Different dosages of vonoprazan for gastroesophageal reflux disease: study protocol for a pragmatic, crossover-cluster, randomized controlled trial with patient preference arms.

BACKGROUND: Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD. METHODS: This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit. DISCUSSION: This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION: https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023. PROTOCOL VERSION: February 18, 2023, Version 2.

Comparing endoscopic mucosal resection with endoscopic submucosal dissection in colorectal adenoma and tumors: Meta-analysis and system review.

AIMS: This study aimed to evaluate the safety, efficacy, and long-term outcomes of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for treating colorectal adenomas and tumors. METHODS: A systematic literature review was conducted using databases including PubMed, Web of Science, and Embase. Parameters such as number of patients or lesions, histological diagnosis, lesion size, surgery time, en-bloc resection, R0 resection, severe postoperative complications, and local recurrence were extracted and pooled for analysis. RESULTS: A total of 12 retrospective studies involving 1289 patients and 1850 lesions were included in the analysis. EMR was found to have a shorter operation time by 53.6 minutes (95% CI: 51.3, 55.9, P<0.001) and fewer incidences of severe postoperative complications such as perforation and delayed bleeding (OR = 0.40, 95%CI: 0.23, 0.71, P<0.001). On the other hand, ESD had higher rates of en-bloc resection (OR = 0.15, 95%CI: 0.07, 0.30, P<0.001) and R0 resection (OR = 0.32, 95%CI: 0.16, 0.65, P<0.001). Recurrence after EMR was found to be significantly higher than that after ESD surgery (OR = 5.88, 95%CI: 2.15, 16.07, P = 0.037). CONCLUSIONS: The study suggests that the choice of surgical method may have a greater impact on recurrence compared to the pathological type, and that ESD may be more suitable for the treatment of malignant lesions despite its higher rates of severe postoperative complications and longer operation time.

Hope During the COVID-19 Epidemic Decreased Anxiety and Depression Symptoms Mediated by Perceived Stress: Coping Style Differences Among Patients with COVID-19.

OBJECTIVE: This study aimed to investigate whether perceived stress mediated the relationship between hope and anxiety/depression symptoms among patients with COVID-19 during the epidemic. In addition, the potential moderating effect of coping styles was examined. METHODS: From February 26 to March 10, 2020, patients with COVID-19 were asked to complete a questionnaire online, which included demographic characteristics, as well as the SCL-90-Anxiety, SCL-90-Depression, Chinese Perceived Stress Scale (CPSS), Herth Hope Index (HHI), and Trait Coping Style Questionnaire (TCSQ). Hierarchical linear regression was performed to explore independent factors of anxiety/depression. A multi-group structural equation modeling with the collected data from patients in the Negative Coping style (NC) group and Positive Coping style (PC) group was used to test the hypothesized mechanism. RESULTS: In total, 382 valid questionnaires of patients were obtained, including 96 from NC patients and 286 from PC patients. In the hierarchical linear regression, hope and perceived stress were independent risk factors for both anxiety and depression in the total sample and PC group. However, hope was not independently related to anxiety/depression in the NC group. As hypothesized, the hope of patients had significant and negative indirect effects on both anxiety and depression that were mediated by perceived stress, However, the direct effect from stress on anxiety and depression was stronger for NC patients than for PC patients. Besides, hope had significant direct effects on anxiety/depression in PC patients, but not in NC patients. CONCLUSION: During the COVID-19 epidemic, perceived stress could mediate the relationship between hope and anxiety/depression symptoms among COVID-19 patients, with coping style moderating this cultivation process.

Endoscopic Delivery of Polymers Reduces Delayed Bleeding after Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

New endoscopic approaches for the prevention of delayed bleeding (DB) after gastric endoscopic submucosal dissection (ESD) have been reported in recent years, and endoscopic delivery of biodegradable polymers for iatrogenic ulcer hemostasis and coverage has emerged as one of the most promising techniques for post-ESD management. However, the comparative efficacy of these techniques remains uncertain. We performed a systematic search of multiple databases up to May 2022 to identify studies reporting DB rates as outcomes in patients undergoing gastric ESD who were treated with subsequent endoscopic management, including endoscopic closure (clip-based methods and suturing), PGA sheet tissue shielding, and hemostatic powder/gel spray (including polymeric sealants and other adhesives). The risk ratios (RRs) of delayed bleeding in treatment groups and control groups were pooled, and the Bayesian framework was used to perform a network meta-analysis (NMA). Among these studies, 16 head-to-head comparisons that covered 2742 lesions were included in the NMA. Tissue shielding using PGA sheets significantly reduced the risk of DB by nearly two thirds in high-risk patients, while hemostatic spray systems, primarily polymer-based, reduced DB in low-risk patients nine-fold. Researchers should recognize the essential role of polymers in the management of ESD-induced ulcers, and develop and validate clinical application strategies for promising materials.

