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1.
Frontline Gastroenterol ; 14(3): 201-221, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056319

RESUMEN

Introduction: In the UK, endoscopy certification is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for colonoscopy training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted between 2019 and 2020 with multisociety expert representation. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on colonoscopy training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer reviewed by JAG and relevant stakeholders for incorporation into the updated colonoscopy certification pathway. Results: In total, 45 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (20), assessment of competence (8) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (1) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, unassisted caecal intubation rate >90%, rectal retroversion >90%, polyp detection rate >15%+, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (2) minimum procedure count 280+; (3) performing 15+ procedures over the preceding 3 months; (4) attendance of the JAG Basic Skills in Colonoscopy course; (5) terminal ileal intubation rates of 60%+ in inflammatory bowel disease; (6) satisfying requirements for formative direct observation of procedure skills (DOPS) and direct observation of polypectomy skills (Size, Morphology, Site, Access (SMSA) level 2); (7) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool; (8) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in colonoscopy have been updated, culminating in a single-stage certification process with emphasis on polypectomy competency (SMSA Level 2+). These standards are intended to support training, improve standards of colonoscopy and polypectomy, and provide support to the newly independent practitioner.

2.
Frontline Gastroenterol ; 14(3): 181-200, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056324

RESUMEN

Introduction: Joint Advisory Group (JAG) certification in endoscopy is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update standards for training and certification in flexible sigmoidoscopy (FS). Methods: A modified Delphi process was conducted between 2019 and 2020 with multisociety representation from experts and trainees. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on FS training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer-reviewed by national stakeholders for incorporation into the JAG FS certification pathway. Results: In total, 41 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (17), assessment of competence (7) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (A) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, rectal retroversion >90%, polyp retrieval rate >90%, patient comfort <10% with moderate-severe discomfort); (B) minimum procedure count ≥175; (C) performing 15+ procedures over the preceding 3 months; (D) attendance of the JAG Basic Skills in Lower gastrointestinal Endoscopy course; (E) satisfying requirements for formative direct observation of procedural skill (DOPS) and direct observation of polypectomy skill (SMSA level 1); (F) evidence of reflective practice as documented on the JAG Endoscopy Training System reflection tool and (G) successful performance in summative DOPS. Conclusion: The UK standards for training and certification in FS have been updated to support training, uphold standards in FS and polypectomy, and provide support to the newly independent practitioner.

3.
Clin Exp Gastroenterol ; 14: 103-111, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790613

RESUMEN

The British Society of Gastroenterology (BSG) and the Bangladesh Gastroenterology Society (BGS) have collaborated on an endoscopy training programme, which has grown up over the past decade from a small scheme borne out of the ideas of consultant gastroenterologists in Swansea, South Wales (United Kingdom) to improve gastroenterology services in Bangladesh to become a formalised training programme with broad reach. In this article, we document the socioeconomic and historical problems that beset Bangladesh, the current training needs of doctors and how the BSG-BGS collaboration has made inroads into changing outcomes both for gastroenterologists in Bangladesh, but also for the populations they serve.

4.
Surg Endosc ; 34(1): 115, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30937617

RESUMEN

The citation for Reference 22 should be replaced with: Kumar NL, Kugener G, Perencevich ML, et al (2018) The SAFE-T assessment tool: derivation and validation of a web-based application for point-of-care evaluation of gastroenterology fellow performance in colonoscopy. Gastrointest Endosc 87(1):262-269.

5.
Surg Endosc ; 34(1): 105-114, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30911922

RESUMEN

BACKGROUND: Validated competency assessment tools and the data supporting milestone development during gastroscopy training are lacking. We aimed to assess the validity of the formative direct observation of procedural skills (DOPS) assessment tool in diagnostic gastroscopy and study competency development using DOPS. METHODS: This was a prospective multicentre (N = 275) analysis of formative gastroscopy DOPS assessments. Internal structure validity was tested using exploratory factor analysis and reliability estimated using generalisability theory. Item and global DOPS scores were stratified by lifetime procedure count to define learning curves, using a threshold determined from receiver operator characteristics (ROC) analysis. Multivariable binary logistic regression analysis was performed to identify independent predictors of DOPS competence. RESULTS: In total, 10086 DOPS were submitted for 987 trainees. Exploratory factor analysis identified three distinct item groupings, representing 'pre-procedure', 'technical', and 'post-procedure non-technical' skills. From generalisability analyses, sources of variance in overall DOPS scores included trainee ability (31%), assessor stringency (8%), assessor subjectivity (18%), and trainee case-to-case variation (43%). The combination of three assessments from three assessors was sufficient to achieve the reliability threshold of 0.70. On ROC analysis, a mean score of 3.9 provided optimal sensitivity and specificity for determining competency. This threshold was attained in the order of 'pre-procedure' (100-124 procedures), 'technical' (150-174 procedures), 'post-procedure non-technical' skills (200-224 procedures), and global competency (225-249 procedures). Higher lifetime procedure count, DOPS count, surgical trainees and assessors, higher trainee seniority, and lower case difficulty were significant multivariable predictors of DOPS competence. CONCLUSION: This study establishes milestones for competency acquisition during gastroscopy training and provides validity and reliability evidence to support gastroscopy DOPS as a competency assessment tool.


