It has been found in many cases that consumers are prone to exhibit impulsive buying behavior that is manifested as being immediate, emotional, and irresponsible especially under short video scenario. Supported by the customer inspiration theory, this study explores the psychological mechanism underlying impulse purchase in short videos that differentiates the traditional web shopping by the strong sense of presence in short video marketing. On the basis of a questionnaire survey and three laboratory experiments, this study examines the relationship among presence, customer inspiration, and impulse purchase intention. The empirical results point to the fact that social presence, co-presence, and physical presence have significant positive effects on impulse purchase intention, and customer inspiration mediates the effect of social presence, physical presence, and co-presence on impulse purchase intention. Furthermore, it is indicated that social and co-presence have stronger influences on impulse purchase intention than physical presence, thus proving a stronger effect of social factors on impulse purchase intention than physical factors in short video environment. The research results testify the impact of presence on consumer behavior in the upgrading short video marketing and provide valuable reference for marketing strategies to shorten consumers' decision-making time in short video purchase. In 2020, when the short video platforms, users, and advertisers were enjoying the visual and audio banquet of short videos, short video marketing was manifesting a rapid and high-quality development. Short videos have been defined as the videos that are played and pushed with high frequency on various new media platforms. Since the length of these short videos usually ranges from seconds to minutes  to changing consumption habits . Inspiration is conceptualized in classic psychology as a unique state of intrinsic motivation characterized by evocation, transcendence, and motivation in social psychology. Evocation refers to the inspiration triggered by external factors than by the recipient. Transcendence, however, describes recipient's positive sense of self-enhancement. Then, motivation happens on the moment when inspiration induces a state that is close to motivation, where the recipient feels compelled to actualize new ideas  were calculated between each item and global item score with statistical significance set at >0.5, as suggested by Churchill. The reliability values of each variable are listed in Cronbach′s α coefficients of all variables in the model are >0.8, and the CITC are >0.7, fully satisfying the criteria that Cronbach′s α is >0.7 and CITC is >0.5, suggesting that the reliability of the questionnaire and the internal structure consistency of variables are high.It can be seen from the reliability analysis that the Validity analysis is to test the rationality and validity of the questionnaire. The high validity level indicates that the measurement results are in good agreement with the measurement targets. In this study, the rationality and validity of the questionnaire were tested through construct validity  that refers to the extent of consistency between the theory and the data. Convergent validity is to assess whether the data of items in one dimension point to the same variable and correlations between different items are high. The discriminant validity refers to the assumption that the items having no correlation with the variables do have no correlation with the variables. Furthermore, the factor analysis was conducted in this study to evaluate the construct validity of the questionnaire.p) is used to judge the adequacy for factor analysis. The results of KMO measure and Bartlett test of sphericity of each variable are listed in The Kaiser–Meyer–Olkin (KMO) measure of variables and the Barlett test of sphericity are required before the factor analysis. The KMO statistic is used to test the partial correlation between the variables. Ranging between 0 and 1, a KMO value >0.9 is considered adequate for the factor analysis. On the other hand, Bartlett test of sphericity is used to assess the independence between the variables. The significance of probability  was used to test the convergent validity of the model. The results of the measurement model are listed in In this study, the discriminant validity was tested using the method of AVE, in which when the square root of AVE  method to test the mediating effect by constructing the structural equation model. Model 1, which includes exogenous  and endogenous variables (impulse purchase intention), is to verify Hypotheses H1a, H1b, and H1c. The results are listed in It can be seen from the results that the social presence has a significant positive impact on impulse buying intention, which supports Hypothesis H1a and is consistent with conclusions from the prior studies that social presence directly promotes impulse buying  may produce stronger impact on impulsive purchase than physical factors . It also confirms the findings in the prior studies that the most obvious inferiority of e-commerce to traditional face-to-face business is the absence of human feeling  and z ≥ 1.96, indicating a mediating effect, and Hypothesis H2b holds. Finally, the non-standard indirect effect of Model 4 shows 0 < lower < upper (0 <0.278 <0.579) and z ≥ 1.96, so the mediating effect exists and Hypothesis H2c proves true.Models 2–4 are constructed to test Hypotheses H2a, H2b, and H2c. Model 2 includes social presence (exogenous variable), customer inspiration (mediating variable), and impulse purchase intention (endogenous variable); Model 3 includes co-presence (exogenous variable), customer inspiration (mediating variable), and impulse purchase intention (endogenous variable); and Model 4 physical presence (exogenous variable), customer inspiration (mediating variable), and impulse purchase intention (endogenous variable). Bootstrapping technique and product of coefficients methods were employed to calculate the mediating effect. The results are listed in According to the results of this empirical study, inspiration plays a mediating role in the impact of physical presence, social presence, and co-presence on impulse buying, which confirms Hypotheses H2a, H2b, and H2c. As addressed by the previous studies, inspiration is in the position to change views and perceptions  is significantly higher than that by video A2 . So, the manipulation on social presence was successful.Sixty subjects were recruited on the Credamo platform, including 16 males and 44 females, who were randomly divided into two groups, and asked to watch videos A1 and A2. Afterward, they were required to fill out the questionnaire for social presence. Independent sample t-test indicates that the co-presence  produced by watching video B1 is significantly higher than that produced by video B2 . Thus, the manipulation of co-presence was successful.Likewise, another 60 subjects, 17 males and 43 females, were recruited on the Credamo platform and randomly divided into two groups. After watching videos B1 and B2, their co-presence was measured by the relevant questionnaire. Independent sample t-test of the data from physical presence questionnaire shows that video C1  triggers higher physical presence than video C2 does , so the physical presence was successfully manipulated.The same procedure was repeated by the researchers to recruit another 60 participants  on the platform as the subjects of test on physical presence. Also, they were divided into two groups, and watched videos C1 and C2, respectively. Consequently, the independent sample Study 2 aims to verify the positive impact of social presence on impulse purchase intention in short video context and the mediating effect of customer inspiration.vs. low) was designed as follows:Videos in Group A in the pretest were selected as the short video material in Study 2. Based on the experimental procedure suggested by Rook and Fisher , a singlExperimental situation: You are going to buy a pair of socks online.Financial condition: Currently your spare money for living is 500 yuan, and still have 5 days to go before the 2000 yuan for living expenses next month added to your account.Shopping discovery: You are to buy socks introduced in a short video before you happen to see another video about a fascia gun, a kind of vibration massage device to relax muscles. You have been longing to have such a gun, and the present discount price for sales is 299 yuan.The fascia guns in video A1 and video A2 were exactly the same in properties such as appearance, material, and price, but the anchor showed better communication skills in A1 than in A2. Therefore, A1 tended to motivate high social presence, while A2 low social presence. The financial constraints were designated in this scenario to highlight the conflict so that the seduced buying behavior in case of a shortage in cash can be confidently identified as impulsive purchase.A total of 150 participants  recruited on the Credamo were randomly arranged to watch videos A1 and A2 after reading the condition described in Study 2  is significantly higher than that by video A2 . The significant difference indicates a success of manipulation on social presence.We first tested whether videos A1 and A2 successfully stimulate social presence of the subjects. It is shown by a one-way analysis of variance (ANOVA) that social presence triggered by video A1  than that with low social presence  as shown in The ANOVA results show a significant higher impulse purchase intention in the group with high social presence  is significantly higher than that of the low social presence group . Then the mediating effect of customer inspiration was tested by Bootstrapping. In specific, Bootstrap procedure was performed with 5,000 samples on model 4 in which social presence was assessed as independent variable, impulse purchase intention as dependent variable, and the customer inspiration as mediating variable. The results show that the mediating effect of customer inspiration is significant (0.6428) when the 95% confidence interval does not contain 0 , which verifies Hypothesis H2a that the customer inspiration plays a mediating role in the impact of social presence on impulse purchase.A one-way ANOVA with customer inspiration as dependent variable indicates that customer inspiration of the high social presence group  was constructed.Experimental situation: You are going to buy a pair of socks online.Financial condition: Currently your spare money for living is 500 yuan, and still have 5 days to go before the 2000 yuan for living expenses next month added to your account.Shopping discovery: You are to buy a pair of socks introduced in a short video before you happen to see another video about a hoodie that is really a kind of your favorites, and the present discount price for sales is 256 yuan.The experimental design was identical to that of Study 2. In spite of the consistency of the basic properties of hoodies in videos B1 and B2, the short video anchor showed a better sense of togetherness in video B1 than in video B2. That is, video B1 stimulated high level of co-presence while B2 low level.A total of 150 participants were recruited on the Credamo platform, including 61 males and 89 females. After reading the experimental condition in Study 3, they were randomly exposed to videos B1 or B2  is significantly higher than that by video B2 , indicating that the manipulation on co-presence was successful.We firstly tested whether videos B1 and B2 successfully inspire the subjects' co-presence. A one-way ANOVA shows that the level of co-presence stimulated by video B1  in high co-presence group is significantly higher than that in the low co-presence group  = 8.71, p = 0.004). As shown in ANOVA indicates that the