Impact of shift work on irritable bowel syndrome and functional dyspepsia: A meta-analysis.

BACKGROUND: The possible association between shift work with irritable bowel syndrome (IBS) and functional dyspepsia (FD) remains controversial. The purpose of the study is to conduct a meta-analysis to explore the potential association between shift work with IBS/FD. METHODS: We searched relevant observational studies on Medline (PubMed) and Embase until June 30, 2021. Two different investigators extracted data and assessed the quality of each study independently. The meta-analysis was used to evaluate the pooled odds risk (OR) between shift work and IBS/FD. RESULTS: Eight studies were included ultimately. Shift workers were more likely to suffer from IBS. The OR of shift work was 1.81 (95% confidence interval 1.42; 2.32) with low heterogeneity (P < .05, I2 = 0%) for IBS. However, no evidence of the association was observed between shift work and the risk of FD. The OR of shift work was 0.87 (95% confidence interval 0.62; 1.23) (P > .05) for FD. CONCLUSIONS: There was a positive association between shift work and IBS. The prevalence of IBS was 81% higher among shift workers than among non-shift workers. Shift work was probably a risk factor for IBS. The low heterogeneity supports the reliability of the results. However, there was no significant association between shift work and FD. The strength of the evidence was limited and further prospective cohort studies were needed.

Self-Assembly of Ultrafine Fibers with Micropores via Cryogenic Electrospinning and Its Potential Application in Esophagus Repair.

Electrospinning (e-spinning) has been widely applied to fabricate flat films accumulated by microfibers for tissue engineering. In order to acquire an uneven surface morphology, two methods have been applied traditionally. The first uses a designed receiving substrate, which is stable, but suppresses the flexibility. The second uses dual solvents to achieve bimodal distribution of the fiber diameter. However, the bimodal fiber diameter causes inhomogeneity. To solve these challenges, cryogenic electrospinning, using a flat substrate and a single solvent, was performed in this study to obtain uneven films. By applying a low temperature to the flat receiving substrate, uneven e-spun films with wall-like structures were achieved through the self-assembly of uniform filaments. In addition, the wall-like structures enhanced the mechanical properties of the e-spun films. Moreover, the cryogenic e-spinning produced micropores on the fiber surface, which have the potential to promote esophageal epithelial cell adhesion, proliferation and differentiation.

Major Impact of Coping Styles on Anxiety and Depression Symptoms in Healthcare Workers During the Outbreak of COVID-19.

Background: In the early days of COVID-19 outbreak, the normally orderly health system was severely challenged by large numbers of feverish patients and shortage of healthcare workers. The outbreak played a harmful role in the mental health of these healthcare workers. Objective: We aim to assess the prevalence of moderate or severe anxiety and depression symptoms (ADSs) of healthcare workers in different regions during COVID-19 disaster and identify the potential risk factors. Methods: We did a cross-sectional study on ADS of healthcare workers in epicenter-Hubei province and regions in lower epidemic-other provinces by questionnaire online. The data of ADS, the demographic characteristics, occupational exposure, physical condition, family situation, and coping styles were collected and analyzed. Results: A total of 24.68% of the respondents had experienced moderate or severe ADS. Moderate or severe ADSs were in a higher prevalence in Hubei (32.39%) than other provinces (18.22%). Suspicious symptoms on their own and in family members were independent risk factors of moderate or severe ADS of all health workers. Working on the frontline was the independent risk factor for participants in Hubei province, whereas quarantine was the independent risk factor for those in other provinces. Moreover, among all participants, those with negative coping style were more than four times more likely to have moderate or severe ADS than those with positive coping style. Conclusion: Moderate or severe ADSs were in a higher prevalence in healthcare workers of Hubei province during COVID-19 outbreak. The coping style may have major impact on ADS in such situation.

