关键词： accreditation   biologic therapy   drug safety   inflammatory bowel disease   measures   pharmacy  

摘要： Purpose. The development of a tool to measure medication safety, therapeutic efficacy, and other quality outcomes in patients receiving self-injectable biologic therapy for the management of inflammatory bowel disease (IBD) at a health-system specialty pharmacy is described. Summary. Through a collaborative initiative by pharmacists, gastroenterologists, and representatives of a pharmacy benefit manager and a pharmaceutical company, a set of clinical and specialty pharmacy quality measures was developed. The clinical measures are intended for use in assessing patient safety, disease status, treatment efficacy, and healthcare resource utilization during 3 assessments (pre-treatment, on-treatment, and longitudinal). The specialty pharmacy measures can be used to assess medication adherence, medication persistence, specialty pharmacy accreditation, and patient satisfaction. The proposed quality measures provide a foundation for evaluating the quality of IBD care and improving patient outcomes within a health-system specialty pharmacy. Future efforts to validate and implement the tool in clinical practice are planned. Conclusion. The proposed quality measures provide a foundation for future inquiry regarding the appropriateness and feasibility of integrating the measures into clinical care. Further work is needed to implement and validate these quality measures and determine their impact in optimizing health outcomes.

关键词： EndoPAT   flow-mediated dilation   reactive hyperaemia index  

摘要： Objectives: Chronic inflammation plays a central role in the etiology of endothelial damage. Endothelial dysfunction (ED) is the inability of the artery to dilate in response to an endothelial stimulus. We assessed the ED by measuring the reactive hyperaemia index (RHI) and the flow-mediated dilation (FMD) in a cohort of pediatric patients affected by inflammatory bowel disease (IBD) and comparing these parameters to a group of healthy controls (HC). Methods: Forty-one patients were consecutive enrolled. ED was evaluated by both the plethysmographic RHI method and the measurement of the FMD of brachial artery after occlusion of the blood flow. Differences between patients and controls were assessed by the Mann-Whitney test. In each patient with IBD, the main inflammation markers were detected and correlated to RHI and FMD by a linear regression test. Results: We enrolled 26 (59%) patients with IBD and 18 (41%) HC. When comparing FMD value at diagnosis it was significantly lower in IBD patients than in HC (P = 0.04). This result was confirmed at follow-up, when this difference became even more significant (P = 0.004). A significant indirect correlation was found between FMD and fecal calprotectin (r(2): 0.17;P = 0.04). No differences were found when comparing RHI. Conclusions: Our results suggest that inflammation could lead to ED assessed by ultrasound FMD. These data were not confirmed by RHI;however, this could be due to the lack of a standardized pediatric cut-off. More studies are necessary to confirm our data.

关键词： Chronic inflammation   Mucosal immunology  

摘要： Inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis are devastating chronic immunopathologies of the intestinal mucosa, which are frequently treated by immunosuppressive glucocorticoids. Endogenous glucocorticoids are not only produced by the adrenal glands, but also by the intestinal epithelium. Local glucocorticoid synthesis critically contributes to the immune homeostasis of the intestinal mucosa. As defective intestinal glucocorticoid synthesis has been associated with the development of IBD, we investigated the expression of steroidogenic enzymes and the key transcriptional regulator Liver Receptor Homolog-1 (LRH-1/NR5A2) in ileal and colonic biopsies human pediatric IBD and control patients. Furthermore, the induction of steroidogenic enzymes and their transcriptional regulation by LRH-1 was investigated in a mouse model of experimental colitis. These analyses revealed that colitis-induced expression of steroidogenic enzymes in the murine colon is dependent on the presence of LRH-1, as intestinal deletion of LRH-1 strongly reduced their colitis-induced expression. Similarly, a strong correlation between the expression of LRH-1 and different steroidogenic enzymes was seen in intestinal biopsies of human pediatric patients. Importantly, reduced expression of hydroxysteroid dehydrogenase 11B1 (HSD11B1) was observed in IBD patients compared to control patients, suggesting that defective local reactivation of glucocorticoids could contribute to the pathogenesis of IBD.

关键词： alcohol use   disease management   health-related quality of life   marijuana use   tobacco use  

摘要： Objectives: Adolescents and young adults (AYAs) with chronic illnesses use substances at similar, if not greater, rates compared to healthy peers. The present study aimed to examine rates and patterns of tobacco use, marijuana use, and binge drinking in AYAs with inflammatory bowel diseases. We expected that substance use would be associated with poorer physical health, psychosocial functioning, and disease management. Methods: One hundred thirty-two AYAs completed a single set of surveys assessing demographics, disease activity, healthcare utilization, health-related quality of life (HRQoL), inflammatory bowel disease-specific self-efficacy, adherence barriers, disease management skills, and substance use in the last 30 days (eg, tobacco use, marijuana use, binge drinking). Exploratory cluster analyses, followed by chi-square tests and analyses of variance examined patterns of substance use and correlates of cluster membership. Results: Four patterns emerged from the sample: Global Users (n = 17), Marijuana Users Engaging in Binge Drinking (n = 18), Exclusive Binge Drinkers (n = 21), and Global Abstainers (n = 76). Groups differed by age, gender, disease activity, healthcare utilization, HRQoL, self-efficacy, and adherence barriers with medium and large effect sizes (P < .05). Conclusions: Older age, male gender, active disease, at least 1 hospitalization in the past year, low self-efficacy, low HRQoL, and high adherence barriers were significantly more likely for those reporting multisubstance use. In addition, all those reporting both marijuana use and binge drinking also reported tobacco use. Future research ought to examine these associations longitudinally and throughout the transition to adult care.

