The social impact of research has usually been analysed through the scientific outcomes produced under the auspices of the research. The growth of scholarly content in social media and the use of altmetrics by researchers to track their work facilitate the advancement in evaluating the impact of research. However, there is a gap in the identification of evidence of the social impact in terms of what citizens are sharing on their social media platforms. This article applies a social impact in social media methodology (SISM) to identify quantitative and qualitative evidence of the potential or real social impact of research shared on social media, specifically on Twitter and Facebook. We define the social impact coverage ratio (SICOR) to identify the percentage of tweets and Facebook posts providing information about potential or actual social impact in relation to the total amount of social media data found related to specific research projects. We selected 10 projects in different fields of knowledge to calculate the SICOR, and the results indicate that 0.43% of the tweets and Facebook posts collected provide linkages with information about social impact. However, our analysis indicates that some projects have a high percentage (4.98%) and others have no evidence of social impact shared in social media. Examples of quantitative and qualitative evidence of social impact are provided to illustrate these results. A general finding is that novel evidences of social impact of research can be found in social media, becoming relevant platforms for scientists to spread quantitative and qualitative evidence of social impact in social media to capture the interest of citizens. Thus, social media users are showed to be intermediaries making visible and assessing evidence of social impact. The social impact of research is at the core of some of the debates influencing how scientists develop their studies and how useful results for citizens and societies may be obtained. Concrete strategies to achieve social impact in particular research projects are related to a broader understanding of the role of science in contemporary society. There is a need to explore dialogues between science and society not only to communicate and disseminate science but also to achieve social improvements generated by science. Thus, the social impact of research emerges as an increasing concern within the scientific community . As BornSeveral authors have approached the conceptualization of social impact, observing a lack of generally accepted conceptual and instrumental frameworks . It is cIn addition, the terms “social impact” and “societal impact” are sometimes used interchangeably. For instance, Bornmann  said thaThis understanding of the social impact of research is connected to the creation of the Social Impact Open Repository (SIOR), which constitutes the first open repository worldwide that displays, cites and stores the social impact of research results . The SIOAdditionally, a common confusion is found among the uses of dissemination, transference (policy impact) and social impact. While dissemination means to disseminate the knowledge created by research to citizens, companies and institutions, transference refers to the use of this knowledge by these different actors (or others), and finally, as already mentioned, social impact refers to the actual improvements resulting from the use of this knowledge in relation to the goals motivating the research project . In the present research , it is aIn fact, the contribution that we develop in this article is based on the creation of a new method to evaluate the evidence of social impact shared in social media. The evaluation proposed is to measure the social impact coverage ratio (SICOR), focusing on the presence of evidence of social impact shared in social media. Then, the article first presents some of the contributions from the literature review focused on the research on social media as a source for obtaining key data for monitoring or evaluating different research purposes. Second, the SISM  methodology developeth, with 319 million active users. Between them are the following social networks: WhatsApp, YouTube, Facebook Messenger, WeChat, QQ, Instagram,Qzone and Tumblr. If we look at altmetrics, the tracking of social networks for mentions of research outputs includes Facebook, Twitter, Google+,LinkedIn, Sina Weibo and Pinterest. The social networks common to both sources are Facebook and Twitter. These are also popular platforms that have a relevant coverage of scientific content and easy access to data, and therefore, the research projects selected here for application of the SISM methodology were chosen on these platforms.Social media research includes the analysis of citizens’ voices on a wide range of topics . AccordiFoodRisc examined the role of social media to illustrate consumers’ quick responses during food crisis situations [Chew and Eysenbach  studied tuations . These tResearch on the synergies between science and citizens has increased over the years, according to Fresco , and theIn this framework, the recent debates on how to increase the impact of research have acquired relevance in all fields of knowledge, and major developments address the methods for measuring it. As highlighted by Feng Xia et al. , social To the best of our knowledge, the assessment of social impact in social media (SISM) has developed according to this gap. At the core of this study, we present and discuss the results obtained through the application of the SICOR  with examples of evidence of social impact shared in social media, particularly on Twitter and Facebook, and the implications for further research.Following these previous contributions, our research questions were as follows: Is there evidence of social impact of research shared by citizens in social media? If so, is there quantitative or qualitative evidence? How can social media contribute to identifying the social impact of research?A group of new methodologies related to the analysis of online data has recently emerged. One of these emerging methodologies is social media analytics , which wTo develop this study, the first step was to select research projects with social media data to be analysed. The selection of research projects for application of the SISM methodology was performed according to three criteria.th Framework Programme (FP7) highlighted by the European Commission [Criteria 1. Selection of success projects in FP7. The projects were success stories of the 7mmission  in the fCriteria 2. Period of implementation. We selected projects in the 2012–2013 period because they combine recent research results with higher possibilities of having Twitter and Facebook accounts compared with projects of previous years, as the presence of social accounts in research increased over this period.Criteria 3. Twitter and Facebook accounts. It was crucial that the selected projects had active Twitter and Facebook accounts.After the selection of projects, we defined the timeframe of social media data extraction on Twitter and Facebook from the starting date of the project until the day of the search, as presented in The second step was to define the search strategies for extracting social media data related to the research projects selected. In this line, we defined three search strategies.Strategy 1. To extract messages published on the Twitter account and the Facebook page of the selected projects. We listed the Twitter accounts and Facebook pages related to each project in order to look at the available information. In this case, it is important to clarify that the tweets published under the corresponding Twitter project account are original tweets or retweets made from this account. It is relevant to mention that in one case, the Twitter account and Facebook page were linked to the website of the research group leading the project. In this case, we selected tweets and Facebook posts related to the project. For instance, in the case of the Twitter account, the research group created a specific hashtag to publish messages related to the project; therefore, we selected only the tweets published under this hashtag. In the analysis, we prioritized the analysis of the tweets and Facebook posts that received some type of interaction  because such interaction is a proxy for citizens’ interest. In doing so, we used the R program and NVivoto extract the data and proceed with the analysis. Once we obtained the data from Twitter and Facebook, we were able to have an overview of the information to be further analysed, as shown in We focused the second and third strategies on Twitter data. In both strategies, we extracted Twitter data directly from the Twitter Advanced Search tool, as the API connected to NVivo and the R program covers only a specific period of time limited to 7/9 days. Therefore, the use of the Twitter Advanced Search tool made it possible to obtain historic data without a period limitation. We downloaded the results in PDF and then uploaded them to NVivo.Strategy 2. To use the project acronym combined with other keywords, such as FP7 or EU. This strategy made it possible to obtain tweets mentioning the project. Strategy 3. To use searchable research results of projects to obtain Twitter data. We defined a list of research results, one for each project, and converted them into keywords. We selected one searchable keyword for each project from its website or other relevant sources, for instance, the brief presentations prepared by the European Commission and published in CORDIS. Once we had the searchable research results, we used the Twitter Advanced Search tool to obtain tweets, as presented in The sum of the data obtained from these three strategies allowed us to obtain a total of 3,425 tweets and 1,925 posts on public Facebook pages. We imported the data obtained from the three search strategies into NVivo to analyse. Next, we select tweets and Facebook posts providing linkages with quantitative or qualitative evidence of social impact, and we complied with the terms of service for the social media from which the data were collected. By quantitative and qualitative evidence, we mean data or information that shows how the implementation of research results has led to improvements towards the fulfilment of the objectives defined in the EU2020 strategy of the European Commission or other official targets. For instance, in the case of quantitative evidence, we searched tweets and Facebook posts providing linkages with quantitative information about improvements obtained through the implementation of the research results of the project. In relation to qualitative evidence, for example, we searched for testimonies that show a positive evaluation of the improvement due to the implementation of research results. In relation to this step, it is important to highlight that social media users are intermediaries making visible evidence of social impact. Users often share evidence, sometimes sharing a link to an external resource . We identified evidence of social impact in these sources.We analysed all tweets and Facebook posts collected  to calculate the ratio of social media data with evidence of social impact in relation to the total amount of social media data extracted from the research projects