Withdrawal of MTX in rheumatoid arthritis patients on bDMARD/tsDMARD plus methotrexate at target: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effect of MTX withdrawal on disease activity and remission rate in patients at target after treatment with biologic DMARDs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) plus MTX. MATERIAL AND METHODS: We searched the PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials (RCTs) on MTX withdrawal in patients with RA at target after combination therapy from inception to 7 March 2022 in order to extract data, including: the change from withdrawal in DAS28 at the endpoint; proportion of low disease activity (LDA) assessed by DAS28, Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI); proportion of remission assessed by DAS28, SDAI CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). RESULTS: Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09, 0.32, I2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to <3.2 [risk ratio (RR) 0.88 (0.80, 0.97), I2 = 0%]. However, MTX withdrawal did not decrease remission rates assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission [RR 0.90 (0.81, 1.01), 0.93 (0.77, 1.11), 0.90 (0.74, 1.11), 0.95 (0.70, 1.29), respectively]. CONCLUSIONS: Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.

Evaluation of the Current State of Chatbots for Digital Health: Scoping Review.

BACKGROUND: Chatbots have become ubiquitous in our daily lives, enabling natural language conversations with users through various modes of communication. Chatbots have the potential to play a significant role in promoting health and well-being. As the number of studies and available products related to chatbots continues to rise, there is a critical need to assess product features to enhance the design of chatbots that effectively promote health and behavioral change. OBJECTIVE: This scoping review aims to provide a comprehensive assessment of the current state of health-related chatbots, including the chatbots' characteristics and features, user backgrounds, communication models, relational building capacity, personalization, interaction, responses to suicidal thoughts, and users' in-app experiences during chatbot use. Through this analysis, we seek to identify gaps in the current research, guide future directions, and enhance the design of health-focused chatbots. METHODS: Following the scoping review methodology by Arksey and O'Malley and guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist, this study used a two-pronged approach to identify relevant chatbots: (1) searching the iOS and Android App Stores and (2) reviewing scientific literature through a search strategy designed by a librarian. Overall, 36 chatbots were selected based on predefined criteria from both sources. These chatbots were systematically evaluated using a comprehensive framework developed for this study, including chatbot characteristics, user backgrounds, building relational capacity, personalization, interaction models, responses to critical situations, and user experiences. Ten coauthors were responsible for downloading and testing the chatbots, coding their features, and evaluating their performance in simulated conversations. The testing of all chatbot apps was limited to their free-to-use features. RESULTS: This review provides an overview of the diversity of health-related chatbots, encompassing categories such as mental health support, physical activity promotion, and behavior change interventions. Chatbots use text, animations, speech, images, and emojis for communication. The findings highlight variations in conversational capabilities, including empathy, humor, and personalization. Notably, concerns regarding safety, particularly in addressing suicidal thoughts, were evident. Approximately 44% (16/36) of the chatbots effectively addressed suicidal thoughts. User experiences and behavioral outcomes demonstrated the potential of chatbots in health interventions, but evidence remains limited. CONCLUSIONS: This scoping review underscores the significance of chatbots in health-related applications and offers insights into their features, functionalities, and user experiences. This study contributes to advancing the understanding of chatbots' role in digital health interventions, thus paving the way for more effective and user-centric health promotion strategies. This study informs future research directions, emphasizing the need for rigorous randomized control trials, standardized evaluation metrics, and user-centered design to unlock the full potential of chatbots in enhancing health and well-being. Future research should focus on addressing limitations, exploring real-world user experiences, and implementing robust data security and privacy measures.

Virtual Reality or Augmented Reality as a Tool for Studying Bystander Behaviors in Interpersonal Violence: Scoping Review.

