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.

Mean Nocturnal Baseline Impedance and Post-reflux Swallow-induced Peristaltic Wave Index Could Identify Gastroesophageal Reflux Disease but pH-Impedance Metrics Alone Might Not Correlate With Proton Pump Inhibitor Response in Chinese Patients With Typical Reflux Symptoms.

Background/Aims: Lyon consensus differentiates acid exposure time (AET) as physiological, borderline, and pathological. Mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) are believed to increase diagnostic yield of gastroesophageal reflux disease (GERD) and correlate with symptom outcome of proton pump inhibitor (PPI) treatment. We aim to explore the clinical characteristics and the correlation of pH-impedance parameters with PPI response in Chinese patients with different AET levels. Methods: We retrospectively investigated 177 patients with typical reflux symptoms who received esophageal function tests. The demographics, GERD questionnaire scores, the proportion of esophagitis and PPI responders, and manometric and pH-impedance parameters were compared among patients with AET < 4%, 4-6%, and > 6%. In patients with AET ≥ 4%, manometric and pH-impedance parameters were compared between PPI responders and non-responders. Results: Among 177 patients, 69 (39.0%) had AET 4-6%, and 53 (29.9%) had AET > 6%. The demographics, esophagogastric junction type, and occurrence of ineffective esophageal motility were similar between patients with AET 4-6% and > 6%, but different from AET < 4%. MNBI and PSPWi were different among different AET levels, but similar between PPI responders and non-responders in patients with AET ≥ 4%. Conclusions: It is reasonable to set 4% as a threshold to define pathological AET in Chinese patients. MNBI and PSPWi could identify GERD patients, but may not correlate with PPI response of Chinese GERD patients.

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.

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.

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.

Reliable and Interpretable Mortality Prediction With Strong Foresight in COVID-19 Patients: An International Study From China and Germany.

Cohort-independent robust mortality prediction model in patients with COVID-19 infection is not yet established. To build up a reliable, interpretable mortality prediction model with strong foresight, we have performed an international, bi-institutional study from China (Wuhan cohort, collected from January to March) and Germany (Würzburg cohort, collected from March to September). A Random Forest-based machine learning approach was applied to 1,352 patients from the Wuhan cohort, generating a mortality prediction model based on their clinical features. The results showed that five clinical features at admission, including lymphocyte (%), neutrophil count, C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase, could be used for mortality prediction of COVID-19 patients with more than 91% accuracy and 99% AUC. Additionally, the time-series analysis revealed that the predictive model based on these clinical features is very robust over time when patients are in the hospital, indicating the strong association of these five clinical features with the progression of treatment as well. Moreover, for different preexisting diseases, this model also demonstrated high predictive power. Finally, the mortality prediction model has been applied to the independent Würzburg cohort, resulting in high prediction accuracy (with above 90% accuracy and 85% AUC) as well, indicating the robustness of the model in different cohorts. In summary, this study has established the mortality prediction model that allowed early classification of COVID-19 patients, not only at admission but also along the treatment timeline, not only cohort-independent but also highly interpretable. This model represents a valuable tool for triaging and optimizing the resources in COVID-19 patients.

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.

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.

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.

Diagnostic value of circulating lncRNAs as biomarkers of digestive system cancers: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors. METHODS: PubMed, Embase, Cochrane Library, and Web of science were searched for relevant articles that were published before April 2019, and a meta-analysis was conducted. RESULTS: 52 studies with 63 lncRNAs were discussed in the meta-analysis. The pooled sensitivity and specificity of diagnosis were 0.80 (95% CI: 0.79-0.81) and 0.76 (95% CI: 0.75-0.77), respectively. The pooled DOR (the diagnostic odds ratio) was 15.63 (95% CI: 12.77-19.12), and the overall AUC (the area under the curve) was 0.87. Besides, subgroup analyzes showed that the DOR and AUC of large sample sizes (>80), multiple lncRNAs, serum-based lncRNAs, and downregulation group were superior to those of small sample sizes (≤80), single lncRNA, plasma-based lncRNAs, and upregulation group, respectively. The current data also highlight that the diagnostic accuracy of circulating lncRNAs in the case of colorectal cancer was higher than gastric cancer, hepatocellular carcinoma, esophageal carcinoma, and pancreatic cancer. And there is no difference in the perspective of geographical regions. CONCLUSION: The circulating lncRNAs have high diagnostic value and accuracy in digestive system cancers and may serve as potential biomarkers.

Assessing the Quality of Global Clinical Practice Guidelines on Gout Using AGREE II Instrument.

