Associated With 30-Day Readmission for Alcoholic Hepatitis.

BACKGROUND: Alcohol abuse and liver disease are associated with high rates of 30-day hospital readmission, but factors linking alcoholic hepatitis (AH) to readmission are not well understood. We aimed to determine the incidence rate of 30-day readmission for patients with AH and to evaluate potential predictors of readmission. METHODS: We used the Nationwide Readmissions Database to determine the 30-day readmission rate for recurrent AH between 2010 and 2014 and examined trends in readmissions during the study period. We also identified the 20 most frequent reasons for readmission. Multivariate survey logistic regression analysis was used to identify factors associated with 30-day readmission. RESULTS: Of the 61,750 index admissions for AH, 23.9% were readmitted within 30-days. The rate of readmission did not change significantly during the study period. AH, alcoholic cirrhosis, and hepatic encephalopathy were the most frequent reasons for readmission. In multivariate analysis female sex, leaving against medical advice, higher Charlson comorbidity index, ascites, and history of bariatric surgery were associated with earlier readmissions, whereas older age, payer type (private or self-pay/other), and discharge to skilled nursing-facility reduced this risk. CONCLUSIONS: The 30-day readmission rate in patients with AH was high and stable during the study period. Factors associated with readmission may be helpful for development of consensus-based expert guidelines, treatment algorithms, and policy changes to help decrease readmission in AH.

Trends of hospitalizations for syncope/collapse in the United States from 2004 to 2013-An analysis of national inpatient sample.

INTRODUCTION: Syncope/collapse is a common reason for emergency department visits, and approximately 30-40% of these individuals are hospitalized. We examined changes in hospitalization rates, in-hospital mortality, and cost of syncope/collapse-related hospital care in the United States from 2004 to 2013. METHODS: We used the US Nationwide Inpatient Sample (NIS) from 2004 to 2013 to identify syncope/collapse-related hospitalizations using ICD-9, code 780.2, as the principal discharge diagnosis. Data are presented as mean ± SEM. RESULTS: From 2004 to 2013, there was a 42% reduction in hospitalizations with a principal discharge diagnosis of syncope/collapse from 54,259 (national estimate 253,591) in 2004 to 31,427 (national estimate 156,820) in 2013 (P < 0.0001). The mean length of hospital stays decreased (2.88 ± 0.04 days in 2004 vs. 2.54 ± 0.02 in 2013; P < 0.0001), while in-hospital mortality did not change (0.28% in 2004 vs. 0.18% in 2013; P  =  0.12). However, mean charges (inflation adjusted) for syncope/collapse-related hospitalization increased by 43.6% from $17,514 in 2004 to $25,160 in 2013 (P < 0.0001). The rates of implantation of permanent pacemakers and implantable cardioverter defibrillator remained low during these hospitalizations, and decreased over time (P for both < 0.0001). CONCLUSIONS: Hospitalization rates for syncope/collapse have decreased significantly in the US from 2004 to 2013. Despite a modest reduction in length of stay, the cost of syncope/collapse-related hospital care has increased.

Clobazam monotherapy for focal or generalized seizures.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the treatment of new focal or generalized seizures. A Cochrane systematic review for clobazam monotherapy is expected to define its place in the treatment of new-onset or untreated seizures and highlight gaps in evidence. OBJECTIVES: To evaluate the efficacy, effectiveness, tolerability and safety of clobazam as monotherapy in people with new-onset focal or generalized seizures. SEARCH METHODS: For the latest update we searched the following databases on 19 March 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946- ), BIOSIS Previews (1969- ), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). There were no language restrictions. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing clobazam monotherapy versus placebo or other anti-seizure medication in people with two or more unprovoked seizures or single acute symptomatic seizure requiring short-term continuous anti-seizure medication, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Primary outcome measure was time on allocated treatment (retention time), reflecting both efficacy and tolerability. Secondary outcomes included short- and long-term effectiveness measures, tolerability, quality of life, and tolerance measures. Two authors independently extracted the data. MAIN RESULTS: We identified three trials fulfilling the review criteria, which included 206 participants. None of the identified studies reported the preselected primary outcome measure. A meta-analysis was not possible. Lack of detail regarding allocation concealment and a high risk of performance and detection bias in two studies prompted us to downgrade the quality of evidence (by using the GRADE approach) for some of our results due to risk of bias.Regarding retention at 12 months, we detected no evidence of a statistically significant difference between clobazam and carbamazepine (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.61 to 1.12; low-quality evidence). There was low-quality evidence that clobazam led to better retention compared with phenytoin (RR 1.43, 95% CI 1.08 to 1.90). We could not determine whether participants receiving clobazam were found to be less likely to discontinue it due to adverse effects as compared to phenytoin (RR 0.10, 95% CI 0.01 to 1.65, low-quality evidence). AUTHORS' CONCLUSIONS: We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naive children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each. At present, the available evidence is insufficient to inform clinical practice.