selected. The aim was to answer the question whether or not there is evidence of social impact shared by citizens in social media. Once we had the tweets and Facebook posts selected for each project, we identified the number of tweets and Facebook posts responding or not to the criteria of presenting evidence of the social impact of research. In the final step of this search, we defined a ratio of coverage adapted to this calculation called the SICOR, the social impact coverage ratio:iγ is the total number of messages obtained about project i with evidence of social impact on social media platforms ;Ti is the total number of messages from project ion social media platforms ; andn is the number of projects selected.The result is expressed in percentages. In this paper, we use the SICOR for Twitter and Facebook thus:The researchers who carried out the analysis of the social media data collected are specialists in the social impact of research and research on social media. Before conducting the full analysis, two aspects were guaranteed. First, how to identify evidence of social impact relating to the targets defined by the EU2020 strategy or to specific goals defined by the call addressed was clarified. Second, we held a pilot to test the methodology with one research project that we know has led to considerable social impact, which allowed us to clarify whether or not it was possible to detect evidence of social impact shared in social media. Once the pilot showed positive results, the next step was to extend the analysis to another set of projects and finally to the whole sample. The construction of the analytical categories was defined a priori, revised accordingly and lastly applied to the full sample.Different observations should be made. First, in this previous analysis, we found that the tweets and Facebook users play a key role as “intermediaries,” serving as bridges between the larger public and the evidence of social impact. Social media users usually share a quote or paragraph introducing evidence of social impact and/or link to an external resource, for instance, a video, official report, scientific article, news story published on media, etc., where evidence of the social impact is available. This fact has implications for our study, as our unit of analysis is all the information included in the tweets or Facebook posts. This means that our analysis reaches the external resources linked to find evidence of social impact, and for this reason, we defined tweets or Facebook posts providing linkages with information about social impact.Second, the other important aspect is the analysis of the users’ profile descriptions, which requires much more development in future research given the existing limitations. For instance, some profiles are users’ restricted due to privacy reasons, so the information is not available; other accounts have only the name of the user with no description of their profile available. Therefore, we gave priority to the identification of evidence of social impact including whether a post obtained interaction  or was published on accounts other than that of the research project itself. In the case of the profile analysis, we added only an exploratory preliminary result because this requires further development. Considering all these previous details, the codebook see  that we To illustrate how we analysed data from Twitter and Facebook, we provide one example of each type of evidence of social impact defined, considering both real and potential social impact, with the type of interaction obtained and the profiles of those who have interacted.QUANESISM. Tweet by ZeroHunger Challenge @ZeroHunger published on 3 May 2016. Text: How re-using food waste for animal feed cuts carbon emissions.-NOSHAN project hubs.ly/H02SmrP0. 7 retweets and 5 likes.The unit of analysis is all the content of the tweet, including the external link. If we limited our analysis to the tweet itself, it would not be evidence. Examining the external link is necessary to find whether there is evidence of social impact. The aim of this project was to investigate the process and technologies needed to use food waste for feed production at low cost, with low energy consumption and with a maximal evaluation of the starting wastes. This tweet provides a link to news published in the PHYS.org portal , which s'Our results demonstrated that with a NOSHAN 10 percent mix diet, for every kilogram of broiler chicken feed, carbon dioxide emissions were reduced by 0.3 kg compared to a non-food waste diet,' explains Montse Jorba, NOSHAN project coordinator. 'If 1 percent of total chicken broiler feed in Europe was switched to the 10 percent NOSHAN mix diet, the total amount of CO2 emissions avoided would be 0.62 million tons each year.'This quantitative evidence “a NOSHAN 10 percent mix diet, for every kilogram of broiler chicken feed, carbon dioxide emissions carbon dioxide emissions were reduced by 0.3 kg to a non-food waste diet” is linked directly with the Europe 2020 target of Climate Change & Energy, specifically with the target of reducing greenhouse gas emissions by 20% compared to the levels in 1990 . The illThis tweet was captured by the Acronym search strategy. It is a message tweeted by an account that is not related to the research project. The twitter account is that of the Zero Hunger Challenge movement, which supports the goals of the UN. The interaction obtained is 7 retweets and 5 likes. Regarding the profiles of those who retweeted and clicked “like”, there were activists, a journalist, an eco-friendly citizen, a global news service, restricted profiles (no information is available on those who have retweeted) and one account with no information in its profile.https://t.co/TocQwMiW3c 9 retweets and 5 likes.The following example illustrates the analysis of QUALESISM: Tweet by @eurofitFP7 published on4 October 2016. Text: See our great new EuroFIT video on youtube! The aim of this project is to improve health through the implementation of two novel technologies to achieve a healthier lifestyle. The tweet provides a link to a video on YouTube on the project’s results. In this video, we found qualitative evidence from people who tested the EuroFit programme; there are quotes from men who said that they have experienced improved health results using this method and that they are more aware of how to manage their health:One end-user said: I have really amazing results from the start, because I managed to change a lot of things in my life. And other one: I was more conscious of what I ate, I was more conscious of taking more steps throughout the day and also standing up a little more. The research applies the well researched scientific evidence to the management of health issues in daily life. The video presents the research but also includes a section where end-users talk about the health improvements they experienced. The quotes extracted are some examples of the testimonies collected. All agree that they have improved their health and learned healthy habits for their daily lives. These are examples of qualitative evidence linked with the target of the call HEALTH.2013.3.3–1—Social innovation for health promotion  that hasTo summarize the analysis, in There is a greater presence of tweets/Fb posts with quantitative evidence (14) than with qualitative evidence (9) in the total number of tweets/Fb posts identified with evidence of social impact. Most of the tweets/Fb posts with quantitative evidence of social impact are from scientific articles published in peer-reviewed international journals and show potential social impact. In The first tweet with quantitative social impact selected is from project 7. The aim of this project was to provide high-quality scientific evidence for preventing vitamin D deficiency in European citizens. The tweet highlighted the main contribution of the published study, that is, “Weekly consumption of 7 vitamin D-enhanced eggs has an important impact on winter vitamin D status in adults” . The quaWith the use of a within-group analysis, it was shown that, although serum 25(OH) D in the control group significantly decreased over winter , there was no change in the 2 groups who consumed vitamin D-enhanced eggs (P>0.1 for both. (p. 629)This evidence contributes to achievement of the target defined in the call addressed that is KBBE.2013.2.2–03—Food-based solutions for the eradication of vitamin D deficiency and health promotion throughout the life cycle . The quaThe second example of this table corresponds to the example of quantitative evidence of social impact provided in the previous section.The third example is a Facebook post from project 3 that is also tweeted. Therefore, this evidence was published in both social media sources analysed. The aim of this project was to measure a range of chemical and physical environmental hazards in food, consumer products, water, air, noise, and the built environment in the pre- and postnatal early-life periods. This Facebook post and tweet links directly to a scientific article  that sho.(p.1)Using 1H NMR spectroscopy we characterized short-term variability in urinary metabolites measured from 20 children aged 8–9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%)This evidence is linked to the target defined in the call “ENV.2012.6.4–3—Integrating environmental and health data to advance knowledge of the role of environment in human health and well-being in support of a European exposome initiative” . The eviWe found qualitative evidence of the social impact of different projects, as shown in The first tweet with qualitative evidence selected is from project 4. The aim of this project is to produce a system that helps in the prevention of obesity and eating disorders, targeting young people and adults . The twiPierre Vial has lost 43 kilos over the past nine and a half months. He and other patients at the eating disorder clinic explain the effects obesity and anorexia have had on their lives. Another patient, Karin Borell, still has some months to go at the clinic but, after decades of battling anorexia, is beginning to be able to visualise life without the illness: “On a good day I see myself living a normal life without an eating disorder, without problems with food. That’s really all I wish right now”.This qualitative evidence shows how the research results contribute to the achievement of the target goals of the call addressed:“ICT-2013.5.1—Personalised health, active ageing, and independent living”.  