Week 2 Adalimumab Levels Predict Short-term Clinical Remission in Patients With Inflammatory Bowel Disease.

BACKGROUND AND GOALS: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. MATERIALS AND METHODS: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. RESULTS: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P =0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P =0.11). CONCLUSIONS: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Acute Flare of Adult-Onset Autoimmune Enteropathy Associated With Cyclophosphamide.

This is a case of adult-onset autoimmune enteropathy (AIE) in a 46-year-old man with multiple autoimmune conditions who presented with worsening disease process after receiving cyclophosphamide. We describe the investigations and management of this patient over a 6-year timeline. The diagnosis and management of AIE is challenging given the heterogeneity in clinicopathologic findings and a small number of adult case reports. We describe the current diagnostic criteria, review the literature on treatment options and outcomes, and discuss the evidence for cyclophosphamide in the treatment of AIE. Adult-onset AIE should be considered in the differential diagnosis of refractory diarrhea and weight loss.

Psychological interventions for reducing anxiety in patients undergoing first-time colonoscopy: a pilot and feasibility study.

OBJECTIVES: To assess the feasibility of a randomized controlled trial (RCT), evaluating the efficacy and patients' perceptions of a psychological intervention aimed at reducing anxiety levels in adults undergoing first-time colonoscopy. METHODS: Adults undergoing first-time colonoscopy were randomized to a psychological intervention vs. sham intervention. The primary outcome was feasibility, defined as a recruitment rate of >50%. Patients' state anxiety was assessed before and after the intervention using the state-trait inventory for cognitive and somatic anxiety (STICSA) score. Follow-up interviews were performed within 1 week with a sample of patients and focus groups with clinical staff. RESULTS: A total of 130 patients were recruited from 180 eligible patients (72%). Eighty were randomized and completed the study (n = 39) in the psychological intervention group and (n = 41) in the sham. In the psychological intervention group, pre- and postmedian STICSA scores were 29 and 24 (P < 0.001), respectively. In the sham group, pre- and postmedian scores were 31 and 25 (P < 0.001), respectively. Follow-up interviews with patients (n = 13) suggested that 100% of patients perceived the psychological intervention as beneficial and would recommend it to others. CONCLUSION: The study was feasible. Patients in both groups improved their anxiety scores, but there were no significant differences between arms. Despite this, patients receiving psychological intervention perceived a benefit from the relaxation exercises.

Endoscopic ultrasound, secretin endoscopic pancreatic function test, and histology: correlation in chronic pancreatitis.

OBJECTIVES: Endoscopic ultrasound (EUS) and hormone-stimulated pancreatic function tests are considered useful, and possibly complementary, in the diagnosis of early chronic pancreatitis (CP). Few past studies have compared either methods with a histological gold standard. The aims were to assess correlations of EUS score and endoscopic pancreatic function test (ePFT) results with the degree of histological fibrosis, as well as the sensitivity of each method for detecting fibrosis. METHODS: This was a retrospective study of patients who underwent EUS, ePFT, or both within 12 months of pancreatic resection or wedge biopsy. EUS scoring was performed using 9 standard criteria, with ≥4 considered abnormal. An ePFT peak bicarbonate concentration <80 mM was considered abnormal. Surgical specimens were reviewed in a blinded manner by an expert pancreatic pathologist and assigned a fibrosis score from 0 to 12. Correlations of the EUS score and ePFT peak bicarbonate with the fibrosis score are reported using the Spearman correlation coefficient. Sensitivity and specificity was calculated for each method against the histological gold standard (fibrosis score ≥2). RESULTS: Twenty-five patients were included. The fibrosis score significantly correlated with the EUS score (r=0.72; 95% confidence interval (CI)=0.43, 0.87; P<0.001) and the ePFT peak bicarbonate (r=-0.57; 95% CI=-0.81, -0.10; P=0.016). EUS had a sensitivity of 84% (95% CI=69, 100) and specificity of 100% (95% CI=40, 100) compared with histology. The ePFT had a sensitivity of 86% (95% CI=67, 100) and specificity of 67% (95% CI=13, 100). When both modalities were combined, the sensitivity increased to 100% (95% CI=63, 100). CONCLUSIONS: Both EUS and ePFT are useful tests in the diagnosis of CP. Combining EUS with ePFT may improve the sensitivity for detection of early fibrosis.

Association Between Age and Complications After Outpatient Colonoscopy.

