A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing Both Morphology and Inflammation.

BACKGROUND & AIMS: Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures. METHODS: The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance. RESULTS: For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study. CONCLUSIONS: The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.

Short and long-term follow-up and clinical outcomes in patients with celiac disease in a large private practice setting.

BACKGROUND: Celiac disease (CD) is caused by an immune response to gluten and treatment is adherence to a gluten-free diet. Guidelines from studies in large academic settings recommend registered dietitian (RD) referrals at time of diagnosis and periodic testing for micronutrient deficiencies. There is limited data to guide follow-up parameters in a large, community-based practice. The purpose of this study was to evaluate guideline adherence in this setting. METHODS: This retrospective study conducted in 2019 assessed CD care based on follow-up rates, micronutrient testing, symptoms, and serology results in cohorts with and without RD referrals. Patients in this study were followed at Rockford Gastroenterology Associates (RGA): a large, private GI practice. Patients were included if they had a diagnosis of CD from 1/2014 through 12/2018, based on positive serology and/or duodenal biopsy. Patient data was collected by chart review and analyzed through Microsoft Excel. Fisher's exact and Chi-square tests were used for the statistical analysis and were calculated through the Statistical Product and Service Solutions (SPSS) software. RESULTS: 320 patients were initially reviewed and a cohort of 126 patients met inclusion criteria. 69.8% had a RD referral. 65.9% had at least one lab test order for any of the 6 micronutrients. Of 63 patients tested for iron, 11 were iron deficient (8 with RD referral). Of 64 patients tested for vitamin D, 21 were deficient (17 with referral). 80.2% attended at least one follow-up appointment, but 34.9% had only one follow-up visit over a mean follow up duration of 5.82 months. 79 patients had follow-up data for symptoms or serology and were separated into 4 categories (with vs. without RD referral): (1) asymptomatic and negative serology (32% vs. 26%), (2) symptomatic and negative serology (28% vs. 16%), (3) asymptomatic and positive serology (27% vs. 32%), (4) symptomatic and positive serology (13% vs. 26%). Category 1 yielded a fisher exact test value of 2.62 (p = 0.466). CONCLUSIONS: RD referral, micronutrient testing, and close follow-up are important parameters that affect outcomes in patients with CD. Rates for dietitian referral, some micronutrient testing and follow-up visits were higher than 50%, though results from this study were not statistically significant. Further standardization of follow-up testing and monitoring for CD will help minimize discrepancies between community-based and large, academic GI practices.

Gluten Degradation, Pharmacokinetics, Safety, and Tolerability of TAK-062, an Engineered Enzyme to Treat Celiac Disease.

BACKGROUND AND AIMS: Celiac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten. Despite adhering to a gluten-free diet (the only management option available to patients with CeD), many patients continue to experience symptoms and intestinal injury. Degradation of immunogenic fractions of gluten peptides in the stomach has been proposed as an approach to reduce toxicity of ingested gluten; however, no enzymes evaluated to date have demonstrated sufficient gluten degradation in complex meals. TAK-062 is a novel, computationally designed endopeptidase under development for the treatment of patients with CeD. METHODS: Pharmacokinetics, safety, and tolerability of TAK-062 100-900 mg were evaluated in a phase I dose escalation study in healthy participants and patients with CeD. Gluten degradation by TAK-062 was evaluated under simulated gastric conditions in vitro and in healthy participants in the phase I study, with and without pretreatment with a proton pump inhibitor. Residual gluten (collected through gastric aspiration in the phase I study) was quantified using R5 and G12 monoclonal antibody enzyme-linked immunosorbent assays. RESULTS: In vitro, TAK-062 degraded more than 99% of gluten (3 g and 9 g) within 10 minutes. In the phase I study, administration of TAK-062 was well tolerated and resulted in a median gluten degradation ranging from 97% to more than 99% in complex meals containing 1-6 g gluten at 20-65 minutes postdose. CONCLUSIONS: TAK-062 is well tolerated and rapidly and effectively degrades large amounts of gluten, supporting the development of this novel enzyme as an oral therapeutic for patients with CeD. (ClinicalTrials.gov: NCT03701555, https://clinicaltrials.gov/ct2/show/NCT03701555.).