Asunto(s)
Competencia Clínica/normas , Evaluación Educacional , Endoscopía del Sistema Digestivo/educación , Gastroscopía/educación , Evaluación Educacional/métodos , Evaluación Educacional/normas , Análisis Factorial , Humanos , Curva de Aprendizaje , Estudios Prospectivos , Reproducibilidad de los Resultados
6.
Am J Gastroenterol ; 115(2): 234-243, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31738285

RESUMEN

INTRODUCTION: Formative colonoscopy direct observation of procedural skills (DOPS) assessments were updated in 2016 and incorporated into UK training but lack validity evidence. We aimed to appraise the validity of DOPS assessments, benchmark performance, and evaluate competency development during training in diagnostic colonoscopy. METHODS: This prospective national study identified colonoscopy DOPS submitted over an 18-month period to the UK training e-portfolio. Generalizability analyses were conducted to evaluate internal structure validity and reliability. Benchmarking was performed using receiver operator characteristic analyses. Learning curves for DOPS items and domains were studied, and multivariable analyses were performed to identify predictors of DOPS competency. RESULTS: Across 279 training units, 10,749 DOPS submitted for 1,199 trainees were analyzed. The acceptable reliability threshold (G > 0.70) was achieved with 3 assessors performing 2 DOPS each. DOPS competency rates correlated with the unassisted caecal intubation rate (rho 0.404, P < 0.001). Demonstrating competency in 90% of assessed items provided optimal sensitivity (90.2%) and specificity (87.2%) for benchmarking overall DOPS competence. This threshold was attained in the following order: "preprocedure" (50-99 procedures), "endoscopic nontechnical skills" and "postprocedure" (150-199), "management" (200-249), and "procedure" (250-299) domain. At item level, competency in "proactive problem solving" (rho 0.787) and "loop management" (rho 0.780) correlated strongest with the overall DOPS rating (P < 0.001) and was the last to develop. Lifetime procedure count, DOPS count, trainer specialty, easier case difficulty, and higher cecal intubation rate were significant multivariable predictors of DOPS competence. DISCUSSION: This study establishes milestones for competency acquisition during colonoscopy training and provides novel validity and reliability evidence to support colonoscopy DOPS as a competency assessment tool.


Asunto(s)
Competencia Clínica , Colonoscopía/educación , Gastroenterología/educación , Cirugía General/educación , Enfermeras Especialistas/educación , Colonoscopía/normas , Gastroenterología/normas , Cirugía General/normas , Humanos , Enfermeras Especialistas/normas , Observación , Reproducibilidad de los Resultados , Reino Unido
7.
Endoscopy ; 51(11): 1017-1026, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31505696

RESUMEN

BACKGROUND: The endoscopic retrograde cholangiopancreatography (ERCP) direct observation of procedural skills (DOPS) is a 27-item competency assessment tool that was developed to support UK ERCP training. We evaluated validity of ERCP DOPS and competency development during training. METHODS: This prospective study analyzed ERCP DOPS performed in the UK between July 2016 and October 2018. Reliability was measured using Cronbach's alpha, and DOPS scores were benchmarked using the contrasting groups method. The percentage of competent scores was averaged for each item, domain, and overall rating, and stratified by lifetime procedure count to evaluate learning curves. Multivariable analyses were performed to identify predictors of DOPS competence. RESULTS: 818 DOPS (109 trainees, 80 UK centers) were analyzed. Overall Cronbach's alpha was 0.961. Attaining competency in 87 % of assessed DOPS items provided the optimal competency benchmark. This was achieved in the domain sequence of: pre-procedure, post-procedure management, endoscopic non-technical skills, cannulation & imaging, and execution of selected therapy, and across all items after 200 - 249 procedures (89 %). After 300 procedures, the benchmark was reached for selective cannulation (89 %), but not for stenting (plastic 73 %; metal 70 %), sphincterotomy (80 %), and sphincteroplasty (56 %). On multivariable analysis, lifetime procedure count (P = 0.002), easier case difficulty (P < 0.001), trainee grade (P = 0.03), and higher lifetime DOPS count (P = 0.01) were predictors of DOPS competence. CONCLUSION: This study provides novel validity, reliability, and learning curve data for ERCP DOPS. Trainees should have a minimum of 300 hands-on ERCP procedures before undertaking summative assessment for independent practice.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Evaluación Educacional/métodos , Gastroenterología/educación , Humanos , Curva de Aprendizaje , Estudios Prospectivos , Reproducibilidad de los Resultados , Reino Unido
8.
Frontline Gastroenterol ; 10(2): 93-106, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31210174

