The impact of medication belief on adherence to infliximab in patients with Crohn's disease.

Objective: Crohn's disease (CD) is an incurable chronic disease that requires long-term treatment. As an anti-tumor necrosis factor (TNF) agent, Infliximab (IFX) is widely used in the treatment of Crohn's disease, while the adherence is not high. The purpose of this study was to investigate the adherence to IFX among CD patients in China and evaluate the association between medication belief and IFX adherence. Methods: Demographic data, clinical information and patients' medication beliefs were collected using an online questionnaire and reviewing electronic medical records (EMRs). The Beliefs about Medicines Questionnaire (BMQ)-specific was used to assess medication beliefs which contains the BMQ-specific concern score and the BMQ-specific necessity score. An evaluation of adherence factors was conducted using univariate and multidimensional logistic regression analyses. Results: In all, 166 CD patients responded the online questionnaire among which 77 (46.39%) patients had high adherence. The BMQ-specific concern score in patients in low adherence was 30.00 and in high adherence patients was 27.50, and patients with lower BMQ-specific concern score had higher adherence (p = 0.013). The multiple regression analysis showed that the BMQ-specific concern score (OR = 0.940, 95% CI: 0.888-0.996) significantly affected the IFX adherence in CD patients. Otherwise, gender, marital status, time spent on the way (including the waiting time in infusion center) and accommodation to the center were also the influencing factors of adherence. Conclusion: The IFX adherence to CD in China was not high. Medicine concerns may be predictive factor of adherence. Education, the duration of IFX therapy and experience of adverse effects were not significantly associated with IFX adherence. By enhancing knowledge and relieving medicine concerns, we may increase patients' adherence to IFX.

Chronic inflammatory demyelinating polyneuropathy with anti-contactin-associated protein 1 antibody and bile duct hamartomas in the liver: a case report.

BACKGROUND: Autoantibodies targeting node of Ranvier proteins are rarely reported in China. CASE PRESENTATION: We present the case of a 66-year-old Chinese man who concomitantly developed chronic inflammatory demyelinating polyneuropathy with anti-contactin-associated protein 1 antibody and bile duct hamartomas in liver, which are rarely reported in China. The man presented with chronic progressive sensory and motor symptoms, bilateral periphery facial paralysis, and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study indicated demyelinating neuropathy. Enhanced magnetic resonance imaging of the liver showed diffuse intrahepatic lesions, which were considered as bile duct hamartomas in the liver. He was suspected as having chronic inflammatory demyelinating polyneuropathy and treated with intravenous immunoglobulin and prednisone. However, his condition got worse. One month later, he was diagnosed with chronic inflammatory demyelinating polyneuropathy associated with anti-contactin-associated protein 1 antibody. He received high-dose methylprednisolone, followed by standard plasma exchange and rituximab therapy. His sensory and motor manifestations were significantly improved at 1 year of follow-up. CONCLUSIONS: This case reminds clinicians to be aware of antiparanodal antibodies, which are associated with specific phenotypes and therapeutic response.

Challenging the Surge of Inflammatory Bowel Disease: The Role of the China Crohn's and Colitis Foundation in the Healthcare Landscape of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and lifelong disease, and patients must ultimately learn to live with and manage the condition. With advances in diagnostics and treatment in IBD, healthcare professionals (HCPs) and patients are now concerned with both quality of care (QOC) and quality of life (QOL). The China Crohn's and Colitis Foundation (CCCF) is committed to improving the QOC and QOL for IBD patients by garnering social resources. This paper details how CCCF has worked for better IBD management over the past 5 years. The foundation has 4 main projects: education programs for IBD HCPs and patients, support activities, public awareness and advocacy, and research programs. CCCF is an increasingly influential public welfare organization providing advocacy for IBD patients in China. The foundation is now entering the next stage of its development in pursuing professional operations and helping to solve the social problems experienced by IBD patients. The CCCF ultimately plans to pioneer reforms in China's medical system and hopefully provide a successful example of IBD advocacy for developing countries to emulate.

Patients with IBD have a more cautious attitude towards COVID-19 vaccination.