impulse purchase intention  in the high co-presence group is significantly higher than that in the low co-presence group . The mediating effect of customer inspiration was then tested by Bootstrapping with 5,000 samples on model 4 considering co-presence as independent variable, impulse purchase intention as dependent variable, and customer inspiration as mediating variable. The result indicates that the effect of mediation was significant (0.6126) if the 95% confidence interval does not contain 0 , which again verifies Hypothesis H2b, namely, customer inspiration acts a mediating role in the impact of co-presence on impulse purchase.First, one-way ANOVA was performed with customer inspiration as the dependent variable. The result shows that the customer inspiration  was adopted. The features of the office chairs introduced in videos C1 and C2 maintained consistent, although video C1 could more effectively arouse the sense of immersiveness than video C2. Thus, it can be asserted that video C1 and C2 stimulated high and low physical presence, respectively. A total of 160 participants recruited on the Credamo platform, including 71 males and 89 females, watched the videos and answered the questionnaire identical to that in Study 3. Screenshots of videos C1 and C2 are shown in Videos in Group C in the pretest were used as the materials in Study 4, and a single-factor experiment on physical presence  was significantly higher than that by video C2 . Such a significant difference indicates a success of manipulation on physical presence.Likewise, stimulation test on physical presence was conducted on the subjects after they had watched videos C1 and C2. A one-way ANOVA shows that the physical presence inspired by video C1  than in the low physical presence group . As shown in The ANOVA test shows a higher intention of impulse purchase in the high physical presence group  is significantly higher than that of the low physical presence group . Second, the mediating effect of customer inspiration was analyzed by Bootstrapping with 5,000 samples on model 4, taking physical presence as independent variable and impulse purchase intention as dependent variable. The result confirms a significant mediating effect (0.8653) when the 95% confidence interval does not contain 0 , which verifies Hypothesis H2c that customer inspiration plays a mediating role in the impact of physical presence on impulse buying.First, one-way ANOVA was conducted with customer inspiration as the dependent variable. It is shown that customer inspiration of the high physical presence group  Social presence, co-presence, and physical presence have significant positive impacts on impulsive purchase intention.(2) Customer inspiration plays a mediating role in the impact of physical, social, and co-presence on impulsive purchase.(3) Social and co-presence have a stronger impact on impulse purchase intention than physical presence, which confirms that social factors produce stronger influence on impulsive purchase in short video environment than physical scenes.“Short video + e-commerce” has presented a comparatively better capacity to guide shopping and marketing than graphs and text in traditional e-business. However, the previous studies on consumer purchasing decision in short video context neither clearly explain why the purchase conversion rate of short video is much higher than that of graphic mode nor clearly explain the psychological mechanism of impulsive purchase. For these reasons, this study, based on the theory of presence—a core difference between short video and traditional graphic displaying, tends to explore from the perspective of customer inspiration the specific mechanism in which the extrinsically stimulated motivation can be transformed to an instant purchasing behavior. It contributes to the theoretical field in the following two aspects:(1) By testing the direct effect of presence—namely, social presence, co-presence, physical presence—on impulse purchase in short videos, the study validates the effect of “presence,” a traditional e-commercial element, on consumer behavior in the booming short video marketing environment. The findings suggest that social presence, co-presence and physical presence have significantly positive impacts on impulse purchase intention, but the influence coefficient indicates social factors  produce stronger impact on impulse purchase than situational factors  in short video context, and thus supporting the prior studies in that the roles of physical presence, co-presence and social presence do not always correlate  This study depicts the mediating mechanism of customer inspiration between presence and customer impulse purchase in the context of short video marketing. It is apparent that short videos create a better user experience with rich and dimensional content than the traditional displaying methods such as text and graphs. The behavioral shift from being attracted to being impulsed to buy, however, requires psychological motivation. Customer inspiration involves the motivation to expand the qualities embodied in the summoned object  on customer inspiration and impulsive purchase intention based on the previous theories on inspiration and characteristics of short video. Unfortunately, despite the antecedents of customer inspiration, other possible drivers of customer inspiration deserve further research that would possibly bring new insight to short video marketing. Second, the this study mainly focuses on the behavioral outcomes from customer inspiration, but lays little emphasis on the impact of customer inspiration on emotion and attitude. Future research could investigate the relationship between customer inspiration and existing marketing constructs . Third, this study does not explore the boundary conditions for customer inspiration in short video. Although the prior studies once suggested the moderating effect of inspiration recipient's traits on customer inspiration, it is still not clear what and how the specific traits of the recipient will moderate inspiration in short video context.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.PG: conceptualization, methodology, writing—review and editing, supervision, funding acquisition, and writing—original draft. YZ: investigation and resources. YC: data curation and visualization. All authors contributed to the article and approved the submitted version.This work was supported by grant from the National Natural Science Foundation of China , Shaanxi Social Science Fund (2018S42), Shaanxi Natural Science Fund (2014JM9370), and Special Research Projects of Shaanxi Provincial Department of Education (18JK0760).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict ofinterest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Accessory spleen torsion is extremely rare, and surgery is often the emergency or elective treatment of choice.A 20-year-old female with no specific medical history presented to our outpatient clinic with a chief complaint of abdominal pain. The patient was diagnosed with accessory spleen torsion by computed tomography. However, the abdominal symptoms and inflammatory reaction based on blood tests were mild, so a conservative treatment was selected. Subsequently, blood tests were normalized, and imaging studies showed that the accessory spleen was shrinking. Contrast-enhanced examination showed contrast enhancement in a portion of the infarcted accessory spleen region, indicating that the accessory spleen torsion had been released. Surgical resection was performed to prevent possible future re-torsion and hemorrhage of the accessory spleen.The removed specimen seemed to be normal accessory spleen tissue with clear infarcted foci edges. This artery showed evidence of luminal organization and untwisting of the occluded artery.This accessory spleen torsion was treated conservatively; however, the patient was referred for surgical treatment. •Surgery is often the treatment of choice for accessory spleen torsion.•This is a rare case of an accessory spleen torsion.•It highlights both conservative and surgical management. The patient was diagnosed with acute gastroenteritis and treated conservatively with an intestinal regimen. Three days later, a computed tomography (CT) scan suggested accessory spleen torsion, and the patient was referred to our surgical department. Abdominal pain improved, and blood tests revealed hemoglobin (Hb) level was 124 g/L, CRP level was 11,300 μ0/L, and no major hematological abnormalities. An accessory spleen was visualized by ultrasonography (US) as a round mass, approximately 26 mm in diameter, caudally to the spleen, with no blood flow signal. There was also an increase in the fatty tissue hyperechoic region around the accessory spleen area, suggesting inflammation a, b. ConConsidering the risk of future re-torsion and bleeding, a prophylactic laparoscopic resection was performed in a right hemisagittal position, using a single port plus one. Intraoperative findings revealed the accessory spleen as a white nodule in the great omentum measuring approximately 20 mm in diameter. The accessory spleen was covered by the great omentum and adherent, suggesting a low risk of re-torsion. The adhesions were dissected, the vascular pattern was clipped, and the accessory spleen was removed a, b. It 3Accessory spleen is a congenital abnormality consisting of ectopic pancreatic tissue separate from the spleen The most common locations for the accessory spleen (22 %) are posteromedial to the spleen, anterolateral to the upper pole of the left kidney, and lateral, posterior, and superior to the pancreatic tail Accessory spleen torsion becomes symptomatic once the adnexa vessels are twisted, and blood flow to the accessory spleen is impaired. Unlike the gallbladder and gastrointestinal tract, the accessory spleen is a sterile organ with no adjacent organs, so it presents nonspecific symptoms  when torsion occurs 99mTc-labeled phytic acid is said to be useful in functional accessory spleen diagnosis; however, it is unlikely to be used in an emergency because the radioactive agent is not taken up by the necrotic tissue caused by the torsion Accessory spleen infarctions appear during US examinations as subcapsular and triangular hypoechoic segmental lesions due to edema and necrosis, with the base parallel to the splenic periphery and the apex oriented outwards. The affected areas show no blood flow on color Doppler US Asymptomatic accessory spleen does not require therapeutic intervention unless there is an underlying disease such as lymphoma, leukemia, thrombocytopenia, or hemosiderosis In terms of surgical technique, the free nature of the accessory spleen allows for easy dissection. Therefore, a single port or single port plus one is sufficient. We used a single port plus one in this case to prevent splenic injury due to intraoperative manipulation. The patient was positioned in the right hemisagittal position to secure an adequate visual field.4We reported a rare case of accessory spleen torsion. The treatment plan should be based on abdominal findings, blood tests, and complications. Contrast studies should be performed if electing for conservative treatment. A single port or a single port plus one is sufficient if surgery is performed.Ethics approval/consent was waived.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.MK acquired and interpreted the data and drafted the article. HT edited the article and participated in the study design and revision of the manuscript. All authors read and approved the final manuscript.Not applicable.1.Name of the registry: N/A2.Unique identifying number or registration ID: N/A3.Hyperlink to your specific registration (must be publicly accessible and will be checked): N/AMasatsugu KuroiwaThere are no conflicts of interest to declare.


