Validation of the X-ray microtomography in the assessment of duodenal morphometry and surface area in celiac disease.

Background: Duodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas. Methods: Endoscopic biopsies from 58 individuals were utilized for the micro-CT imaging, selecting histological changes ranging from normal to severely damaged mucosa. The imaging protocol was optimized for practicability and resolution. The Bland-Altman method was applied to test intra- and interobserver variations in the blinded measurements. Results: The 3D micro-CT reconstructions enabled easy and precise digital cutting with optimal orientation and computer-assisted measurement of the surface area. Intraobserver analysis of morphological measurements showed a mean difference of 0.011 with limits of agreement (LA) from -0.397 to 0.375 and a standard deviation (SD) of 0.197. The corresponding figures for interobserver analysis were 0.080, from -0.719 to 0.537 and 0.320, respectively. The intraclass correlation coefficients (ICC) for the intraobserver and interobserver variations were 0.981 and 0.954, respectively. Intraobserver surface area analysis yielded a mean difference of 0.010, LA from -0.764 to 0.785 and an SD of 0.395, and an interobserver analysis mean difference of 0.028, LA from -0.642 to 0.698 and SD of 0.342. The respective ICCs for the intra- and interobserver variations were 0.963 and 0.972. Conclusions: Micro-CT showed excellent accuracy and reproducibility in the evaluation of mucosal morphometry and surface areas. The improved sensitivity for histological changes is a powerful tool for the diagnosis of celiac disease and for clinical and pharmacological studies.

Assessment of Duodenal Intraepithelial Lymphocyte Composition (Lymphogram) for Accurate and Prompt Diagnosis of Celiac Disease in Pediatric Patients.

INTRODUCTION: Quantitative and phenotypic analyses of duodenal intraepithelial lymphocytes (IELs) by flow cytometry (IEL lymphogram) confer specificity and enable the diagnosis even in unconventional presentations of celiac disease (CD). To evaluate the validity of the IEL lymphograms in the pediatric population for new insights into their use as biomarkers in the natural history of CD. METHODS: We retrospectively included 1,211 children (602 with active CD, 92 on a gluten-free diet, 47 with potential CD, and 470 nonceliac controls) who required duodenal biopsies in this study. The cutoff values for IEL subsets were established to calculate the probability of disease according to the lymphogram. RESULTS: A celiac lymphogram (a ≥15% increase in gamma-delta T-cell receptor IELs and a simultaneous ≤6% decrease in CD3 surface-negative [sCD3-]) IELs was strongly associated with the diagnosis of active CD, which was present in 89.7% of the confirmed patients. The remaining 10% of the celiac patients had a partial celiac lymphogram (≥15% increase gamma-delta T-cell receptor IELs or ≤6% decrease in sCD3- IELs), with lower diagnostic certainty. On a gluten-free diet, nearly 20% of the patients were indistinguishable from nonceliac subjects based on the lymphogram. In potential CD, a decrease in sCD3- IELs was a risk marker of progression to villous atrophy and a diagnosis of active CD. DISCUSSION: If a biopsy is clinically indicated, the IEL lymphogram adds specificity to the histological findings, reducing diagnostic delays and misdiagnoses. The lymphogram is useful for monitoring the natural progression of the disease and predicting the transition from potential celiac to overt CD.

Is Endoscopic Assessment of the Esophagus and Stomach Enough to Determine the Need for Biopsy at These Sites in Pediatric Patients Undergoing Endoscopy for Elevated TTG?

OBJECTIVES: The goal of our study was to determine whether visual assessment of the esophagus and stomach could predict abnormal histology and determine the frequency of interventions based on biopsies in patients undergoing endoscopy for elevated tissue transglutaminase immunoglobulin A antibody (TTG). METHODS: Pathology records were searched for patients with biopsy performed for elevated TTG. Pathology report, endoscopy report, and follow-up were obtained and slides from the duodenum reviewed. Pathology was considered gold standard for sensitivity and specificity calculations. RESULTS: 240 patients were included. 215 patients had esophageal biopsies performed. Esophageal endoscopic visual assessment had sensitivity of 47% and specificity of 93% for abnormal histology. 16(7%) patients had therapy or referral related to results and, of these, 6(38%) had visually normal endoscopy. 237 biopsies were performed of stomach. Gastric endoscopic visual assessment had a sensitivity and specificity of 20% and 87%. 24(10%) patients had therapy based on findings and, of these, 12 (50%) had visually normal endoscopy. CONCLUSIONS: Endoscopic assessment of esophagus and stomach has low sensitivity and high specificity for pathologic abnormalities when indication for endoscopy is elevated TTG. When endoscopy is visually normal clinical interventions based on biopsy are rare, and foregoing biopsy may be considered.