Background: To understand the awareness of COVID-19 vaccine, the willingness to vaccinate and the influencing factors of willingness to vaccinate in inflammatory bowel disease (IBD) patients. Methods: The online questionnaire was distributed to conduct a survey to analyze and evaluate the willingness, awareness and trust in vaccines of IBD patients. Bivariate analyses and logistic regression models were used to analysis influencing factors. Results: We sent the questionnaire to the WeChat group for patient management and 304 patients responded, out of which 16 respondents had to be excluded and 288 respondents were included for the analysis. Among them, 209 patients vaccinated with COVID-19 vaccine. Among the non-vaccinated 79 patients, the main reasons for their concerns were afraid of vaccination aggravating IBD and fear of adverse effects. Our results showed that IBD patients with long disease duration were more willing to receive COVID-19 vaccination (P<0.05). We also observed that a high perception of benefits and cues to action to receive the vaccine were the two most important constructs affecting a definite intention for COVID-19 vaccination (P<0.05). Conclusions: Patients with IBD have a more cautious attitude towards COVID-19 vaccination, which may lead to a higher rate of vaccine hesitancy. Further efforts should be made to protect patients with IBD from COVID-19 infections and achieve adequate vaccination coverage.

Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease.

Mental health is a significant yet overlooked aspect of inflammatory bowel disease (IBD) patient care, with challenges in determining optimal treatments and psychological health resources. The most common psychological conditions in patients with IBD are anxiety and depression. The increased prevalence of these mental disorders appeals to mental screening of each person diagnosed with IBD at initial consultation. There are simple and clinically viable methods available to screen for mental problems. Psychological methods may be as or even more significant as a therapeutic modality. Herein we discuss the three major areas of psychological co-morbidity in IBD: (1) the prevalence and risk factors associated with anxiety and depression disorders for patients with IBD; (2) diagnosis of psychological disorders for patients with IBD; (3) treatment with patients with IBD and mental disorders. The gastroenterologists are encouraged to screen and treat these patients with IBD and mental disorders, which may improve outcomes.

Medication Belief is Associated with Improved Adherence to Exclusive Enteral Nutrition in Patients with Crohn's Disease.

BACKGROUND: The prevalence of Crohn's disease (CD) has been increasing rapidly in China, and the role of exclusive enteral nutrition (EEN) in the management of adult patients with active CD is evolving. Adherence is a key factor in the effective treatment of many chronic diseases. AIM: The aim of this study was to assess adherence to EEN of CD patients and to evaluate the relationship between medication belief and EEN adherence. METHODS: A cross-sectional study was conducted, and demographic information, adherence to EEN, and beliefs about EEN were investigated. Medication belief was measured using the Beliefs about Medicines Questionnaire (BMQ)-Specific. RESULTS: In all, 131 CD patients completed the questionnaire and were enrolled in this study. The high adherence rate was 73.3% (96 of 131 patients), and we found that medication belief, residency, medical insurance, and history of enteral nutrition therapy were factors affecting EEN adherence. More patients with a high BMQ score had high adherence to EEN (n = 54, 56.2%) compared to those with a low BMQ (n = 42, 43.8%). Moreover, price, taste, storage method, portability, and purchase convenience of EEN were not associated with adherence. CONCLUSION: The adherence to EEN among patients with CD is relatively high and is related to medication belief, residency and history of enteral nutrition. The type of enteral nutrition, taste, storage, and convenience of purchase were not associated with EEN adherence. Future study is warranted to explore the possible role of improving patients' beliefs in increasing adherence.

Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis.

BACKGROUND AND AIMS: Intestinal fibrosis is a common complication of Crohn's disease [CD]. It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. METHODS: We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures [13 zones collected in five patients]. Proteins of interests were validated by immunohistochemistry [IHC] in ileal and colonic samples of stricturing CD [n = 44], pure inflammatory CD [n = 29], and control [n = 40] subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. RESULTS: Proteomic study revealed an endoplasmic reticulum [ER] stress proteins increase in the epithelium of CD ileal fibrotic strictures, including anterior gradient protein 2 homologue [AGR2] and binding-immunoglobulin protein [BiP]. This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation. CONCLUSIONS: The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.

