关键词： Cost savings   Trough concentrations   Infliximab   Inflammatory bowel disease   Rheumatoid arthritis  

摘要： Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to a,notsign13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

关键词： Miltirone   Inflammatory bowel disease   IQGAP2   TLR4/NF-kappa B signaling pathway  

摘要： Inflammatory bowel disease (IBD) is characterized by a radical imbalance in the activation of proinflammatory and anti-inflammatory signaling pathways in the gut. This study was conducted to evaluate the anti-inflammation effect of miltirone against IBD in vitro and in vivo, and try to explore the underlying mechanisms. Miltirone could extenuate the loss of colon length and weight caused by TNBS. Additionally, macroscopic scores and DAI were reduced significantly compared with the TNBS group. The levels of TNF-alpha, IL-1 beta, IL-6 and IL-8 were increased significantly with the induction by TNBS (100 mg/kg) or LPS (0.5 mg/mL). Interestingly, miltirone could down-regulate the levels of these increased proinflammatory factors in a dose-dependent manner both in vivo and in vitro. The protein and mRNA expressions of TLR4, MyD88, NF-kappa B p65 were up-regulated by TNBS or LPS stimulation. CRX-526, the TLR4 inhibitor, as well as miltirone could significantly suppress the increased protein and mRNA expressions. Miltirone could up-regulate the descreased IQGAP2 expression induced by LPS. All these revealed that the anti-inflammatory effect of miltirone on IBD may be via regulating TLR4/NF-kappa B/IQGAP2 signaling pathway. The findings might supply beneficial hints for the drug research to cure the IBD. (C) 2016 Elsevier Masson SAS. All rights reserved.

关键词： Children   inflammatory bowel disease   Saudi   variation of care  

摘要： Background/Aim: Although international guidelines in inflammatory bowel disease (IBD) management are currently available, variations in IBD care still exist. The aim of this study was to determine the extent of the variation in IBD care among Saudi pediatric gastroenterologists. Materials and Methods: A cross-sectional survey was conducted among all pediatric gastroenterologists who were members of the Saudi Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SASPGHAN) from August 2015 to December 2015. The questionnaire included items on demographic characteristics and utilization of different diagnostic and therapeutic interventions in IBD care. Results: Of the 45 registered pediatric gastroenterologists surveyed, 37 (82%) returned the survey from 20 centers across the country;75.7% were practicing in tertiary care centers. There was a considerable variation in the use of different diagnostic tests during the initial evaluation of the disease. Utilization of calprotectin assays, magnetic resonance imaging enterography, and bone densitometry seemed to vary the most between physicians practicing at tertiary and secondary care centers. There were statistically significant differences in the prescription of biological therapy between the two groups. Conclusions: We found a considerable variation in the use of different diagnostic and therapeutic interventions in the management of pediatric IBD patients. Such variations could lead to unintended differences in patient outcomes. Implementation of the available evidence-based guidelines may limit such variations and ultimately could improve the quality of IBD care provided.

关键词： SNP   Genetic Analysis   Risk Factor   Trans-Ethnic  

摘要： BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 x 10(-8) in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 x 10(-6)): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD;IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD;and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. CONCLUSIONS: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population;we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of A

关键词： Diet   IBD   Microbial metabolism   Microbiota   Pathogenesis  

摘要： The rising incidence of inflammatory bowel diseases in recent decades has notably paralleled changing lifestyle habits in Western nations, which are now making their way into more traditional societies. Diet plays a key role in IBD pathogenesis, and there is a growing appreciation that the interaction between diet and microbes in a susceptible person contributes significantly to the onset of disease. In this review, we examine what is known about dietary and microbial factors that promote IBD. We summarize recent findings regarding the effects of diet in IBD epidemiology from prospective population cohort studies, as well as new insights into IBD-associated dysbiosis. Microbial metabolism of dietary components can influence the epithelial barrier and the mucosal immune system, and understanding how these interactions generate or suppress inflammation will be a significant focus of IBD research. Our knowledge of dietary and microbial risk factors for IBD provides important considerations for developing therapeutic approaches through dietary modification or re-shaping the microbiota. We conclude by calling for increased sophistication in designing studies on the role of diet and microbes in IBD pathogenesis and disease resolution in order to accelerate progress in response to the growing challenge posed by these complex disorders.

