Clinical utility of the fracture risk assessment tool (FRAX) in biopsy-confirmed coeliac disease.

BACKGROUND: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD. METHODS: We retrospectively collected data for consecutive adult patients with biopsy-proven CD between 2001 and 2015 who underwent DXA scanning within 1 year of diagnosis and were followed up for a minimum of 7 years. Fracture risk was assessed using FRAX scores, and the incidence of major osteoporotic fractures during the follow-up period was analysed. RESULTS: A total of 593 patients (median age 45.0 years, 68.5% female) were included. The prevalence of osteopenia and osteoporosis were 32.3% and 14.5%, respectively. Increasing age (OR 1.06, p < .0001), decreasing BMI (OR 0.90, p = .003), and higher baseline immunoglobulin A-tissue tissue transglutaminase titre (OR 1.04, p = .03) were significantly associated with increased risk of osteoporosis. The sensitivity, specificity, positive and negative predictive values of the FRAX tool to predict MOF were 21.2%, 91.3%, 16.3%, 93.5%, respectively. A higher risk of fractures was associated with ongoing gluten exposure (OR 1.86, p = .02), previous fractures (OR 2.69, p = .005), and older age (OR 1.03, p < .0001). CONCLUSION: Osteoporosis is a common finding in patients with CD. The FRAX tool showed high specificity in predicting osteoporotic fractures and could be used to aid with patient selection for DXA scanning in some cases.

Patient preferences for the diagnosis of coeliac disease: A discrete choice experiment.

BACKGROUND: There is potential for a paradigm shift from a biopsy-to a serology-based diagnosis of coeliac disease in selected adult patients. However, it remains unknown if this approach would be acceptable to patients. We aimed to explore patients' preferences regarding the no-biopsy approach for coeliac disease diagnosis. METHODS: We developed a discrete choice experiment survey containing 12 different scenarios with two possible alternatives (endoscopy & biopsy or serology) to estimate patient preferences. The scenarios were based on 5 attributes: risk of false positive results, risk of missed diagnosis, waiting time to start treatment, risk of complications, discomfort, or pain. Patient preferences and the relative importance of the attributes were estimated using a mixed logit model. RESULTS: In total, 385 people (70.6% female, 98.2% white) across the four nations of the United Kingdom completed the survey. Respondents preferred a serology-based diagnosis over endoscopy and duodenal biopsies (59% vs. 41%, ß coefficient 1.54, p < 0.001). Diagnostic test accuracy (p < 0.001), shorter waiting time to start treatment (p < 0.001), and discomfort levels during the procedure (p < 0.001) were the most important attributes to respondents. The risk of complications, including perforation and bleeding, did not significantly influence respondents' choices. Respondents with previous endoscopy experience were more willing to undergo endoscopy compared with those who never had one. CONCLUSION: The no-biopsy approach to diagnosing coeliac disease is acceptable and preferred by patients over endoscopy and biopsy. Our findings highlight the importance of patient-centred care and shared decision-making in guiding diagnostic strategies for optimal patient outcomes.

Role of endoscopy in the diagnosis of coeliac disease: a narrative review.

Background and Objective: Coeliac disease (CD) is a common autoimmune disorder triggered by gluten consumption in genetically predisposed individuals. CD is characterised by chronic inflammation in the small bowel mucosa with an influx of lymphocytes, followed by crypt hyperplasia and villous atrophy. The gold standard test to diagnose CD is endoscopy with duodenal biopsies. However, variations in practice between endoscopists can lead to missed diagnoses. This review aims to discuss the role of endoscopy in the diagnosis of CD, highlighting the performance measures of endoscopy in CD and the advancement in endoscopic techniques for the optical diagnosis of villous atrophy. Methods: We searched PubMed and Google Scholar from their inception to December 2023 for relevant articles on the role of endoscopy in CD. Two authors reviewed these references, and relevant studies were included in the discussion section of this review. Key Content and Findings: We provide an up-to-date assessment of the diagnostic accuracy of endoscopic markers of CD and the performance of enhanced endoscopic imaging to identify villous atrophy during endoscopy. We propose a set of benchmarks for endoscopy in CD and discuss the potential role of artificial intelligence (AI) in the endoscopic diagnosis of CD. Conclusions: Performing high-quality endoscopy and identifying strategies to reduce inter-endoscopist variations may reduce missed diagnoses. Adopting advanced endoscopic techniques and embracing new technologies such as AI could enhance diagnostic accuracy and improve patient care.