Economic Burden and Health Care Access for Patients With Inflammatory Bowel Diseases in China: Web-Based Survey Study.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) has imposed heavy financial burdens for Chinese patients; however, data about their financial status and access to health care are still lacking. This information is important for informing patients with IBD about disease treatment budgets and health care strategies. OBJECTIVE: The aim of this study was to evaluate the economic status and medical care access of patients with IBD through the China Crohn's & Colitis Foundation web-based platform in China. METHODS: Our study was performed in 14 IBD centers in mainland China between 2018 and 2019 through WeChat. Participants were asked to complete a 64-item web-based questionnaire. Data were collected by the Wenjuanxing survey program. We mainly focused on income and insurance status, medical costs, and access to health care providers. Respondents were stratified by income and the associations of income with medical costs and emergency visit times were analyzed. RESULTS: In this study, 3000 patients with IBD, that is, 1922 patients with Crohn disease, 973 patients with ulcerative colitis, and 105 patients with undetermined colitis were included. During the last 12 months, the mean (SD) direct and indirect costs for per patient with IBD were approximately US $11,668.68 ($7944.44) and US $74.90 ($253.60) in China. The average reimbursement ratios for most outpatient and inpatient costs were less than 50%. However, the income of 85.5% (2565/3000) of the patients was less than ¥10,000 (US $1445) per month. Approximately 96.5% (2894/3000) of the patients were covered by health insurance, but only 24.7% (741/3000) of the patients had private commercial insurance, which has higher imbursement ratios. Nearly 98.0% (2954/3000) of the patients worried about their financial situation. Thus, 79.7% (2392/3000) of the patients with IBD tried to save money for health care and even delayed their medical treatments. About half of the respondents (1282/3000, 42.7%) had no primary care provider, and 52.2% (1567/3000) of the patients had to visit the emergency room 1-4 times per year for the treatment of their IBD. Multivariate analysis revealed that lower income (P=.001) and higher transportation (P=.004) and accommodation costs (P=.001) were significantly associated with the increased number of emergency visits of the patients. CONCLUSIONS: Chinese patients with IBD have enormous financial burdens and difficulties in accessing health care, which have increased their financial anxiety and inevitably influenced their disease outcomes. Early purchase of private insurance, thereby increasing the reimbursement ratio for medical expenses, and developing the use of telemedicine would be effective strategies for saving on health care costs.

Assessing Oral Medication Adherence and Identifying Predictors of Low Adherence in Chinese Inflammatory Bowel Disease Patients.

BACKGROUND: Poor medication adherence in inflammatory bowel disease (IBD) had a negative impact on disease outcomes. In this study, we aimed to determine predictors of low adherence in the Chinese IBD populations and also aimed to compare a self-reported scale to a pharmacy refill index in assessing adherence of 5-ASA and azathioprine taken by Chinese IBD patients. PATIENTS AND METHODS: Adult patients with IBD who had been taking 5-ASA or azathioprine for at least 3 months were recruited from hospital outpatient clinics. The MPR was calculated from previous six-month pharmacy refill data and the self-reported Morisky Medication Adherence Scale (MMAS-8) was issued through QR code questionnaires. Intentional and unintentional adherence scores were calculated according to specific items. Non-adherence was defined as MMAS-8 scores <6 or MPR < 0.8. RESULTS: The response rate in the IBD patients was as high as 97%. 5-ASA non-adherence rate assessed by MPR was 30% and 37% by MMAS-8, and azathioprine non-adherence rate assessed was 33% by both MPR and MMAS-8. In a linear regression analysis, MPR value was significantly correlated with MMAS-8 score in 5-ASA group (r=0.4, p=0.003), and significantly correlated with unintentional adherence score (r=0.47, p<0.001). No significant correlation was observed between MPR value and MMAS-8 score in azathioprine group. Multivariate analysis demonstrated that age (OR: 1.08; 95% CI: 1.02-1.13; P=0.0015) and previous abdominal surgery (OR: 3.18; 95% CI: 2.09-4.27; P=0.04) were associated with high medication adherence. While patients who had small intestine lesion (OR: 0.09; 95% CI: 0.01-0.17; P=0.006) were associated with low adherence. CONCLUSION: Predictors of low adherence were young age, lesions on small intestine, whereas previous abdominal surgery was a protective factor. This study also demonstrated that the MMAS-8 scale was a valid instrument for assessing 5-ASA adherence in IBD patients. Unintentional non-adherence was significantly related to the total non-adherence, which would allow to use the tool to seek ways for adherence improvement.

Beneficial effects of dual TORC1/2 inhibition on chronic experimental colitis.