In this The second example is a Facebook post from project 9, which provides a link to a Euronews video. The aim of this project is to bring some tools from the lab to the farm in order to guarantee a better management of the farm and animal welfare. In this video , there aCameras and microphones help me detect in real time when the animals are stressed for whatever reason,” explained farmer Twan Colberts. “So I can find solutions faster and in more efficient ways, without me being constantly here, checking each animal.”This evidence shows how the research results contribute to addressing the objectives specified in the call “KBBE.2012.1.1–02—Animal and farm-centric approach to precision livestock farming in Europe” , particuThe analysis of tweets and Facebook posts providing linkages with information about social impact was conducted following a content analysis method in which reliability was based on a peer review process. This sample is composed of 3,425 tweets and 1,925 Fb/posts. Each tweet and Facebook post was analysed to identify whether or not it contains evidence of social impact. Each researcher has the codebook a priori. We used interrater reliability in examining the agreement between the two raters on the assignment of the categories defined through Cohen’s kappa. We used SPSS to calculate this coefficient. We exported an excel sheet with the sample coded by the two researchers being 1  and 0  to SPSS. The cases where agreement was not achieved were not considered as containing evidence of social impact. The result obtained is 0.979; considering the interpretation of this number according to Landis & Koch , our levStep 1. Data analysis I. We included all data collected in an excel sheet to proceed with the analysis. Prior to the analysis, researchers read the codebook to keep in mind the information that should be identified.Step 2. Each researcher involved reviewed case by case the tweets and Facebook posts to identify whether they provide links with evidence of social impact or not. If the researcher considers there to be evidence of social impact, he or she introduces the value of 1into the column, and if not, the value of 0.Step 3. Once all the researchers have finished this step, the next step is to export the excel sheet to SPSS to extract the kappa coefficient.Step 4. Data Analysis II. The following step was to analyse case by case the tweets and Facebook posts identified as providing linkages with information of social impact and classify them as quantitative or qualitative evidence of social impact.Step 5. The interaction received was analysed because this determines to which extent this evidence of social impact has captured the attention of citizens .Step 6. Finally, if available, the profile descriptions of the citizens interacting through retweeting or sharing the Facebook post were considered.Step 7. SICOR was calculated. It could be applied to the complete sample  or to each project, as we will see in the next section.The total number of tweets and Fb/posts collected from the 10 projects is 5,350. After the content analysis, we identified 23 tweets and Facebook posts providing linkages to information about social impact. To respond to the research question, which considered whether there is evidence of social impact shared by citizens in social media, the answer was affirmative, although the coverage ratio is low. Both Twitter and Facebook users retweeted or shared evidence of social impact, and therefore, these two social media networks are valid sources for expanding knowledge on the assessment of social impact. The analysis of each of the projects selected revealed some results to consider. Of the 10 projects, 7 had evidence, but those projects did not necessarily have more Tweets and Facebook posts. In fact, some projects with fewer than 70 tweets and 50 Facebook posts have more evidence of social impact than other projects with more than 400 tweets and 400 Facebook posts. This result indicates that the number of tweets and Facebook posts does not determine the existence of evidence of social impact in social media. For example, project 2 has 403 tweets and 423 Facebooks posts, but it has no evidence of social impact on social media. In contrast, project 9 has 62 tweets, 43 Facebook posts, and 2 pieces of evidence of social impact in social media, as shown in The ratio of tweets/Fb posts to evidence is 0.43%, and it differs depending on the project, as shown below in Considering the three strategies for obtaining data, each is related differently to the evidence of social impact. In terms of the social impact coverage ratio, as shown in Once tweets and Facebook posts providing linkages with information about social impact(ESISM)were identified, we classified them in terms of quantitative (QUANESISM) or qualitative evidence (QUALESISM)to determine which type of evidence was shared in social media. First, the results obtained indicated that the SISM methodology aids in calculating the social impact coverage ratio of the research projects selected and evaluating whether the social impact of the corresponding research is shared by citizens in social media. The social impact coverage ratio applied to the sample selected is low, but when we analyse the SICOR of each project separately, we can observe that some projects have a higher social impact coverage ratio than others. Complementary to altmetrics measuring the extent to which research results reach out society, the SICOR considers the question whether this process includes evidence of potential or real social impact. In this sense, the overall methodology of SISM contributes to advancement in the evaluation of the social impact of research by providing a more precise approach to what we are evaluating.This contribution complements current evaluation methodologies of social impact that consider which improvements are shared by citizens in social media. Exploring the results in more depth, it is relevant to highlight that of the ten projects selected, there is one research project with a social impact coverage ratio higher than those of the others, which include projects without any tweets or Facebook posts with evidence of social impact. This project has a higher ratio of evidence than the others because evidence of its social impact is shared more than is that of other projects. This also means that the researchers produced evidence of social impact and shared it during the project. Another relevant result is that the quantity of tweets and Fb/posts collected did not determine the number of tweets and Fb/posts found with evidence of social impact. Moreover, the analysis of the research projects selected showed that there are projects with less social media interaction but with more tweets and Fb/posts containing evidence of social media impact. Thus, the number of tweets and Fb/posts with evidence of social impact is not determined by the number of publication messages collected; it is determined by the type of messages published and shared, that is, whether they contain evidence of social impact or not.The second main finding is related to the effectiveness of the search strategies defined. Related to the strategies carried out under this methodology, one of the results found is that the most effective search strategy is the searchable research results, which reveals a higher percentage of evidence of social impact than the own account and acronym search strategies. However, the use of these three search strategies is highly recommended because the combination of all of them makes it possible to identify more tweets and Facebook posts with evidence of social impact.Another result is related to the type of evidence of social impact found. There is both quantitative and qualitative evidence. Both types are useful for understanding the type of social impact achieved by the corresponding research project. In this sense, quantitative evidence allows us to understand the improvements obtained by the implementation of the research results and capture their impact. In contrast, qualitative evidence allows us to deeply understand how the resultant improvements obtained from the implementation of the research results are evaluated by the end users by capturing their corresponding direct quotes. The social impact includes the identification of both real and potential social impact.After discussing the main results obtained, we conclude with the following points. Our study indicates that there is incipient evidence of social impact, both potential and real, in social media. This demonstrates that researchers from different fields, in the present case involved in medical research, public health, animal welfare and genomics, are sharing the improvements generated by their research and opening up new venues for citizens to interact with their work. This would imply that scientists are promoting not only the dissemination of their research results but also the evidence on how their results may lead to the improvement of societies. Considering the increasing relevance and presence of the dissemination of research, the results indicate that scientists still need to include in their dissemination and communication strategies the aim of sharing the social impact of their results. This implies the publication of concrete qualitative or quantitative evidence of the social impact obtained. Because of the inclusion of this strategy, citizens will pay more attention to the content published in social media because they are interested in knowing how science can contribute to improving their living conditions and in accessing crucial information. Sharing social impact in social media facilitates access to citizens of different ages, genders, cultural backgrounds and education levels. However, what is most relevant for our argument here is how citizens should also be able to participate in the evaluation of the social impact of research, with social media a great source to reinforce this democratization process. This contributes not only to greatly improving the social impact assessment, as in addition to experts, policy makers and scientific publications, citizens through social media contribute to making this assessment much more accurate. Thus, citizens’ contribution to the dissemination of evidence of the social impact of research yields access to more diverse sectors of society and information that might be unknown by the research or political community. Two future steps are opened here. On the one hand, it is necessary to further examine the profiles of users who interact with this evidence of social impact considering the limitations of the privacy and availability of profile information. A second future task is to advance in the articulation of the role played by citizens’ participation in social impact assessment, as citizens can contribute to current worldwide efforts by shedding new light on this process of social impact assessment and contributing to making science more relevant and useful for the most urgent and poignant social needs.S1 FileThis file contains the SPSS file with the result of the calculation of Cohen’s Kappa regards the interrater reliability. The word document exported with the obtained result is also included.(ZIP)Click here for additional data file.S2 FileThis excel contains four sheets, the first one titled “data collected” contains the number of tweets and Facebook posts collected through the three defined search strategies; the second sheet titled “sample” contains the sample classified by project indicating the ID of the message or code assigned, the type of message (tweet or Facebook post) and the codification done by researchers being 1  and 0 ; the third sheet titled “evidence found” contains the number of type of evidences of social impact founded by project (ESISM-QUANESIM or ESISM-QUALESIM), search strategy and type of message (tweet or Facebook posts); and the last sheet titled “SICOR” contains the Social Impact Coverage Ratio calculation by projects in one table and type of search strategy done in another one.(XLSX)Click here for additional data file.