BACKGROUND: To provide participants with a more real and immersive intervening experience, virtual reality (VR) and/or augmented reality (AR) technologies have been integrated into some bystander intervention training programs and studies measuring bystander behaviors. OBJECTIVE: We focused on whether VR or AR can be used as a tool to enhance training bystanders. We reviewed the evidence from empirical studies that used VR and/or AR as a tool for examining bystander behaviors in the domain of interpersonal violence research. METHODS: Two librarians searched for articles in databases, including APA PsycInfo (Ovid), Criminal Justice Abstracts (EBSCO), Medline (Ovid), Applied Social Sciences Index & Abstracts (ProQuest), Sociological Abstracts (ProQuest), and Scopus till April 15, 2020. Studies focusing on bystander behaviors in conflict situations were included. All study types (except reviews) written in English in any discipline were included. RESULTS: The search resulted in 12,972 articles from six databases, and the articles were imported into Covidence. Eleven studies met the inclusion and exclusion criteria. All 11 articles examined the use of VR as a tool for studying bystander behaviors. Most of the studies were conducted in US young adults. The types of interpersonal violence were school bullying, dating violence, sexual violence/assault, and soccer-associated violence. VR technology was used as an observational measure and bystander intervention program. We evaluated the different uses of VR for bystander behaviors and noted a lack of empirical evidence for AR as a tool. We also discuss the empirical evidence regarding the design, effectiveness, and limitations of implementing VR as a tool in the reviewed studies. CONCLUSIONS: The reviewed results have implications and recommendations for future research in designing and implementing VR/AR technology in the area of interpersonal violence. Future studies in this area may further contribute to the use of VR as an observational measure and explore the potential use of AR to study bystander behaviors.

Giant Atrial Septal Artery Aneurysm with a Fistula to the Right Atrium.

An atrial septal artery aneurysm is a rare disease, especially accompanied with a fistula. During clinical practice, it is very important to clear the anatomical details of the coronary aneurysm before operation. In the current article, we report a giant atrial septal artery aneurysm originating from a branch of the RCA combined with a coronary right atrial fistula. The coronary artery aneurysm should be evaluated using multiple diagnostic and imaging modalities, such as echocardiography, coronary artery angiography, magnetic resonance imaging, and cardiac CT, especially three-dimensional reconstruction, which could help us to distinguish the physiological and anatomical characteristics of the CAA and fistula.

Understanding the Relationship Between Sports-Relevant Gambling and Being At-Risk for a Gambling Problem Among American Adolescents.

Fantasy sports is a growing industry with a reported 56.8 million individuals participating in the United States and Canada alone in 2015. Whereas this activity has attracted considerable public attention, little research has examined its impact on adolescents in spite of their high rates of gambling. The current study examined the relationship between regular participation (more than once a month) in sport-relevant gambling activities among adolescents and those identified as being at-risk for a gambling problem. Questionnaire responses were collected from high school students (N = 6818; 49 % male) in Wood County, Ohio, United States. Statistical analyses revealed that regular involvement in sports betting, fantasy sports betting, and daily fantasy sports betting among adolescents was associated with a higher risk of gambling problems. Further, although males participate more frequently in these activities, females who participate have a stronger likelihood of being at-risk. Students aged 16-19 years old are at a higher risk for developing a gambling problem compared to younger adolescents when regularly engaging in sports-related gambling. Moreover, regularly participating in daily fantasy sports is the strongest predictor of at-risk gambling behavior in 13-15 year old students. A hierarchical logistic regression supports that controlling for gender and age, all forms of sport-relevant gambling activities are significant predictors of at-risk gambling. This study contributes to a more comprehensive understanding of the impact of sports betting and fantasy sports on adolescents and establishes an initial step for future studies to further investigate these relationships.

[Establishment of an animal model of blunt scrotal trauma and evaluation of the lesion by conventional and contrast-enhanced ultrasonography].