Assessment of disease severity on capsule endoscopy in patients with small bowel villous atrophy.

BACKGROUND AND AIM: There is a lack of uniformity of reporting on features of celiac disease (CD) on small bowel capsule endoscopy (SBCE). This makes determining extent of disease and comparison of severity of disease challenging. METHODS: De-identified SBCEs of 300 patients (78 CD [26%], 18 serology negative villous atrophy [6%], and 204 controls with normal duodenal histology [68%]) were included. Videos were reviewed by two experts. All patients had duodenal histology taken within 2 weeks of SBCE. The degree of agreement in CD features and extent of disease was then determined. The resulting score for each factor was used to determine overall severity of disease. RESULTS: There was substantial agreement in the kappa coefficient for the detection of CD features between reviewers (0.67). Agreement for extent of affected small bowel (SB) mucosa was high (0.97). On multiple regression analysis, several features of CD correlated with extent of affected SB mucosa for both reviewers. The odds ratios derived from this analysis were then used to score features of CD, enabling scores of severity to be calculated for each patient. The median overall scores for patients increased significantly according to the independent classification of severity by the capsule reviewers: mild (20, 0-79), moderate (45, 25-123), and severe (89, 65-130) (P = 0.0001). CONCLUSION: The good correlation of CD scores between expert reviewers confirms the validity of features of CD on SBCE. An objective score of CD features in the SB is useful in the follow up of patients with CD and serology negative villous atrophy.

[Celiac disease: causes, pathology, and nutritional assessment of gluten-free diet. A review]. / Enfermedad celiaca: causas, patología y valoración nutricional de la dieta sin gluten. Revision.

INTRODUCTION: Introduction: celiac patients suffer deficiencies before and during their maintenance of a gluten-free diet. This is due to malabsorption, associated with the disease, and to non-enriched, mostly processed foods high in saturated fats and deficient in the minerals typically present in wheat. Objectives: the main objective of this review was to determine the molecular basis of celiac disease and the nutritional deficiencies that gluten-free diet entails, as well as an assessment of gluten-free diet and its nutritional deficiencies once the intestinal microvilli have been restored. Material and methods: a bibliographic search was carried out through electronic databases. The content of the review focuses on the pathogenesis of celiac disease and the assessment of gluten-free diet when established for treatment. Results: the main deficiencies that occur in untreated celiac patients are (calcium, iron, fiber, folic acid, omega-3, vitamin B12, and vitamin D). It has been observed that the quality of life of celiac patients, after starting treatment, is reduced, and this leads to low adherence to gluten-free diet. In addition, these gluten-free diets without proper follow-up by a nutritionist entail other deficits such as: an increase in the risk of cardiovascular, metabolic, overweight and obesity diseases. Conclusion: gluten-free diet, as followed by celiac patients, usually entails certain deficiencies such as group-B vitamins, vitamin D, calcium, iron, folic acid, and fiber, which is mainly due to the poor nutritional quality of gluten-free products as compared to their equivalents with gluten, and a scarce monitoring by health professionals.

INTRODUCCIÓN: Introducción: los pacientes celiacos sufren deficiencias antes y durante el mantenimiento de la dieta sin gluten; esto se debe a la malabsorción asociada a la enfermedad y a los alimentos no enriquecidos, en su mayoría procesados, altos en grasas saturadas y deficientes en los minerales típicamente presentes en el trigo. Objetivos: el principal objetivo de la presente revisión bibliográfica es recopilar aquellos trabajos que centren su atención en determinar las bases moleculares de la enfermedad celiaca y que pudieran explicar las deficiencias nutricionales que conlleva dicha dieta, y efectuar una valoración de la dieta sin gluten y sus deficiencias nutricionales una vez restauradas las microvellosidades intestinales. Material y métodos: se ha realizado una búsqueda bibliográfica a través de bases de datos electrónicas. El contenido de la revisión se ha centrado en la patogénesis de la enfermedad celiaca y la valoración de la dieta sin gluten que se instaura como tratamiento. Resultados: numerosos estudios encuentran una deficiencia nutricional de micronutrientes en los pacientes celiacos sin tratar, principalmente en términos de calcio, hierro, fibra, ácido fólico, omega-3, vitamina B12 y vitamina D. Se ha observado que la calidad de vida de los pacientes celiacos, una vez iniciado el tratamiento, se ve reducida y que ello conlleva una baja adherencia a la dieta sin gluten. Además, estas dietas sin gluten, en el caso de que se sigan sin la supervisión de un especialista en nutrición, conllevan un aumento del riesgo de sufrir enfermedades cardiovasculares y metabólicas, sobrepeso y obesidad. Conclusión: la dieta sin gluten que siguen los pacientes celiacos suele conllevar ciertas deficiencias nutricionales como, por ejemplo, déficits de vitaminas del grupo B, vitamina D, calcio, hierro, ácido fólico y fibra, lo que se debe principalmente a la deficiente calidad nutricional de los productos sin gluten con respecto a sus equivalentes con gluten y a un bajo seguimiento por parte de los profesionales sanitarios.