The proposed classification, based on diagnostic certainty, provides a framework for determining initial empiric and subsequent targeted therapy. >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales. To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 wounds) injured in Afghanistan (2009–2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for  We modified case definitions from the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group for use with trauma patients  within 10 days of initiation of antifungal medication were also included because both events could lead to withdrawal of antifungal medication. The low-suspicion group included wounds that met deep SSTI criteria but were attributed by the treating physician to bacteria, wounds that failed to meet deep SSTI criteria, and deep SSTIs for which the patient received antifungal medication for <10 days.Wounds not meeting criteria for IFI were classified as being of high or low suspicion for IFI. We modified National Healthcare Safety Network (NHSN) definitions for skin and soft tissue infections (SSTI) and used them to differentiate between high-suspicion and low-suspicion wounds. The NHSN definition of SSTI relies on the presence of localized signs and symptoms  without another recognized cause  and patient-level characteristics . Patients with 2 wounds that met different classifications were classified according to the highest level . We performed a restricted analysis for patients with wounds that met criteria for a single classification.Aspergillus (with/without other fungi), fungi of genus Fusarium (with/without other fungi), and all other fungi. Polymicrobial wounds may be counted under multiple fungal groups . Data from patients who had undergone multiple debridements and multiple specimen collections were pooled for the wound site.Fungal culture results were categorized into 4 main groups: all fungi belonging to the order Mucorales (with/without fungi of other genera), fungi of the genus 2 tests. We compared overall continuous variable distributions by using the Kruskal-Wallis test and performed statistical analyses in SAS version 9.3 (https://www.sas.com). We defined significance as p<0.05.We compared categorical variables by using the Fisher exact and χ>1 wound with laboratory evidence of fungal infection  had penetrating wounds and operative cultures/histopathology findings submitted for evaluation. Of these, 246 (34%) had nfection . All pat>2 debridements; 167 wounds) or because laboratory evidence of fungal infection was evident early  but not in subsequent samples (103 wounds). Of the 270 non-IFI wounds, 194 met criteria for deep SSTI; 120 of those were treated with directed antifungal therapy and were classified as high-suspicion wounds . Of the 150 low-suspicion wounds, 76 did not meet criteria for deep SSTI and 74 met the criteria for deep SSTI but were treated with either directed antibiotic therapy (36 wounds) or antifungal therapy for <10 days (38 wounds). Most wounds classified as low suspicion had only positive culture results (125 [83.3%] wounds), and none showed angioinvasion histopathologically.The 246 patients had 413 wounds with laboratory evidence of a filamentous fungus. Of these, 143 wounds (94 patients) met the criteria for an IFI . The rem>26: 98% in the proven group, 90% probable, and 88% possible . Thus, a large proportion of patients with wounds classified in all 3 groups had undergone amputations . Between high-suspicion and low-suspicion wounds, the proportions of growth of fungi of the order Mucorales (p = 0.003), Fusarium spp. (p = 0.001), and other fungi (p<0.001) differed significantly.Among 413 wounds with documented laboratory evidence of fungal infection, fungal cultures had been submitted for 97% and culture results were negative for 11% ; Table 4Enterococcus spp. (38%) and Escherichia coli (17%); not commonly isolated was Staphylococcus aureus (0.5%). The bacteria isolated differed among the 3 groups of wounds. Acinetobacter baumannii was more frequently isolated from patients in the IFI group (22%) than from patients in the other 2 groups (9% with high-suspicion wounds [p = 0.006] and 5% with low-suspicion wounds [p<0.001]). In addition, the proportion of multidrug-resistant organisms isolated was higher among patients with IFI (37%) than among those with low-suspicion (17%) wounds (p<0.001).Bacterial cultures collected within 14 days of injury were assessed for 378 (92%) of wounds; only 1% were negative for bacteria . Most frThe proportion of deaths or surgical amputations did not differ significantly between patients in the IFI and high-suspicion groups. A higher proportion of patients in the IFI group required a surgical amputation  or died  than did patients in the low-suspicion group . The numAs part of our comprehensive evaluation of IFIs among US military personnel wounded in Afghanistan, we propose definitions for the risk stratification of wounds with laboratory evidence of fungal infection . Using our definitions, wounds can be grouped into 3 relatively homogeneous groups with different probabilities of IFI: wounds with IFI, those at high suspicion for IFI, and those at low suspicion for IFI. The categorization of wounds into risk groups is designed to provide a framework to help with clinical decision making and reduce practice variations and to provide definitions that could be used to group wounds for clinical and epidemiologic research.>2 debridements and laboratory evidence of filamentous fungi at any time (either early or late) were classified as IFI  of all admissions for battlefield trauma during 2009–2014; however, it should be noted that specimens were not consistently collected for histopathologic examination until late 2010. Of 94 IFI patients, 8 (9%) died and about half underwent surgical amputations. Two thirds of wounds with laboratory evidence of fungal infection did not meet our definition of IFI. Specifically, one third of wounds were classified as low suspicion, and patients with these wounds generally had very severe injuries; however, by the time of admission to a US hospital, they were not critically ill, as evidenced by a median SOFA score of 1, and they were less likely to undergo subsequent surgical amputation. Laboratory evidence for these patients was often based on isolation of fungi (83%) with negative histopathologic findings. These patients were also less likely to receive antifungal medications (only 15%) and to receive them for a shorter duration . Among this group, approximately half of the wounds had no evidence of deep SSTI, which confirms that isolation of fungus from a wound, even in critically injured patients with blast injuries sustained on foot patrol, is not enough evidence to suggest an IFI (>10 days) in our classification schema. Although this measure is based on the provider’s judgment, we believe that the focus on local signs and symptoms of a wound, along with wound mycology, can be used for clinical decision making; however, our classification needs to be validated prospectively in other civilian and military trauma settings, outside of the Afghanistan theater, and ideally prospectively. Given the substantial morbidity associated with IFI, in February 2011, a hospital-based clinical practice guideline was implemented at LRMC to enable earlier IFI diagnosis and initiation of antifungal therapy with the goal of improving clinical outcomes. Per the guideline, based on previously identified independent risk factors, specimens for histopathologic examination and fungal/bacterial cultures were systematically collected from at-risk patients after the first wound debridement  predominated in IFI wounds, and other fungi were more frequent in low-suspicion wounds (46%). The negative effect that fungi associated with IFIs have on wound healing has been previously demonstrated; fungi from the order Mucorales are associated with a statistically significant longer time to wound closure , especially in the absence of objective signs of deep SSTIs, identifies wounds at low risk for IFI. When close clinical follow-up can be ensured, these wounds can be monitored without the immediate use of antifungal therapy. The characteristics of the fungi isolated also seem to stratify wound risk; isolation of fungi of the order Mucorales is associated with wounds with IFI or highly suspicious of IFI. Our proposed definitions help divide wounds into 3 groups based on the certainty of diagnosis, providing a framework to support clinical decision making, both initial empiric and subsequent targeted antifungal therapy, and reductions in practice variations.