Perceived trust is a key factor affecting the behavior to donate online. In order to further explore the factors and influencing mechanisms that affect the success of medical crowdfunding projects, this paper, combined with the Stimulus-Organism-Response (S-O-R) theory, introduces the mediating variable of social presence and perceived differences in trust, and constructs a model of online users’ donation behavior to medical crowdfunding projects. We collected 437 valid samples through a questionnaire survey, and processed the data with SPSS and Amos software to test and analyze the theoretical model. The research results showed that project description and user participation have a significant positive effect on social presence; project transparency and patient identity have a significant negative effect on perceived differences in trust; social presence has a positive effect on donation behavior, while the perceived difference in trust has a negative effect; social presence and perceived differences in trust play a mediating role respectively; there is no significant effect of patient status on social presence. This study further expands the application of social presence and perceived differences in trust in medical crowdfunding, and provides a theoretical basis for the success of medical crowdfunding projects. Compared with the traditional public welfare crowdfunding, the medical crowdfunding appeared under the internet background not only has the functions of traditional charity to help people in need but also has the advantages of mobilizing friends around to raise funds in a short time in terms of fundraising ability . The emeCurrently, users mostly use social media for medical crowdfunding, connecting people with unmet medical needs with charity donors . Only byGiven the above background and problems, this paper constructs an intermediary effect model through the social presence and perceived differences in trust which can identify the motivation of donation from a cognitive perspective, and deeply studies the influence mechanism in donation behavior of medical crowdfunding projects. Through empirical analysis, this paper explores the influence mechanism of online users on the donation behavior of medical crowdfunding projects and verifies the mediating roles of the social presence and perceived differences in trust, and then provides the practical theoretical basis and practical guidance for stimulating online users’ donation behavior and enhancing the vitality of the crowdfunding industry.This paper can be divided into the following parts: In section 1, the background, content, and significance of the research are presented; section 2 reviews relevant theories such as social presence, perceived differences in trust and S-O-R theory, and puts forward the research hypothesis and constructs the research model; section 3 entails the details about the “Research Methods,” especially designs the scale; in section 4, the hypothesis test and mediation effect test are carried out; and finally in section 5, the research is summarized, and the future research direction is pinpointed.Social presence was first proposed by researchers such as Professor Short at the University of Maryland , who extThe potential donors among social media users mainly learn about the detailed content of the patients by browsing the text words of donation instructions, pictures and videos released by donation platforms, etc. Detailed introduction to project content and video presentations can make donors feel high quality . TherefoHypothesis 1: The richness of project descriptions has a positive effect on social presence.Hypothesis 2: The completeness of the patient status display has a positive effect on social presence.The diffusion of medical crowdfunding projects is mainly through internet applications, and most of the donors are social media users. Users can interact through media, and this interaction and participation can be directly measured by likes, comments, and forwards . User paHypothesis 3: User participation has a positive effect on the social presence.Individual donation behavior is often referred to as the public welfare consumption behavior. Therefore, crowdfunding donors, as a special kind of consumers, also have a sense of social presence in the process of participating in crowdfunding. This paper believes that the social presence of medical crowdfunding consists of two aspects, the perception of the psychological reality of the patient when users browse the project information released by the donation platform through media such as network platforms, and the perception of the psychological reality of other donors through online interaction. That is to say, it is the psychological perception that users can produce a kind of presence with others in media such as network platforms. This perception of social presence can promote the generation of donation behavior by perceiving the presence of others . TherefoHypothesis 4: Social presence has a positive effect on donation behavior.The psychologist In the context of medical crowdfunding, the drive of trust influences investment behaviors . In termHypothesis 5: Perceived differences in trust have a negative effect on donation behavior.In general, potential donors to medical crowdfunding need to carefully check the quality of the project and judge its credibility before deciding to donate. When the quality information displayed by the platform institutions is limited, for example, the donors do not know how the funds are used, etc., it will cause the supporters of donation to have a sense of distrust . FurtherHypothesis 6: Project transparency has a negative effect on perceived differences in trust.It is worth mentioning that since there is an effect between empathy and trust , empathyHypothesis 7: The vulnerability of the patient’s identity has a negative effect on perceived differences in trust.The S-O-R (Stimulus-Organism-Response) theory, which originated from environmental psychology, was proposed by environmental psychologists Based on the above studies, it can be found that many scholars have confirmed that many online behaviors of individuals follow the dynamic process of stimulus-organism-response based on the SOR theory. Therefore, based on this theoretical model, this paper combs the psychological mechanism of Stimulus -Organism -Response (donation behavior), and verifies the mediating roles of the social presence and perceived differences in trust, and then analyzes the individuals’ donation behavior in the field of medical crowdfunding.According to the above hypotheses and the S-O-R theory, the research model of this paper is proposed, as shown in The empirical research approach is adopted in the research to test the proposed research hypothesis. The data used in the empirical research are collected from the questionnaire. The reason why we use this research approach is that it is a popular method, and its conclusions on the phenomena studied are objective and can be tested according to experience and facts.This paper will collect data by means of a questionnaire survey. The distributed questionnaire mainly includes two parts: demographic variables and variable questions. When the questionnaires were officially distributed, a total of 497 questionnaires were distributed. After excluding invalid questionnaires, 437 valid questionnaires were obtained, with a questionnaire return rate of 87.93%.The measurement question items of the relevant variables in this paper are set based on the existing research at home and abroad, referring to the relevant literature in the field of medical crowdfunding, and making appropriate modifications in combination with the research questions. The variables were measured using the Likert 5 score scale, with 1 for a strong disagreement and 5 for strong agreement. The measuring items of variables in this study are shown in This paper uses SPSS 25.0 and AMOS 25.0 to analyze the questionnaire data to verify the consistency and validity of the measurement scale. According to the test results of the scale, the overall KMO test value is 0.937, the factor loading of each item of all variables is above 0.7, the Cronbach’s coefficient of each variable is above 0.7, the CR value is all above 0.7, and most of the AVE values are above 0.5, indicating that the scale has a good internal consistency and good convergent validity. The specific test results are shown in In this paper, we also use multiple linear regression to further test the multicollinearity. The results show that the Durbin-Watson test value is 2.049 and there is no autocorrelation, and the VIF value of each variable is less than the critical value of 10, which indicates that there is no serious multicollinearity problem in this study.In the analysis based on reliability and validity, the paper uses AMOS 25.0 to build a structural equation model for confirmatory factor analysis. The results are shown in In this paper, under the premise of acceptable model fitness, the hypothesis of the model is tested, and the specific results are shown in In addition, from the analysis results, it can be seen that the patient status does not have a significant effect on the social presence, and the hypothesis H2 is not supported.This paper uses the Bootstrap function of AMOS 25.0 to conduct 5,000 repeated samplings with the confidence interval of 95% to test whether the perceived differences in trust and social presence generated by users in the process of participating in medical crowdfunding can play a mediating role. The analysis results are shown in This paper explores the internal mechanism of social presence and perceived differences in trust under medical crowdfunding. The following conclusions were drawn from this study.Firstly, social presence plays a mediating role between project description and donation behavior, and between user participation and donation behavior. The project description has a significant positive effect on the social presence, which shows that the medical crowdfunding website can make the visitor feel high quality and promote the generation of social presence by displaying rich text descriptions and pictures. Patient status has no significant effect on social presence. The reason may be that once the patient releases too much information about their own content, it will lead to an overload of browsing user information, which will not only affect their understanding of the information content, but also make them feel that their browsing freedom is restricted. The higher the user participation, the more it can promote the generation of social presence. This shows that in the Internet environment, the interaction and participation behaviors of social media users will enhance the perception of connection and existence between each other, which is conducive to the formation of social presence.Secondly, perceived differences in trust play a mediating role between project transparency and donation behavior, and between patient identity and donation behavior. The more transparent the project, the more it reduces perceived differences