OBJECTIVE: The aim of this study was to assess the quality of global clinical practice guidelines (CPGs) on gout. METHODS: We systematically searched MEDLINE, CBM (Chinese Biomedical Literature database), GIN (Guidelines International Network), NICE (National Institute for Health and Clinical Excellence), NGC (National Guideline Clearinghouse), WHO (World Health Organization), SIGN (Scottish Intercollegiate Guidelines Network), DynaMed, UpToDate, and Best Practice databases from their inception until January 2017 to identify and select CPGs related to gout. Two reviewers independently assessed the eligible gout CPGs using the AGREE II instrument. RESULTS: We evaluated 15 CPGs published between 2007 and 2017, produced by 13 different developers. Quality of evidence and strength of recommendations were presented in 14 (93%) and 13 (87%) CPGs, respectively. The mean scores (±SD) for each AGREE II domain were as follows: (i) scope and purpose: 75% (±17%), (ii) stakeholder involvement: 39% (±19%), (iii) rigor of development: 43% (±17%), (iv) clarity and presentation: 82% (±14%), (v) applicability: 31% (±12%), and (vi) editorial independence: 23% (±29%). CONCLUSIONS: The quality of gout CPGs was suboptimal, and various incompatible grading systems of quality of evidence and strength of recommendations were used. The use of a standardized international grading system is essential to ensure high methodological quality of gout CPGs. Tools such as AGREE II could substantially improve the development and update of future gout CPGs.

Recommendations in clinical practice guidelines on gout: systematic review and consistency analysis.

OBJECTIVES: To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines. METHODS: We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed. RESULTS: A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation. CONLUSIONS: A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.

Quality appraisal of clinical practice guidelines for diabetes mellitus published in China between 2007 and 2017 using the AGREE II instrument.

OBJECTIVE: The aim of this study was to systematically evaluate the quality of the clinical practice guidelines (CPGs) for diabetes mellitus published in China over the period of January 2007 to April 2017. METHODS: We searched the China National Knowledge Infrastructure, Chinese Biomedical Literature database, VIP database and WanFang databases and guideline websites for CPGs for diabetes mellitus published between January 2007 and April 2017 in China. Two reviewers independently screened the literature according to the inclusion and exclusion criteria and extracted data. We used the the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool (Canadian Institutes of Health Research, Ottawa, Canada) to evaluate the quality of the included guidelines, calculated the scores of each domain and evaluated the consistency among the assessors via use of the intragroup correlation coefficient. And then we compared the results with Chinese CPGs and international CPGs. We conducted a subgroup analysis based on different classification criteria and compared scores of each domain subgroup analyses. RESULTS: A total of 98 guidelines were identified. The correlation coefficient within the group was 0.93, suggesting that the consistency between the evaluators was good. The scores of the six domains of AGREE II were described in median (IQR) as follows: scope and purpose 53.7 (50.0-59.7), stakeholder involvement 31.5 (27.3-37.0), rigour of development 19.1 (15.3-22.2), clarity of presentation 59.3 (50.0-64.8), applicability 18.1 (13.9-25.7) and editorial independence 0.0 (0.0-0.0). The mean score in each domain of quality of Chinese diabetes CPGs was lower than that of CPGs published worldwide but higher than the mean score of Chinese guidelines of all topics. A funding source, the updated version, organisation and publishers of the guidelines and target fields are all the factors influencing the quality of CPGs to a certain degree. CONCLUSIONS: A large number of Chinese diabetes CPGs have been produced. Their quality remain unsatisfactorily low compared with CPGs worldwide, there is still room for improvement. Chinese guideline developers should pay more attention to the transparency of methodology, and use the AGREE II instrument to develop and report guidelines.

A TSR Visual Servoing System Based on a Novel Dynamic Template Matching Method.

The so-called Tethered Space Robot (TSR) is a novel active space debris removal system. To solve its problem of non-cooperative target recognition during short-distance rendezvous events, this paper presents a framework for a real-time visual servoing system using non-calibrated monocular-CMOS (Complementary Metal Oxide Semiconductor). When a small template is used for matching with a large scene, it always leads to mismatches, so a novel template matching algorithm to solve the problem is presented. Firstly, the novel matching algorithm uses a hollow annulus structure according to a FAST (Features from Accelerated Segment) algorithm and makes the method be rotation-invariant. Furthermore, the accumulative deviation can be decreased by the hollow structure. The matching function is composed of grey and gradient differences between template and object image, which help it reduce the effects of illumination and noises. Then, a dynamic template update strategy is designed to avoid tracking failures brought about by wrong matching or occlusion. Finally, the system synthesizes the least square integrated predictor, realizing tracking online in complex circumstances. The results of ground experiments show that the proposed algorithm can decrease the need for sophisticated computation and improves matching accuracy.