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND & AIMS: In celiac disease (CeD), gluten induces immune activation, leading to enteropathy. TAK-101, gluten protein (gliadin) encapsulated in negatively charged poly(dl-lactide-co-glycolic acid) nanoparticles, is designed to induce gluten-specific tolerance. METHODS: TAK-101 was evaluated in phase 1 dose escalation safety and phase 2a double-blind, randomized, placebo-controlled studies. Primary endpoints included pharmacokinetics, safety, and tolerability of TAK-101 (phase 1) and change from baseline in circulating gliadin-specific interferon-γ-producing cells at day 6 of gluten challenge, in patients with CeD (phase 2a). Secondary endpoints in the phase 2a study included changes from baseline in enteropathy (villus height to crypt depth ratio [Vh:Cd]), and frequency of intestinal intraepithelial lymphocytes and peripheral gut-homing T cells. RESULTS: In phase 2a, 33 randomized patients completed the 14-day gluten challenge. TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (-0.63, P = .002), but not in the TAK-101 group (-0.18, P = .110), although the intergroup change from baseline was not significant (P = .08). Intraepithelial lymphocyte numbers remained equal. TAK-101 reduced changes in circulating α4ß7+CD4+ (0.26 vs 1.05, P = .032), αEß7+CD8+ (0.69 vs 3.64, P = .003), and γδ (0.15 vs 1.59, P = .010) effector memory T cells. TAK-101 (up to 8 mg/kg) induced no clinically meaningful changes in vital signs or routine clinical laboratory evaluations. No serious adverse events occurred. CONCLUSIONS: TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases. ClinicalTrials.gov identifiers: NCT03486990 and NCT03738475.

Anemia Etiology and the Response to a Gluten-Free Diet in Untreated Patients With Celiac Disease: A 2-Year Follow-Up.

INTRODUCTION: Anemia and micronutrient deficiencies are common in newly diagnosed patients with celiac disease (CeD). We aim to determine the prevalence and etiology of anemia in a cohort of patients with CeD in the United States and examine the effect of a gluten-free diet (GFD) on the laboratory parameters related to anemia in CeD. METHODS: We analyzed a prospectively collected cohort of adults with biopsy-proven CeD followed in a specialized CeD center between January 2000 and June 2016. We used the level of hemoglobin (Hb) and micronutrients suggested by the World Health Organization to establish the diagnosis of anemia or deficiencies. Demographic data and laboratory parameters related to anemia and micronutrients were recorded at the time of diagnosis and on a GFD. A celiac expert nutritionist or gastroenterologist evaluated all patients. RESULTS: In 572 patients with laboratory evaluation before starting a GFD, approximately 25% presented with anemia at the time of diagnosis of CeD. Iron deficiency was present in 50.8% of the cohort and in 78.8% of the patients with anemia. Within the anemic population, 84.4% of female patients as compared with 58.3% of male patients ( P = 0.02) showed iron deficiency. Folate deficiency (23.2%), vitamin B12 deficiency (11%), and anemia of chronic diseases (7.8%) were also part of both sexes' anemia etiology. Of the initially anemic patients, 81% and 89% normalized their Hb levels within 1 year and 2 years of beginning a GFD, respectively. All patients received appropriate supplementation when needed. DISCUSSION: Approximately 25% of individuals have anemia at CeD diagnosis. The anemia etiology included iron deficiency, vitamin deficiencies, and anemia of chronic diseases. Most of the patients will normalize their Hb levels and the anemia laboratory parameters 1 year after starting a strict GFD.

Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study.

GOALS: This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS). BACKGROUND: While gluten-induced neurocognitive impairment (GINI; eg, "celiac fog" or "brain fog") is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences. STUDY: A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument. RESULTS: The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts. CONCLUSIONS: This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.

Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD. METHODS: We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence. RESULTS: We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain. CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD.

Enteric-Release Budesonide May Be Useful in the Management of Non-Responsive Celiac Disease.

