Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): a study protocol for a randomized controlled trial.
团体认知行为疗法 (GCBT) 与常规治疗 (TAU) 治疗肠易激综合征 (IBS): 一项随机对照试验的研究方案。
- 作者列表："Kikuchi S","Oe Y","Sasaki Y","Ishii H","Ito Y","Horikoshi M","Sozu T","Seno H","Furukawa TA
BACKGROUND:Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS. METHODS:The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18-75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis. DISCUSSION:GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS. TRIAL REGISTRATION:UMIN, CTR-UMIN000031710. Registered on March 13, 2018.
背景: 肠易激综合征 (IBS) 是影响患者生活质量和社会功能的常见疾病。内脏焦虑目前被认为是 IBS 发病和加重的关键因素，针对内脏焦虑的认知行为疗法 (CBT) 被认为是有效的。然而，由于缺乏训练有素的治疗师、治疗所需的大量时间和相关费用，CBT 的获取受到限制。组 CBT (GCBT) 可能会解决其中的一些问题。因此，我们计划进行这项试验，以检查 GCBT 对 IBS 的疗效。 方法: 本试验为两支武装、平行组、开放标签、分层区组随机优势试验。研究组将由 112 名符合 IBS (罗马-III 或 IV 标准) 的参与者 (年龄 18-75 岁) 组成。参与者将被随机分配到 1:1 (i) 干预组: 10 周 GCBT 加治疗照常 (TAU) 或 (ii) 对照组: 等候名单 (WL) 加上 TAU。共同主要结局是 IBS 严重程度或疾病特异性生活质量从基线到第 13 周 (治疗结束后 1 个月) 的变化。GCBT 对 IBS 的疗效将通过混合效应重复测量分析来检查。 讨论: GCBT 如果被发现有效，可以解决治疗师短缺的问题，以及所需的时间和与个人 CBT 相关的费用。临床上，这些发现将有助于有效的 CBT 方案以较低的成本提供给大量心疼的 IBS 患者。从理论上讲，该结果将阐明 IBS 与心理应激的关系，并将有助于阐明 IBS 的潜在机制。 试用注册: UMIN，CTR-UMIN000031710。2018年3月13日注册。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.