Celiac Dietary Adherence Test and Standardized Dietician Evaluation in Assessment of Adherence to a Gluten-Free Diet in Patients with Celiac Disease.

Adherence to a gluten-free diet (GFD) is currently the mainstay of treatment strategy for celiac disease (CD). The aim of our study was measuring a GFD adherence in CD patients using two newly validated methods of dietary assessment-Standardized Dietician Evaluation (SDE) and the Celiac Dietary Adherence Test (CDAT). Ninety-two adults with CD were evaluated by a registered dietitian with extensive experience with the use of SDE and CDAT. Duodenal biopsy was performed and blood was drawn for serum anti-endomysial, anti-deamidated gliadin peptide and anti-tissue transglutaminase antibodies in forty four of those patients. The results of CDAT and SDE were very convergent, but SDE scores better correlated with serologic and histologic findings. As many as 24-52% of study participants did not adhere well enough to a GFD. Insufficient adherence to a GFD in CD patients is still a significant problem. The knowledge about gluten content in food ingredients and additives is very low among adults with CD. SDE is the most accurate method in assessing compliance with a GFD and is especially helpful in determining hidden sources of gluten. The CDAT may be a fast tool for screening for a GFD adherence in CD patients.

Impact of a Child's Celiac Disease Diagnosis and Management on the Family.

BACKGROUND: Little attention has been paid to family-wide repercussions of a child's celiac disease diagnosis and concomitant gluten-free diet management. AIMS: We quantitatively and qualitatively describe positive and negative family-wide effects of a child's celiac disease diagnosis and disease management. METHODS: We interviewed 16 families with at least one child currently following a gluten-free diet, with a biopsy-confirmed celiac disease diagnosis ≥ 1 year prior. Mothers and fathers independently rated child's dietary adherence, concern about child's health status, burden in caring for child's dietary needs, and level of change in various aspects of life post- diagnosis. Children rated their own celiac-specific quality of life through a validated scale. Seventy-one in-depth semi-structured interviews were conducted with 16 children with celiac disease, 31 parents, and 24 siblings. RESULTS: Mothers and fathers rated the effects of their child's celiac disease differently, with mothers reporting more lifestyle changes and heavier burden. Negative and positive themes emerged from the interviews. Mothers felt the burden of managing a gluten-free diet. Fathers felt guilty for carrying a celiac disease-associated gene and both fathers and siblings regretted limited food choices at restaurants and home. The need to be a more creative cook was seen as a positive effect by mothers. Fathers appreciated new family traditions. Siblings felt they had developed empathy for others. A framework is proposed to illustrate these family-wide interactions. CONCLUSIONS: A child's celiac disease diagnosis and disease management affects the entire family. Our results will inform family-centered interventions that maximize quality of life for families.

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease.

BACKGROUND AND AIM: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non-invasive biomarker(s) that can predict the presence of villous abnormalities. METHODS: Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I-FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut-off values were derived, and the results were further validated in a prospective validation cohort. RESULTS: While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten-free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was  ≤ 30 µM/L and I-FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut-off values of citrulline and I-FABP. CONCLUSIONS: Plasma citrulline  ≤ 30 µM/L is the most consistent, highly reproducible non-invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.

Assessment of Machine Learning Detection of Environmental Enteropathy and Celiac Disease in Children.