Importance: There are insufficient data describing the incidence and risk factors of postcolonoscopy complications in older individuals. Objective: To assess the association between older age (≥75 years) and the risk of postcolonoscopy complications. Design, Setting, and Participants: This population-based retrospective cohort study included adults (≥50 years) undergoing outpatient colonoscopy between April 2008 and September 2017, identified from Ontario administrative databases. Individuals with inflammatory bowel disease and hereditary colorectal cancer syndromes were excluded. The study population was subdivided into a colorectal cancer screening-eligible cohort (patients aged 50-74 years) and an older cohort (patients aged ≥75 years). The statistical analysis was conducted from December 2018 to September 2019. Exposures: Older age (≥75 years). Main Outcomes and Measures: The primary outcome was postcolonoscopy complications, defined as the composite of hospitalization or emergency department visits in the 30-day period after the outpatient colonoscopy. Secondary outcomes included incidence of surgically treated colorectal cancer and all-cause mortality at 30 days. Independent variables associated with postcolonoscopy complications were also assessed. Results: The study sample included 38 069 patients; the mean (SD) age was 65.2 (10.1) years, there were 19 037 women (50.0%), and 27 831 patients (73.1%) underwent a first colonoscopy. The cumulative incidence of complications was 3.4% (1310 patients) in the overall population, and it was higher in individuals aged 75 years or older (515 of 7627 patients [6.8%]) than in screening-eligible cohort (795 of 30 443 patients [2.6%]) (P < .001). Independent risk factors for postcolonoscopy complications were age 75 years or older (odds ratio [OR], 2.3; 95% CI, 2.0-2.6), anemia (OR, 1.4; 95% CI, 1.2-1.7), cardiac arrhythmia (OR, 1.7; 95% CI, 1.2-2.2), congestive heart failure (OR, 3.4; 95% CI, 2.5-4.6), hypertension (OR, 1.2; 95% CI, 1.0-1.5), chronic kidney disease (OR, 1.8; 95% CI, 1.1-3.0), liver disease (OR, 4.7; 95% CI, 3.5-6.5), smoking history (OR, 3.2; 95% CI, 2.4-4.3), and obesity (OR, 2.3; 95% CI, 1.2-4.2). The number of previous colonoscopies was associated with a lower risk of complications (OR, 0.9; 95% CI, 0.7-1.0). The incidence of surgically treated colorectal cancer was higher in the older cohort than the screening-eligible cohort (119 patients [1.6%] vs 144 patients [0.5%]; P < .001). All-cause mortality rates were 0.1% overall (39 patients) and 0.1% (19 patients) for individuals aged 50 to 74 years and 0.2% (20 patients) for those aged 75 years and older (P < .001). Conclusions and Relevance: In this population-based cohort study of individuals living in southern Ontario, age of 75 years and older was associated with a higher risk of 30-day postprocedure complications after outpatient colonoscopy. These findings suggest that the decision to perform a colonoscopy should be carefully considered in patients older than 75 years, especially in the presence of comorbidities. Further studies are needed to better understand the benefits of invasive procedures as opposed to less invasive approaches for colorectal cancer screening and surveillance among older patients.

Criteria for use of composite end points for competing risks-a systematic survey of the literature with recommendations.

BACKGROUND: Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. OBJECTIVES: To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. METHODS, DATA SOURCES, STUDY SELECTION AND DATA EXTRACTION: We searched MEDLINE, CINAHL, EMBASE, The Cochrane's Central & Systematic Review databases including the Health Technology Assessment database, and the Cochrane's Methodology register from inception to April 2015, and candidate textbooks, to identify all articles providing guidance on this issue. Eligible publications explicitly addressed the issue of a composite outcome to address competing risks. Two reviewers independently screened the titles and abstracts for full-text review; independently reviewed full-text publications; and abstracted specific criteria authors offered for use of composite end points to address competing risks. RESULTS: Of 63,645 titles and abstracts, 166 proved potentially relevant of which 43 publications were included in the final review. Most publications note competing risks as a reason for using composite end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs with sufficiently high frequency to influence the interpretation of the effect of intervention on the end point of interest. These criteria will seldom be met. Review of heart failure trials published in the New England Journal of Medicine revealed that many of them use the composite end point of death or hospitalization; none of the trials, however, satisfied our criteria. CONCLUSION: The existing literature fails to provide clear guidance regarding use of composite end point for competing risks. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs sufficiently often.

Deep Learning in Gastrointestinal Endoscopy.

Gastrointestinal (GI) endoscopy is used to inspect the lumen or interior of the GI tract for several purposes, including, (1) making a clinical diagnosis, in real time, based on the visual appearances; (2) taking targeted tissue samples for subsequent histopathological examination; and (3) in some cases, performing therapeutic interventions targeted at specific lesions. GI endoscopy is therefore predicated on the assumption that the operator-the endoscopist-is able to identify and characterize abnormalities or lesions accurately and reproducibly. However, as in other areas of clinical medicine, such as histopathology and radiology, many studies have documented marked interobserver and intraobserver variability in lesion recognition. Thus, there is a clear need and opportunity for techniques or methodologies that will enhance the quality of lesion recognition and diagnosis and improve the outcomes of GI endoscopy. Deep learning models provide a basis to make better clinical decisions in medical image analysis. Biomedical image segmentation, classification, and registration can be improved with deep learning. Recent evidence suggests that the application of deep learning methods to medical image analysis can contribute significantly to computer-aided diagnosis. Deep learning models are usually considered to be more flexible and provide reliable solutions for image analysis problems compared to conventional computer vision models. The use of fast computers offers the possibility of real-time support that is important for endoscopic diagnosis, which has to be made in real time. Advanced graphics processing units and cloud computing have also favored the use of machine learning, and more particularly, deep learning for patient care. This paper reviews the rapidly evolving literature on the feasibility of applying deep learning algorithms to endoscopic imaging.

Endoscopic ultrasonography to evaluate pancreatitis.

Endoscopic ultrasonography (EUS) has become a well-accepted test in the workup of acute and chronic pancreatitis. However, further studies are needed to define its diagnostic role in patients with recurrent acute pancreatitis and minimal-change chronic pancreatitis.