Role of capsule endoscopy and double-balloon enteroscopy in the management of adult patients with coeliac disease and persisting symptoms.

BACKGROUND: Small bowel capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are recommended for the management of patients with nonresponsive or refractory coeliac disease (CD). However, there is a paucity of data regarding the clinical profiles and outcomes of patients undergoing these investigations. METHODS: We conducted a retrospective analysis of two databases of adult patients with CD who underwent CE and/or DBE between 2017 and 2022 at the National Centre for Refractory CD in England. Patient demographic, clinical and endoscopic data were collected, and clinically relevant outcomes were reported. RESULTS: A total of 132 patients (median age 53 years, 64.4 % female) underwent 146 CEs and 25 DBEs. The most common symptoms were diarrhoea (51.5 %), abdominal pain (37.8 %), bloating (34.8 %), and weight loss (29.5 %). The overall detection rate of CE and DBE was 87.6 % and 92 %, respectively. Following CE and DBE, 14 patients (10.6 %) were diagnosed with CD-related complications such as ulcerative jejunitis, strictures and malignancy. Seven patients (5.3 %) died during follow-up, with five of these deaths directly attributed to CD. Older age, weight loss and anaemia were associated with poor outcomes. CONCLUSIONS: The sequential approach of CE and DBE identified CD-related complications in almost 1 in 10 patients with nonresponsive or refractory CD. Older patients with persistent villous atrophy, weight loss and anaemia require close monitoring to help with the early diagnosis and management of complications.

Factors influencing gastrostomy tube removal.

BACKGROUND: When commencing enteral feeding, patients and families will want to know the likelihood of returning to an oral diet. There is a paucity of data on the prognosis of patients with gastrostomies. We describe a large dataset of patients, which identifies factors influencing gastrostomy removal and assesses the likelihood of the patient having at home enteral nutrition. METHODS: Retrospective data was collected on patients from Sheffield Teaching Hospitals who had received a gastrostomy and had outpatient enteral feeding between January 2016 and December 2019. Demographic data, indication and outcomes were analysed. RESULTS: A total of 451 patients were assessed, median age: 67.7. 183/451(40.6%) gastrostomies were for head and neck cancer, 88/451 (19.5%) for stroke, 28/451 (6.2%) for Motor Neuron Disease, 32/451 (7.1%) for other neurodegenerative causes, 120/451 (26.6%) other. Of the 31.2% who had their gastrostomy removed within 3 years, head and neck cancer was the most common indication (58.3%) followed by stroke (10.2%), Motor Neuron Disease (7.1%) and other neurodegenerative diseases (3.1%). Gastrostomy removal was significantly influenced by age, place of residence, and having head and neck cancer (p < 0.05). There was the greatest likelihood of removal within the first year (24%). 70.5% had enteral feeding at home. CONCLUSION: This large cohort study demonstrates 31.2% of patients had their gastrostomy removed within 3 years. Head and neck cancer patients, younger age and residing at home can help positively predict removal. Most patients manage their feeding at home rather than a nursing home. This study provides new information on gastrostomy outcomes when counselling patients to provide realistic expectations.

Monitoring coeliac disease in 2024, time to change practice?

PURPOSE OF REVIEW: Persistent villous atrophy is associated with morbidity in coeliac disease and most commonly due to ongoing gluten ingestion. Current methods for assessing gluten exposure and persisting villous atrophy include dietary questionnaires and repeat duodenal biopsy, which have limited accuracy or are invasive. This review discusses adjunctive and/or novel tests that could be used to overcome these challenges. RECENT FINDINGS: Small bowel capsule endoscopy is well tolerated and helps to evaluate for persisting villous atrophy and importantly, complications associated with coeliac disease. Testing for urinary and/or stool gluten immunogenic peptides may help identify recent gluten exposure, but further studies are still warranted to evaluate the accuracy and applicability of this approach. Measuring spikes in circulating Interleukin-2 following gluten challenge has shown promise for coeliac disease diagnosis, and thus may serve as a useful confirmatory test in those with persisting symptoms but provides no information on mucosal inflammation. No specific gut microbial signature has been identified in coeliac disease; however, studies have shown a reduced microbial diversity in active disease, which with future refinement may prove clinically useful. SUMMARY: There is no evidence to support alternative methods for assessing persisting villous atrophy in coeliac disease over performing an up-to-date duodenal biopsy. Monitoring for adherence to a gluten-free diet remains clinically challenging and should be a priority for future research.