BACKGROUND AND AIM: AZD8055, a new immunosuppressive reagent, a dual TORC1/2 inhibitor, had been used successfully in animal models for heart transplantation. The aim of this study was to evaluate the effects and mechanisms of AZD8055 on chronic intestinal inflammation. METHODS: Dextran sulfate sodium (DSS) - induced chronic colitis was used to investigate the effects of AZD8055 on the development of colitis. Colitis activity was monitored by body weight assessment, colon length, histology and cytokine profile analysis. RESULTS: AZD8055 treatment significantly alleviated the severity of colitis, as assessed by colonic length and colonic damage. In addition, AZD8055 treatment decreased the colonic CD4+ T cell numbers and reduced both Th1 and Th17 cell activation and cytokine production. The percentages of Treg cells in the colon were also expanded by AZD8055 treatment. Furthermore, AZD8055 effectively inhibited mTOR downstream proteins and signal transducer and activator of transcription related proteins in CD4+ T cells of intestinal lamina propria. CONCLUSIONS: These findings increased our understanding of DSS-induced colitis and shed new lights on mechanisms of digestive tract chronic inflammation. Dual TORC1/2 inhibition showed potent anti-inflammatory and immune regulation effects by targeting critical signaling pathways. The results supported the strategy of using dual mTOR inhibitor to treat inflammatory bowel disease.

Treatments for Crohn's Disease-Associated Bowel Damage: A Systematic Review.

BACKGROUND & AIMS: Despite significant advances in the treatment of Crohn's disease (CD), most patients still develop stricturing or penetrating complications that require surgical resections. We performed a systematic review of mechanisms and potential treatments for tissue damage lesions in CD patients. METHODS: We searched the PubMed, MBASE, and Cochrane databases from January 1960 to July 2017 for full-length articles on CD, fibrosis, damage lesions, mesenchymal stem cells, and/or treatment. We also searched published conference abstracts and performed manual searches of all reference lists of relevant articles. RESULTS: Mechanisms of intestinal damage in patients with CD include fibroblast proliferation and migration, activation of stellate cells, recruitment of intestinal or extra-intestinal fibroblast, and cell trans-differentiation. An altered balance of metalloproteinases and tissue inhibitors of metalloproteinases might contribute to fistula formation. Treatment approaches that reduce excessive transforming growth factor beta (TGFB) activation might be effective in treating established intestinal damage. Stem cell therapies have been effective in tissue damage lesions in CD. Particularly, randomized controlled trials have shown local injections of mesenchymal stem cells to heal perianal fistulas. CONCLUSION: In a systematic review of mechanisms and treatments of bowel wall damage in patients with CD, we found a need to test drugs that reduce TGFB and increase healing of transmural damage lesions and to pursue research on local injection of mesenchymal stem cells.

Rapid detection of aflatoxin B1 in medicinal materials of radix and rhizome by gold immunochromatographic assay.

A rapid screening of the most toxic aflatoxin B1 (AFB1) in medicinal materials of radix and rhizome was performed by an immune chromatography method for the first time. The colloidal gold immunochromatographic strip was prepared after optimization of the conjugation of gold particles with monoclonal antibody, the test line and the control line. Under optimized conditions, the detection limit of the constructed test strip was as low as 0.1 ng mL-1 and the total analysis was conducted within 15 min by naked eyes. Four kinds of medicinal materials (Gastrodia elata, Poria cocos, Bletilla striata and Radix Angelicae Dahuricae) were investigated by the strip. Various complex matrixes pay a significant influence on the feasibility and effectiveness of the strip screening in medicinal materials. Aiming to the characteristics of selected medicinal materials, the screening was successfully proceeded with extraction by 70% methanol-water as well as three-fold dilution in Gastrodia elata and Radix Angelicae Dahuricae, 70% methanol-PBS as well as four-fold dilution in Poria cocos., and 60% methanol-water as well as four-fold dilution in Bletilla striata. Among the collected 40 samples, one was found to be positive of AFB1 with level above 5 µg kg-1. The result was in a good agreement with those obtained from LC-MS/MS determination (6.12 µg kg-1). The gold immunochromatographic strip was demonstrated as a rapid, cost-effective, reliable and on-site screening technique for mycotoxins in starch and polysaccharides-rich herbal medicines.

Determination and pharmacokinetic study of guaiol in rat plasma by gas chromatography-mass spectrometry with selected ion monitoring.