in trust and promotes perceived trust. This shows that the timely update of the fundraising dynamic and timely announcement of funds on the medical crowdfunding platform enable donors to have a comprehensive understanding of the project and enhance their trust. The patient identity has a negative effect on perceived differences in trust, indicating that compared with the general group, vulnerable groups can arouse the sympathy and trust of potential donors.Finally, in terms of influencing the donation behavior, social presence has a significant positive effect on the donation behavior, but perceived differences in trust have a significant negative effect. The results of this study are consistent with the conclusions of Based on the S-O-R research framework, this paper extends social presence and perceived differences in trust to the medical crowdfunding context. Moreover, compared with previous direct relationship studies, this paper constructs an intermediary effect model through the social presence and perceived differences in trust to deeply study the influence mechanism of donation behavior of medical crowdfunding projects. While exploring the influencing factors and mechanisms of donation behavior, it not only confirms the significant effect of social presence and perceived differences in trust on donation behavior, but also finds the mediating roles of them, which expands the application of these theories.On the one hand, the medical crowdfunding platform should focus on reducing perceived differences in trust and enhancing perceived trust. These platforms can pay attention to the disclosure of the project fundraising process and the use of funds while supervising and reviewing the project, and must fully display the high-quality project content to ensure that the visitors have a multi-faceted understanding and cognition of the project. On the other hand, Platform operators should focus on creating a social presence on the platform. And should pay attention to users’ needs for interaction, guide and establish a good communication and interaction mechanism between users, and continuously develop and optimize the interactive mode of the comment area to promote the improvement of users’ social presence. This can not only provide potential donors with more clues of cognition, but also make them feel more emotional value and a sense of substitution while alleviating their concerns, and stimulate a stronger sense of social presence, in order to promote the donors’ donation behavior and enhance the vitality of the relevant crowdfunding industry.The original contributions presented in the study are included in the article/Supplementary material; further inquiries can be directed to the corresponding author.TZ and QZ designed the research and wrote the manuscript. RJ and TG collected the data and offered modification suggestions. MY provided guidance throughout the entire research process. All authors contributed to the article and approved the submitted version.This research was supported by National Natural Science Foundation of China (nos. 11861071 and 71462036), Yunnan Fundamental Research Projects (nos. 202101AT070211 and 202201AT070142), and School-level Project of Yunnan University of Finance and Economics (no. 2021B02).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The 2022 European of Society of Cardiology (ESC) Guidelines on cardio-oncology, developed by the ESC Cardio-Oncology Task Force in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society, represent an essential resource for health care providers, including not only cardiologists, cardio-oncologists, and primary care physicians, but also medical oncologists prescribing cancer therapeutics that may adversely impact cardiovascular health, and ultimately cancer survivorship.Although the 2022 ESC guidelines are uniquely comprehensive in scope and represent a major overhaul of prior ESC guidelines published in 2016,In order to exemplify the conundrum posed by having discordant expert-derived guidelines, we focus here on discordance between the 2022 ESC guidelines and 2016 ASCO guidelines for monitoring of patients receiving anti-HER2 therapy, as summarized in The primary value of cardiac surveillance, whether with TTE and/or cardiac biomarkers, is to not only to confirm symptomatic cardiac therapy–related cardiac dysfunction (CTRCD), the term used by the ESC panel, but perhaps more importantly detect asymptomatic CTRCD that may trigger interrupting or even withholding anti-HER2 therapy, and/or initiating cardioprotective therapy such as beta blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. According to Table 25 of the ESC guidelines, anti-HER2 therapy should be interrupted if there is symptomatic moderate-to-severe CTRCD (as defined in Table 3), or asymptomatic CTCRD with left ventricular ejection fraction <40%. In addition, the guidelines recommend that anti-HER2 therapy be continued with guideline-directed medical therapy for asymptomatic CTRCD with a left ventricular ejection fraction of at least 40%. Although these criteria provide clear and valuable guidance regarding continuing anti-HER2 therapies in those with asymptomatic CTRCD, there remain 3 fundamental issues regarding universal screening in all cardiac risk groups and normal cardiac function at baseline for asymptomatic CTRCD.,First, the risk of CTRCD associated with anti-HER2 therapy, specifically monoclonal antibodies including trastuzumab or the trastuzumab/pertuzumab combination, is greatest when following anthracycline therapy, which are much less commonly used as adjuvant or neoadjuvant therapy for breast cancer given the comparable effectiveness of nonanthracycline regimens. For patients with a low baseline cardiovascular risk receiving nonanthracycline chemotherapy regimens, the likelihood in asymptomatic patients meeting any of the criteria for interrupting anti-HER2 therapy and/or initiating cardioprotective therapy by the 2022 ESC guidelines is very low for both localized and metastatic disease,Second, other commonly used HER2-targeted therapies such as anti-HER2 tyrosine kinase inhibitors  and antibody-drug conjugates  are also associated with very low CTRCD risk.Finally, the level of evidence supporting the specific ESC recommendations for cardiac monitoring during and in the first 12 months after HER2 therapy is low. For each guideline, the ESC panel provided a class of recommendation , and level of evidence supporting the guideline, including Level of Evidence: A , Level of Evidence: B , or Level of Evidence: C . Of the 9 recommendations applicable to cardiac surveillance in patients receiving anti-HER2 therapy, 7 are supported by consensus opinion and the lowest level of evidence (C), whereas a lower B level of evidence was cited as supporting 3 monthly cardiac surveillance using TTE. In fact, of the 156 Class 1 recommendations summarized at the end of the ESC guidelines, only 5 (3%) were supported by the highest level of evidence (Level of Evidence: A), whereas 118 (76%) were supported by expert consensus without robust data (Level of Evidence: C). This highlights the need to harvest and mine real-world data, develop prospective registries designed to address knowledge gaps, and develop traditional and pragmatic clinical trials, all of which will ultimately generate the evidence required to better inform and revise current guidelines. The ESC panel indeed recognized “gaps in the evidence”—we agree that substantial gaps exist and suggest that evaluation and validation of cardiac surveillance algorithms for the entire spectrum of anti-HER2 therapy be added as a knowledge gap and identified as a research priority. We also particularly emphasize the evidence gap and need for additional research regarding “optimal follow-up…after treatment for cancer,” especially after cardiotoxic anthracycline therapy, in which follow-up surveillance beyond 12 months after completing therapy is currently not recommended in the ESC guidelines, but risk of insidious and delayed CTRCD may be high.In conclusion, the 2022 ESC Guidelines on cardio-oncology represent an impressive and important effort for providing greater clarity in defining cardiotoxicities of emerging anticancer agents, minimizing the potential cardiovascular complications of myriad cancer therapies, and assuring healthy cancer survivorship. The authors of the guidelines and the organizations supporting their development need to be congratulated for their important efforts and encouraged to lead the charge in generating the evidence required to support and refine the current guidelines.This work was supported in part by grants from the Department of Health and Human Services and the National Institutes of Health, National Cancer Institute (P30CA196521). Dr Sparano has served as a paid consultant for AstraZeneca, Roche, and Seagen. Dr. Sahni has reported that she has no relationships relevant to the contents of this paper to disclose.


This study aims to assess the validity and reliability of the Coronavirus-Related Health Literacy Questionnaire adapted to Turkey and examine the levels of coronavirus-related health literacy among the adults.This cross-sectional study was carried out in Turkey. The tools were applied to a total sample population of 452 people. Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were calculated to determine the construct validity of the questionnaire with the IBM SPSS Amos program version 24.0.The validity and reliability analyses of the Coronavirus-Related Health Literacy (HLS-COVID-Q22) questionnaire were adapted to Turkish. Internal consistency was very high  and construct validity suggests a sufficient model fit, making HLS-COVID-Q19 a feasible tool for assessing coronavirus-related health literacy in population surveys. The findings show that the questionnaire is a valid and reliable tool consisting of 19 items and 3 subdivisions. The mean coronavirus-related health literacy score of the participants was found to be 2.92 (±0.51), meaning that it was on average. The coronavirus-related health literacy level of 18.8% of the participants was found to be ‘inadequate’ while 37.8% had ‘problematic’ and 43.4% ‘sufficient’ health literacy. The HLS-COVID-Q19-TR scores of those in the young age group (18-29 years old), married, employed, university graduates, and vaccinated against COVID-19 were found to be higher, and a statistically significant difference was found .The results of the research reveal that the HLS-COVID-Q19-TR is a valid and reliable tool. In this study, more than half of the participants were found to have “inadequate” or “problematic” coronavirus-related health literacy levels. For this reason, studies aimed at improving society's coronavirus-related health literacy should be conducted.There is now a valid tool to assess the Covid 19 health literacy level of individuals in Turkey. It will contribute to the determination of Covid 19 health literacy level in Turkey.An adequate level of health literacy helps people make informed decisions by combating misinformation about COVID-19 and supporting individuals’ self-management.


