Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease.

Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease.

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.

Systematic Literature Review of the Economic Burden of Celiac Disease.

BACKGROUND: The prevalence of celiac disease (CD) has rapidly increased over recent decades, but costs related to CD remain poorly quantified. OBJECTIVE: This systematic review assessed the economic burden of CD in North America and Europe. METHODS: MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were systematically searched to identify English-language literature from 2007 to 2018 that assessed costs, cost effectiveness, and health resource utilization for CD. RESULTS: Forty-nine studies met the inclusion criteria, of which 28 (57.1%) addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost per positive CD diagnosis of testing patients already undergoing esophagogastroduodenoscopy for other indications ranged from 1300 Canadian dollars ($Can) in Canada (2016 value) to €44,712 in the Netherlands (2013 value). Adding the CD test was cost effective when it combined diagnostic modalities (e.g., serology and biopsy). Direct annual excess costs to a US payer per diagnosed CD patient totaled $US6000 (2013 value) more than for a person without CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and medication use were more common with CD. After initiating a gluten-free diet (GFD), patients visited primary care providers less often, used more medications, and missed fewer days from school and work. CONCLUSIONS: Most of the few available economic studies of CD assess testing and diagnosis costs, especially in Europe. Methods of testing generally are considered cost effective when they combine diagnostic modalities in symptomatic patients. Most costs to a payer of managing CD derive from outpatient care. Following GFD initiation, patients lose fewer days from work and school than pretreatment.

A Novel Patient-Derived Conceptual Model of the Impact of Celiac Disease in Adults: Implications for Patient-Reported Outcome and Health-Related Quality-of-Life Instrument Development.

BACKGROUND: Celiac disease is a chronic inflammatory condition with wide ranging effects on individual's lives caused by a combination of symptoms and the burden of adhering to a gluten-free diet (GFD). OBJECTIVES: To further understand patients' experience of celiac disease, the impact it has on health-related quality of life (HRQOL), and to develop a conceptual model describing this impact. METHODS: Adults with celiac disease on a GFD reporting symptoms within the previous 3 months were included; patients with refractory celiac disease and confounding medical conditions were excluded. A semistructured discussion guide was developed exploring celiac disease symptoms and impact on patients' HRQOL. An experienced interviewer conducted in-depth interviews. The data set was coded and analyzed using thematic analysis to identify concepts, themes, and the inter-relationships between them. Data saturation was monitored and concepts identified formed the basis of the conceptual model. RESULTS: Twenty-one participants were recruited, and 32 distinct gluten-related symptoms were reported and data saturation was reached. Analysis identified several themes impacting patients' HRQOL: fears and anxiety, day-to-day management of celiac disease, physical functioning, sleep, daily activities, social activities, emotional functioning, and relationships. The conceptual model highlights the main areas of impact and the relationships between concepts. CONCLUSIONS: Both symptoms and maintaining a GFD have a substantial impact on patient functioning and HRQOL in adults with celiac disease. The conceptual model derived from these data may help to design future patient-reported outcomes as well as interventions to improve the quality of life in an individual with celiac disease.

Capnographic Monitoring of Moderate Sedation During Low-Risk Screening Colonoscopy Does Not Improve Safety or Patient Satisfaction: A Prospective Cohort Study.

OBJECTIVES: Appropriate monitoring during sedation has been recognized as vital to patient safety in procedures outside of the operating room. Capnography can identify hypoventilation prior to hypoxemia; however, it is not clear whether the addition of capnography improves safety or is cost effective during routine colonoscopy, a high volume, low-risk procedure. Our aim was to evaluate the value of EtCO2 monitoring during colonoscopy with moderate sedation. METHODS: We conducted a prospective study of sedation safety and patient satisfaction before and after the introduction of EtCO2 monitoring during outpatient colonoscopy with midazolam and fentanyl using the validated PROcedural Sedation Assessment Survey (PROSAS). Complications of sedation and PROSAS scores were compared among colonoscopies with and without capnography. RESULTS: A total of 966 patients participated in our study, 465 in the pre-EtCO2 group and 501 in the EtCO2 group. On multivariate analysis, patients and nurses reported higher levels of procedural discomfort after adoption of capnography (1.71 vs. 1.00, P<0.001). No serious adverse events were seen, and minor sedation-related adverse events occurred with similar frequency in both groups (8.2% pre-EtCO2 vs. 11.2% EtCO2, P=0.115). The cost of implementing EtCO2 in our unit was $40,169.95 and added $11.68 per case. CONCLUSIONS: Colonoscopy with moderate sedation is a low-risk procedure, and the addition of EtCO2 did not improve safety or patient satisfaction but did increase cost. These data suggest that routine capnography in this setting may not be cost effective and that EtCO2 might be reserved for patients at higher risk of adverse events.