Importance: Duodenal biopsies from children with enteropathies associated with undernutrition, such as environmental enteropathy (EE) and celiac disease (CD), display significant histopathological overlap. Objective: To develop a convolutional neural network (CNN) to enhance the detection of pathologic morphological features in diseased vs healthy duodenal tissue. Design, Setting, and Participants: In this prospective diagnostic study, a CNN consisting of 4 convolutions, 1 fully connected layer, and 1 softmax layer was trained on duodenal biopsy images. Data were provided by 3 sites: Aga Khan University Hospital, Karachi, Pakistan; University Teaching Hospital, Lusaka, Zambia; and University of Virginia, Charlottesville. Duodenal biopsy slides from 102 children (10 with EE from Aga Khan University Hospital, 16 with EE from University Teaching Hospital, 34 with CD from University of Virginia, and 42 with no disease from University of Virginia) were converted into 3118 images. The CNN was designed and analyzed at the University of Virginia. The data were collected, prepared, and analyzed between November 2017 and February 2018. Main Outcomes and Measures: Classification accuracy of the CNN per image and per case and incorrect classification rate identified by aggregated 10-fold cross-validation confusion/error matrices of CNN models. Results: Overall, 102 children participated in this study, with a median (interquartile range) age of 31.0 (20.3-75.5) months and a roughly equal sex distribution, with 53 boys (51.9%). The model demonstrated 93.4% case-detection accuracy and had a false-negative rate of 2.4%. Confusion metrics indicated most incorrect classifications were between patients with CD and healthy patients. Feature map activations were visualized and learned distinctive patterns, including microlevel features in duodenal tissues, such as alterations in secretory cell populations. Conclusions and Relevance: A machine learning-based histopathological analysis model demonstrating 93.4% classification accuracy was developed for identifying and differentiating between duodenal biopsies from children with EE and CD. The combination of the CNN with a deconvolutional network enabled feature recognition and highlighted secretory cells' role in the model's ability to differentiate between these histologically similar diseases.

Random duodenal biopsy to exclude coeliac disease as a cause of anaemia is not cost-efective and should be replaced with universally performed pre-endoscopy serology in patients on a suspected cancer pathway.

BACKGROUND: Random duodenal biopsy to exclude coeliac disease during upper gastrointestinal endoscopy for the investigation of iron deficiency anaemia remains a common procedure, but is expensive and time-consuming. Serological investigation for coeliac disease is also recommended, having excellent accuracy with the added benefit of lower cost. This study sought to examine the utility of duodenal biopsy and coeliac serology in the diagnosis of coeliac disease. METHODS: A prospectively maintained database was interrogated to identify all patients having upper gastrointestinal endoscopy for the investigation of anaemia between January 01, 2016, and December 31, 2016. RESULTS: Of the 1131 patients having an endoscopy, coeliac serology was measured in only 412 (36%) and was positive in 9 cases (2%), leading to 6 histological diagnoses of coeliac disease and 3 false positives. Two-hundred and seventy-four patients with negative serology had biopsies taken which were all negative. Only 2/451 (0.4%) patients who had biopsies performed in the absence of a serology test were histologically positive for coeliac disease. The cost per diagnosis of a case of coeliac disease in those with either negative or absent coeliac serology was £18,839 (US$25,244, €21,196). CONCLUSIONS: Random duodenal biopsy is not a cost-effective method of diagnosing coeliac disease and should be replaced with pre-endoscopy coeliac serology.

Validation of an algorithm to identify children with biopsy-proven celiac disease from within health administrative data: An assessment of health services utilization patterns in Ontario, Canada.