Arthroscopic Treatment of Calcific Tendinitis of Gemellus Superior and Gemellus Inferior: A Case Report and Literature Review.

BACKGROUND: Tendon calcification is a common disease, and it could happen in the tendons of the shoulder, wrist, etc. However, tendon calcification in the superior and inferior gemellus is rare, and in this region is likely to be misdiagnosed. CASE PRESENTATION: Here, our case report first reported a 53-year-old female patient with an unusual case of calcific tendinitis of the gemellus superior and gemellus inferior muscles. The patient presented with severe pain in the right hip and lower extremities, not relieved using nonsteroidal anti-inflammatory drugs (NSAIDs). The preoperative physical examination indicated an abnormality in the hip joint. Preoperative imaging confirmed the results of the physical examination and showed a right hip lesion. We did not make a definite diagnosis preoperatively but considered that the patient might have an osteochondroma. However, surgical findings indicated that the lesion was not in the hip capsule on subsequent arthroscopic surgery, which suggested that the preoperative diagnosis might be wrong. We opened the posterior capsule and found a "toothpaste-like" lesion in the superior and inferior gemellus muscles' tendon. We thought this might be the calcified tendon. Then the arthroscopic surgery was finished to remove the lesion, and the removed tissue was sent to the pathology department for pathological examination. The pathological report confirmed the diagnosis of the calcified tendon. Postoperative follow-up was conducted. The effect of the operation was noticeable. Postoperative symptoms were relieved. CONCLUSIONS: Calcification of the tendons of the superior and inferior gemellus muscles can be easily misdiagnosed, and the disease can be treated minimally with arthroscopy.

Resolvin D1 ameliorates hepatic steatosis by remodeling the gut microbiota and restoring the intestinal barrier integrity in DSS-induced chronic colitis.

BACKGROUND AND PURPOSE: The maintenance of intestinalmucosalbarrier function plays an important role in hepatic steatosis. Increasing evidence has shown that resolvin D1 (RVD1) exerts a potential effect on hepatic steatosis. The aims of this study were to explore the mechanisms of RVD1 on hepatic steatosis based on the gut-liver axis and intestinal barrier function. EXPERIMENTAL APPROACH: We established a DSS-induced chronic colitis model to evaluate hepatic steatosis. RVD1 was administered i.p. during the last 4 weeks. The colon and liver samples were stained with hematoxylin and eosin for histopathological analysis. The expression levels of intestinal tight junction genes and inflammatory genes were determined by quantitative PCR. The serum levels of glucose, cholesterol, triglycerides and LPS were measured, and the gut microbiota was analyzed by 16S rRNA gene sequencing. KEY RESULTS: RVD1 prevented weight loss, histopathological changes, and elevated levels of inflammatory cytokines. Moreover, RVD1 administration attenuated DSS-induced hepatic steatosis and inflammatory responses in mice. In addition, RVD1 improved intestinal barrier function by increasing levels of tight junction molecules and decreasing the plasma LPS levels. The RVD1-treated mice also showed a different gut microbiota composition compared with found in the mice belonging to the DSS group but similar to that in normal chow diet-fed mice. CONCLUSIONS AND IMPLICATIONS: RVD1 treatment ameliorates DSS-induced hepatic steatosis by ameliorating gut inflammation, improving intestinal barrier function and modulating intestinal dysbiosis.

Resolvin D1 Prevents Epithelial-to-Mesenchymal Transition and Reduces Collagen Deposition by Stimulating Autophagy in Intestinal Fibrosis.

BACKGROUND: Intestinal fibrosis is the most common complication of inflammatory bowel disease; nevertheless, specific therapies are still unavailable. Resolvin D1 (RvD1), a typical endogenous ω-3 fatty acid-derived lipid mediator, has attracted wide attention due to its remarkable anti-fibrosis effects. However, the efficacy and mechanisms of RvD1 in intestinal fibrosis remain unclear. AIM: To investigate the protective effect of RvD1 in a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and explore the molecular mechanisms underlying its anti-fibrotic effect. METHODS: A DSS-induced intestinal fibrosis model and intestinal epithelial-to-mesenchymal transition (EMT) model were used to observe the efficacy of RvD1, and fibroblasts were stimulated with conditioned medium with or without TGF-ß1 to investigate the probable mechanisms of RvD1 in intestinal fibrosis disease. RESULTS: Intestinal fibrosis was effectively alleviated by RvD1 in a DSS-induced model, both preventively and therapeutically, and autophagy inhibition-induced EMT in intestinal epithelial cells was significantly suppressed in vivo and in vitro. Furthermore, RvD1 reduced epithelial cell EMT paracrine signaling, which promoted the differentiation of local fibroblasts into myofibroblasts. CONCLUSIONS: Our results suggested that RvD1 reduces autophagy-induced EMT in intestinal epithelial cells and ameliorates intestinal fibrosis by disrupting epithelial-fibroblast crosstalk.