RESUMEN

The Joint Advisory Group on Gastrointestinal Endoscopy (JAG) was initially established in 1994 to standardise endoscopy training across specialties. Over the last two decades, the position of JAG has evolved to meet its current role of quality assuring all aspects of endoscopy in the UK to provide the highest quality, patient-centred care. Drivers such as changes to healthcare agenda, national audits, advances in research and technology and the advent of population-based cancer screening have underpinned this shift in priority. Over this period, JAG has spearheaded various quality assurance initiatives with support from national stakeholders. These have led to the achievement of notable milestones in endoscopy quality assurance, particularly in the three major areas of: (1) endoscopy training, (2) accreditation of endoscopy services (including the Global Rating Scale), and (3) accreditation of screening endoscopists. These developments have changed the landscape of UK practice, serving as a model to promote excellence in endoscopy. This review provides a summary of JAG initiatives and assesses the impact of JAG on training and endoscopy services within the UK and beyond.

9.
Endosc Int Open ; 7(4): E551-E560, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30957005

RESUMEN

Introduction In the UK, endoscopy certification is administered by the Joint Advisory Group on Gastrointestinal Endoscopy (JAG). Since 2011, certification for upper and lower gastrointestinal endoscopy has been awarded via a national (JETS) e-portfolio to the main training specialties of: gastroenterology, gastrointestinal surgeons (GS) and non-medical endoscopists (NME). Trends in endoscopy certification and differences between trainee specialties were analyzed. Methods This prospective UK-wide observational study identified trainees awarded gastroscopy, sigmoidoscopy, colonoscopy (provisional and full) certification between June 2011 - 2017. Trends in certification, procedures and time-to-certification, and key performance indicators (KPIs) in the 3-month pre- and post-certification period were compared between the three main training specialties. Results Three thousand one hundred fifty-seven endoscopy-related certifications were awarded to 1928 trainees from gastroenterology (52.3 %), GS (28.4 %) and NME (16.5 â€Š%) specialties. During the study period, certification numbers increased for all modalities and specialties, particularly NME trainees. For gastroscopy and colonoscopy, procedures-to-certification were lowest for GS ( P  < 0.001), whereas time-to-certification was consistently shortest in NMEs ( P  < 0.001). A post-certification reduction in mean cecal intubation rate (95.2 % to 93.8 %, P  < 0.001) was observed in colonoscopy, and D2 intubation (97.6 % to 96.2 %, P  < 0.001) and J-maneuver (97.3 % to 95.8 %, P  < 0.001) in gastroscopy. Overall, average pre- and post-certification KPIs still exceeded national minimum standards. There was an increase in PDR for NMEs after provisional colonoscopy certification but a decrease in PDR for GS trainees after sigmoidoscopy and full colonoscopy certification. Conclusion Despite variations among trainee specialties, average pre- and post-certification KPIs for certified trainees met national standards, suggesting that JAG certification is a transparent benchmark which adequately safeguards competency in endoscopy training.