BACKGROUND: Non-responsive celiac disease (NRCD) has many aetiologies, including gluten exposure. Budesonide may be used for refractory celiac disease (RCD) and celiac crisis. AIMS: We reviewed the effectiveness of budesonide to induce clinical and histologic response in NRCD with villous atrophy (VA). METHODS: Case series of adult cases with NRCD and VA prescribed budesonide at two celiac centers. Clinical variables and mucosal recovery (i.e., normal villous architecture within 1 year of treatment) were evaluated. RESULTS: Forty-two cases [77% female, median age 45.0 (IQR 28.3-60.0) years] were included. Most common symptoms were diarrhea (64%) and abdominal pain (62%). Budesonide was initiated at 9 mg (83%) for a median duration of 16.0 weeks (IQR 6.8-25.0 weeks). In total, 57% exhibited a clinical response, positively associated with diarrhea (adjusted OR 6.08 95% CI 1.04-35.47) and negatively with fatigue (adjusted OR 0.18 95% CI 0.03-0.98). Clinical response was higher among those with dietitian counseling prior to budesonide (n = 29, 70 vs. 23%, p < 0.01). Mucosal recovery was observed in 11/24 with follow-up duodenal biopsies. There was no association between clinical response and mucosal recovery, and 79% of clinical responders had a symptomatic relapse. RCD (48%) and chronic gluten exposure (24%) were the main suspected aetiologies of NRCD. Most individuals without a clinical response subsequently received an IBS-related diagnosis. CONCLUSIONS: Budesonide may be effective to induce clinical response in NRCD presenting with diarrhea and VA, but clinical recurrence and lack of mucosal recovery are frequent after tapering. Other diagnoses, including coexisting IBS, may be considered in non-responders to budesonide therapy.

Efficacy of Enteric-Release Oral Budesonide in Treatment of Acute Reactions to Gluten in Patients With Celiac Disease.

Celiac disease (CeD) is a common gluten-responsive T cell-mediated enteropathy. The only current treatment is gluten avoidance; however, even when attempting to adhere to a gluten-free diet (GFD), symptomatic gluten exposures are frequent.1.

Inter- and Intra-assay Variation in the Diagnostic Performance of Assays for Anti-tissue Transglutaminase in 2 Populations.

Tissue transglutaminse-2 (TG2)-based immunoassays are the cornerstone of diagnosis in celiac disease (CeD), with a reported pooled sensitivity as high as 98%.1 However, a few small, single-center studies have questioned their sensitivity in clinical practice.2-5 Moreover, commercial kits use variable TG2 antigens,6 with cutoffs determined by using small, poorly defined populations. Variation in diagnostic performance of anti-TG2 assays in different racial and geographic populations has not yet been studied. We compared the interassay and intra-assay variations in diagnostic performance of 4 immunoglobulin (Ig)A-anti-TG2 assays in Canadian and Indian populations.

Healthcare Resource Utilization and Costs in Celiac Disease: A US Claims Analysis.

INTRODUCTION: Celiac disease (CeD) is a lifelong immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction in the small intestine. This retrospective cohort study examines healthcare resource utilization (HRU) and costs between patients with CeD and matched controls. METHODS: Patients with CeD (cases) with an endoscopic biopsy and ≥2 medical encounters with a CeD diagnosis between January 1, 2010, and October 1, 2015, were identified in the MarketScan databases. The date of the first claim with a CeD diagnosis on or after the endoscopic biopsy was the index date. Cases were matched 1:1 to patients without CeD (controls) on demographic characteristics and Deyo-Charlson Comorbidity Index score. Clinical characteristics, all-cause, and CeD-related HRU and costs (adjusted to 2017 US dollars) were compared between cases and controls during the 12 months before (baseline) and 24 months after (follow-up) the index date. RESULTS: A total of 11,008 cases (mean age 40.6 years, 71.3% women) were matched to 11,008 controls. During the follow-up, a higher proportion of cases had all-cause and CeD-related HRU including inpatient admissions, emergency department visits, gastroenterologist visits, dietician visits, endoscopic biopsies, and gastroenterology imaging (all P ≤ 0.002). Incremental all-cause and CeD-related costs were in the first ($7,921 and $2,894) and second ($3,777 and $935) year of follow-up, driven by outpatient services costs. DISCUSSION: In this US national claims database analysis, there was evidence of an increase in both all-cause and CeD-related HRU and related costs in patients with CeD compared with matched patients without CeD, suggesting a significant economic burden associated with CeD.

Concepts and Instruments for Patient-Reported Outcome Assessment in Celiac Disease: Literature Review and Experts' Perspectives.