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Cost-benefits and environmental impact of the no-biopsy approach for the diagnosis of coeliac disease in adults.

Objective: Recent evidence suggests that adult patients with IgA tissue transglutaminase levels of ≥10× the upper limit of normal could be accurately diagnosed with coeliac disease without undergoing endoscopy and biopsy. We aimed to evaluate the cost-benefits and the environmental impact of implementing the no-biopsy approach for diagnosing coeliac disease in clinical practice. Design: We calculated the overall direct and indirect costs of the conventional serology-biopsy approach and the no-biopsy approach for the diagnosis of coeliac disease based on the national average unit costs and the Office of National Statistics data. We further estimated the environmental impact of avoiding endoscopy based on the estimated greenhouse gas emissions from endoscopy. Results: Approximately 3000 endoscopies for suspected coeliac disease could be avoided each year in the UK. Implementing the no-biopsy approach for the diagnosis of coeliac disease in adults could save the National Health Service over £2.5 million in direct and indirect costs per annum and reduce endoscopy carbon footprint by 87 tonnes of CO2 per year, equivalent to greenhouse gas emissions from driving 222 875 miles, carbon emissions from charging over 10 million smartphones and the carbon sequestrated by 1438 trees grown for 10 years. Conclusion: The implementation of this non-invasive green approach could be an essential first step in the 'Reduce' strategy advocated by the British Society of Gastroenterology and other international endoscopy societies for sustainable endoscopy practice.

Road map to small bowel endoscopy quality indicators.

PURPOSE OF REVIEW: Quality indicators for upper and lower gastrointestinal endoscopy are well established and linked to patient outcomes. However, there is a perceived gap in the development and implementation of quality indicators for small bowel endoscopy. In this review, we aimed to discuss the development of quality indicators in small bowel endoscopy and their implementation in clinical practice. RECENT FINDINGS: The proposed quality indicators for small bowel endoscopy focus on process measures, which mainly evaluate the procedural aspects, rather than the outcomes or the overall patient experience. These quality indicators have rarely been studied in clinical practice, leading to a limited understanding of their applicability and impact on patient outcomes and experience. SUMMARY: Real-world studies evaluating the quality indicators of small bowel endoscopy are warranted to establish an evidence-based framework for their practical application and effectiveness. Linking these indicators to relevant patient outcomes is crucial for their broader acceptance and implementation.

Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. RESULTS: A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains. CONCLUSION: The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

Device-assisted enteroscopy performance measures in the United Kingdom: DEEP-UK quality improvement project.

BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.

The debate in the diagnosis of coeliac disease - time to go 'no-biopsy'?

PURPOSE OF REVIEW: Duodenal biopsies have been central to making a diagnosis of coeliac disease for the last 70 years. Recent paediatric guidelines have reduced the emphasis on duodenal biopsies with the incorporation of a 'no-biopsy' arm to the diagnostic pathway. This review discusses the no-biopsy approach in adults and highlights advances in alternative (non-biopsy) diagnostic modalities in coeliac disease. RECENT FINDINGS: Evidence suggests that a no-biopsy approach for the diagnosis of adult coeliac disease is accurate. However, a number of factors still favour duodenal biopsy sampling in specific patient groups. Moreover, several factors need to be considered if this pathway is implemented into local gastroenterology services. SUMMARY: Duodenal biopsies remain an important step in the diagnosis of adult coeliac disease. However, an alternative approach that removes the necessity for biopsies may be an option in selected adults. If further guidelines incorporate this pathway, then efforts should focus on supporting a dialogue between primary and secondary care to facilitate the appropriate implementation of this approach.

Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults?

Celiac disease is a common autoimmune condition characterized by small intestinal inflammation and mucosal damage triggered by an inappropriate immune response to ingested gluten. Gastroscopy and duodenal biopsy are currently the gold standard approach to diagnosing celiac disease in adults. However, the emergence of highly accurate serological tests for celiac disease in the last 2 decades led to a change in the pediatric guidelines to diagnose celiac disease without biopsy in selected patients. Adopting this no-biopsy approach to diagnose celiac disease in adults remains controversial, but the evidence supporting it is growing.