To investigate the effects of acoustic stimulation intensity on ocular and cervical vestibular evoked myogenic potential (oVEMP and cVEMP) responses elicited by air-conducted sound (ACS) in healthy children.Thirteen healthy children aged 4–10 years and 20 healthy adults aged 20-40 years with normal hearing and tympanometry were enrolled in this study. All subjects received oVEMP and cVEMP tests under different acoustic stimulation intensities . Mean n1 latency, p1 latency, interpeak latency, amplitude and response rate were investigated and analyzed.p < 0.05). Regarding cVEMP, the response rate of children decreased from 100%  to 88.46% (116 dB SPL), 53.85% (111 dB SPL) and 26.92% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 85% (116 dB SPL), 37.5% (111 dB SPL) and 7.5% (106 dB SPL). A statistically significant difference was found in amplitude at different acoustic stimulation intensities in both children and adults (p < 0.05). When stimulated by 131 dB SPL acoustic stimulation, there were lower n1 latency, p1 latency and higher amplitude in children in oVEMP and cVEMP compared with adults (p < 0.05).As the acoustic stimulation intensity decreased, for oVEMP, the response rate of children decreased from 100%  to 57.69% (116 dB SPL), 26.92% (111 dB SPL) and 11.54% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 55% (116 dB SPL), 12.5% (111 dB SPL) and 2.5% (106 dB SPL). There were lower n1 latency, p1 latency and higher amplitude in children when comparing by acoustic stimulation intensities (The response rate and amplitude of oVEMP and cVEMP in children and adults presented significant differences with a decrease in acoustic stimulation intensity. In this study, using 121 dB SPL for children and 126 dB SPL for adults during VEMP test could be regarded as safer stimulation intensities and thus reduced sound exposure. Vestibular evoked myogenic potential (VEMP) has been utilized in neuro-otology clinics as a test for evaluation of otolith function and vestibular nerves , 2. It iVestibular loss often resulted in delayed motor development and reduced quality of life in children with normal hearing . The previa ACS are objective, non-invasive and safe to perform in children as long as a safe acoustic stimulation is maintained  and 20 healthy adults  were enrolled in this study. All subjects had no history of any ear disorders and vestibular disorders, and were further checked with pure tone audiometry, acoustical immittance and otoscope tests. Each subject underwent oVEMP and cVEMP elicited by ACS. This study was approved by the institutional review board of the Xinhua Hospital of Shanghai Jiaotong University School of Medicine. Each child's parent and each adult signed the informed consent to take part in the study.A sound-proof and comfortable examination room was employed for tests. The electromyographic signals were amplified through the ICS Chartr EP 200 Evoked Potential System  for further analysis.ACS with 500 Hz short tone burst  was delivered through the inserted earphone. The band-pass filter was set at 1–1000 Hz, and the responses to 50 stimuli were averaged twice. The stimulation rate was 5 Hz, and the analysis window of each response was 50 ms. The initial acoustic stimulus used was a short tone burst, with an intensity of 131 dB SPL. The stimulation intensity was then decreased in steps of 5 dB SPL until no oVEMP or cVEMP were present. A clear and repeatable biphasic waveform comprised of peaks n1 and p1 was considered positive response, and unrepeatable biphasic waveform was considered no response. The length of time between 0 ms and the peak n1 or p1 was regarded as n1 latency or p1 latency, respectively. The duration between peaks n1 and p1 was recorded as interpeak latency, which includes n1-p1 latency and p1-n1 latency. We regarded the vertical distance of voltage between peaks n1 and p1 as the amplitude.Each subject was in the supine position during the test. Before attaching electrodes, the skin of all subjects should be cleaned with abrasive paste. Two active electrodes were positioned around 1 cm below the center of the two lower eyelids. Two reference electrodes were placed around 1–2 cm below the two active electrodes, and the ground electrode was placed on the middle of the forehead. The electrode impedance was kept below 5 kΩ. Each subject was asked to look upward at a small fixed target above 1 m from the eyes when hearing the sound through the inserted earphone . ResponsEach subject was in the supine position during the test. Before attaching electrodes, the skin of all subjects was cleaned with abrasive paste. Two active electrodes were placed on the middle and upper third of the sternocleidomastoid (SCM) muscle, and the two reference electrodes were positioned on jugular notch. The ground electrode was placed on the middle of the forehead. The electrode impedance was kept below 5 kΩ. Each subject was instructed to raise his/her head off the pillow in order to increase the tension of the SCM when the sound was presented through the inserted earphone . Responsp < 0.05 is considered significant.Data were analyzed using IBM SPSS Statistics 26.0.0. Kruskal-Wallis test was used for comparisons of n1 latency, p1 latency, interpeak latency and amplitude of oVEMP or cVEMP among different acoustic stimulation intensities. All data were expressed as mean ± standard deviation. A significance of p < 0.0001) and p1 (p = 0.010) and decreased amplitude (p < 0.0001) significantly. Whereas, no significant difference was observed in the n1-p1 latency (p = 0.418).All healthy children completed ACS-oVEMP test following different acoustic stimulation intensities, which included 131, 126, 121, 116, 111 and 106 dB SPL . Regardip < 0.0001). However, statistically significant differences were not found in terms of p1 latency (p = 0.310), n1 latency (p = 0.542) and p1-n1 latency (p = 0.826).All healthy children completed ACS-cVEMP test under 131, 126, 121, 116, 111 and 106 dB SPL acoustic stimulation intensities . Regardip < 0.0001), p1 latency (p = 0.015) and amplitude (p < 0.0001), but not in the n1-p1 latency (p = 0.690).All healthy adults presented ACS-oVEMP test induced by 131, 126, 121, 116, 111 and 106 dB SPL acoustic stimulation intensities . The resp = 0.002), no statistically significant differences were not found in terms of p1 latency (p = 0.277), n1 latency (p = 0.974) and p1-n1 latency (p = 0.190).All healthy adults completed ACS-cVEMP test induced by 131, 126, 121, 116, 111 and 106 dB SPL acoustic stimulation intensities . The resp = 0.007), but not in the p1 latency (p = 0.288), n1-p1 latency (p = 0.752) and amplitude (p = 0.807). For cVEMP, mean p1 latency, n1 latency, p1-n1 latency and amplitude were 14.96 ± 1.08 ms, 21.45 ± 1.58 ms, 6.52 ± 1.00 ms and 369.6 ± 177.9 μV for children, while 17.15 ± 1.94 ms, 24.97 ± 1.87 ms, 7.82 ± 1.37 ms and 279.5 ± 151.2 μV for adults, respectively, indicating that children had shorter latencies and lower amplitudes than that in adults. A significant difference existed between children and adults in terms of p1 latency (p < 0.0001), n1 latency (p < 0.0001), p1-n1 latency (p < 0.0001) and amplitude (p = 0.021).All children and adults presented VEMPs following 131 dB SPL acoustic stimulation . RegardiVEMPs have been widely utilized in children suspected with peripheral vestibular disorders due to early maturation of the crossed VOR and the VCR . Though In the current study, our results revealed that the response rates were 100% when stimulated by 131, 126 and 121 dB SPL acoustic stimulations in children. Compared to children, the response rates of adults were 100% under 131 and 126 dB SPL acoustic stimulations. Based upon these results, 121 and 126 dB SPL were regarded as the appropriate initial acoustic stimulation intensity for VEMPs test in children and adults, respectively. This indicated that VEMPs stimuli for children may not need to be presented adopting adults stimulation levels. As reported by Rodriguez et al., children receive around 3 dB higher peak equivalent SPL in the ear in response to acoustic stimulation due to the smaller equivalent ear canal volumes (ECV) of children compared to adults. Therefore, a 120 dB SPL acoustic stimulation intensity is recommended for VEMPs test in children with ECV below 0.8 cm, which is similar to our results , The Key International Cooperation Project of Shanxi Province (Grant No. 2020-KWZ-019), Technology Project of Shanghai Science and Technology Commission (Grant No. 21S31900600), and Clinical Research Plan of SHDC (Grant No. SHDC2022CRD013).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The 2021 American College of Rheumatology (ACR) rheumatoid arthritis (RA) guideline considers the specific context of the United States which differs from that of Saudi Arabia in many aspects that may impact recommendations. The objective of this project was to adapt a set of prioritized recommendations from the 2021 ACR guideline for the treatment of rheumatoid arthritis RA for the context of Saudi Arabia, by the Saudi Society for Rheumatology (SSR).The process followed the GRADE-ADOLOPMENT methodology, and the reporting adhered to the RIGHT-Ad@pt checklist. Working groups included a coordination group and a 19-member panel representing different stakeholder groups. The Evidence to Decision (EtD) tables included evidence on health effects from the source guideline and contextual information from the Saudi setting.The panel prioritized and adapted five recommendations from the source guideline. The process led to modifying two out of the five prioritized recommendations, all listed here. In naive patients with low disease activity, methotrexate (MTX) is conditionally recommended over sulfasalazine (SSZ) (modified direction); hydroxychloroquine (HCQ) is conditionally recommended over SSZ (unmodified). Initiation of csDMARDs with short-term glucocorticoids is conditionally recommended over csDMARDs alone in naive patients with moderate to high disease activity (modified direction). Switch to subcutaneous MTX is conditionally recommended over addition/switch to alternative DMARD(s) in patients taking oral MTX who are not at target (unmodified). Discontinuation of MTX is conditionally recommended over gradual discontinuation of the bDMARD or tsDMARD for patients taking MTX plus a bDMARD or tsDMARD who wish to discontinue a DMARD (unmodified).Rheumatologists practicing in Saudi Arabia can use the adoloped recommendations generated by this project while adopting the rest of the recommendations from the 2021 ACR guidelines.The online version contains supplementary material available at 10.1186/s41927-022-00301-y. The global prevalence of rheumatoid arthritis (RA) is estimated to be 460 per 100,000 persons  and globTreatment guidelines for RA have been developed by well-established societies such as the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) , 6. ReceThe 2021 ACR RA recommendations consider the specific context of the United States (U.S.) which differs from that of Saudi Arabia in many aspects that may impact recommendations, e.g., costs, values, and preferences. Notably, the Saudi health system currently consists of several sectors that report to different authorities and have individualized health resources such as infusion units and medication formulary. Healthcare is free for National civilians through the Ministry of Health (MoH) and university institutions. In contrast, the military staff is followed in their respective military hospitals. On the other hand, expatriates can only access hospitals of the private sector and business centers of governmental institutions through their insurance plans.Developing new guidelines is very time- and resource-intensive. A more reasonable alternative is to adapt the recommendations for the local context to ensure applicability and subsequent uptake . The objSimilar to the source guidelines, the target population are RA patients fulfilling the 2010 ACR/EULAR classification criteria . In SaudThis project was a collaborative effort between the Saudi Society for Rheumatology (SSR), ACR, and the American University of Beirut (AUB) GRADE Center. The SSR was established in 2010 to improve education, research, and patient care in rheumatology. Working groups included a coordination group and a guideline panel.The coordination group included two content experts  and three methodologists . Its