OBJECTIVE: To establish an animal model of acute blunt scrotal trauma (BST) and evaluate the types of lesion by conventional ultrasonography (CUS) and contrast-enhanced ultrasonography (CEUS). METHODS: We made acute BST models in 21 healthy male New Zealand rabbits by striking 3 - 12 times the unilateral testes randomly selected with a 0. 5 kg iron ball falling freely from a 30 cm height. Then we evaluated the lesion types in the models by CUS and CEUS and verified our evaluation against pathological results. RESULTS: Acute BST models were successfully established in all the 21 animals, including contusion in 10, hematoma in 6, and rupture in 5, all confirmed by pathology. CUS clearly manifested the morphology, internal echoes, and blood flow of the testes, but had a low rate of accurate diagnosis in testicular contusion for over 6 hours as well as in complex lesions. CEUS revealed an earlier perfusion of the contrast agent and shorter arriving time (AT) and time to peak intensity ( TP) in testicular contusion than in the control testes (P <0.05) , but showed no statistically significant difference between the two groups in the half time of descending peak intensity (P>0.05). For testicular hematoma, contrast agent clearly presented its outline and a delayed low enhancement in the surrounding tissue, with significant differences from the control in AT and TTP. In severe testis rupture, occasional outflow but no perfusion of contrast agent was observed. CONCLUSION: BST models can be established in rabbits by repeated strikes of the unilateral testes lesion of contrast agent was observed. with a freely falling iron ball. Simple contusion injury can be induced by less than 6 strikes, while complex injuries can be inflicted by more than 10. Combined application of CUS and CEUS can improve the accuracy of diagnosis of different types of lesion.

Assessment of the Characteristics of Patent Foramen Ovale Associated with Cryptogenic Stroke.

OBJECTIVE: This study aims to comprehensively assess the characteristics of patent foramen ovale (PFO) in relation to Cryptogenic Strok (CS) by utilizing transesophageal echocardiography (TEE) and contrast transthoracic echocardiography (c-TTE) and to identify high-risk factors associated with PFO-related CS. BACKGROUND: Transcatheter PFO closure has demonstrated its effectiveness in preventing PFO-related CS. Therefore, understanding the specific structural attributes of PFO associated with CS is imperative. METHODS: Enrollment comprised 113 test patients who experienced CS in conjunction with PFO and 117 control patients diagnosed with migraine with PFO but without a history of stroke. The characteristics of the PFO were observed by TEE and c-TTE. A comparative analysis was undertaken to assess the variations in PFO characteristics between the test patients and controls, and to uncover the independent factors relevant to CS. RESULTS: The patients in the test group were older than the controls. Both the height and length of the PFO during Valsalva exhibited greater dimensions in the test group when contrasted with controls. Notably, the test group presented higher incidence rates of low-angle PFO (defined as an angle between the inferior vena cava (IVC) and PFO ≤ 10°) and atrial septal aneurysm (ASA) as contrasted with the control group. Right-to-left shunt (RLS) III during Valsalva demonstrated a significantly elevated occurrence within the test group as opposed to the controls. Conversely, RLS II during Valsalva exhibited a significantly higher frequency in the controls in contrast to the tests. No significant disparities were observed between the two groups with respect to RLS I during Valsalva and all grades of RLS at rest. Multivariate analysis revealed that the length of the PFO during Valsalva, the presence of ASA, RLS III during Valsalva and low-angle PFO were independent relevant factors associated with CS. CONCLUSIONS: The length of the PFO tunnel, low-angle PFO, RLS III during Valsalva and the presence of ASA were independent risk factors for CS. The combined utilization of TEE and c-TTE may prove valuable in identifying PFO patients at a heightened risk of CS and in facilitating the screening process for transcatheter PFO closure.

[Contrast-enhanced ultrasonography for detecting testicular perfusion in acute testis contusion in rabbits].

OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.

Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.

Background and purpose: FXR is a promising target for the treatment of human cholestatic liver disease (CLD). SIRT1 is a deacetylase which promotes FXR activity through deacetylating FXR. Pterostilbene (PTE) is an activator of SIRT1. However, the role of PTE in cholestasis has so far not been investigated. We examined whether PTE treatment alleviate liver injury in DDC or ANIT-induced experimental cholestasis, and explored the underlying mechanisms. Experimental approach: Mice with DDC- or ANIT-induced cholestasis were treated with different dose of PTE. Primary hepatocytes and bone marrow derived macrophages were used in vitro to assess the molecular mechanism by which PTE may improve CLD. Identical doses of UDCA or PTE were administered to DDC- or ANIT-induced cholestasis mice. Key results: PTE intervention attenuated DDC or ANIT-induced cholestasis. PTE inhibited macrophage infiltration and activation in mouse liver through the SIRT1-p53 signaling pathway, and it improved hepatic bile metabolism through the SIRT1-FXR signaling pathway. Compare with UDCA, the same doses of PTE was more effective in improving cholestatic liver injury caused by DDC or ANIT. Conclusion and implications: SIRT1 activation in macrophages may be an effective CLD treatment avenue. Using CLD models, we thus identified PTE as a novel clinical candidate compound for the treatment of CLD.