10.
J Pediatr Gastroenterol Nutr ; 69(1): 18-23, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30889133

RESUMEN

INTRODUCTION: The paediatric series of direct observation of procedural skills (DOPS) were introduced into the UK national endoscopy training curriculum in 2016, but lack validity evidence. We aimed to present validity evidence for paediatric colonoscopy DOPS and study competency development in a national trainee cohort. METHODS: This prospective UK-wide study analysed formative paediatric colonoscopy DOPS which were submitted to the e-Portfolio between 2016 and 2018. Item, domain, and average DOPS scores were correlated with the overall DOPS rating to evidence internal structure validity. Overall DOPS ratings were compared over lifetime procedure count to demonstrate learning curves (discriminant validity). Consequential validity was founded on receiver operating characteristic curve analyses. RESULTS: A total of 203 DOPS assessments were completed for 29 trainees from 11 UK training centres. Internal structure validity was provided through item-total correlation analyses. DOPS scores positively correlated with trainee seniority (P < 0.001) and lifetime procedure count (P < 0.001). Competency acquisition followed the order of: "preprocedure," "postprocedure," "endoscopic nontechnical skills," "management," "procedure" domains, followed by overall DOPS competency, which was achieved in 81% of the cohort after 125 to 149 procedures. Mean DOPS scores could be used to predict overall procedure competence (area under receiver operating characteristic curve 0.969, P < 0.001), with a mean score of 3.9 demonstrating optimal sensitivity (93.5%) and specificity (87.6%). CONCLUSIONS: This study provides validity evidence supporting the use of paediatric colonoscopy DOPS as an in-training competence assessment tool. DOPS may also be used to measure competency development and benchmark performance during training, which may be of value to trainees, trainers, and training programmes.


Asunto(s)
Competencia Clínica , Colonoscopía/educación , Colonoscopía/normas , Pediatría/educación , Pediatría/normas , Humanos , Curva de Aprendizaje , Observación/métodos , Estudios Prospectivos , Curva ROC
11.
J Gastrointestin Liver Dis ; 28(1): 33-40, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30851170

RESUMEN

BACKGROUND AND AIMS: Data supporting milestone development during flexible sigmoidoscopy (FS) training are lacking. We aimed to present validity evidence for our formative direct observation of procedural skills (DOPS) assessment in FS, and use DOPS to establish competency benchmarks and define learning curves for a national training cohort. METHODS: This prospective UK-wide (211 centres) study included all FS formative DOPS assessments submitted to the national e-portfolio. Reliability was estimated from generalisability theory analysis. Item and global DOPS scores were correlated with lifetime procedure count to study learning curves, with competency benchmarks defined using contrasting groups analysis. Multivariable binary logistic regression was performed to identify independent predictors of DOPS competence. RESULTS: This analysis included 3,616 DOPS submitted for 468 trainees. From generalisability analysis, sources of overall competency score variance included: trainee ability (27%), assessor stringency (15%), assessor subjectivity attributable to the trainee (18%) and case-to-case variation (40%), which enabled the modelling of reliability estimates. The competency benchmark (mean DOPS score: 3.84) was achieved after 150-174 procedures. Across the cohort, competency development occurred in the order of: pre-procedural (50-74), non-technical (75-149), technical (125-174) and post-procedural (175-199) skills. Lifetime procedural count (p<0.001), case difficulty (p<0.001), and lifetime formative DOPS count (p=0.001) were independently associated with DOPS competence, but not trainee or assessor specialty. CONCLUSION: Sigmoidoscopy DOPS can provide valid and reliable assessments of competency during training and can be used to chart competency development. Contrary to earlier studies, based on destination-orientated endpoints, overall competency in sigmoidoscopy was attained after 150 lifetime procedures.


Asunto(s)
Competencia Clínica , Evaluación Educacional/métodos , Gastroenterólogos/educación , Médicos Generales/educación , Curva de Aprendizaje , Sigmoidoscopía/educación , Cirujanos/educación , Análisis y Desempeño de Tareas , Diseño de Equipo , Humanos , Docilidad , Estudios Prospectivos , Sigmoidoscopios , Sigmoidoscopía/instrumentación , Especialización , Reino Unido
12.
J Pediatr Gastroenterol Nutr ; 67(6): e111-e116, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30216204

