Patient dissatisfaction with medical therapy for chronic constipation or irritable bowel syndrome with constipation: analysis of N-of-1 prospective trials in 81 patients.
患者对药物治疗慢性便秘或肠易激综合征伴便秘的不满: 81 例患者 N-of-1 前瞻性试验分析。
- 作者列表："Basilisco G","Italian Society of Neurogastroenterology Motility (SINGEM) Study Group.
BACKGROUND:Patients with chronic constipation (CC) or with irritable bowel syndrome with constipation are often dissatisfied about their medical therapy, but their condition remains poorly defined. AIMS:To evaluate the patients' satisfaction rates and which factors predict favourable outcomes through the aggregate analysis of N-of-1 trials. METHODS:Eighty-one outpatients with CC or with irritable bowel syndrome with constipation underwent N-of-1 trials with at least a one-month cycle of effective treatment. Three primary endpoints (satisfaction with therapy, improvement after treatment and an extended satisfaction criterion including both endpoints) were adopted to define satisfaction with therapy. Dyssynergia, resting anal pressure, colonic transit time and somatisation were assessed. The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire and its Modified version (M-PAC-SYM) measured constipation severity. Straining at defecation, stool frequency and form were daily recorded. K statistics for agreement and logistic regression were used at statistical analysis. RESULTS:Satisfaction with therapy was not achieved by 43% of patients, who had a significantly lower Body Mass Index (BMI) and more severe constipation at baseline. Only the change in constipation severity according to M-PAC-SYM remained significantly associated with satisfaction with therapy (OR = 4.3; P < 0.001) at multivariate analysis. CONCLUSIONS:Satisfaction with therapy is often an unmet need for patients with CC or with irritable bowel syndrome with constipation. Lower BMI and more severe constipation are associated with worse outcome. Changes in M-PAC-SYM reflect satisfaction with therapy. ClinicalTrials.gov no. NCT02813616.
背景: 慢性便秘 (CC) 或伴有便秘的肠易激综合征患者往往对其药物治疗不满意，但其病情仍不明确。 目的: 通过 N-of-1 试验的汇总分析，评估患者的满意率和预测有利结果的因素。 方法: 81 例 CC 或肠易激综合征伴便秘的门诊患者接受了至少 1 个月周期有效治疗的 N-of-1 试验。采用三个主要终点 (治疗满意度、治疗后改善和包括两个终点的扩展满意度标准) 来定义治疗满意度。评估协同失调、静息肛门压、结肠传输时间和躯体化。便秘症状患者评估 (PAC-SYM) 问卷及其修订版 (M-PAC-SYM) 测量便秘严重程度。每日记录排便用力情况、大便次数和大便形态。统计学分析采用 K 统计学进行一致性分析和 logistic 回归。 结果: 43% 的患者没有达到对治疗的满意度，他们在基线时体重指数 (BMI) 显著降低，便秘更严重。根据 M-PAC-SYM，只有便秘严重程度的变化仍然与治疗满意度显著相关 (OR = 4.3; P
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.