Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease:relapse and recapture rates, with predictive factors in 237 patients

Background: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. Aim: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. Methods This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. Results: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4–8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). Conclusion Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis

Evaluation of INDUSCHIP-1 and selected low-density SNP panel for imputation to higher density in Gir dairy cattle of Gujarat

Application of Genomic Selection among other selection methods mainly depends upon the cost of genotyping, as cheaper the cost more animals can be genotyped to increase reference population size. Imputation approaches have been useful in reducing the cost. Imputation strategies and GS have been comprehensively studied in several taurine dairy cattle populations but very limited information is available on Bos Indicus populations. Factors that affect the efficiency of imputation are population structure, linkage disequilibrium between markers, and marker density in target and reference SPN panels. For present study, INDUSCHIP-1, a customized Illumina bovine microarray chip for indigenous cattle breeds, designed by NDDB, Anand was used for genotyping Gir cattle in India. The objective of the study is to evaluate the performance of INDUSCHIP-1 for imputation to Illumina BovineHD and also to select an LD SNP panel useful to impute at INDUSCHIP-1 level in Gir cattle. A fivefold cross validation by masking genotypes of animals to keep either INDUSCHIP-1 SNPs or LD SNPs and imputing to either HD level or at INDUSCHIP-1 level respectively, was performed. Population-based imputation algorithm BEAGLE was used without including pedigree information. Imputation accuracies evaluated as concordance level (allele correct rate expressed in percentage). All imputation accuracy, represented as % concordance between actual genotypes and imputed genotypes were showed as an average of five replicates for each chromosome. Mean concordance of 92.33% was observed when INDUSCHIP-1 genotypes were imputed at Illumina HD 777K level. The use of INDUSCHIP-1 as a HD Panel resulted in the accuracy of 88.42%. SNP selection criteria used for LD panel in the present study was very simple and seems effective. Distribution of polymorphic SNPs along the length of chromosomes and across all the chromosomes showed that this custom selected panel is a promising option for developing LD genotyping chip for Gir cattle.</jats:p

Effectiveness of Competitive Examination Training Material in Teaching Some Units of Competitive Exam in context to Gender

Competition is nothing but the fight for acquiring scarce resources, services or posts by a large number of people. It has been an ongoing process even before the dawn of mankind as we know it today. In fact Competition is a way of life. Look around you, a child competes for the mother’s attention, an athlete competes for the medal, boys compete to woo the best girl in college, party workers compete for the leaders blessings, vegetable vendors compete with each other to woo the buyer, job aspirants compete for the best post and around 2 lakh students compete for 1200 seats in the IIMs. Education and competition are two universal ingredients of all human cultures, in fact, of almost all animal life. Humans have always considered education and competition important issues, both in the past and in the present. Of course, there have been fluctuations in emphasis and much has changed throughout the centuries. Education and academic competitions are two most important ingredients of human life and these two have always been considered as important issues. In this article, Researcher is going to discuss about the role of academic competitions in education as well as in student life.</jats:p

Genetic association analysis reveals differences in the contribution of NOD2 variants to the clinical phenotypes of orofacial granulomatosis

Background Orofacial granulomatosis (OFG) is a rare, inflammatory disorder of the mouth, in which some patients also have intestinal Crohn’s disease (CD). The etiology remains largely unknown, although there is a high prevalence of atopy, and oral granulomas are also seen in other immune disorders particularly CD and sarcoidosis. We investigated whether genetic variants associated with an increased risk of CD, sarcoidosis, or atopy were also associated with susceptibility to OFG. Methods Patients were stratified clinically as isolated oral manifestations (OFG only) or concurrent intestinal CD (OFG+CD). We genotyped 201 patients and 1023 healthy controls for risk variants in NOD2, IRGM, IL23R, ATG16L1 (CD), BTNL2 (sarcoidosis), and FLG (atopy). The coding regions of the NOD2 gene were screened for rare, potentially pathogenic variants in OFG. Results A combined analysis of 3 CD-risk variants in NOD2 showed no association with any OFG subgroup. NOD2 p.L1007insC was associated with OFG +CD (P = 0.023) and IL23R p.R381Q with all OFG (P ¼ 0.031). The sarcoidosis risk variant rs2076530 in BTNL2 was associated with all OFG (P = 0.013). We identified 7 rare missense NOD2 alleles in 8 individuals with OFG, 4 OFG-only patients and 4 patients with OFG+CD. There was a significant enrichment of NOD2 variants in the OFG+CD group compared to the OFG-only group (P = 0.008, common variants; P = 0.04, all common and rare variants). Conclusions Our findings suggest that genetic variants in NOD2 are only associated with OFG in patients with concurrent intestinal disease. A genome-wide association scan is needed to fully define the genetic architecture of OFG.</p

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease:Relapse and recapture rates, with predictive factors in 237 patients

BackgroundThiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD ) and ulcerative colitis (UC ). Indefinite use of these drugs is tempered by long‐term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.AimTo investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.MethodsThis was a multicentre retrospective cohort study from 11 centres across the UK . Patients included had a definitive diagnosis of IBD , continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow‐up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.Results237 patients were included in the study (129 CD ; 108 UC ). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4–8.4). At follow‐up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P  = 0.035).Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P  = 0.005), while an elevated white cell count was predictive at 12 months for UC (P  = 0.007).ConclusionThiopurine withdrawal in the context of sustained remission is associated with a 1‐year moderate‐to‐severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.</p