Nocebo response intensity and influencing factors in the randomized clinical trials of irritable bowel syndrome: A systematic review and meta-analysis.

Objective: To estimate the magnitude of the nocebo response and explore its influencing factors in irritable bowel syndrome (IBS). Methods: The PubMed, Embase, and Cochrane Library databases were searched up to March 2021. We performed a random effects meta-analysis of the proportion of adverse events (AEs) in placebo-treated patients with IBS who are involved in parallel-designed, randomized, placebo-controlled trials investigating pharmacological interventions and evaluated the effect of trial characteristics on the magnitude of the nocebo response rate. Results: A total of 6,107 studies were identified from the databases. After evaluation, 53 met the eligibility criteria and were included. The overall pooled nocebo response rate was 32% (95% CI: 26-38%). The most commonly reported AEs were headache (9%), nasopharyngitis (7%), abdominal pain (4%), and nausea (4%). The nocebo response rate was low compared with that in the treatment group applying probiotics, antispasmodics, and Traditional Chinese medicine, but high compared with that in antibiotic treatment group. The nocebo rate in patients using diaries to record AEs was lower than the average, and was higher in patients recording through checkup. Discussion: Patients with IBS have significant nocebo response intensity in clinical trials. Based on findings in this study, we recommend the researchers pay attention to the common AEs and carefully analyze the relation to the intervention.

Risk factors for depression and anxiety in healthcare workers deployed during the COVID-19 outbreak in China.

PURPOSE: This study was conducted to evaluate the status of depression and anxiety of healthcare workers and to explore the risk factors during the outbreak of COVID-19 in China. METHODS: A cross-sectional study was designed using convenience sampling to obtain a sample of healthcare workers. A structured questionnaire was designed to collect the information of the basic characteristics, workload, and the health condition. Burnout, coping style, anxiety, and depression were measured by specific scales. Multiple logistic regression model was performed to explore the risk factors of anxiety or depression. RESULTS: There were 902 questionnaires received between February 9, 2020 and February 11, 2020. The proportion of healthcare workers with symptoms of moderate/severe anxiety and moderate/severe depression were 16.63% and 18.29%, respectively. There were 24.50% healthcare workers experiencing moderate/severe anxiety and depression at the same time. The increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, having family member needs to be taken care of, negative coping style, and job burnout were the independent risk factors of anxiety. Furthermore, the increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, negative coping style, and job burnout were the independent risk factors of depression. CONCLUSION: More attention should be paid to the mental health of frontline healthcare workers at the outbreak of COVID-19 in China. Taking steps to reduce the intensity of the work and burnout will be effective to stabilize the mental state of them.

Alternation of the Autonomic Nervous System Is Associated With Pulmonary Sequelae in Patients With COVID-19 After Six Months of Discharge.

Previous studies suggest that autonomic dysfunction is associated with disease severity in acute phase in patients with coronavirus disease 2019 (COVID-19). However, the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 is unknown. We conducted a prospective study to investigate the association between autonomic dysfunction and pulmonary sequelae in patients with COVID-19 discharged for 6 months. We included 40 eligible participants and collected the following indicators: heart rate variability (HRV), pulmonary function tests (PFTs), lung X-ray computed tomography (CT), routine blood parameters, liver function parameters, and lymphocyte subsets. We found that at 6 months post-discharge, HRV still had a tight correlation with pulmonary fibrosis. There was a significant difference in HRV between patients with and without diffusion dysfunction, but HRV did not differ between patients with or without ventilatory dysfunction. Diffusion dysfunction and pulmonary fibrosis were tightly associated, and HRV index changes in patients with diffusion dysfunction had the same trend as that of patients with pulmonary fibrosis. They had a lower standard deviation of NN intervals (SDNN), the standard deviation of the average NN intervals (SDANN), and the triangular index, but a higher ratio between LF and HF power (LF/HF). In addition, WBC, neutrophils, and CD4/CD8 were correlated with pulmonary fibrosis and HRV. We concluded that autonomic dysfunction is closely associated with pulmonary fibrosis and diffusion dysfunction, and immune mechanisms may potentially contribute to this process.