关键词： RASSF1A   p14   ARF   Methylation-specific PCR   Inflammatory bowel disease   Colorectal cancer  

摘要： Ras-related domain family member 1 transcript variant A (RASSF1A) controls apoptosis and cell proliferation while p14/ARF gene has a regulatory role in cellular senescence. Failure of apoptosis and cellular senescence occurs during inflammatory bowel disease (IBD) and colorectal cancer (CRC). To reveal the role of peripheral leukocyte promoter methylation of RASSF1A and p14/ARF in the pathogenesis of IBD subtypes and CRC we investigated the methylation state of the two genes by methylation-specific polymerase chain reaction (MSP-PCR) in 60 CRC patients, 60 patients with IBD;27 with ulcerative colitis and 33 had Crohn's disease and also in 30 healthy subjects. Methylated RASSF1A and p14/ARF genes were detected in 55% and 60% of CRC, while the frequency of the methylated RASSF1A and p14/ARF genes was 23.3% and 43.3% in IBD patients and 3.3% and 13.3% in the control group (P = 0.000 each). Also, the frequency of methylated RASSF1A gene was significantly higher in ulcerative colitis than in Crohn's disease, while a non-significant frequency of methylated p14/ARF was detected between ulcerative colitis and Crohn's disease. Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location. Results suggest that methylated RASSF1A and p14/ARF are related to CRC and IBD pathogenesis and may be used as molecular biomarkers for early detection of CRC and IBD.

关键词： Inflammatory bowel disease   Thionucleosides   Drug-related side effects and adverse reactions   Leucopenia   Metabolism   Pharmacogenetics  

摘要： Thiopurines have been widely used for the maintenance of remission or steroid sparing in patients with inflammatory bowel disease. However, potential drug-related adverse events frequently interfere with their use. Indeed, drug withdrawals associated with adverse reactions have been reported in approximately 25% of patients. To balance the efficacy, safety, and tolerability of thiopurines, regular monitoring of biomarkers (complete blood cell count, liver function test, and metabolic profiles), steady dose escalation, and pretreatment thiopurine S-methyltransferase (TPMT) genotype screening have been routinely recommended. However, the complex thiopurine metabolic pathway and individual differences attributed to pharmacogenetic diversity limit the effectiveness of these strategies in the optimization of thiopurine therapy. Recently, in an effort to facilitate more accurate and personalized prediction of thiopurine response or toxicity, novel genetic markers including NUDT15 and FTO genes were discovered. These discoveries are remarkable because TPMT screening has minimal efficacy for predicting myelosuppression especially in Asian populations, despite the fact that thee populations have a higher frequency of myelosuppression than Western populations. This review focuses on the current understanding of the metabolic pathway and the pharmacogenetics of thiopurines and suggests a personalized preventive strategy against potential adverse drug reactions to optimize their therapeutic application.

关键词： Inflammatory bowel disease   Immune mechanisms   Pathologic evaluation   Neoplastic risk  

摘要： The inflammatory mechanisms that lead to the clinical symptoms that are grouped under the term inflammatory bowel disease have not been fully characterized. Although a specific mechanism has not been identified, inflammatory bowel disease is believed to be related to an inability by the immune system to shut active inflammation within the intestine. Many contributing factors have been implicated in the disease process. Based on population studies, patients with inflammatory bowel disease have an increased risk for neoplastic development. Although no specific immune cell has been implicated in neoplastic development within this patient population, several immune cells have been implicated as possible etiologies in inflammatory bowel disease. In this review, we will review the clinical evidence about the risk for neoplastic development in inflammatory bowel disease and the current clinical guidelines to survey this patient population. We will also review the pathologic assessment of inflammation within this patient population as well the underlying immune cells and cytokines that have been implicated in the etiology of inflammatory bowel disease.

关键词： depressive symptoms   gut-brain-axis   inflammation   inflammatory bowel disease   microbiome  

摘要： Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.

摘要： This study aimed at exploring the link among individual concentrations, pharmacokinetic parameters, and the probability of relapse after de-escalation in a real-world prospective cohort of patients with inflammatory bowel disease (IBD) who underwent infliximab treatment de-escalation. Ninety-one patients were included. A time-varying compartment model was used to estimate individual pharmacokinetic parameters and trough concentrations. A Cox model was implemented to explore the parameters influencing the probability of relapse after de-escalation. Volume, clearance, and trough before and after de-escalation were linked to the relapse risk at the univariate step. Independent predictors of relapse were tobacco use and/or ulcerative colitis (P = 0.0093), a higher C-reactive protein (CRP;P = 0.00064), and an infliximab trough < 2.4 mu g/mL after de-escalation (P = 0.0001). Patients with trough > 5.7 mu g/mL are eligible to de-escalation, but infliximab pharmacokinetics is highly variable in time. Therefore, drug monitoring is mandatory after de-escalation to maintain trough > 2.4 mu g/mL. Clearance monitoring seems an appealing approach for patient selection and relapse prediction.

关键词： Multiple sclerosis   Depression   Information needs   Survey   Inflammatory bowel disease   Rheumatoid arthritis  

摘要： Objective: We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. Methods: We surveyed participants with MS, IBD and RA regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. Results: 328 participants provided complete responses (MS: 141, IBD: 114, RA: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%);this did not differ between groups. Conclusions: Persons affected by MS, IBD and RA are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. Practice implications: These findings can be used to design information resources to meet information needs regarding depression in MS, IBD and RA. (C) 2019 The Authors. Published by Elsevier B.V.