primary responsibilities included oversight of the work, designing the process and methodology, coordinating the prioritization of questions, summarizing findings for the panel through the preparation of Evidence to Decision (EtD) tables, and coordinating panel meetings.The panel comprised 19 members representing the following stakeholder groups: 15 rheumatologists, one pharmacist, one patient representative, and two policymakers. The panel was balanced in gender, Saudi regions, and type of practice . It also included two international experts: the chair of the source guidelines (LF) and the chair of the 2015 ACR guideline for treating rheumatoid arthritis (JAS). Additional file The panel was involved in prioritizing questions and outcomes, providing relevant newly published studies, providing relevant contextual information, and participating in the final meeting in formulating the final recommendations.For developing these guidelines, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE)-ADOLOPMENT methodology  and the The SSR selected the 2021 ACR guideline for the treatment of RA as the source guideline. The ACR guidelines follow rigorous methods for guideline development, including generation of population, intervention, comparator, and outcomes (PICO) questions, selection of critical outcomes, systematic literature review, and conflict of interest (COI) management. Although the ACR guidelines did not address all contextual factors included in GRADE EtD tables, they addressed patient values and preferences, cost-effectiveness studies, and cost information .We used a structured and standardized process to prioritize five recommendations from the ACR guidelines. First, the coordination group asked the panelists to rate the priority of each of the original ACR recommendations based on whether the recommended intervention differed in the Saudi Arabian context (from the U.S. context) in terms of feasibility, acceptability, resource use, impact on equity and current practice. Additional file For the evidence on health effects, and as the adaptation project was launched shortly following the publication of the source guideline, we opted to use the evidence reports as published by the source guideline  and did not formally update the systematic literature review for the adaptation process. However, we solicited panelists to share any newly published relevant studies. Two methodologist members of the coordination group (SY and JK) assessed the eligibility of these studies in duplicate and independently. For eligible studies, the two methodologists abstracted data and assessed the risk of bias in duplicate and independently and updated the evidence reports accordingly.We adopted the source guideline's ratings for the importance of outcomes . For patient values and preferences, we relied on the systematic review on the topic used by the source guidelines  and the The panel relied on cost data collected from the National Unified Procurement Company (NUPCO) for the governmental sector  and the www.gradepro.org) [In the event of no update of the evidence report, we adopted the source guideline's assessments about the certainty of the evidence. For the updated evidence reports, the methodologist members of the coordination group  assessed the certainty of the evidence according to the GRADE methodology and using the GRADEpro GDT software (pro.org) . In addipro.org) , 18.www.gradepro.org), which included both information on health effects from the evidence reports and contextual information. Then, in preparation for the panel meetings, we used the PANELVoice function in GRADEpro GDT to invite panel members to review the EtDs, comment on the included information, and vote on the EtD criteria and recommendations.For each question, the coordination group developed GRADE EtD tables using the GRADEpro GDT software  disclosure of interests form  and sentBelow are the five adapted recommendations, associated remarks, and justifications. Figure The Saudi panel suggests using methotrexate (MTX) over sulfasalazine (SSZ) in DMARD-naive patients with low disease activity .Recommendation modified ; certainty of evidence unmodified.This recommendation applies to patients with low disease activity for which medication treatment is judged to be necessary.The choice should account for the patient's views on the expected benefits and harms of the respective medications.The choice should consider the availability of the medications.It is important to monitor adverse events and adjust medications accordingly.Rationale: The panel favored MTX over SSZ because of the dosing convenience of MTX (once weekly) and its lower cost compared with SSZ.The Saudi panel suggests using hydroxychloroquine (HCQ) over SSZ in DMARD-naive patients with low disease activity .Recommendation unmodified; certainty of evidence unmodified.This recommendation applies to patients with low disease activity for which medication treatment is judged to be necessary.The choice should account for the patient's views on the expected benefits and harms of the respective medications.The choice should consider the availability of the medications.It is important to monitor adverse events and adjust medications accordingly.Rationale: The panel favored HCQ over SSZ because of the dosing convenience (once daily) and the safety profile of HCQ compared to SSZ.The Saudi panel suggests initiating a csDMARD with short-term (< 3 months) glucocorticoids over initiating a csDMARD without short-term glucocorticoids in DMARD-naive patients with moderate-to-high disease activity .Recommendation modified ; certainty of evidence unmodified.The physician should clearly communicate to the patient the potential benefits and harms of glucocorticoids.The choice should account for the patient's views on the expected benefits and harms of glucocorticoids. It should also account for the ability to taper/discontinue glucocorticoids.The glucocorticoid treatment regimen should use the lowest dose for the shortest period possible to reduce harm, with caution in the elderly.It is important to monitor for the adverse events of glucocorticoids.Rationale: The use of short-term (< 3 months) glucocorticoids when initiating a csDMARD was judged by the panel to be the standard of care. The panel judged the benefit of rapid alleviation of symptoms at the time of diagnosis and during flares to outweigh the risks of glucocorticoids. The panel unanimously agreed that the long-term use of glucocorticoids is associated with harm and damage that outweigh benefit. The panel recommended a shared decision making approach in decisions related to initiating and discontinuing glucocorticoids.The Saudi panel suggests a switch to subcutaneous MTX over addition/switch to alternative DMARD(s) in patients taking oral MTX who are not at target .Recommendation unmodified; certainty of evidence unmodified.This recommendation typically applies to patients with moderate or high disease activity but may apply to patients with low disease activity.Target may differ based on initial disease activity status.The choice should consider the availability of the medications.It is important to monitor adverse events and adjust the regimen accordingly.Rationale: The panel favored switching to subcutaneous MTX over addition/switch to alternative DMARD(s) because of the convenience of once-weekly dosing of subcutaneous MTX compared to daily dosing of alternative DMARD(s), and the higher effectiveness of subcutaneous MTX.The Saudi panel suggests gradual discontinuation of MTX over gradual discontinuation of the bDMARD or tsDMARD for patients taking MTX plus a bDMARD or tsDMARD who wish to discontinue a DMARD .Recommendation unmodified; certainty of evidence modified (from very low to moderate).Patient’s health coverage in the private sector should be considered when applying this recommendation.The patient and the physician should closely monitor the progression of symptoms during and following discontinuation.Rationale: The recommendation was based on newly identified evidence suggesting decreased disease worsening with gradual discontinuation of MTX compared to gradual discontinuation of the bDMARD or tsDMARD.We describe the adaptation of five prioritized recommendations from the 2021 ACR guideline for the treatment of RA for the context of Saudi Arabia, following GRADE-ADOLOPMENT methodology. For each recommendation, an EtD table was produced using evidence as published in the source guideline, newly published relevant studies solicited by the panel, and contextual information from Saudi Arabia.Out of five adoloped recommendations, the panel modified two (#1 and #3). For recommendation 1, the panel judged that a generally low rate of adherence to medications in Saudi Arabia favored MTX (administered weekly) over SSZ (administered twice daily). In addition, the cost of a 12-week treatment course of SSZ is substantially higher than that of MTX. Moreover, the KSA panel judged that alcohol-related undesirable effects of MTX were less relevant to the KSA setting given restrictions on alcohol use. These factors tilted the balance of desirable and undesirable effects in favor of MTX.As for recommendation 3, the KSA panel judged that the balance of effects “probably favors” short-term (< 3 months) glucocorticoids when initiating a csDMARD. Although valuation information by the ACR panel for this specific recommendation is not available, the KSA panel highly valued rapid alleviation of symptoms at the time of diagnosis and during flares. Still, the KSA panel acknowledged challenges with glucocorticoid treatment and detailed them in the rationale as a note of caution to users.An additional contextual factor considered by the KSA panel was the increased risk of hemolysis with the use of HCQ in Saudi Arabia due to the relatively high prevalence of glucose-6-phosphatedehydrogenase (G6PD) deficiency in this population . HoweverThe implementation of these five adoloped recommendations should help with standardizing the care of patients with RA in Saudi Arabia. In fact, these recommendations were based not only on a synthesis of the best available evidence, but also on a careful consideration of the Saudi Arabian context. The SSR will lead efforts to disseminate these five adoloped recommendations, as well as the remaining recommendations adopted from the 2021 ACR guidelines.There are two important factors that would enhance the implementation of the recommendations. First, the specific management choice should account for the patient's views on the expected benefits and harms of the respective alternatives. Second, the choice should consider the availability of the medications, given the variability across regions and health systems. Indeed, in a national survey of Saudi rheumatologists conducted in 2014, 24% of respondents reported not using parenteral MTX because of unavailability in the hospital formulary . It is bFor recommendation 5, the decision of tapering csDMARDs is associated with an increased cost in the short term compared to tapering bDMARDs or tsDMARDs. In patients who pay from pocket or have a co-pay insurance system, tapering bDMARDs/tsDMARDs would be a reasonable option. Of note, non-profit organizations such as the Charitable Association for Rheumatic Diseases provide free-of-charge biologics that can help clinicians provide the best standard of care regarding drug tapering.Previously, members of this group contributed to an adolopment exercise of the 2015 ACR RA guidelines for the Middle East and North Africa region , 23. UnlThere is a need for research on how the target population values the outcomes of interest. It is also important to define 'decision thresholds' for judging the extent of benefits and harms  based on the reported effect measures . The SSR will aim to update these recommendations in parallel to future updates by the ACR. Future efforts should address questions related to the use of biosimilar , 25, an Rheumatologists practicing in Saudi Arabia can use the five adoloped recommendations generated by this project while adopting the rest of the recommendations from the 2021 ACR guidelines.Additional file 1. List of KSA panel members.Additional file 2. Prioritized questions for the adolopment of the 2021 American College of Rheumatology (ACR) Guideline for the Treatment of Rheumatoid Arthritis (RA) in Saudi Arabia.Additional file 3. Evidence to Decision tables.