IMPORTANCE: Celiac disease (CD) is a common pediatric illness, and awareness of gluten-related disorders including CD is growing. Health administrative data represents a unique opportunity to conduct population-based surveillance of this chronic condition and assess the impact of caring for children with CD on the health system. OBJECTIVE: The objective of the study was to validate an algorithm based on health administrative data diagnostic codes to accurately identify children with biopsy-proven CD. We also evaluated trends over time in the use of health services related to CD by children in Ontario, Canada. STUDY DESIGN AND SETTING: We conducted a retrospective cohort study and validation study of population-based health administrative data in Ontario, Canada. All cases of biopsy-proven CD diagnosed 2005-2011 in Ottawa were identified through chart review from a large pediatric health care center, and linked to the Ontario health administrative data to serve as positive reference standard. All other children living within Ottawa served as the negative reference standard. Case-identifying algorithms based on outpatient physician visits with associated ICD-9 code for CD plus endoscopy billing code were constructed and tested. Sensitivity, specificity, PPV and NPV were tested for each algorithm (with 95% CI). Poisson regression, adjusting for sex and age at diagnosis, was used to explore the trend in outpatient visits associated with a CD diagnostic code from 1995-2011. RESULTS: The best algorithm to identify CD consisted of an endoscopy billing claim follow by 1 or more adult or pediatric gastroenterologist encounters after the endoscopic procedure. The sensitivity, specificity, PPV, and NPV for the algorithm were: 70.4% (95% CI 61.1-78.4%), >99.9% (95% CI >99.9->99.9%), 53.3% (95% CI 45.1-61.4%) and >99.9% (95% CI >99.9->99.9%) respectively. It identified 1289 suspected CD cases from Ontario-wide administrative data. There was a 9% annual increase in the use of this combination of CD-associated diagnostic codes in physician billing data (RR 1.09, 95% CI 1.07-1.10, P<0.001). CONCLUSIONS: With its current structure and variables Ontario health administrative data is not suitable in identifying incident pediatric CD cases. The tested algorithms suffer from poor sensitivity and/or poor PPV, which increase the risk of case misclassification that could lead to biased estimation of CD incidence rate. This study reinforced the importance of validating the codes used to identify cohorts or outcomes when conducting research using health administrative data.

The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015).

BACKGROUND: Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general. OBJECTIVES: To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA. DESIGN: Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre. A diagnosis of either seronegative CD (SNCD) or seronegative non-CD (SN-non-CD) was reached. Baseline comparisons were made between the groups, with 343 seropositive CD subjects serving as controls. RESULTS: Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-CD 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-CD group comprised infections (27%, n=54), inflammatory/immune-mediated disorders (17.5%, n=35) and drugs (6.5%, n=13; two cases related to A2RBs). However, no cause was found in 18% (n=36) and of these 72% (n=26/36) spontaneously normalised duodenal histology while consuming a gluten-enriched diet. Following multivariable logistic regression analysis an independent factor associated with SN-non-CD was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-whites had GI infections. On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-CD mimicking the changes associated with refractory CD. CONCLUSIONS: Most patients with SNVA do not have CD, in particular those who are not white. Furthermore, a subgroup with no obvious aetiology will show spontaneous histological resolution while consuming gluten. These findings suggest caution in empirically prescribing a gluten-free diet without investigation.

Cost effectiveness of routine duodenal biopsies in iron deficiency anemia.

AIM: To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results. METHODS: We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed. RESULTS: Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION: Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status.

Current technologies for the endoscopic assessment of duodenal villous pattern in celiac disease.

Currently, standard endoscopy is not considered enough reliable for the evaluation of celiac disease, neither to drive biopsy sampling. The diagnostic reliability of the endoscopic assessment of celiac disease has been increased by the recent advancement of software and hardware technologies. Several endoscopic technologies have been investigated so far for the diagnostic evaluation of celiac disease, including: water-immersion techniques, dye-based and dye-less chromoendoscopy techniques (Narrow band imaging; Fujinon Intelligeng Chromo Endoscopy; I-scan); optical coherence tomography; confocal laser endomicroscopy; high-resolution magnification endoscopy; videocapsule endoscopy; enteroscopy. Such a technologic improvement brought us to higher diagnostic possibilities in the evaluation and management of CD. A wider application of advanced diagnostic endoscopic techniques is therefore warranted to decrease the number of misdiagnoses and related healthcare costs of celiac disease.

Screening for celiac disease in Danish adults.

OBJECTIVE: The prevalence of celiac disease (CD) as recorded in the Danish National Patient Registry is ∼50/100,000 persons. This is much lower than the reported prevalence of CD in other Nordic countries and underdiagnosis is suspected. Our aim was to estimate the prevalence of CD in a population-based study of Danish adults. METHODS: A total of 2297 adults aged 24-76 years living in the southwestern part of Copenhagen were screened for CD by immunoglobulin (Ig)A and IgG antibodies to transglutaminases and deamidated gliadin. IgA/IgG-positive participants were invited to a clinical evaluation, including biopsies, by a gastroenterologist. RESULTS: Of the invited 56 participants, 40 underwent a full clinical evaluation and 8 persons were diagnosed with CD; 2 of the 16 persons, who did not complete the clinical evaluation, were considered by experts to have probable CD. None of the above 56 participants had a known history of CD or a recorded diagnosis of CD in National Patient Registry. By combining cases of biopsy-proven CD (n = 8), probable CD (n = 2), and registry-recorded CD (n = 1), the prevalence of CD was estimated to be 479/100,000 (11/2297) persons (95% CI: 197-761). CONCLUSION: In this general adult population, the prevalence of CD as estimated by screening and clinical evaluation was 10 times higher than the registry-based prevalence of CD. Of 11 participants diagnosed with CD in our screening study, 10 were unaware of the diagnosis prior to the study. Thus, our study suggests that CD is markedly underdiagnosed in Danish adults.