Mechanism of Fei-Xian Formula in the Treatment of Pulmonary Fibrosis on the Basis of Network Pharmacology Analysis Combined with Molecular Docking Validation.

OBJECTIVE: This study aimed to clarify the mechanism of Fei-Xian formula (FXF) in the treatment of pulmonary fibrosis based on network pharmacology analysis combined with molecular docking validation. METHODS: Firstly, ingredients in FXF with pharmacological activities, together with specific targets, were identified based on the BATMA-TCM and TCMSP databases. Then, targets associated with pulmonary fibrosis, which included pathogenic targets as well as those known therapeutic targets, were screened against the CTD, TTD, GeneCards, and DisGeNet databases. Later, Cytoscape was employed to construct a candidate component-target network of FXF for treating pulmonary fibrosis. In addition, for nodes within the as-constructed network, topological parameters were calculated using CytoHubba plug-in, and the degree value (twice as high as the median degree value for all the nodes) was adopted to select core components as well as core targets of FXF for treating pulmonary fibrosis, which were subsequently utilized for constructing the core network. Furthermore, molecular docking study was carried out on those core active ingredients together with the core targets using AutoDock Vina for verifying results of network pharmacology analysis. At last, OmicShare was employed for enrichment analysis of the core targets. RESULTS: Altogether 12 active ingredients along with 13 core targets were identified from our constructed core component-target network of FXF for the treatment of pulmonary fibrosis. As revealed by enrichment analysis, the 13 core targets mostly concentrated in regulating biological functions, like response to external stimulus (from oxidative stress, radiation, UV, chemical substances, and virus infection), apoptosis, cell cycle, aging, immune process, and protein metabolism. In addition, several pathways, like IL-17, AGE-RAGE, TNF, HIF-1, PI3K-AKT, NOD-like receptor, T/B cell receptor, and virus infection-related pathways, exerted vital parts in FXF in the treatment of pulmonary fibrosis. CONCLUSIONS: FXF can treat pulmonary fibrosis through a "multicomponent, multitarget, and multipathway" mean. Findings in this work lay foundation for further exploration of the FXF mechanism in the treatment of pulmonary fibrosis.

The prevalence of frailty in patients on hemodialysis: a systematic review and meta-analysis.

PURPOSE: Coexistence of frailty and hemodialysis is related to higher risk of hospitalization, falls and mortality. Given the potential reversibility of frailty, reaching the epidemiology of frailty in hemodialysis is of great importance. However, estimates of the prevalence of frailty in patients on hemodialysis vary widely. We tried to synthesize the existing body of literature on the prevalence of frailty in patients on hemodialysis. METHODS: We searched Pubmed, Embase, Web of Science and Cochrane for studies of the prevalence in patients on hemodialysis. The prevalence of frailty was synthesized across eligible studies using a random-effects model. We explored potential origin of heterogeneity in the estimates by meta-regression analysis. RESULTS: Prevalence range from 6.0 to 82.0% and the pooled prevalence of frailty in patients on dialysis was 34.3% (95% confidence interval (CI) 24.5-44.1%; z = 6.87; p = 0.00). The pooled estimates of prevalence for patients aged < 55, 55-65, and ≥ 65 were 56.0% (95% CI 28.9-83.2%; z = 4.04; p = 0.00), 32.3% (95% CI 22.9-41.7%; z = 6.74; p = 0.00), and 20.3% (95% CI 7.9-32.8%; z = 3.2; p = 0.00), respectively. There were no significant relationships between frailty in hemodialysis and factors such as years of publication, sample size (continuous), sample size(> 500 vs ≤ 500), diagnostic method (the Fried Frailty vs other), country (Europe & USA vs Asia) and duration of hemodialysis. CONCLUSIONS: Frailty influences almost three in ten patients on hemodialysis. Understanding the underlying pathophysiology mechanisms and weakening the impacts of frailty in patients on hemodialysis are called on to action in the future work.