RESUMEN

OBJECTIVES: Direct observation of procedural skills (DOPS) are competence-assessment tools in endoscopy. Formative paediatric gastroscopy DOPS were implemented into the UK curriculum in 2016 but lack validity evidence; we aimed to assess validity evidence using a recognised contemporary validity framework. METHODS: We performed a prospective UK-wide analysis of formative paediatric gastroscopy DOPS submitted to the e-Portfolio over 1 year. Internal structure validity was assessed using interitem correlations between DOPS items, average domain, and skillset scores and with the overall competency rating. Overall competence scores and mean DOPS scores were compared by trainee seniority and procedure count (discriminative validity). Receiver operating characteristic curve analysis was performed to explore if DOPS scores could be used to delineate procedural competency (consequential validity). RESULTS: A total of 157 DOPS assessments were completed by 20 trainers for 17 trainees. Strengths of correlations varied between DOPS components, with overall competency correlating most with technical-predominant items, domains and skillsets. Both the overall assessor's rating and mean DOPS scores increased with trainee seniority (P < 0.001) and lifetime procedure count (P < 0.001). Overall competency could be delineated using mean DOPS scores (area under receiver operating characteristic curve 0.95, P < 0.001), with a threshold of 3.9 providing optimal sensitivity (94.4%) and specificity (89.7%). CONCLUSIONS: Competencies in paediatric gastroscopy, as assessed using DOPS, vary in their correlation with overall competence and increase with trainee experience. Formative DOPS thresholds could be used to indicate readiness for summative assessment. Our study therefore provides evidence of internal structure, discriminative, and consequential validity in support of formative paediatric gastroscopy DOPS.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Evaluación Educacional/métodos , Gastroscopía/educación , Pediatría/educación , Adulto , Curriculum , Femenino , Humanos , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Reino Unido
14.
Endoscopy ; 50(8): 770-778, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29614526

RESUMEN

BACKGROUND: Direct Observation of Procedural Skills (DOPS) is an established competence assessment tool in endoscopy. In July 2016, the DOPS scoring format changed from a performance-based scale to a supervision-based scale. We aimed to evaluate the impact of changes to the DOPS scale format on the distribution of scores in novice trainees and on competence assessment. METHODS: We performed a prospective, multicenter (n = 276), observational study of formative DOPS assessments in endoscopy trainees with ≤ 100 lifetime procedures. DOPS were submitted in the 6-months before July 2016 (old scale) and after (new scale) for gastroscopy (n = 2998), sigmoidoscopy (n = 1310), colonoscopy (n = 3280), and polypectomy (n = 631). Scores for old and new DOPS were aligned to a 4-point scale and compared. RESULTS: 8219 DOPS (43 % new and 57 % old) submitted for 1300 trainees were analyzed. Compared with old DOPS, the use of the new DOPS was associated with greater utilization of the lowest score (2.4 % vs. 0.9 %; P < 0.001), broader range of scores, and a reduction in competent scores (60.8 % vs. 86.9 %; P < 0.001). The reduction in competent scores was evident on subgroup analysis across all procedure types (P < 0.001) and for each quartile of endoscopy experience. The new DOPS was superior in characterizing the endoscopy learning curve by demonstrating progression of competent scores across quartiles of procedural experience. CONCLUSIONS: Endoscopy assessors applied a greater range of scores using the new DOPS scale based on degree of supervision in two cohorts of trainees matched for experience. Our study provides construct validity evidence in support of the new scale format.


Asunto(s)
Competencia Clínica/normas , Pólipos del Colon/cirugía , Gastroscopía/normas , Observación , Sigmoidoscopía/normas , Evaluación Educacional/métodos , Gastroscopía/educación , Humanos , Estudios Prospectivos , Sigmoidoscopía/educación
15.
Gut ; 65(12): 1923-1929, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27531829

RESUMEN

Colonoscopy should be delivered by endoscopists performing high quality procedures. The British Society of Gastroenterology, the UK Joint Advisory Group on GI Endoscopy, and the Association of Coloproctology of Great Britain and Ireland have developed quality assurance measures and key performance indicators for the delivery of colonoscopy within the UK. This document sets minimal standards for delivery of procedures along with aspirational targets that all endoscopists should aim for.


Asunto(s)
Adenoma/diagnóstico , Competencia Clínica , Neoplasias del Colon/diagnóstico , Pólipos del Colon/diagnóstico , Colonoscopía/normas , Detección Precoz del Cáncer , Garantía de la Calidad de Atención de Salud/normas , Adenoma/cirugía , Biopsia/normas , Competencia Clínica/normas , Neoplasias del Colon/cirugía , Pólipos del Colon/cirugía , Colonoscopía/efectos adversos , Sedación Consciente/normas , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Gastroenterología/normas , Humanos , Reino Unido
16.
Can J Gastroenterol ; 24(5): 297-302, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20485703

RESUMEN

BACKGROUND/OBJECTIVE: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn's disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed. METHODS: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively. RESULTS: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively). CONCLUSION: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.