Socioeconomic Risk Factors for Celiac Disease Burden and Symptoms.

BACKGROUND & AIMS: Celiac disease (CD) affects approximately 1% of the population and negatively affects aspects of life including physical and social function. The relationship between socioeconomic (SE) factors, symptom severity, and perceived burden of living with CD is not well understood. The objective of this study was to assess the relationships between income, symptoms, and perceived burden of CD. METHODS: In this survey study conducted at a tertiary care center, 773 patients 18 years of age or more with biopsy confirmed CD were eligible to participate. Patients completed a survey with information on SE data, the validated Celiac Symptom Index (CSI), and visual analog scales (VAS) assessing overall health, CD-related health, difficulty in following a gluten-free diet (GFD), and importance of following a GFD. RESULTS: Three hundred forty one patients completed the survey. Higher income predicted better overall health, better CD related health, and fewer symptoms. In the logistic regression model, low income was associated with greater CD symptoms (odds ratio=6.04, P=0.002). Other factors associated with greater symptoms were younger age, poor overall health state, and more physician visits. Factors associated with increased burden of CD included hospitalizations, more symptoms, poor overall health state, and burden of following a GFD. CONCLUSIONS: Patients with lower incomes have worse CD-related health and greater symptoms. Those with low income had 6 times the odds of greater symptoms compared with those with high income. Our data suggest that income is associated with perceived overall health, CD-related health, and CD symptoms.

Fellowship Colonoscopy Training and Preparedness for Independent Gastroenterology Practice.

GOALS: To objectively assess when gastroenterology (GI) fellows achieve technical competency to perform colonoscopy independently. BACKGROUND: New guidelines to assess the procedural competency of GI fellows in training have been developed. Although comprehensive, they do not account for the quality metrics to which independently practicing gastroenterologists are held. STUDY: We performed a prospective study examining consecutive colonoscopies performed by GI fellows from November 2013 through March 2014 at an academic medical center. Using a brief postprocedure questionnaire and the online medical record, we measured rates of independent fellow cecal intubation rate (CIR), insertion time to the cecum (cecal IT), and independent polypectomy rate. Our secondary outcomes were adenoma detection rate and polyp detection rate. RESULTS: A total of 898 colonoscopies performed by 10 GI fellows were analyzed. In the multivariate analysis, CIR [odds ratio (OR)=1.29, P=0.012], cecal IT (ß-coefficient=0.19, P=0.006), and rates of unassisted independent snare polypectomy (OR=1.36, P<0.001) all improved significantly with increased number of procedures performed (OR and ß-coefficient per 100 colonoscopies performed). After performing 500 colonoscopies, fellows achieved a mean CIR>90%, cecal IT between 7 and 10 minutes, and independent polypectomy rate of 90% with further improvement in cecal IT to <7 minutes, and independent snare polypectomy of >95% after 700 cases. CONCLUSIONS: Current procedural recommendations for fellowship training may underestimate the technical skill necessary for independent GI practice upon completion of fellowship. Technical proficiency in snare polypectomy may lag behind proficiency in cecal intubation.

Development and validation of the PROcedural Sedation Assessment Survey (PROSAS) for assessment of procedural sedation quality.