Peer-assisted learning is well established in medical education; however, peer tutors rarely act as assessors for the OSCE. In the compulsory, near-peer teaching programme covering basic medical skills at the University of Heidelberg, peer tutors serve as assessors on a formative OSCE. This study aimed to investigate the feasibility and acceptance of peer assessors and to survey the perceived advantages and disadvantages of their use.In 2016 and 2017 all OSCE peer assessors  and all of the peer-assessed students in 2017  were invited to participate in a survey. Both groups were asked to complete a tablet-based questionnaire immediately after the OSCE. Peer assessors were asked to rate eight statements and the peer-assessed students to rate seven statements on a five-point Likert scale. Both were asked to comment on the advantages and disadvantages of peer-assessors.Overall, 74 of 76 peer assessors and 307 of 308 peer-assessed students participated in the study. 94% (67/74) of peer assessors and 90% (276/307) of the peer-assessed group thought that it is important to have peer tutors as assessors. Of the peer assessors, 92% (68/74) felt confident in giving structured feedback during the OSCE and 66% (49/74) felt they had improved their teaching skills. Of the peer-assessed students, 99% (306/307) were satisfied with their peers as OSCE assessors and 96% (292/307) considered the peer feedback during the OSCE as helpful. The participants mentioned structural benefits, such as lower costs, and suggested the quality of the OSCE was higher due to the use of peer assessors. The use of peer assessors was found to be beneficial for the learners in the form of high-quality feedback and an overall reduction in stress. Furthermore, the use of peer assessors was found to be beneficial for the peer assessors .From a learner’s perspective, the use of peer assessors for a formative OSCE that is part of a near-peer teaching program aimed at junior medical students is favourable for all. A broad implementation of peer assessment in the formative OSCE should be encouraged to investigate effects on quality and stress-reduction. The Objective Structured Clinical Examination (OSCE) aims to examine the medical student’s clinical competence . In genePeer-assisted learning, also known as (near-)peer tutoring or (near-)peer teaching, represents an educational approach in which more experienced students teach younger and less experienced ones , 11. Theplus) imparts basic medical skills in history-taking, physical examination and practical skills to all medical students (approximately 320 per year) and culminates in a formative OSCE at the end of the second year. As of 2013, peer tutors in AaLplus have been deployed as assessors for the OSCE . The peer assessors and peer-assessed students agreed that deploying peer tutors as OSCE assessors improves quality because peer assessors undergo more in-depth training than the professional staff and that because they have served as peer tutors within the 2 years prior to the OSCE, peer assessors have better knowledge of the course content. Furthermore, peer assessors claimed that they can easily judge a student’s level of knowledge and that they understand how to answer students’ questions [“We are more familiar with the curricular material and can often better understand the problems students are having.”]. Peer-assessed students mentioned that peer assessors are often more aware of and refer to current standards.Both the peer-assessed students and their peer assessors identified structural benefits for the AaLsense of transparency about own OSCEs”].The benefits for peer assessors include the improvement of teaching, feedback and clinical skills. They also gain personal benefits such as the improvement of social skills and the opportunity to assume responsibility. Finally, the experience of serving as an assessor provides peer assessors with useful knowledge regarding their own upcoming examinations and, especially, OSCEs [“student-focused feedback”]. Third, “peer feedback is better because students find it easier to ask follow-up questions about the feedback and therefore get clearer takeaways.”In regard to the benefits for peer-assessed students, they along with peer assessors often mentioned the provision of high-quality feedback, the creation of a pleasant atmosphere and an overall reduction in stress. First, both groups suggest that peer-assessed students accept feedback from peer assessors more easily because they are on the same level academically and they have established a personal relationship. Second, it was reported that the peer assessors’ feedback is of a higher quality because peer assessors are mindful of the students’ personal situations and take more time to provide feedback. Their recommendations are more useful because they personally understand what students are going through .Another main advantage mentioned by nearly all in the peer-assessed group was the overall reduction in stress; nearly every peer-assessed student reported that peer assessors create a comfortable atmosphere. This was due to the presence of the peer assessors and the more minimal difference in academic and social hierarchy. Some peer-assesses even considered the pleasant atmosphere as a fun learning environment . One student wrote, “Peer assessors can remove the fear of failure, for both the OSCE and medical study.” Finally, the close social and academic standing between peer-assessed students and peer assessors resulted in behaviour that improves the overall atmosphere of the OSCE and enabled high levels of knowledge transfer [“Peer assessors are more focused  and are not bored during the examination”].In addition, peer assessors and peer-assessed students often highlighted valuable information regarding future OSCEs and the knowledge gained during the OSCE . For peer assessors this could be caused by a difficulty maintaining an atmosphere appropriate to a compulsory examination, as was mentioned by one peer assessor.The structural disadvantages reported by the two groups included the limited professional competencies of peer assessors and a possible lack of objectivity on the part of peer assessors. In general, both groups identified less obligation and limited professionalism on the part of peer assessors. Less experience as assessors, a lower level of medical skill and limited clinical knowledge were all identified as disadvantages to using peer tutors as assessors. Furthermore, peer assessors may not be as objective as professional staff due to the relaxed atmosphere and personal relationship. Furthermore, personal relationships between peer assessed students and peer assessors can lead to awkward situations [“The disadvantage for the peer-assessed students is that they might not take the OSCE seriously enough. Finally, 65 peer-assessed students (22%) and 15 peer assessors (20%) responded that there are no disadvantages to having peer tutors act as assessors for the OSCE.In this study we found an overwhelming approval of using peers as OSCE assessors by both the learners and the peer assessors. We found that the implementation of peer assessment in the compulsory medical curriculum is feasible. From the learner’s perspective, peer assessed students benefit greatly from the use of peer assessors because the feedback is detailed and precise, making it more helpful than feedback from professional staff. Peer assessors benefit personally from improved clinical, social and teaching skills. Finally, from learner’s point of view peer assessors contribute to a profound reduction in stress within the formative OSCE, which is felt to be pivotal for individual success in learning.To the best of our knowledge this is the first study to report on broad implementation of a formative OSCE with peer-assessors in routine. We have more than 5 years of experience in the mandatory curriculum and more than 1500 medical students have passed the formative peer-led OSCE within the last 5 years. Our results indicate that medical students generally accepted peers as examiners in a formative OSCE. First published in 2010, a mock OSCE was found to be beneficial for student nurses . In 2014The benefits for peer assessors, including improvement in feedback and teaching skills and the consolidation of knowledge through teaching and administering examinations, has also been summarised in a scoping review by Khan et al. . Those aInterestingly, both peers assessed students and peer assessors claimed that there is an improvement in quality connected to the use of peer assessors compared to professional staff. Surprisingly, the few studies on peer tutors as OSCE assessors found only little difference between peer tutors as OSCE assessors compared to professional staff as OSCE assessors , 36–38. Finally we have shown that peer assessors in a formative OSCE at the conclusion of a mandatory near-peer teaching programme imparting basic medical skills could be successfully implemented in the curriculum of a large medical school with 320 students annually. The hidden curriculum of the formative OSCE at the end of the second year is to familiarise students with the OSCE’s format and decrease negative expectations or even fears of the OSCE in subsequent years of medical school. Our study indicates that we have fulfilled this goal. We have learned that if students have been previously trained as peer tutors, they are able to perform successfully as OSCE assessors. Other medical schools should be encouraged to implement peer assessments in near-peer teaching programs for junior medical students in routine.In this explorative study we showed that deploying peers as assessors remains a successful practice. One limitation of this study is that the close relationship between the peer assessors and the peer-assessed students may have resulted in less critical responses from peer-assessed students relating to the performance of peer tutors as OSCE assessors (effect of benignity). Second, this study was implemented as part of the routine evaluation. An extended study design, such as interviewing key actors, might have supplied further information. Finally, many participants are convinced that utilising peers as assessors reduces the level of stress for peer-assessed students, whereas the formative nature of the OSCE itself might also reduce stress levels. Therefore, the belief in the beneficial effect of stress reduction caused by the use of peer assessors may be a biased point of view and the amount of stress-reduction by peers as assessors could be overemphasised. Future studies and broad use of peers as assessors in qualifying OSCE are necessary to improve our understanding on the effect of stress-reduction.The use of peer assessors in the OSCE in a near-peer teaching programme for junior medical students is feasible and could be successfully implemented into medical curricula. Furthermore, over 90% of the peer assessors and peer-assessed students believe it is important to have peers as assessors. From an organisational point of view, deploying peer assessors enables the implementation of compulsory formative OSCE training for a high volume of medical students while reducing the impact on faculty resources. For peer assessors, the experience of acting as OSCE assessors provides valuable knowledge and improves physician competencies . Peer-assessed students respect peer assessors and appreciate the high quality of feedback they provide and the relaxed atmosphere during their first and formative OSCE. In contrast to this clear and self-confident point of view of the learner’s, it remains to us to prove or refute the equivalence or even improvement of quality as well as the effect of stress-reduction by student led peer assessment in the (mock) OSCE .Additional file 1. Questionnaire for peer assessors.Additional file 2. Questionnaire for peer-assessed-students.


