关键词： Infliximab   Drug monitoring   Pediatric inflammatory bowel disease  

摘要： Background/Aims: Infliximab (IFX) often loses its therapeutic effect in initial responders with inflammatory bowel disease (IBD) over time. Low serum IFX trough levels (TLs) are linked to poor clinical response and outcomes. Maintenance of optimal therapeutic IFX concentrations is important for sustaining response and achieving good clinical outcomes. Measurement of serum IFX TLs is helpful for determining a further proper therapeutic plan. However, adequate therapeutic IFX TLs in pediatric IBD is uncertain. We aimed to identify the cutoff values for IFX TLs associated with laboratory response to IFX maintenance therapy. Methods: Patients with pediatric IBD who had received IFX infusions between December 2008 and March 2015 at Samsung Medical Center were retrospectively investigated. We analyzed 239 blood samples that were collected from 103 pediatric patients. We measured IFX TLs at induction (6 and 14 weeks) and during maintenance therapy (>22 weeks, 8 weeks interval) by fluid-phase radioimmunoassays. Results: A significant association was found between the erythrocyte sedimentation rate (ESR) and IFX TLs during maintenance (correlation coefficient, -0.11: p=0.0005). A cutoff value of 18 mm/hr for ESR was used to define higher levels. Receiver operating characteristic analysis identified optimal cutoff values: IFX TL >1.58 mu g/mL (sensitivity 82% and specificity 73%). Conclusions: Cutoff values are considered a prerequisite for further investigating the clinical usefulness of measurements of IFX in patients maintained with IFX treatment.

关键词： Crohn disease   inflammatory bowel disease   patient engagement   pediatric   priority setting   research priorities   ulcerative colitis  

摘要： Introduction: Including individuals with lived experience in pediatric inflammatory bowel disease (IBD) is essential to establishing a research agenda that is mutually impactful to both those treating and those experiencing the disease. Methods: Using the James Lind Alliance approach to research priority setting, a 10-member steering committee composed of current and former pediatric patients with IBD, caregivers, and clinicians was formed. A national survey, disseminated across Canada, elicited uncertainties which were divided into unanswered and answered research questions. Subsequently a research prioritization survey was disseminated where respondents ranked their top 20 research uncertainties. A final prioritization meeting was held to agree upon the top 10 uncertainties. Results: From 1209 research questions submitted by 363 participants, the list was reduced to 105 indicative questions that were within scope and deemed unanswered in the literature. Via the national research prioritization survey, this list was further reduced. The top 10 uncertainties identified at the final research consensus meeting, with 21 participants from all stakeholder groups, included "What are the causes of IBD?," "Can IBD be prevented?," "What role does diet have in the management of pediatric IBD?." Other questions concerned flare ups, biomarkers, optimal patient education, long-term effects of medication and early-diagnosis, role of psychological support, and optimal approach to diagnosis. Conclusion: This research adds a unique perspective by deriving a list of pediatric IBD research uncertainties important by patients and caregivers and clinicians.

关键词： Clostridium difficile   Crohn disease   inflammatory bowel diseases   surgery   ulcerative colitis  

摘要： Objective To investigate the clinical features of Clostridium difficile infection (CDI) in hospitalized patients with inflammatory bowel disease (IBD) and to analyze the impact of CDI on IBD. Methods A prospective study on patients newly diagnosed with IBD was conducted at the IBD center at Sir Run Run Shaw Hospital from March 2015 to May 2016. Stool samples for anaerobic culture and polymerase chain reaction were used to test CDI and to detect the different toxins in the groups. The patients were followed up for 2 years. Results Altogether 230 patients with IBD were enrolled, including 77 with ulcerative colitis (UC) and 153 with Crohn's disease (CD). The incidence rate of CDI was 13.9% (32/230). Patients with UC were more susceptible to CDI than those with CD (24.7% vs 8.5%, P < 0.01). Among UC patients, a long disease course, prior hospitalization, proton pump inhibitor use, and disease severity were associated with an increased risk of CDI (all P < 0.05). CDI prolonged hospital stay and increased the rate of long-term surgery rate in UC (both P < 0.05). Among patients with CD, CDI increased both short- and long-term surgery rates during the 2-year follow-up (P < 0.05) and increased repeated hospitalization in the follow-up study (odds ratio 2.41, P = 0.02). Conclusions A high incidence rate of CDI in patients hospitalized with IBD was related with longer hospital stay and higher surgery rates in our center. Patients with UC are more vulnerable to CDI than those with CD.