COVID-19 Outbreak Can Change the Job Burnout in Health Care Professionals.

Background: The outbreak of COVID-19 in China was a sudden bio-disaster, which may bring a negative impact on the job burnout of health care professionals (HCPs). Objective: We aim to find out the association factors, especially those closely related to this outbreak, of job burnout in Chinese HCPs. Method: The cross-sectional survey about HCPs' job burnout based on a network platform was conducted in high and low infection regions during the COVID-19 outbreak in China. The demographic characteristics, medical-work-related factors, risk of getting infected due to occupational exposure, and family factors were collected by the self-reported questionnaire. The Chinese version of the Maslach Burnout Inventory (CMBI) and the Trait Coping Style Questionnaire (TCSQ) were employed in this study to evaluate the job burnout and coping style, respectively. Furthermore, statistical analysis was done to find out the associated factors of job burnout. Results: We collected 880 complete questionnaires from doctors and nurses from February 9, 2020 to February 11, 2020. In this study, the positive rates of three dimensions of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) and overall burnout were 9.09, 50.57, 56.59, and 73.98%, respectively. After the statistical analysis, we found that several factors can independently affect the dimensions. Working in the high infection region and negative coping styles can affect all three dimensions at once. More night shift quantity and having symptoms could increase emotional exhaustion and depersonalization, while higher work intensity and senior title could increase emotional exhaustion and reduce personal accomplishment, respectively. Conclusion: The rate of moderate and severe burnout had increased due to the outbreak. More attention should be paid to burnout in HCPs, especially those with negative coping. There were some potential ways to reduce burnout, such as reducing their workload and providing better protection from the virus.

Impact of Clinical Outcome Measures on Placebo Response Rates in Clinical Trials for Chronic Constipation: A Systematic Review and Meta-analysis.

OBJECTIVES: Chronic constipation (CC) is a recurrent functional bowel disorder worldwide. The purpose of this study is to examine its pooled placebo response rate and compare placebo response level in randomized controlled trials (RCTs) with different endpoint assessments. METHODS: PubMed, Cochrane Library, and Embase were electronically searched for therapeutic RCTs of CC with placebo control. Data extraction and assessment of risk of bias were performed independently by 2 reviewers. All the statistical calculation and analysis were performed using R 3.6.0. Our protocol has registered in PROSPERO with registration number: CRD42019121287. RESULTS: There were 46 studies included with 5,992 constipated patients allocated to the placebo arm in total. The pooled placebo response rate was 28.75% (95% confidence interval: 23.83%-33.67%) with significant heterogeneity among trials ((Equation is included in full-text article.)= 93.6%). Treatment efficacy assessed using subjective improvement had a significantly higher placebo response rate than that assessed with improvement in complete (spontaneous) bowel movements or composite improvement (41.40% vs 18.31% or 20.35%, P < 0.001). According to the results of meta-regression, active treatment and endpoint assessment were most likely to lead to the huge heterogeneity among studies. DISCUSSION: Patients with CC have significant response level to placebo. Based on findings in this study, we do not recommend subjective improvement as endpoint while designing therapeutic RCTs for chronic constipated patients.

Placebo response rate in patients with chronic constipation: A protocol for systematic review.

OBJECTIVE: The aim of this systematic review and meta-analysis is to calculate the pooled placebo response rate in patients with chronic constipation (CC) in randomized controlled trial (RCT) and its related factors. METHOD: This systematic review and meta-analysis will be conducted under the guidance of Cochrane Handbook. The inclusive and exclusive criteria and search strategies for PubMed, Cochrane Library, and Embase will be introduced in this protocol. Data collection, extraction, and assessment of risk of bias will be conducted independently by 2 reviewers. The pooled placebo response rate and its 95% confidence interval (95%CI) will be calculated and the heterogeneity assessment, publication bias assessment, and subgroup analysis will be performed using R 3.6.0. This study has been registered on the PROSPERO platform (CRD42019121287). RESULT: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.