BACKGROUND: More than 20 million invasive procedures are performed annually in the United States. The vast majority are performed with moderate sedation or deep sedation, yet there is limited understanding of the drivers of sedation quality and patient satisfaction. Currently, the major gap in quality assurance for invasive procedures is the lack of procedural sedation quality measures. OBJECTIVE: To develop and validate a robust, patient-centered measure of procedural sedation quality, the PROcedural Sedation Assessment Survey (PROSAS). DESIGN: Through a series of interviews with patients, proceduralists, nurses, anesthesiologists, and an interactive patient focus group, major domains influencing procedural sedation quality were used to create a multipart survey. The pilot survey was administered and revised in sequential cohorts of adults receiving moderate sedation for GI endoscopy. After revision, the PROSAS was administered to a validation cohort. SETTING: GI endoscopy unit. PATIENTS: A expert panel of proceduralists, nurses, and anesthesiologists, an initial survey development cohort of 40 patients, and a validation cohort of 858 patients undergoing sedation for outpatient GI endoscopy with additional surveys completed by the gastroenterologist, procedure nurse, and recovery nurse. MAIN OUTCOMES AND MEASUREMENTS: Survey characteristics of the PROSAS. RESULTS: Patients were able to independently complete the PROSAS after procedural sedation before discharge. Of the patients, 91.6% reported minimal discomfort; however, 8.4% of patients reported significant discomfort and 2.4% of patients experienced hemodynamic and/or respiratory instability. There was a high correlation between patient-reported intraprocedure discomfort and both clinician assessments of procedural discomfort and patient recall of procedural pain 24 to 48 hours post procedure (P < .001 for all), suggesting high external validity. LIMITATIONS: Single-center study, variability of sedation technique between providers, inclusion of patients with chronic pain taking analgesics. CONCLUSIONS: The PROSAS is a clinically relevant, patient-centered, easily administered instrument that allows for standardized evaluation of procedural sedation quality. The PROSAS may be useful in both research and clinical settings.

Patient perception of treatment burden is high in celiac disease compared with other common conditions.

OBJECTIVES: The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of CD, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares with other medical treatments, and there are limited data on the socioeconomic factors influencing treatment adherence. In this study, we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence. METHODS: Survey was mailed to participants with CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome, inflammatory bowel disease, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, and end-stage renal disease (ESRD) on dialysis. Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific health status, and overall health status. RESULTS: We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education, and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment. CONCLUSIONS: Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for CD argues for the need for safe adjuvant treatment, as well as interventions designed to lower the perceived burden of the GFD.

Open conformation tissue transglutaminase testing for celiac dietary assessment.

OBJECTIVES: Anti tissue-transglutaminase antibody is the mainstay of celiac disease serologic testing. Whilst it has high sensitivity in patients on an unrestricted diet, sensitivity is poor for evaluation of gluten free diet adherence. AIM: To assess the utility of a novel assay measuring Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase in assessment of ongoing gluten exposure in celiac disease patients on an alleged gluten free diet. METHODS: Through prospective assessment, 147 patients with celiac disease were divided into good and poor adherence. Open and closed (conventional) tissue-transglutaminase titres were measured using standard enzyme linked immunosorbent assay. 50 patients with inflammatory bowel disease served as disease controls. RESULTS: Overall 128 patients had been on gluten free diet for more than six months and 19 were found to be poorly adherent on dietary review. Within this group 13 (68.4%) and 10 (52.6%) patients respectively were positive for the open conformation and conventional assay (p=0.51). Two and one control patients tested positive for closed and open assays respectively. CONCLUSIONS: Compared to native assays open conformation tissue-transglutaminase may have higher sensitivity in the poor gluten free diet adherence group and higher specificity in the control population. Larger population studies are warranted to assess whether the open conformation tissue-transglutaminase assay may be superior to the conventional assay.

The incidence and cost of unexpected hospital use after scheduled outpatient endoscopy.