Similar Risk of Cardiopulmonary Adverse Events Between Propofol and Traditional Anesthesia for Gastrointestinal Endoscopy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Even though propofol use for gastrointestinal endoscopic procedures has increased over the past decade, there is a perception that it causes a higher rate of cardiopulmonary adverse events. The aim of this study was to compare the sedation-related adverse events associated with use of propofol vs nonpropofol agents for endoscopic procedures. We also wanted to determine the influence of duration or complexity of the procedures and endoscopist-directed (gastroenterologist) vs non-gastroenterologist-directed sedation on the outcomes. METHODS: A search was conducted using Medline, EMBASE, and the Cochrane controlled trials registry. The following cardiopulmonary adverse events were assessed: hypoxia, hypotension, and arrhythmias. The procedures were divided into 2 groups based on the procedure length: a nonadvanced endoscopic procedure group consisting of esophagogastroduodenoscopy, colonoscopy, and sigmoidoscopy, and an advanced endoscopic procedures group including endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, balloon enteroscopy, and endoscopic submucosal dissection. Pooled odds ratios for complications were calculated for all the procedures combined and then separately for the 2 groups. Random-effects models were used for 2-proportion comparisons. RESULTS: Of the 2117 citations identified, 27 original studies qualified for this meta-analysis and included 2518 patients. Of these, 1324 received propofol, and 1194 received midazolam, meperidine, pethidine, remifentanil, and/or fentanyl. Most of the included studies were randomized trials of moderate quality and nonsignificant heterogeneity (Cochran Q, 26.07; P = .13). Compared with traditional sedative agents, the pooled odds ratio with the use of propofol for developing hypoxia for all the procedures combined was 0.82 (95% confidence interval [CI], 0.63-1.07), and for developing hypotension was 0.92 (95% CI, 0.64-1.32). In the nonadvanced endoscopic procedure group, those who received propofol were 39% less likely to develop complications than those receiving traditional sedative agents (odds ratio, 0.61; 95% CI, 0.38-0.99). There was no difference in the complication rate for the advanced endoscopic procedure group (odds ratio, 0.86; 95% CI, 0.56-1.34). A subgroup analysis did not show any difference in adverse events when propofol was administered by gastroenterologists or nongastroenterologists. CONCLUSIONS: Propofol sedation has a similar risk of cardiopulmonary adverse events compared with traditional agents for gastrointestinal endoscopic procedures. Propofol use in simple endoscopic procedures was associated with a decreased number of complications. When used for gastrointestinal endoscopic procedures of a complex nature and longer duration, propofol was not associated with increased rates of hypoxemia, hypotension, or arrhythmias. Administration of propofol by gastroenterologists does not appear to increase the complication rates.

Release of Cathepsin B in Cytosol Causes Cell Death in Acute Pancreatitis.

BACKGROUND & AIMS: Experimental studies in acute pancreatitis (AP) suggest a strong association of acinar cell injury with cathepsin B-dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death is not clear. In this study, we have explored intra-acinar events downstream of trypsin activation that lead to acinar cell death. METHODS: Acinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen 7, or cathepsin B-deleted) were stimulated with supramaximal cerulein, and the cytosolic activity of cathepsin B and trypsin was evaluated. Permeabilized acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis. RESULTS: Both in vitro and in vivo studies have suggested that during AP cathepsin B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin B into the cytosol can lead to cell death through necrosis. CONCLUSIONS: This report defines the role of trypsin in AP and shows that cytosolic cathepsin B but not trypsin activates cell death pathways. This report also suggests that trypsin is a requisite for AP only because it causes release of cathepsin B into the cytosol.

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.

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.

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.

Dose-Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis.

BACKGROUND: Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously. METHODS AND RESULTS: Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose-response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]-min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67-0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87-0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77-0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58-0.73) the minimum guideline-recommended levels. CONCLUSIONS: There is an inverse dose-response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.

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.

Risk of cancer in inflammatory bowel disease: going up, going down, or still the same?

PURPOSE OF REVIEW: There has been increasing use of immunosuppressive medications as well as better surveillance techniques in inflammatory bowel disease (IBD), which is associated with an increased risk of intestinal and extraintestinal malignancies. We assessed the temporal trends of cancer incidence in IBD patients by reviewing the biomedical literature, performing meta-regression of existing studies, and examining trends in hospitalizations for cancer in IBD patients using a national hospitalization database. RECENT FINDINGS: The overall risk of colorectal cancer in ulcerative colitis has decreased in the last 3 decades. The risk of small bowel cancer is significantly elevated among Crohn's disease patients, but there has been no change in incidence rates. The overall risk of non-Hodgkin lymphoma has increased over the last 16 years, and IBD patients on thiopurines and antitumor necrosis factor agents are at increased risk of non-Hodgkin lymphoma. The risk of melanoma in IBD patients is increased, with no significant change over time. The risk of nonmelanoma skin cancer is higher in patients using thiopurines compared with the non-IBD background population, with no significant change over time. SUMMARY: This study points toward a decrease in the incidence of colorectal cancer in ulcerative colitis patients, but an increase in the incidence of lymphoproliferative disorders and nonmelanoma skin cancers with the use of immunosuppressive medications in IBD.