BACKGROUND: In diseases where there is a large subjective component, such as celiac disease (CD), patient reported-outcomes (PRO) endpoints are highly relevant. However, there is a gap in knowledge about which PRO endpoints and instruments should be used for clinical trials for treatment of celiac disease. OBJECTIVES: To identify patient-centered symptom, impact, and health-related quality of life (HRQoL) concepts in CD and relevant PRO instruments, and to gather expert input on concepts and instruments to inform selection of PRO endpoints for use in clinical trials of new CD treatments. METHODS: A targeted literature review was conducted to identify symptom, impact, and HRQoL concepts, including those captured in PROs further reviewed against U.S. Food and Drug Administration standards for development and validation as endpoints. US and European clinicians, payers, and a patient advocate (n = 21) were interviewed to assess the identified concepts' relative importance in measuring treatment benefit and to gauge the value of potential PROs as endpoints for market access/reimbursement. RESULTS: Thirty-four published studies were identified: 27 elucidated patient-centered concepts and 7 detailed the development or validation of PRO instruments. The Celiac Disease Symptom Diary and Celiac Disease Patient Reported Outcome instrument were deemed most appropriate for use as endpoints; however, each had limitations related to conceptual coverage, evidence for measurement properties, and feasibility for use in clinical trials. Experts reported gastrointestinal symptoms as most important to treat, with extra-intestinal symptoms burdensome from the patient perspective as well. Payers emphasized measuring both frequency and severity of symptoms and targeting patients nonresponsive to the gluten-free diet for treatment. CONCLUSIONS: With emerging treatment options for CD, further work is needed to operationalize PRO symptom endpoints that are meaningful to patients, valued by payers, and acceptable to regulators in demonstrating efficacy.

Patients over Age 75 Are at Increased Risk of Emergency Department Visit and Hospitalization Following Colonoscopy.

BACKGROUND: The age to stop screening or surveillance colonoscopy is not well established, and unplanned hospital use after colonoscopy in the elderly is not well understood. AIMS: To evaluate unplanned emergency department (ED) visits and hospitalization in patients over 75 within 7 days of outpatient colonoscopy. METHODS: In this retrospective, single-center, cohort study, we reviewed outpatient screening or surveillance colonoscopies in patients ≥ 50 in a tertiary care academic medical center or affiliated facility between January 2008 and September 2013. Colonoscopies were divided by age based on USPSTF recommendations. The rate of ED visits and hospitalizations per colonoscopy for each age-group was determined. Predictors of ED visit and hospitalization were assessed through univariate and multivariate logistic regressions, and mortality following colonoscopy was evaluated using Kaplan-Meier analysis. RESULTS: A total of 30,409 colonoscopies were performed in 27,173 patients (51% male) by 40 endoscopists. ED visits occurred after 188 colonoscopies (0.62%). Age over 75 years was independently associated with ED visit (OR 1.58, 95% CI 1.05-2.37, p = 0.027) and hospitalization (OR 3.7, 95% CI 2.03-6.73, p < 0.001) within 7 days of colonoscopy. Higher number of medication classes, recent ED visit, polypectomy, and endoscopic mucosal resection were also independent variables associated with ED utilization after procedure. The mortality rate at the end of the follow-up (median 4.4; IQR 2.7-6 years) was 1.9, 8.6, and 15.8% for the age-groups 50-75, 76-85, and > 85 years, respectively. CONCLUSION: Patients over age 75 are 1.6 times as likely to use the ED and 3.7 times as likely to be hospitalized after colonoscopy. Further prospective studies are needed to assess the risk/benefit of nondiagnostic colonoscopy in geriatric patients.

Association Between Endoscopist Personality and Rate of Adenoma Detection.

BACKGROUND & AIMS: There is significant variation among endoscopists in their adenoma detection rates (ADRs). We explored associations between ADR and characteristics of endoscopists, including personality traits and financial incentives. METHODS: We collected electronic health record data from October 2013 through September 2015 and calculated ADRs for physicians from 4 health systems. ADRs were risk-adjusted for differences in patient populations. Physicians were surveyed to assess financial motivations, knowledge and perceptions about colonoscopy quality, and personality traits. Of 140 physicians sent the survey, 117 responded. RESULTS: The median risk-adjusted ADR for all surveyed physicians was 29.3% (interquartile range, 24.1%-35.5%). We found no significant association between ADR and financial incentives, malpractice concerns, or physicians' perceptions of ADR as a quality metric. ADR was associated with the degree of self-reported compulsiveness relative to peers: among endoscopists who described themselves as much more compulsive, the ADR was 33.1%; among those who described themselves as somewhat more compulsive, the ADR was 32.9%; among those who described themselves as about the same as others, the ADR was 26.4%; and among those who described themselves as somewhat less compulsive, the ADR was 27.3%) (P = .0019). ADR was also associated with perceived thoroughness (much more thorough than peers, ADR = 31.5%; somewhat more, 31.9%; same/somewhat less, 27.1%; P = .0173). Physicians who reported feeling rushed, having difficulty pacing themselves, or having difficulty in accomplishing goals had higher ADRs. A secondary analysis found the same associations between personality and adenomas per colonoscopy. CONCLUSIONS: We found no significant association between ADR and financial incentives, malpractice concerns, or perceptions of ADR as a quality metric. However, ADRs were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals.