BACKGROUND: Data on complications of gastrointestinal endoscopic procedures are limited. We evaluated prospectively the incidence and cost of hospital visits resulting from outpatient endoscopy. METHODS: We developed an electronic medical record-based system to record automatically admissions to the emergency department (ED) within 14 days after endoscopy. Physicians evaluated all reported cases for relatedness of the ED visit to the prior endoscopy based on predetermined criteria. RESULTS: We evaluated 6383 esophagogastroduodenoscopies (EGDs) and 11 632 colonoscopies (7392 for screening and surveillance). Among these, 419 ED visits and 266 hospitalizations occurred within 14 days after the procedure. One hundred thirty-four (32%) of the ED visits and 76 (29%) of the hospitalizations were procedure related, whereas 31 complications were recorded by standard physician reporting (P < .001). Procedure-related hospital visits occurred in 1.07%, 0.84%, and 0.95% of all EGDs, all colonoscopies, and screening colonoscopies, respectively. The mean costs were $1403 per ED visit and $10 123 per hospitalization based on Medicare standardized rates. Across the overall screening/surveillance colonoscopy program, these episodes added $48 per examination. CONCLUSIONS: Using a novel automated system, we observed a 1% incidence of related hospital visits within 14 days of outpatient endoscopy, 2- to 3-fold higher than recent estimates. Most events were not captured by standard reporting, and strategies for automating adverse event reporting should be developed. The cost of unexpected hospital visits postendoscopy may be significant and should be taken into account in screening or surveillance programs.

Integration of racial, cultural, ethnic, and socioeconomic factors into a gastrointestinal pathophysiology course.

BACKGROUND & AIMS: Our study describes a faculty development program to encourage the integration of racial, cultural, ethnic, and socioeconomic factors such as obesity, inability to pay for essential medications, the use of alternative medicine, dietary preferences, and alcoholism in a gastrointestinal pathophysiology course. METHODS: We designed a 1-hour faculty development session with longitudinal reinforcement of concepts. The session focused on showing the relevance of racial, ethnic, cultural, and socioeconomic factors to gastrointestinal diseases, and encouraged tutors to take an active and pivotal role in discussion of these factors. The study outcome was student responses to course evaluation questions concerning the teaching of cultural and ethnic issues in the course as a whole and by individual tutorials in 2004 (pre-faculty development) and in 2006 to 2008 (post-faculty development). RESULTS: Between 2004 and 2008, the proportion of students reporting that "Issues of culture and ethnicity as they affect topics in this course were addressed" increased significantly (P = .000). From 2006 to 2008, compared with 2004, there was a significant increase in the number of tutors who "frequently" taught culturally competent care according to 60% or greater of their tutorial students (P = .003). The tutor's age, gender, prior tutor experience, rank, and specialty did not significantly impact results. CONCLUSIONS: An innovative faculty development session that encourages tutors to discuss racial, cultural, ethnic, and socioeconomic issues relevant to both care of the whole patient and to the pathophysiology of illness is both effective and applicable to other preclinical and clinical courses.

Update on the evaluation and diagnosis of celiac disease.

PURPOSE OF REVIEW: Our understanding of the pathophysiology of celiac disease has advanced with associated improvement in diagnostic modalities. Recent studies have placed the prevalence of celiac disease in Western populations at between 1:250 and 1:67. Celiac disease is common throughout the world and most cases go undiagnosed. Understanding the risk factors, clinical presentations and diagnostic modalities is necessary to identify and treat patients with this commonly misdiagnosed disorder. RECENT FINDINGS: Increased prevalence of celiac disease in individuals with autoimmune diseases, reduced bone mineral density and undiagnosed liver disease have been confirmed. However, celiac disease may not be associated with Down's syndrome or epilepsy. Evidence supports high sensitivity and specificity of endomysial- and tissue transglutaminase-based tests in most settings. In children, high or low tissue transglutaminase levels may preclude the need for duodenal biopsy. Cost-effectiveness studies suggest using tissue transglutaminase or endomysial initially, while distal duodenal or jejunal biopsy may confirm celiac disease in the absence of proximal changes. SUMMARY: There is insufficient evidence to support mass screening for celiac disease. However, case finding in individuals with risk factors for celiac disease is recommended. Further study is necessary to define diagnostic algorithms and target populations likely to benefit from testing.