关键词： Biological   Crohn's disease   Ulcerative colitis   Rheumatoid arthritis   Psoriasis  

摘要： The aim of this study was to determine the proportion of biological prescriptions over time. This study is based on data from IMS (R) Diagnosis Monitor and included patients who had received a biological drug in dermatology practices due to psoriasis (PSO), gastroenterology practices due to Crohn's disease (CD) or ulcerative colitis (UC), or rheumatology practices due to rheumatoid arthritis (RA) between April 2015 and December 2018. We analyzed 1,748,948 CD/UC-related prescriptions, 3,968,879 RA-related prescriptions, and 7,321,496 PSO-related prescriptions. Of these, 343,263 (19.6%) prescriptions for IBD, 92,343 (16.2%) prescriptions for RA, and 169,573 (6.9%) prescriptions for PSO were for biologicals. The proportion of biologicals has increased continuously over 4 years, namely from 16.3% to 21.3% (p < 0.01) for CD/UC treatment prescribed by gastroenterologists, from 12.4% to 16.0% (p < 0.01) for RA treatment prescribed by rheumatologists, and from 3.2% to 7.7% (p < 0.01) for PSO treatment prescribed by dermatologists. The proportions of biological therapies and their increase over time were age-and sex-dependent. In summary, we were able to show a significant increase in the proportion of biologicals used to treat CD/UC, RA, and PSO over the last four years.

关键词： Inflammatory bowel diseases   Crohn's disease   Ulcerative colitis   S100A8   S100A9   mRNA   Blood-based biomarker  

摘要： Background and study aims: Non-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics. Patients and methods: In this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR. Results: The mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%. Conclusion: The S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD. (C) 2019 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

关键词： Endoscopy   Ischemic bowel disease   Health outcomes   Mortality   Cost   Length of stay  

摘要： Background and Aims Providing diagnostic and therapeutic interventions, lower gastrointestinal endoscopy is a salient investigative modality for ischemic bowel disease (IB). As studies on the role of endoscopic timing on the outcomes of IB are lacking, we sought to clarify this association. Methods After identifying 18-to-90-year-old patients with a primary diagnosis of IB from the 2012-2014 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, we grouped them based on timing of endoscopy into three: early (n = 9268), late (n = 3515), and no endoscopy (n = 18,452). We explored the determinants of receiving early endoscopy, the impact of endoscopic timing on outcomes (mortality and 13 others), and the impact of the type of endoscopy (colonoscopy vs. sigmoidoscopy) on these outcomes among the early group (SAS 9.4). Results Less likely to receive early endoscopy were Blacks compared to Whites (adjusted odds ratio [aOR] 0.81 95% CI [0.70-0.94]), and individuals on Medicaid, Medicare, and uninsured compared to the privately insured group (aOR 0.80 [0.71-0.91], 0.70 [0.58-0.84], and 0.68 [0.56-0.83]). Compared to the late and no endoscopy groups, patients with early endoscopy had less mortality (aOR 0.53 [0.35-0.80] and 0.09 [0.07-0.12]), shorter length of stay (LOS, 4.64 [4.43-4.87] days vs. 8.87 [8.40-9.37] and 6.62 [6.52-7.13] days), lower total hospital cost (THC, $41,055 [$37,995-$44,361] vs. $72,598 [$66,768-$78,937] and $68,737 [$64,028-$73,793]), and better outcomes. Similarly, among those who received early endoscopy, colonoscopy had better outcomes than sigmoidoscopy for mortality, THC, LOS, and adverse events. Conclusion Early endoscopy, especially colonoscopy, is associated with better clinical outcomes and decreased healthcare utilization in IB. Unfortunately, there are disparities against Blacks, and non-privately insured individuals in receiving early endoscopy.