Guaiol has been used for thousands of years as a traditional Uygur medicine and is the primary active component found in Ferula ferulaeoides (Steud.) Korov (F. ferulaeoides). In our present study, a rapid, selective, and sensitive method of monitoring selected ions was established based on gas chromatography-mass spectrometry. This method was optimized for the quantification and pharmacokinetic analysis of guaiol in rat plasma following oral administration of chloroform extract from Ferula ferulaeoides. Plasma was extracted using liquid-liquid extraction with ethyl acetate and was analyzed on a HP-5MS column (30 m × 250 µm × 0.25 µm) with a mass selective detector. Detection was carried out under selected ion monitoring mode, and three selected ion monitoring ions (m/z 59.1, 107.1, and 161.1 for guaiol) were used for the quantitative determination of that under investigation. The assay demonstrated excellent linearity in the range of 1-200 ng/mL (r = 0.9993, n = 8) in the case of guaiol measured in rat plasma. The limit of detection and the limit of quantification for guaiol in rat plasma were found to be 0.25 ng/mL and 1 ng/mL, respectively. Intra-day and inter-day precisions were expressed as the relative standard deviation for the method and were in the range of 97.49%-106.16% and 97.04%-105.91%, respectively. Extraction efficiencies were all determined to be >90%, and recoveries were ranged from 91.25% to 96.24%. This method has been successfully applied for the pharmacokinetic evaluation of chloroform extract isolated from F. ferulaeoides following a single oral administration dose (157.5 mg/kg) in rats. The guaiol pharmacokinetic study demonstrated that the half-life of guaiol was 9.18 ±â€¯3.75 h, the mean residence time was 9.07 ±â€¯3.86 h, the maximum guaiol concentration in the plasma was 28.63 ±â€¯6.82 ng/mL, and the maximum time guaiol was in the plasma was 0.50 h.

Correction: Inhibition of neddylation regulates dendritic cell functions via Deptor accumulation driven mTOR inactivation.

[This corrects the article DOI: 10.18632/oncotarget.9543.].

[Application of natural plant pigments in enlarged health industry].

Natural plant pigment is rich in resources, with the features of natural color and environment friendly, which has a broad space for development and market prospects. In order to further develop and utilize of natural plant pigment, this paper mainly introduces the natural plant dyes in the domains of food, cosmetics and health care products on the historical development process and their application. In addition,this paper summarizes the application of representative natural plant pigment, dyes, and prospects the market of natural plant pigment, so as to provide reference for the development of natural plant pigment in the enlarged health industry of China.

[Research progress of rapid detection of ochratoxin A and its application prospect in traditional Chinese medicine].

Ochratoxin A (OTA) is a toxic secondary metabolite mainly produced by Aspergillus and Penicillium species, with strong renal toxicity, teratogenic, carcinogenic, mutagenic effect. Studies have shown that OTA is not only widely contaminated in food and feed crops, but also has been widely contaminated in Chinese herbal medicines such as spices, licorice and so on. In view of OTA's universality and harmfulness, this paper summarizes the flow visualization test strip, microsphere, electrochemical sensor, surface enhanced Raman spectroscopy technology in OTA rapid detection, which provides reference for the research and application of high throughout detection instrument miniaturization in order to achieve OTA quick detection and simple operation.

Potential model for differential diagnosis between Crohn's disease and primary intestinal lymphoma.

AIM: To evaluate the usefulness of different parameters to differentiate Crohn's disease (CD) from primary intestinal lymphoma (PIL). METHODS: The medical records of 85 patients with CD and 56 patients with PIL were reviewed retrospectively. Demographic, clinical, laboratory, endoscopic, and computed tomographic enterography (CTE) parameters were collected. The univariate value of each parameter was analyzed. A differentiation model was established by pooling all the valuable parameters. Diagnostic efficacy was analyzed, and a receiver operating characteristic (ROC) curve was plotted. RESULTS: The demographic and clinical parameters that showed significant values for differentiating CD from PIL included age of onset, symptom duration, presence of diarrhea, abdominal mass, and perianal lesions (P < 0.05). Elevated lactate dehydrogenase and serum ß2-microglobulin levels suggested a PIL diagnosis (P < 0.05). The endoscopic parameters that showed significant values for differentiating CD from PIL included multiple-site lesions, longitudinal ulcer, irregular ulcer, and intraluminal proliferative mass (P < 0.05). The CTE parameters that were useful in the identification of the two conditions included involvement of ≤ 3 segments, circular thickening of the bowel wall, wall thickness > 8 mm, aneurysmal dilation, stricture with proximal dilation, "comb sign", mass showing the "sandwich sign", and intussusceptions (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the differentiation model were 91.8%, 96.4%, 93.6%, 97.5%, and 88.5%, respectively. The cutoff value was 0.5. The area under the ROC curve was 0.989. CONCLUSION: The differentiation model that integrated the various parameters together may yield a high diagnostic efficacy in the differential diagnosis between CD and PIL.

The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn's Disease: Experience from a Tertiary Medical Center in China.

Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn's disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P = 0.004 and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P > 0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P > 0.05). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen.

Correction: mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile.

[This corrects the article DOI: 10.1371/journal.pone.0154564.].