Review article: Physical and psychological comorbidities associated with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by physicians in primary and secondary care. Patients with IBS commonly present with various extraintestinal complaints, which account for a substantial clinical and economic burden. The common extraintestinal comorbidities associated with IBS include anxiety, depression, somatisation, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, interstitial cystitis, sexual dysfunction and sleep disturbance. The presence of comorbidity in IBS poses a diagnostic and therapeutic challenge with patients frequently undergoing unnecessary investigations and interventions, including surgery. This review discusses the different physical and psychological comorbidities associated with IBS, the shared pathophysiological mechanisms and potential management strategies.

Impact of the National Endoscopy Database (NED) on colonoscopy withdrawal time: a tertiary centre experience.

OBJECTIVE: Colonoscopy withdrawal time (CWT) is a key performance indicator affecting polyp detection rate (PDR) and adenoma detection rate (ADR). However, studies have shown wide variation in CWT and ADR between different endoscopists. The National Endoscopy Database (NED) was implemented to enable quality assurance in all endoscopy units across the UK and also to reduce variation in practice. We aimed to assess whether CWT changed since the introduction of NED and whether CWT affected PDR. METHODS: We used NED to retrospectively collect data regarding CWT and PDR of 25 endoscopists who performed (n=4459 colonoscopies) in the four quarters of 2019. We then compared this data to their performance in 2016, before using NED (n=4324 colonoscopies). RESULTS: Mean CWT increased from 7.66 min in 2016 to 9.25 min in 2019 (p=0.0001). Mean PDR in the two periods was 29.9% and 28.3% (p=0.64). 72% of endoscopists (18/25) had CWT>6 min in 2016 versus 100% (25/25) in 2019, the longer CWT in 2019 positively correlated with the PDR (r=0.50, p=0.01). Gastroenterology consultants and trainee endoscopists had longer CWT compared with colorectal surgeons both before and after using NED. CONCLUSION: NED usage increased withdrawal times in colonoscopy. Longer withdrawal times were associated with higher PDR. A national colonoscopy audit using data from NED is required to evaluate whether wide variations in practice across endoscopy units in the UK still exist and to ensure minimum colonoscopy quality standards are achieved.

High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria.

BACKGROUND: A high prevalence of primary bile acid diarrhoea (BAD) has been reported for Rome III defined irritable bowel syndrome (IBS)-diarrhoea and functional diarrhoea. We determined whether this still applies under the contemporaneous Rome IV criteria, given that the latter characterises IBS-diarrhoea as having more frequent abdominal pain compared with previous iterations, whilst no longer recognising abdominal discomfort. METHODS: Patients referred for a 75SeHCAT test completed a baseline questionnaire comprising, i) demographic data, ii) risk factors for BAD (inflammatory bowel disease, bowel resection, cholecystectomy, microscopic colitis, celiac disease, abdominal-pelvic radiotherapy), iii) the Rome III and IV bowel disorder questionnaire, and iv) mood and somatisation scores. A diagnosis of BAD constituted a 75SeHCAT of ≤15%, with moderate to severe disease being defined as ≤10% and ≤5%, respectively. FINDINGS: Of 300 patients with complete dataset, 184 had no risk factors for BAD and fulfilled criteria for either IBS-diarrhoea or functional diarrhoea. The prevalence of primary BAD was 38% (n = 70/184), with almost half having moderate (n = 16) to severe (n = 17) disease. Using the Rome III criteria, the prevalence of primary BAD was 36% in IBS-diarrhoea (n = 63/173) and 64% (n = 7/11) in functional diarrhoea; p = 0.11. Using the Rome IV criteria, the prevalence of primary BAD was 38% (n = 53/139) in IBS-diarrhoea and 38% (n = 17/45) in functional diarrhoea; p = 0.97. Patients with primary BAD experienced more frequent loose stools (p = 0.01) and had a higher body mass index (p<0.0001) compared to those without BAD, but otherwise no significant differences were seen in age, gender, mood, somatisation, or abdominal pain. The presence of primary BAD in patients classified as overweight or obese was approximately 40% and 60%, respectively. INTERPRETATION: Over a third of patients with Rome IV IBS-diarrhoea or functional diarrhoea have primary BAD, similar to Rome III. We therefore recommend that, in secondary care settings, generic testing for primary BAD should be considered in patients presenting with chronic diarrhoea of presumed functional origin regardless of concomitant abdominal pain. Centres that lack tests for primary BAD, and who empirically treat instead, may consider targeting patients who are overweight or obese.