关键词： Ulcerative colitis   Crohn's disease   Biologics   Novel therapies   S1P receptors   Integrins   Janus kinases  

摘要： The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with antitumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation. The latter issues necessitate the use of medications with different mechanisms of action. Besides the biologics natalizumab, vedolizumab and ustekinumab that have already been approved for the treatment of IBD new non-anti-TNF therapies are currently under investigation including small molecule drugs against Janus kinase and sphingosine-1-phosphate receptors. This manuscript will review the medications that are in the later stages of development for the treatment of IBD and directed against immune targets other than TNF.

关键词： diet   inflammatory bowel diseases   intestinal microbiology   metabolomics   micronutrients  

摘要： Objectives Microbiota dysbiosis in inflammatory bowel disease (IBD) has been widely reported. The gut microbiota connect diet to the metabolism by producing small molecules via diverse metabolic pathways. In this study we aimed to investigate the dietary preferences of IBD patients, and to explore the interactions among gut microbiota composition, dietary components, and metabolites in relation to IBD. Methods Dietary preferences of IBD patients (including those with ulcerative colitis [UC] and Crohn's disease [CD]) and health controls were investigated, and their gut microbiota were analyzed using 16S rRNA gene sequencing and metagenomic analyses of fecal and biopsy samples. The metabolite profiles of the samples were then analyzed using gas and liquid chromatography-mass spectrometry analyses. Results The daily intake of folic acid, niacin, vitamins C and D, calcium, and selenium differed significantly between patients with IBD and healthy controls. A decrease in long-chain (such as arachidic, and oleic acid) and medium-chain fatty acids (sebacic acid and isocaproic acid) as well as bile acid was observed in patients with IBD. Compared with healthy controls, 22 microbial species (including Sulfolobus acidocaldarius, and Clostridium clostridioforme CAG132) in the UC group and 37 microbial species (such as Bacteroides fragilis and Fusobacterium nucleatum) in the CD group were found to be correlated to diet and metabolites. Bacteroides fragilis was enriched in patients with IBD and associated with multi-nutrients, and 21 metabolites including 25-hydroxyvitamin D-3 and taurolithocholic acid. Conclusions This study provides an interaction network to identify key micronutrients, microbiota components and metabolites that contribute to IBD.

关键词： Adherence   Databases   Drug administration   Inflammatory bowel disease   Monoclonal antibodies   Outcomes research/analysis  

摘要： Introduction: Patients' adherence to and persistence on treatment for inflammatory bowel disease (IBD) can vary, depending on type and distribution of disease and treatment modality. We aim to identify differences in adherence and persistence with treatments with different administration routes (intravenous vs oral) in IBD. Methods: A retrospective cohort analysis of a claims database of adult patients diagnosed with IBD or rheumatoid arthritis (RA) who began treatment with vedolizumab, tofacitinib, or infliximab from January 2015 through December 2015. Adherence evaluated by proportion of days covered (PDC) and cumulative days with gaps at least 20% beyond expected interval (CG20) using multivariable generalized linear equation models. Persistence assessed as time to treatment discontinuation over 12 months of follow-up using Kaplan-Meier estimates and Cox proportional hazards models;proportion of persistent patients determined via multivariable logistic regression. Indirect comparisons across disease states adjusted using infliximab data. Results: After indirect adjustment by disease, mean PDC difference was significantly higher (difference of 4.7%;P = 0.0376) and mean CG20 was lower (difference of 15 days;P = 0.0646) but not statistically significant in vedolizumab/IBD than tofacitinib/RA. Conclusion: We describe a novel adjustment method for interdisease treatment differences using infliximab treatment patterns to bridge differences between IBD and RA. After adjustment, adherence was higher with infusions than oral medications, which may affect outcomes. Indirect comparisons between vedolizumab and tofacitinib are not generalizable and should be confirmed in tofacitinib-treated IBD patients.