Patients with chronic obstructive pulmonary disease (COPD) face limitedtreatment options and inadequate access to palliative care.To provide a pragmatic overview of clinical guidelines and produceevidence-based recommendations for severe COPD. Interventions for whichthere is inconsistent evidence to support their use and areas requiringfurther research were identified.Practice review of guidelines supported by scoping review methodology toexamine the evidence reporting the use of guideline-recommendedinterventions.An electronic search was undertaken in MEDLINE, EMBASE, PsycINFO, CINAHL andThe Cochrane Database of Systematic Reviews, complemented by web searchingfor guidelines and publications providing primary evidence (July 2021).Guidelines published within the last 5 years and evidence in the last 10years were included.Severe COPD should be managed using a multidisciplinary approach with aholistic assessment. For stable patients, long-actingbeta-agonist/long-acting muscarinic antagonist and pulmonary rehabilitationare recommended. Low dose opioids, self-management, handheld fan andnutritional support may provide small benefits, whereas routinecorticosteroids should be avoided. For COPD exacerbations, systematiccorticosteroids, non-invasive ventilation and exacerbation action plans arerecommended. Short-acting inhaled beta-agonists and antibiotics may beconsidered but pulmonary rehabilitation should be avoided duringhospitalisation. Long term oxygen therapy is only recommended for patientswith chronic severe hypoxaemia. Short-acting anticholinergic inhalers,nebulised opioids, oral theophylline or telehealth are not recommended.Recommended interventions by guidelines are not always supported byhigh-quality evidence. Further research is required on efficacy and safetyof inhaled corticosteroids, antidepressants, benzodiazepines, mucolytics,relaxation and breathing exercises. What is already known about the topic?Patients with severe COPD face frequent exacerbations, hospitalisation andshortened survival but limited access to palliative care.Neither standardised guidelines nor synthesis is available on recommendationsfor severe COPD.Many clinicians are unsure how to best treat or support severe COPD.What this paper adds?Not all guidelines are developed based on robust evidence.There is a lack of high-quality studies focussing on patients with severeCOPD.Evidence supports the multidisciplinary approach with combination inhaledtherapies.Practical recommendations are made for the management of stable COPD and COPDexacerbations respectively balancing the efficacy and harms.Implications for practice, theory or policySevere COPD should be managed by a multidisciplinary approach with a holisticassessment.Stable patients will benefit from combination inhaled therapies such aslong-acting beta-agonist/long-acting muscarinic antagonist are preferredover monotherapies, low dose opioids and non-pharmacological interventionssuch as self-management, pulmonary rehabilitation, a handheld fan canprovide small benefits, but routine corticosteroids should be avoided.For COPD exacerbations, systematic corticosteroids, non-invasive ventilationand exacerbation action plans are recommended, short-acting inhaledbeta-agonists and antibiotics may provide benefits but pulmonaryrehabilitation should be avoided during hospitalisation.Long term oxygen therapy is only recommended for patients with chronic severehypoxaemia.Short-acting anticholinergic inhalers, nebulised opioids, oral theophyllineor telehealth are not recommended.Further research is required to investigate the efficacy and safety ofinhaled corticosteroids, antidepressants, benzodiazepines, mucolytics,relaxation and breathing exercises in patients with severe COPD. Poorly managed severe COPD (forced expiratory volume in 1 s (FEV1) <50% predicted) may lead to frequent exacerbations, hospitalisation and shortened survival. Patients experience a similar symptom burden to those with lung cancer withunmet palliative care needs, yet have limited access and lower uptake of palliative care often due tounpredictable prognosis.Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. many health systems are not set up to provide trained palliative careclinicians to patients and many clinicians experience difficulties in when, how andwhat to initiate palliative care, leading to inadequate provision of palliative care for COPD patients.Palliative care is shown only frequently to be provided within the last few weeks oflife in patients with severe COPD instead of their last year of life, and it is morelikely for patients to receive it if a lung cancer co-diagnosis exists. We aim to (1) provide a critical yet pragmatic overview of clinicalguidelines, (2) produce evidence-based recommendations for practice and (3) identifygaps that require further research.Palliative care has predominately focussed on malignant disease, neither standardisedguidelines nor synthesis is available for end of life of non-malignant diseases orthe management of patients with severe COPD concerning early palliative caremeasures. In addition, not all guidelines are evidence-based. Although a growingbody of research supports early palliative care approaches for better health outcomes,Supplemental Material 1). References lists of guidelines andsupporting evidence were scrutinised. Guideline and supporting study eligibility areshown in This practice review is to provide an overview of current guidelines with asupporting evidence based summary of recommendations drawn from the availableevidence. National and international guidelines that described the management ofCOPD in adults were searched and examined and interventions recommended byguidelines were identified. A scoping review was then undertaken to provide evidencebase supporting the recommendation of these interventions and identify areas wherethe evidence-base is lacking, and further research is required. A series of searchesin MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Database of Systematic Reviewswere made using a range of keywords and subject headings .Identified citations were exported to EndNote for deduplication and selected afterindependent screening of titles and abstracts by two researchers  anydiscrepancies resolved by discussion with a third author. Results are presentedaccording to Preferred Reporting Items for Systematic reviews and Meta-Analysesextension for Scoping Reviews was followedEach intervention was allocated to a practice recommendation of ‘Do’, ‘Don’t’ or‘Don’t know’ based on consistency and quality of the supporting empirical evidence.The strength of recommendation was rated as ‘strong’, ‘moderate’ and ‘tentative’balancing benefits and harms according to criteria listed in Supplemental Material 3.Twenty four guidelines were identified but 18 were included as six guidelines usedother guidelines as the prime evidence base. A summary of guidelines withrecommendations is presented in 10 Arandomised controlled trial (RCT) finds early integration of palliative careincreases survival rate for patients.A multidisciplinary approach is strongly recommended. Multidisciplinary andmulti-treatment improve breathlessness, dysponea, fatigue, disease impactand activity and reduce hospital admissions and hospitalisation days. Mixedevidence on emotional and symptom mastery are observed. and symptom burden by COPD Assessment Test (CAT), exercise capacity by the 6-minute walking distance,15oxygen saturation, history of hospital admissions and exacerbations18should be undertaken. Comorbidities and Alpha-1 antitrypsin deficiency should be assessed. Blood eosinophil counts should also be used in combination with clinical assessment ofexacerbation risk to predict the treatment effect of inhaled corticosteroidscontaining regimes.Holistic assessment is recommended and severity of airflow limitation shouldbe indicated. A comprehensive assessment of symptoms measuringbreathlessness by MRC scale23Cochrane reviews provide moderate to high-quality evidence thatlong-acting beta-agonist (LABA) is associated with improvement in lungfunction, exacerbations and quality of life (QoL), but no impact onmortality.24 Tiotropiumreduces risk of exacerbations  andclinical deterioration, with an increase in clinical improvement andQoL.2527 An associated risk of increased mortality isobserved in patients with soft mist inhaler compared with placebo but no difference in deaths with ipratropium bromide.Long-acting muscarinic antagonist (LAMA) are recommended to reduceexacerbation.2832recommend the use of a combination of medications over monotherapieswith different mechanisms that may increase overall efficacy and loweradverse effects.GuidelinesRecent evidence is limited on the use of SABA/SAMA but suggested apotential effect on exacerbation, patients also showed a preference forusing Respimat inhaler.3336in moderate and severe patients, leading to a strong Do. Cochranereviews further suggest a small improvement in lung function and QoLwith LABA/LAMA but inconsistent effects on exacerbations which may becaused by heterogeneity.38 Compared withnebulised SABA/SAMA, effect on FEV1 is not superior over 6h with aslower reaching of lower peak FEV1 in dry powder with LABA/LAMA.Long term efficacy and safety of LABA/LAMA are demonstrated acrossmultiple trials for bronchodilation and dyspnoea4042 