The extensive performance of splenectomy worldwide for patients suffered from splenic trauma has given rise to high risks of postoperative complications, which has been attracting increasing attention in recent years. Nowadays the spleen is regarded as a versatile organ of the human body, invested with various excellent properties. The spleen has been recognized to take a great part in lipid metabolism. While removal of the spleen intends to alter lipid values, especially with an elevated LDL, splenic autotransplantation is able to normalize these lipid alterations. What is more, conservative surgical procedures like subtotal or partial splenectomy, could as well, afford a correction of dyslipidemia. At the same time, clinically, splenectomy demonstrates a high rate of atherosclerosis (AS), whereas non-surgical treatment after splenic trauma shows unchanged propagation of AS. Based on the intimate relationship between serum lipids and AS, the lipid changes modulated by splenectomy are believed to be responsible for the development of AS. Therefore, a “splenic factor” is most likely present in the regulation of lipidation and AS. Several theories have been postulated to elucidate the possible mechanism involved, among which most are primarily based on its forceful natural immune function, that is to say, the mononuclear phagocytic system.However, the accurate mechanisms behind this mysterious phenomenon still remain unclear so far. Of importance, lipid fractions should be monitored consecutively in case of inevitable splenectomy. Insufficient knowledge about the spleen had popularized the performance of splenectomy during the past decades, particularly for patients suffered from splenic injuries, until complications ensued gradually one after another in the subsequent years, among which some would be even severe and fatal. The most worrisome is the overwhelming postsplenectomy infection (OPSI), which is characterized as fulminant sepsis caused by encapsulated bacteria . OPSI coAwakened by the growing awareness of the potential complications following splenectomy, more and more surgeons have paid special attention to the importance of spleen, and have already recognized it as a useful organ of the human body, invested with various excellent properties. To date, it has been well known that the spleen is endowed with powerful filtration, immunological, along with hematopoietic and storage functions . RemovalIt has been well established that the spleen is devoted to a wide spectrum of metabolic control, including the metabolism of all metals, albuminoids alongside with indirect bilirubins from senescent erythrocytes . As a maIn 1914, King reported an increase in plasmatic cholesterol levels after splenectomy in dogs . SupposeAt the same time, while splenectomy tended to alter lipid values in animals, splenic autotransplantation was able to normalize these lipid alterations , 25, 26.Clinically, the spleen does interfere with the evolution of some diseases associated with lipid disorders. It is the lysosomes of cells of the mononuclear phagocytic system in the spleen that are most frequently present with metabolic changes in times of lipid deposits . Take GaSplenomegaly is inclined to maneuver the cholesterolemia over against splenectomy, which is most likely to develop hypocholesterolemia as a consequence of overfunction of the mononuclear phagocytic system . MyeloprIn light of these available findings, we have reasons to believe that the spleen participates in lipid metabolism to an extreme extent, although lack of adequate convincing evidences. Therefore, a “splenic factor” proposed by Asai et al.  is most AS is the leading cause of cardiovascular disease (CVD), which most of the time features acute heart attack and stroke , and accIn 1977, the long-term observation of veterans subjected to tramatic splenectomy during World War II disclosed an intensive susceptibility to coronary atherosclerotic heart disease . Based oAs expected, it seemed extremely evident in animals , 25, 33 Therefore, it is justified to speculate that, the absence of spleen apparently determines the occurrence of AS on account of deterioration of serum lipids, indicating a protective splenic effects .A number of studies have been carried out to evaluate influence of the spleen in lipid manipulation, which however, have created different and controversial results, with a vast preponderance of elevated lipid parameters by splenectomy.Experimentally, the majority of studies have provided evidences of increased concentrations of TG, TC, LDL, and decreased HDL, in combination with promotion of atherosclerotic changes in the absence of spleen , 25, 27,Clinically, splenectomy is equally coupled with a capability of modifying lipid values, especially with an elevated LDL , 14, 28.On the other hand, apart from the above-mentioned lipid disturbances, there are even discrepant outcomes. Some study revealed reduced LDL, and increased HDL , whereasTherefore, the role of spleen in lipid metabolism and AS still remains debated, irrespective of the strong supportive evidences.As in human being, a diet is the first-line management for plasmatic lipid levels and cardiovascular disease , it coulOnce again, some other voices arise representing different standpoints. An author argued that worsening of lipid fractions was entirely ascribed to the quality of chow other than splenectomy in rats . In contThe plasma lipids are fats or complex fat-like molecules, mainly referring to triglycerides, cholesterols, as well as phospholipids (PL) and free fatty acids (FFA). In brief, the process of lipid metabolism encompasses digestion and absorption in the small intestine, transportation within lipoproteins through the blood, and then biosynthesis in the liver. It is extremely intricate and subtle, requiring the help of a great deal digestive enzymes, and the liver is the pivotal organ during this course. Trouble in any steps of this process is likely to bring about lipid metabolism disorders, which are associated with an increase in the concentrations of plasma lipids.Among the numerous studies focused on dyslipidemia upon splenectomy, very few conferred deep insight into the mechanism implicated in lipid regulation by the spleen, thus further acting on the development of AS. There is still a long way for us to completely unveil its mysterious piths. Several theories have been postulated to elucidate the possible mechanism, among which most are primarily based on its forceful natural immune function, in other words, the mononuclear phagocytic system. But none of them have been well accepted. On the other hand, a number of potential predisposing factors different from lipid dysfunctions, like disturbance in coagulation, abnormal macrophage involvement in the plaque , in combThe most common and popular explanation was initially proposed by Schmidt et al., comparing the spleen to a storage reservoir for lipids . In caseFrom a metabolic point of view, the spleen has been established as an important site of LDL catabolism by the efficient macrophage activity . It has Noticeably, it needs to figure out that the liver is the principle organ in view of lipoprotein synthesis and excretion. The changes in lipid parameters by splenectomy are more likely to originate from exaggerated hepatic production of triglyceride-rich lipoproteins rather than attenuated catabolism, which would be more eligible to take charge of a decrement in HDL levels . In paraNeedless to say, the production along with purification of lipoproteins modulated by the spleen, is an extremely sophisticated course, and during this course, a variety of mediators may be drawn into. For instance, ATP-binding cassette (ABC) transporter ABCA1 favors macrophage cholesterol efflux to lipid-poor apolipoproteins like apoA-I , thus faAuthentically, AS has been declared to arise from vascular inflammation coupled with dyslipidemia, and LDL has been well considered as a risk factor for AS. Deposits of LDL in the arterial wall would aggravate the formation of atheromatous plaque. According to the oxidative theory , depositThe spleen has been established to be the staple organ responding to blood antigens, specifically to the oxLDL , 33, 38,By this token, the spleen is not only dedicated to the production of anti-oxLDL antibodies, but also to the clearance of antigen-antibody complexes . HoweverThe spleen may also interfere with the lipidic metabolic change of the liver on account of decreased lipid peroxidation following splenectomy . As far In addition, LDL receptors (LDLR) also partake in the modulation of dyslipidemia upon splenectomy. Upon removal of the spleen, enhanced LDLR activities are elicited in the liver , as mentLPL, as an enzyme responsible for the transportation and storage of lipids as well as hydrolyzation of chylomicrons and TGs, is most active in the hepatocytes. It can be stimulated by ApoC-II and suppressed by ApoC-III . AmazingNew-emerging disciplines on the noncoding sequences of miRNAs have corroborated their functions as the posttranscriptional regulation of gene expressions . miRNAs It is a very common phenomenon that PLT counts experience uprising upon splenectomy, which could otherwise be reverted under the conditions of splenic autotransplantation , 27. It Needless to say, the spleen is a multipurpose organ, massively synthesizing and accommodating large quantities of granulocytes, megakaryocytes, alongside with lymphocytes and macrophages, which have been verified to make great contributions to the process of AS. It is the major organ obligated to lymphocytes in the human body, and assumes the duties of maintenance of the immune system, by regulating both local and systemic immunity .Reportedly, a predominant number of memory B cells are pooled herein, which following activation, are apt to protect against atherosclerotic lesion formation , most prOn the contrary, Th1 lymphocytes, which are responsible for IFN-γ production and macrophage activation , in conjTaken altogether, it has even been declared that, following removal of the spleen, an integrated combination of macrophages, T cells together with an imbalance between the Th1/Th2 patterns , B cellsIn contrast, certain explanations appear likewise plausible with respect to improvement of AS by splenectomy. Reportedly, the spleen is regarded as a key manufacturer for monocytes and the most critical section of the mononuclear phagocyte system. It has stated that in the setting of acute myocardial infarction, the spleen is capable of rapidly mobilizing large quantities of mononuclear phagocytes directly onto the endothelium in the vessel wall in response to acute inflammation . MoreoveIn addition, a characteristic infiltration of macrophages in the vascular tissue could be found in response to lipid deposited in the atherosclerotic lesions . TheoretIn view of the conflicting results alongside with the obscure mechanism, contradictions will persist in the future as regards the role of splenectomy in lipid control and AS, and more relevant experimental and clinical studies will be needed. With the growing recognition of the spleen being an important organ with versatile functions apart from its impact on metabolic control, multiple modalities of spleen-conserving procedures such as vascular occlusions, splenorrhaphies, as well as partial splenectomies, have been utilized in recent years, so as to preserve the splenic tissues. Splenic tissue autotransplantation is an effective approach to partially reconstitute its structure and function in case of unavoidable splenenctomy, which is substantially capable of restoring the lipid and platelet (PLT) parameters , 27. FurOn the other hand, it should be admitted that this very role of splenectomy in dylipidemia and AS may be highly regulated, albeit extremely intricate. It involves probably the synergistic interactions between nutritional condition, immunologic response, as well as metabolic control and coagulation, and is in the meantime influenced by numerous other factors, such as demographics, poor diet, sedentary lifestyle, along with hormonal and genetic predisposition. Thereby, it is indeed problematic and challenging for clinicians to deal with, and lipid fractions should be monitored consecutively in patients subjected to splenectomy.