Routine duodenal biopsy to screen for coeliac disease is not effective.

BACKGROUND: Routine duodenal biopsies during upper gastrointestinal endoscopy (UGE) have been suggested to be useful in detecting coeliac disease (CD). However results from previous studies are not conclusive. The aim of this study is to investigate the diagnostic yield and cost-effectiveness of routine duodenal biopsy during UGE. METHODS: In this retrospective single-centre study, we studied 6442 patients undergoing first-time UGE at the Rijnstate Hospital, Arnhem, the Netherlands, from January 2009 to December 2010. All UGE reports were analysed for indication, duodenal intubation, and endoscopic aspect of duodenal mucosa. Endomysium and tissue transglutaminase antibody titre, when present, were scored as positive or negative. CD was defined as Marsh 3a or higher. Costs of duodenal biopsies and pathology analysis were calculated. Comparisons were done with T-tests for continuous data and Chi-square tests for categorical data. RESULTS: Forty-one patients had newly diagnosed CD; 34 of these 41 patients had definite indications for biopsy prior to UGE, e.g. positive serology or symptoms. Thus, routine duodenal biopsies identified seven patients as having CD, who otherwise would not have been biopsied. The number needed to biopsy was therefore 577, spending more than v 30,000 per case. CONCLUSIONS: We do not recommend routine duodenal biopsy to screen for coeliac disease because of the high number needed to biopsy as well as high costs.

Diagnostic yield and economic implications of endoscopic colonic biopsies in patients with chronic diarrhoea.

AIMS: Random colonic biopsies are recommended to exclude microscopic colitis in patients with chronic diarrhoea especially when mucosa is macroscopically normal at endoscopy. This study aimed to assess the clinical outcome and economic impact of such a policy in an unselected group of patients with macroscopically normal mucosa. METHODS: All new patients undergoing colonoscopy for investigation of chronic diarrhoea between April and December 2009 were included. Patients were divided into two groups: macroscopically normal mucosa and macroscopically inflamed mucosa. Endoscopic findings were correlated with histology of random biopsies and haematological parameters. Symptom status and any treatment were established from follow-up. The breakdown and overall cost of random biopsies for each patient with a macroscopically normal mucosa were determined, and cost incurred per diagnosis of microscopic colitis was established. RESULTS: Altogether 137 (90.1%) of 152 patients with chronic diarrhoea had macroscopically normal mucosa at colonoscopy. Overall incidence of microscopic colitis in the study was 1.3% (2/152); both patients belonged to the macroscopically normal mucosa group. At follow-up, both these patients had spontaneous symptom resolution without any specific treatment. The policy of undertaking random biopsies in patients with macroscopically normal mucosa incurred an extra cost of £22,057 to diagnose two cases of microscopic colitis but did not alter medical treatment. CONCLUSIONS: In unselected patients with chronic diarrhoea and macroscopically normal mucosa, random colonic biopsies have a low diagnostic yield and incur a high cost. Continued research for predictive markers to improve patient selection for targeted biopsies is needed to develop a cost-effective investigative algorithm in chronic diarrhoea.

Systematic assessment of performance prediction techniques in medical image classification: a case study on celiac disease.

In the context of automated classification of medical images, many authors report a lack of available test data. Therefore techniques such as the leave-one-out cross validation or k-fold validation are used to assess how well methods will perform in practice. In case of methods based on feature subset selection, cross validation might provide bad estimations of how well the optimized technique generalizes on an independent data set. In this work, we assess how well cross validation techniques are suited to predict the outcome of a preferred setup of distinct test- and training data sets. This is accomplished by creating two distinct sets of images, used separately as training- and test-data. The experiments are conducted using a set of Local Binary Pattern based operators for feature extraction which are using histogram subset selection to improve the feature discrimination. Common problems such as the effects of over fitting data during cross validation as well as using biased image sets due to multiple images from a single patient are considered.