Celiac disease: a comprehensive current review.

BACKGROUND: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.

Diagnostic Accuracy of Point of Care Tests for Diagnosing Celiac Disease: A Systematic Review and Meta-Analysis.

GOALS: To perform a systematic review and meta-analysis to estimate the overall diagnostic accuracy of point of care tests (POCTs) for diagnosing celiac disease (CD). BACKGROUND: Recently, POCTs for CD have been developed and are commercially available. Studies have reported significant variability in their sensitivity (70% to 100%) and specificity (85% to 100%). STUDY: We searched MEDLINE, EMBASE databases, and the Cochrane library through June 2017. Positive reference test was defined as villous atrophy along with positive celiac-specific serology and/or clinical improvement after gluten-free diet. Normal duodenal biopsy was defined as negative reference test. Bivariate random-effect model was used to present the summary estimates of sensitivities and specificities along with 95% confidence regions We assessed methodologic quality using the quality assessment of diagnostic accuracy studies-2 tool. RESULTS: The pooled sensitivity and specificity of all POCTs (based on tTG or DGP or tTG+Anti-gliadin antibodies) for diagnosing CD were 94.0% [95% confidence interval (CI), 89.9-96.5] and 94.4% (95% CI, 90.9-96.5), respectively. The pooled positive and negative likelihood ratios for POCTs were 16.7 and 0.06, respectively. The pooled sensitivity and specificity for IgA-tTG-based POCTs were 90.5% (95% CI, 82.3-95.1) and 94.8% (95% CI, 92.5-96.4), respectively. CONCLUSIONS: The pooled sensitivity and specificity of POCTs in diagnosing CD are high. POCTs may be used to screen for CD, especially in areas with limited access to laboratory-based testing. Further research assessing the diagnostic accuracy of individual POCTs and comparing it with other available POCTs is needed.

Effect of Consent and Educational Adjuncts to Consent on Patient Perceptions About Colonoscopy.

BACKGROUND AND AIMS: Informed consent is a vital preprocedural step for endoscopy but there are substantial variations in its delivery. We therefore sought to assess a multifaceted intervention to improve the consent process. METHODS: Gastroenterologists at a tertiary center were educated on the recommended components of informed consent. Following this, 3 cohorts of patients undergoing colonoscopy were surveyed before and after consent. In one cohort, the effect of optimized verbal consent alone was assessed. In the second and third groups, the effects of the addition of either a handout or a video describing colonoscopy and its risks were evaluated. The primary outcomes were the changes between preconsent and postconsent survey responses regarding confidence in understanding the procedure's purpose, likelihood of adverse events, and levels of anxiety. RESULTS: In total, 240 patients were included with 79 to 81 patients per group. There were no significant differences among the groups' survey responses. Compared with patients receiving verbal consent alone, fewer patients in the handout and video groups increased their perceived risk of adverse events following consent, but this difference did not reach significance (P=0.08). Examining all groups together, anxiety levels changed significantly after consent (P=0.003), with 31% of patients reducing their anxiety level, 8% increasing it, and 62% having no change. CONCLUSIONS: The consent process appears to decrease patient anxiety about colonoscopy. When used in conjunction with a high-quality verbal consent, written or video educational adjuncts provided on the day of colonoscopy likely have no effect on patient perceptions.

Diagnosis and Treatment Patterns in Celiac Disease.

Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

OBJECTIVE: Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. DESIGN: MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). RESULTS: Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. CONCLUSIONS: Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.

Outcome measures in coeliac disease trials: the Tampere recommendations.

OBJECTIVE: A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. DESIGN: Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. RESULTS: We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. CONCLUSION: Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.