Acute lateral ankle ligament sprains (LALS) are a common injury seen by many different clinicians. Knowledge translation advocates that clinicians use Clinical Practice Guidelines (CPGs) to aid clinical decision making and apply evidence-based treatment. The quality and consistency of recommendations from these CPGs are currently unknown. The aims of this systematic review are to find and critically appraise CPGs for the acute treatment of LALS in adults.Several medical databases were searched. Two authors independently applied inclusion and exclusion criteria. The content of each CPG was critically appraised independently, by three authors, using the Appraisal of Guidelines for REsearch and Evaluation (AGREE II) instrument online version called My AGREE PLUS. Data related to recommendations for the treatment of acute LALS were abstracted independently by two reviewers.This study found CPGs for physicians and physical therapists (Netherlands), physical therapists, athletic trainers, physicians, and nurses (USA) and nurses . Seven CPGs underwent a full AGREE II critical appraisal. None of the CPGs scored highly in all domains. The lowest domain score was for domain 5, applicability  achieving an exceptionally low joint total score of 9% for all CPGs. The five most recent CPGs scored a zero for applicability. Other areas of weakness were in rigour of development and editorial independence.The overall quality of the existing LALS CPGs is poor and majority are out of date. The interpretation of the evidence between the CPG development groups is clearly not consistent. Lack of consistent methodology of CPGs is a barrier to implementation.CRD42015025478).Systematic review registered with PROSPERO (The online version of this article (10.1186/s12891-019-2750-6) contains supplementary material, which is available to authorized users. Lateral ankle ligament sprains (LALS) are common , 2 and cLALS are a common occurrence in the general population, indoor sports , field aAn acute LALS may be seen by many different people some of whom are not experienced highly trained clinicians. This is suboptimal as the condition requires correct diagnosis and if necessary, a referral. Acute LALS injuries may present to first aid officers at the workplace or at sporting events, to emergency departments , 21 or tKnowledge translation has been described by Lang as “any activity or process that facilitates the transfer of high quality evidence from research into effective changes in health policy, clinical practice or products” . It invoThe primary aim of this systematic review is to find and critically appraise all CPGs related to the treatment of acute LALS in adults. The secondary aim is to determine if CPGs are using the same studies to support their treatment recommendations for acute LALS.The search strategy, inclusion and exclusion criteria were specified and documented in advance and registered with PROSPERO (registration number: CRD42015025478).An electronic search was conducted across medical literature databases. All searches were performed in October 2017. The Cochrane Library, MEDLINE, CINAHL, Sportdiscus, Web of Science, Scopus, USA National Guideline Clearinghouse and PEDro databases were searched to find all CPGs for treatment of LALS. The search strategy was agreed upon after discussion with an experienced librarian and was refined through team discussion. The search strategy of medical databases used medical subject headings and free text search terms (mesh). Specifically, terms of (“ankle injur*” OR “ankle sprain*” OR “sprained ankle*”) and guideline* were used. In addition, other sources such as Google Scholar, handsearching and personal communication supplied guidelines. Only CPGs published in English were retrieved. See Additional file Records were imported into referencing software  and all duplicates were removed using this software.The review considered CPGs for adults 18 years and older with LALS and acute treatment recommendations.The review did not consider CPGs for adults 18 years and older with diagnoses of ankle fractures or syndesmosis ankle sprains. The authors are aware that distal fibular avulsion fractures are common in LALS and are managed as LALS.Study inclusion was determined by 2 authors  who independently considered title, abstract and full text. There was an absolute rate of agreement between the two reviewers of 94% and a prevalence-adjusted and bias-adjusted kappa  of 0.88 The Appraisal of Guideline Research and Evaluation II (AGREE II)  is a staThe AGREE II  has undehttp://www.agreetrust.org/agree-ii/). All CPGs were reviewed independently, and conflicts were resolved by discussion until consensus was reached between all 3 authors. This was consistent with the methodology of a systematic review of osteoarthritis guidelines [.Three authors  read the AGREE II user manual and watched the online tutorials from the AGREE II website (idelines  and a syidelines .A data abstraction form in Microsoft Excel (2016)) was developed, piloted, and changed, as necessary. Data was later abstracted by one reviewer (TG) and verified independently by another reviewer (GW). Recommendations for the treatment of acute LALS were abstracted. Recommendations from CPGs about the use of specific treatment options were dichotomized to “recommended” or “not recommended”. In addition, a descriptive synthesis of the recommendations and their supporting evidence was undertaken. It was assessed if the same evidence had been used during formulation of the CPGs.Forty-three articles were exported to Endnote X7 . Twenty Two CPGs were written for nurses , 39, oneThe AGREE II scores, which were derived from the three independent reviewers’ scores as a percentage of the maximum possible score, are shown in Fig. The lowest overall domain score was for domain 5: applicability  scoring a joint total score of 9% for all CPGs. The five most recent CPGs scored a zero for applicability. The second lowest domain score was domain 6: editorial independence. Three CPGs scored zero for this domain , 41, 42.For each of the appraised CPGs, the Level of Evidence (LOE) and Strength of Recommendation (SOR) grading scales used in the formulation of the respective recommendations were extracted from the guideline and tabulated  or first aid officers. It is common for acute LALS patients to seek free advice at pharmacies. First aid officers also offer free advice and early care to thousands of acute LALS patients at work, sporting, and public events. In a New Zealand study , 96 % ofThis study is the first systematic review to evaluate the quality of LALS CPGs using the AGREE II tool. The AGREE II consists of 23 items, which are grouped into six domains: scope and purpose (3 items), stakeholder involvement (3 items), rigour of development (8 items), clarity of presentation (3 items), applicability (4 items), and editorial independence (2 items). None of the CPGs scored highly in all domains. The highest domain scores were for domain 4, clarity of presentation with all CPGs scoring above 61%. The second highest domain score was domain 1, scope and purpose with 5 CPGs scoring above 67%. The 2012 Dutch CPG  was the The lowest domain score was for domain 5, applicability  achieving an exceptionally low joint total score of 9% for all CPGs. The five most recent CPGs scored zero for applicability. This is a disturbing finding and further research is needed as to why these CPGs did not address these key components of knowledge translation for clinicians. However, it is probably due to the guidelines being published in peer reviewed journals, the authors being limited by the space available for description of the guideline development process. Conversely, peer review may explain any high scores in editorial independence .Failure to assess whether CPGs are being used correctly is also of concern. Fortunately, this has been assessed independent of the guideline developers. Several papers published by Dutch research groups investigating compliance with an LALS CPG have found moderate compliance by physical therapists in the Netherlands , 110. ReThe views of the funding body have not influenced the content of the CPG.Competing interests of members of the CPG development group have been recorded and addressed.The second lowest domain score was domain 6, editorial independence. Three scored zero for this domain , 41, 42.The third lowest domain score was for domain 3, rigour of development. Five of the CPGs –39, 41 sThis systematic review found poor consistency in the reporting of the levels of evidence and strength of acute recommendations. Two CPGs , 39 failThe first CPG assessed in this study was published in 2006, the last in 2013. Factors that might necessitate CPGs to be updated have been discussed in the literature , 116. ThThe secondary aim of this study was to determine if CPGs use the same studies to support their recommendations in the acute phase of a LALS. In this systematic review, there is a trend for CPG developers in different disciplines/fields to use the same studies to support their recommendations. However, this secondary objective has not been adequately achieved, in part based on a lack of an appropriate assessment tool. A previous systematic review of CPGs for the physical treatment of osteoarthritis categorised recommendations by grouped treatments with their associated LOE and SOR and then converted these into a scale from − 4 to + 4 . This apInconsistency across CPGs suggests that the most contemporary high-level evidence is not being used by all CPG developers, however this criticism may be tempered by consideration of the differing ages of the CPGs. CPGs can recommend that a treatment be not recommended. For example, in a recent systematic review evaluating treatment strategies for acute LALS the authors found there was insufficient evidence to support the use of ultrasound as an treatment for LALS . This reWhen comparing the recommendations for treatments between American and Dutch guidelines there seems to be disparity. Graded joint mobilisations or mobilisation with movement, pulsating shortwave diathermy, electrotherapy, and low-level laser are not recommended by the Dutch CPGs. However, they are recommended by the American physical therapy CPG, despite some common studies used in development of both CPGs