关键词： Demographic characteristics   environmental epidemiology   socio-economic risk factors   ZIP codes  

摘要： Aim Inflammatory bowel disease (IBD) and microscopic colitis are characterized by different geographical distributions across the USA. In this cross-sectional study we utilized demographic and socio-economic information associated with individual ZIP codes to further delineate the epidemiological characteristics of the two diseases. Method A total of 813 057 patients who underwent colonoscopy between 2008 and 2014 were extracted from an electronic database of histopathology reports. The prevalence of patients with IBD or microscopic colitis was expressed as percentage of the population associated with specific demographic (age, sex, ethnicity) and socio-economic characteristics (population size, housing value, annual income, tertiary education). Results Both diseases were more common among subjects from ZIP codes with predominantly White residents and less common among subjects from ZIP codes with predominantly non-White residents such as Black, Hispanic and Asian. These ethnic variations were more pronounced in microscopic colitis than IBD. Markers of affluence, such as average residential house value and annual income, were positively associated with IBD and negatively with microscopic colitis. The prevalence of both diseases was positively correlated with tertiary education. Conclusion The occurrence of both IBD and microscopic colitis is influenced by environmental risk factors. The differences in the demographic, ethnic and socioeconomic distributions of the two diseases suggest that different sets of risk factors affect the two diseases and that their aetiology is unrelated.

关键词： Arterial stiffness   IBD   Carotid intima-media thickness   Early atherosclerosis  

摘要： Background & Aims: Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients. Methods: We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45 years old (median age 31.6 +/- 8.1 years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx). Results: Total cholesterol (P < 0.013) and LDL-cholesterol (P < 0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P < 0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P < 0.006 and P < 0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P < 0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis. Conclusions: Young IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

关键词： Inflammatory bowel diseases   microbiota   virome  

摘要： Inflammatory bowel disease (IBD) includes a spectrum of diseases from ulcerative colitis (UC) to Crohn's disease (CD). Many studies have addressed the changes in the microbiota of individuals affected by UC and CD. A decrease in biodiversity and depletion of the phyla Bacteroidetes and Firmicutes has been reported, among others. Changes in microbial composition also result in changes in the metabolites generated in the gut from microbial activity that may involve the amount of butyrate and other metabolites such as H2S being produced. Other factors such as diet, age, or medication need to be taken into consideration when studying dysbiosis associated with IBD. Diverse bacterial species have been associated specifically or non-specifically to IBD, but none of them have been demonstrated to be its ethiological agent. Recent studies also suggest that micro-eukaryotic populations may also be altered in IBD patients. Last, but not least, viruses, and specially bacteriophages, can play a role in controlling microbial populations in the gastrointestinal tract. This may affect both bacterial diversity and metabolism, but possible implications for IBD still remain to be solved. Dysbiosis in the oral microbiome associated with IBD remains an emerging field for future research.

关键词： biomarkers   IBD   NGAL   lipocalin 2  

摘要： Background and AimAccurate, noninvasive biomarkers are needed to diagnose and monitor inflammatory bowel disease (IBD). Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin 2, is expressed in inflamed colonic epithelium and neutrophilic granulocytes. This study explores its properties as a biomarker in feces and plasma and, for the first time, compares fecal NGAL systematically with the existing fecal biomarker calprotectin. MethodsNeutrophil gelatinase-associated lipocalin was measured in feces from 73 patients with IBD, 21 patients with infectious enterocolitis, 21 patients with irritable bowel syndrome, and 23 healthy subjects using ELISA. The results were correlated to calprotectin, clinical score, endoscopic score, and high-sensitive C-reactive protein. Plasma from 119 patients with IBD and 28 healthy controls was analyzed for NGAL. ResultsFecal NGAL levels (median and interquartile range) were significantly elevated in active ulcerative colitis (UC) 6.05 (3.6-15.1) mg/kg and Crohn's disease (CD) 4.9 (1.5-7.7) mg/kg, compared with patients with inactive UC 1.3 (0.4-2.6) mg/kg, inactive CD 1.5 (0.5-1.7) mg/kg, irritable bowel syndrome 0.4 (0.2-0.6) mg/kg, and healthy controls (HC) 0.3 (0.1-0.4) mg/kg. Patients with infectious enterocolitis had significantly higher fecal-NGAL levels, 2.7 (1.4-5.6) mg/kg than HC. Sensitivity and specificity was 94.7% and 95.7%, respectively, for distinguishing between active IBD and HC. Stability of NGAL in stool was excellent for 7days in room temperature. Plasma NGAL was significantly elevated in UC and CD compared with HC. ConclusionsFecal NGAL is a promising biomarker for IBD. As existing biomarkers are expressed mainly in granulocytes, NGAL's epithelial localization may give supplementary diagnostic information.

关键词： INFLAMMATORY bowel disease treatment   DRUG efficacy   VEDOLIZUMAB  

摘要： Linked Content This article is linked to Stallmach et al paper. To view this article visit https://***/10.1111/apt.13813. [ABSTRACT FROM AUTHOR]