Asunto(s)
Proteínas Portadoras/genética , Enfermedad de Crohn/genética , ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Receptores de Interleucina/genética , Proteínas Relacionadas con la Autofagia , Proteínas Portadoras/metabolismo , Enfermedad de Crohn/metabolismo , Genotipo , Humanos , Receptores de Interleucina/metabolismo , Factores de Riesgo
17.
Gastroenterology ; 129(2): 437-53, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16083701

RESUMEN

BACKGROUND & AIMS: Two G-protein-coupled cannabinoid receptors, termed CB1 and CB2, have been identified and several mammalian enteric nervous systems express CB1 receptors and produce endocannabinoids. An immunomodulatory role for the endocannabinoid system in gastrointestinal inflammatory disorders has been proposed and this study sought to determine the location of both cannabinoid receptors in human colon and to investigate epithelial receptor function. METHODS: The location of CB1 and CB2 receptors in human colonic tissue was determined by immunohistochemistry. Primary colonic epithelial cells were treated with both synthetic and endogenous cannabinoids in vitro, and biochemical coupling of the receptors to known signaling events was determined by immunoblotting. Human colonic epithelial cell lines were used in cannabinoid-binding studies and as a model for in vitro wound-healing experiments. RESULTS: CB1-receptor immunoreactivity was evident in normal colonic epithelium, smooth muscle, and the submucosal myenteric plexus. CB1- and CB2-receptor expression was present on plasma cells in the lamina propria, whereas only CB2 was present on macrophages. CB2 immunoreactivity was seen in the epithelium of colonic tissue characteristic of inflammatory bowel disease. Cannabinoids enhanced epithelial wound closure either alone or in combination with lysophosphatidic acid through a CB1-lysophosphatidic acid 1 heteromeric receptor complex. CONCLUSIONS: CB1 receptors are expressed in normal human colon and colonic epithelium is responsive biochemically and functionally to cannabinoids. Increased epithelial CB2-receptor expression in human inflammatory bowel disease tissue implies an immunomodulatory role that may impact on mucosal immunity.


Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Colon/patología , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/patología , Receptores de Cannabinoides/metabolismo , Cicatrización de Heridas/fisiología , Biomarcadores/análisis , Biopsia con Aguja , Moduladores de Receptores de Cannabinoides/análisis , Estudios de Casos y Controles , Células Cultivadas , Colon/metabolismo , Células Epiteliales/citología , Células Epiteliales/fisiología , Femenino , Humanos , Inmunohistoquímica , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Receptores de Cannabinoides/análisis , Valores de Referencia , Muestreo , Sensibilidad y Especificidad , Técnicas de Cultivo de Tejidos
18.
Br J Pharmacol ; 141(7): 1091-7, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15023855

RESUMEN

1. Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNF alpha and IFN gamma was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. 2. TNF alpha induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E(2) synthesis. 3. Co-stimulation of TNF alpha with IFN gamma resulted in reduced COX-2 mRNA and protein expression. 4. IFN gamma had no effect on the stability of TNF alpha-induced COX-2 mRNA. 5. TNF alpha-induced PGE(2) biosynthesis was significantly enhanced by the simultaneous addition of IFN gamma and was COX-2 dependent. 6. The combination of IFN gamma and TNF alpha induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE(2) synthesis. 7. These results suggest that, in terms of PGE(2) biosynthesis, IFN gamma plays a negative regulatory role at the level of COX-2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFN gamma in inflammatory diseases.


Asunto(s)
Colon/metabolismo , Células Epiteliales/metabolismo , Interferón gamma/farmacología , Prostaglandinas E/biosíntesis , Animales , Células CACO-2 , Colon/efectos de los fármacos , Colon/patología , Inhibidores de la Ciclooxigenasa/metabolismo , Dactinomicina/farmacología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Estudios de Evaluación como Asunto , Células HT29 , Humanos , Interferón-alfa/metabolismo , Interferón-alfa/farmacología , Interferón gamma/antagonistas & inhibidores , Interferón gamma/metabolismo , Oxidorreductasas Intramoleculares/genética , Oxidorreductasas Intramoleculares/metabolismo , Ratones , Microsomas/enzimología , Prostaglandina-E Sintasas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba
19.
Eur J Gastroenterol Hepatol ; 14(5): 529-34, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11984151

RESUMEN

OBJECTIVE: To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis. DESIGN AND OUTCOME MEASURES: A case-control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. SETTING: District general hospital (secondary care institution). PARTICIPANTS: Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. RESULTS: Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease. CONCLUSION: The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.


Asunto(s)
Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Exposición a Riesgos Ambientales , Femenino , Helicobacter pylori/aislamiento & purificación , Humanos , Modelos Logísticos , Masculino , Factores de Riesgo , Estudios Seroepidemiológicos , Encuestas y Cuestionarios
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