Background: Patients over 65 years of age taking multiple medications face several risks, and pharmaceutical interventions can be useful to improve quality of care and reduce those risks. However, there is still no consensus on the effectiveness of these interventions aimed at promoting changes in clinical, epidemiological, economic, and humanistic outcomes for various service delivery, organizational, financial, and implementation-based interventions. The objective of this overview of systematic reviews was to summarize evidence on the effectiveness of community-level pharmaceutical interventions to reduce the risks associated with polypharmacy in the population over 65 years of age.Method: This overview used a previously described protocol to search for systematic review articles, with and without meta-analysis, and economic evaluations, without any language or time restrictions, including articles published up to May 2018. The following databases were searched: the Cochrane Library, Epistemonikos, Health Evidence, Health Systems Evidence, Virtual Health Library, and Google Scholar. The basic search terms used were “elderly,” “polypharmacy,” and “pharmaceutical interventions.” The findings for outcomes of interest were categorized using a taxonomy for health policies and systems. Equity-related questions were also investigated. The studies were evaluated for methodological quality and produced a narrative synthesis.Results: A total of 642 records were retrieved: 50 from Health Evidence, 197 from Epistemonikos, 194 from Cochrane, 116 from Health Systems Evidence, and 85 from the Virtual Health Library. Of these, 16 articles were selected: 1 overview of systematic reviews, 12 systematic reviews, and 3 economic evaluations. There is evidence of improvement in clinical, epidemiological, humanistic, and economic outcomes for various types of community-level pharmaceutical interventions, but differences in observed outcomes may be due to study designs, primary study sample sizes, risk of bias, difficulty in aggregating data, heterogeneity of indicators and quality of evidence included in the systematic reviews that were assessed. It is necessary to optimize the methodological designs of future primary and secondary studies.Conclusion: Community-level pharmaceutical interventions can improve various clinical, epidemiological, humanistic and economic outcomes and potentially reduce risks associated with polypharmacy in the elderly population. It is estimated that 21% of the world's population will be over 65 years of age by the year 2050. The elderly have complex health needs as they often have multiple comorbidities. An estimated 30% of elderly persons are prescribed 5 to 12 medications , there are several types of interventions targeted at various levels and components of health systems  Interventions targeted at professionals to improve their prescribing practices; (ii) Interventions targeted at consumers to improve the use of medications.Organizational: Interventions that involve a change in the structure or delivery of health care.Financial: Interventions that focus on professional reimbursement, incentives, and penalties.Regulatory: Interventions that aim to change the provision of health services through regulatory frameworks.These interventions require health professionals to analyze the pharmacotherapeutic strategy established for a patient. This is a continuous process that identifies and solves DRP and/or DNO based on need, efficacy and safety, with the goal of increasing effectiveness and decreasing the risks of pharmacotherapy. Examples include therapeutic strategy-related interventions, interventions related to the quantity of drugs and health education interventions , and Google Scholar. There was no language or time restriction, including articles published up to May 2018. Systematic reviews, with or without meta-analysis, and economic evaluations were included. The search strategy included medical subject headings (MeSH) and health sciences descriptors (DeCS), using the keywords “Elderly,” “Polypharmacy,” and “Pharmaceutical intervention.” The search was adapted to the various electronic databases. Details of the search strategies are provided in This study addressed the following question: Which community-level pharmaceutical interventions reduce the risks associated with polypharmacy in the elderly population over 65 years of age? In accordance with the PICO guidelines . During the screening, 472 articles were excluded due to inadequacies regarding outcomes, target population, design and/or type of study and type of publication. A total of 53 articles were preselected based on the inclusion criteria. After reading the full text of the articles, 27 were excluded because of the scenarios, intervention types and outcomes. In the end, 16 articles were selected for this overview. The list of excluded articles is available in A narrative-descriptive synthesis was prepared. This synthesis describes the interventions and evidence found, including the main findings relevant to the aims of this overview.The quality assessment was performed independently for each study by two reviewers , and the results were compared. Disagreements were resolved by consensus. We used A MeaSurement Tool to Assess systematic Reviews (AMSTAR) , methods for aggregating study results, evaluation, and documentation of scientific quality of included studies, evaluation of probability of publication bias, the inclusion of gray literature, and declaration of conflicts of interest.The results presented in Hajjar et al. , Kaur etKaur et al. , AlldredKaur et al. , Hajjar Kaur et al. , OlaniyaOlaniyan et al.  presenteKaur et al.  presenteKaur et al. , MathumaPatterson et al.  and OlanMathumalar et al. , PattersOlaniyan et al.  presenteKaur et al.  presenteAmong the evaluated articles, no article specifically addressed this type of intervention, although there is evidence that such interventions can be effective in improving prescribing quality. It should be noted, however, that the CADTH has published evidence on interventions related to the improvement of prescribing quality using financial interventions  demonstrated the benefits of pharmaceutical care for improving outcomes in the elderly over 65 years of age. There is evidence that an adequate system for managing, prescribing, monitoring, and evaluating the use of medications is effective in reducing polypharmacy and improving adherence to medications, while decreasing drug costs, medication errors, drug-related problems, adverse drug reactions, drug-drug interactions, drug-related negative health outcomes, and hospital admissions. Such systems also improve access to services, the use of safe and adequate medications and health-related quality of life.In terms of implications for research, there is a substantial number of international studies showing that community-level interventions that reduce the risks associated with polypharmacy are complex and varied; there is no single path. However, authors of the systematic reviews selected in this overview highlight issues that remain unanswered, namely:Is there a difference between the socioeconomic and cultural profile of the elderly in terms of equity and clinical, humanistic, epidemiological, and economic outcomes?What types and/or models of pharmaceutical interventions provide monetary gains when compared to other intervention models?Is there a good cost-effectiveness and/or cost-utility ratio  in the long term for pharmaceutical care users?Are there psychological effects on patients receiving pharmaceutical care in terms of clinical, humanistic, epidemiological, and economic outcomes?Is there a positive impact of pharmaceutical care on the cognitive function and functional capacity of elderly patients?Which indicators are more specific and sensitive in measuring pharmaceutical interventions and their correlation with clinical, humanistic, epidemiological, and economic outcomes?Do multifaceted strategies for pharmaceutical care have a synergistic effect on clinical, humanistic, epidemiological, and economic outcomes?What is the minimum time  and/or frequency  of pharmaceutical care provided to elderly patients necessary to be effective and/or efficient?Are the positive effects on clinical, humanistic, epidemiological, and economic outcomes persistent in the long-term?There is a need for further investigation of the effect of various types of pharmaceutical interventions  on the improvement of pharmaceutical care in the elderly over 65 years of age.As for the implications for policies and programs, pharmaceutical care stands out from an economic perspective as it is an efficient intervention to optimize prescribed medications and improve the quality of life in elderly persons taking multiple medications. Results from a cost-utility analysis suggest that pharmaceutical care is cost-effective.There is evidence—with 80% probability—that pharmaceutical care is economically viable and profitable. This supports its incorporation into pharmaceutical assistance programs and/or policies, especially in universal healthcare systems based on access, quality and rational and sustainable use of medications at all levels of health care.We know how important it is to ensure the establishment and implementation of evidence-based policies. Thus, we reiterate that, in universal and sustainable healthcare systems, pharmaceutical assistance and/or pharmaceutical care must be based on evidence of the efficacy and safety of the drugs, the effectiveness of the medications and the efficiency of the treatments.Finally, we recommend that pharmaceutical professionals committed to efficient health policies should be included in multidisciplinary care teams to ensure that the elderly have access to high-quality and safe pharmacotherapy and a better quality of life.OS defined the research questions and prepared the research protocol in conjunction with JB. OS designed the study and conducted the bibliographic searches and the analyses. JB refined the research question in the original draft and contributed to the study design by helping with the literature review and article review. The authors read and approved the final version of the manuscript.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.