However anincreased risk of pneumonia is noted in patients on combined inhalers.Cochrane reviews suggest that ICS/LABA reduces exacerbations andpotentially improves mortality, lung function, symptoms and QoL,compared with ICS, LABA or usual care.4345 A Cochrane reviewprovides good quality evidence ICS/LABA/tiotropium has a small effect onlung function and QoL compared with tiotropium alone. No conclusioncould be drawn on impact on exacerbations due to heterogeneity between trials.Triple therapy decreases the risk of exacerbations and improves QoL inpatients with and without a history of exacerbations in the past year,however it increases the risk of pneumonia compared withLABA/LAMA. Short courses of oral corticosteroids are in favour leading to adecrease in pneumonia admissions and all-cause mortality. Risk of adverse effects such as hyperglycaemia is increased.There is high-quality evidence to recommend systemic corticosteroids foracute exacerbations, which improve symptoms and lung function, reducetreatment failure and relapse and duration of hospitalisation. Reviews suggest a reduction in breathlessness with systemicopioids in stable severe COPD without effect on exercise capacity. Opioid-related adverse events including nausea, vomiting andconstipation are common but often self-limiting on withdrawal. Trials suggest improvement in patient’s breathlessness with lowdose opioids.52 Future studies to investigate longer-termbenefits and risks are needed.A tentative recommendation is made for low dose (10–30 mg daily) opioids.5357 A Cochrane reviewfinds small effects in outpatients on treatment failure, no effect ininpatients with severe exacerbations, but a large effect among patientsin the intensive care unit patients. Routine use of macrolides shows aclinically meaningful reduction in exacerbations.5860Serious adverse events are reported including hearing impairment, longQTc and tinnitus.60Antibiotics are tentatively recommended concerning antibiotic resistanceand other adverse events.2 ⩽ 7.3 kPa). Cochrane reviews and trials suggest survival benefits in patientswith severe hypoxaemia but improve breathlessness only during exercise in mildly hypoxaemicand non-hypoxaemic patients. No effect is observed on QoL or hospitalisation, although seriousadverse events are rare.6365 For patients withadvanced life-limiting diseases with PaO2 > 7.3 kPa,palliative oxygen does not improve breathlessness relief compared withair66 although studies are undertaken with a majority ofcancer patients. Regular assessment and support should be undertaken toensure compliance, along with monitoring for hypercapnia and optimal oxygensaturation.Oxygen for more than 15 h per day is recommended for patients with chronicsevere hypoxaemia  of systemiccorticosteroids  do not reduce the risk oftreatment failure, relapse or time to re-exacerbation compared with shortercourses in severe or very severe patients. No difference in the likelihoodof adverse events is found, including hyperglycaemia, hypertension,gastrointestinal tract bleeding and symptoms of congestive heart failure orischaemic heart disease. Another review demonstrates a lack of benefit on exercise capacityand breathlessness. Common adverse effects include lightheadedness,dizziness and mild nausea. A moderate Do not recommendation is made due to lack of clinicalbenefit in studies of poor quality.A Cochrane review with low-quality of evidence finds no evidence thatnebulised opioids are more effective than placebo although a wide range ofdoses is delivered (1–50 mg).94 A possible increasedrisk of overall exacerbations is reported.Recent research is limited and not in favour of theophylline concerning thelikelihood of serious adverse events and no additional benefit in reducingexacerbations. suggests PDE₄ is associated with a small improvement in FEV1, QoL andexacerbation frequency in moderate to very severe patients. No effects areobserved on symptoms or exercise tolerance. However patients experienceincreased depressive symptoms and insomnia, weight loss and diarrhoea,nausea and vomiting.Routine use of PDE₄ should be avoided given the small benefit but a range ofadverse events. A Cochrane review Trials demonstrate no difference in readmission or recovery ofphysical function but a slightly higher mortality rate. Higher rates of adverse events relating to fall, blood pressure,heart rate although not severe are reported.97When Pulmonary rehabilitation is initiated early during acute admission forexacerbation, no consistent improvement is observed on mortality, hospitalreadmission, QoL or exercise capacity. which has no impact on mortality but a possible improvement on QoLand emergency department and hospital attendance, with no excessive costs incurred. However, a recent review suggests a lack of effect compared withusual care. A large RCT finds no benefit on psychological outcomes or QoL.Telehealth is remote delivery of healthcare or monitoring disease,101103 Thepotential benefit for severe COPD needs careful consideration and highquality evidence is urgently needed.There is some evidence for a beneficial effect of albuterol with side effectsreported related to heart rate in non COPD contexts.56 with conflictingevidence. A Cochrane review with good quality evidence suggests routine useof ICS reduces mean rate of exacerbations with no benefits on FEV1 andmortality. Although there is a slower decline in QoL, likelihood oforopharyngeal candidiasis, hoarseness and pneumonia increases. A possible higher mortality rate is reported in a trial in patientswith fluticasone propionate alone compared with placebo. Research on long term adverse effects is needed.Inconsistent recommendation is made for use of ICSShort term nortriptyline has some effect on depressive symptoms but not ondyspnoea, FEV1, hospital utilisation, exercise tolerance or QoL. Evidencesupporting use of selective serotonin reuptake inhibitors is lacking withreported nausea and dizziness. A longitudinal cohort study observes an association between higherbenzodiazepines doses and increased mortality.Benzodiazepines do not improve breathlessness in patients with advancedcancer and COPD regardless of type of benzodiazepine, dose, delivery routeand frequency or duration with more adverse events of drowsiness comparedwith placebo but less compared to morphine.Mucolytics may reduce likelihood of an acute exacerbation. A possible benefiton days of disability and hospitalisations is observed with no associationwith increased adverse events. A meta-analysis with a high degree of heterogeneity in interventioncomponents concludes only small effects on FEV1, anxiety and QoL. An explorative RCT suggests benefit of a brief relaxation exercise. RCT’s evidence is needed to determine comparative effectiveness forthis low risk and inexpensive intervention.Although relaxation is recommended as a way to strengthen coping andfunctional ability however no high-quality evidence is available to supportits routine practice. from a Cochrane review with low-quality evidence. Another reviewsuggests no improvement in dyspnoea but a beneficial effect on respiratory rate. Further evidence is needed due to large variability among studiesexamined in current reviews.No consistent effects of breathing exercises (with or without supervision)can be drawn on patients’ dyspnoea or QoL,A scoping review rather than a systematic review was undertaken. No quality appraisalwas performed on supporting evidence. Not all evidence focussed solely on patientswith severe COPD. Concerns were given to the current validity of guidelines, allguidelines published within the last 5 years and more than half published within thelast 3 years, which is within the timeframe that they may be considered current.A multidisciplinary approach with holistic assessment should be implemented.Treatment with LABA or LAMA is effective, but combination inhaled therapies providegreater benefits without additional adverse effects. However an ICS as part ofcombination therapy needs to be used with caution considering risk of pneumonia.For stable patients, LABA/LAMA and pulmonary rehabilitation are recommended,low dose opioids, self-management, handheld fan and nutritional support maybe beneficial. However routine corticosteroids should be avoided.For COPD exacerbations, systematic corticosteroids, non-invasive ventilationand exacerbation action plans are recommended, short-acting inhaledbeta-agonists and antibiotics may be beneficial but pulmonary rehabilitationshould be avoided during hospitalisation.Long term oxygen therapy is only recommended for patients with chronic severehypoxaemia.Short-acting anticholinergic inhalers, nebulised opioids, oral theophyllineor telehealth are not recommended.Recommendations by guidelines are not always consistent with robust evidence. Thereis a lack of high-quality studies focussing on patients with severe COPD. Moreresearch is needed to investigate efficacy and safety of ICS, antidepressants,benzodiazepines, mucolytics and supportive care targetting severe COPD.Click here for additional data file.Supplemental material, sj-pdf-1-pmj-10.1177_02692163221079697 for Evidence-basedmanagement approaches for patients with severe chronic obstructive pulmonarydisease (COPD): A practice review by Yu Fu, Emma J Chapman, Alison C Boland andMichael I Bennett in Palliative Medicine