Philanthropists, charity leaders and policy-makers have increasingly recognised that the process of giving resources needs to be grounded in evidence—sometimes referred to as ‘evidence-based’ or ‘data-driven’ philanthropy. Yet few philanthropists practise evidence-based philanthropy, and some contend that there is insufficient evidence on which to base their funding decisions. This review aims to identify factors that promote or limit the use of evidence by philanthropists and to rigorously evaluate all existing research on this issue.To identify, synthesise, and evaluate appropriate and rigorous research, examining factors which act as barriers to or facilitators of the use of evidence by philanthropists.dx.doi.org/10.17504/protocols.io.wbsfane). We searched 10 interdisciplinary databases using a highly sensitive search strategy, developed in consultation with an information scientist. We also contacted experts and searched a range of websites. Studies were included if they comprised primary research into or systematic reviews of the barriers to and facilitators of the use of evidence by philanthropists or funders when determining which charities  to fund. All studies were appraised for quality, and the results synthesised using thematic analysis.This review was conducted according to Cochrane standards and reported following PRISMA guidelines. The review protocol was pre-registered  inadequate knowledge transfer and difficulties accessing evidence, (2) challenges in understanding the evidence and (3) insufficient resources. The three key factors that expedite the use of evidence are (1) improved knowledge transfer and more accessible/relevant high-quality information, (2) access to professional advisors and networks and (3) broadening the definition of what counts as credible evidence along with standardisation of reporting.The authors of this review found several compelling arguments for promoting the use of evidence by philanthropists to inform their philanthropy. If evidence-based philanthropy is to flourish, then they recommed the following actions: Firstly, philanthropy should be underpinned by a commitment to 'do no harm'. Secondly, the definition of evidence should be expanded and funding decisions based upon consideration of 'all available evidence'. Finally, there should be more investment in synthesizing evidence and in the infrastructure for knowledge transfer. Kids Company, a large charity that had attracted considerable funding from both private philanthropy and the public sector. PACAC raised concerns about safeguarding commenting that ‘There are a number of safeguarding issues which have come to PACAC’s attention during the conduct of this inquiry into Kids Company….’ . donors’ ( p.51). WToday, there is growing awareness among philanthropists, charity leaders and policy-makers that the process of giving resources needs to be grounded in high-quality evidence. Accordingly, we have seen the emergence of both ‘evidence-based’ and ‘strategic’ philanthropy, as philanthropists seek to be more outcomes-focused in their giving. Philanthropists and funders are also increasingly recognising that collaboration, sharing knowledge and ‘learning from mistakes’ are a good practice ( p.6). ThHow donors direct their money to charities matters today more than ever, as government funding to the voluntary sector has declined in both the UK and USA. In the UK, the voluntary sector experienced a fall in government funding of £1.9 billion (down from £15.2 billion to £13.1 billion) between 2009 and2013 ( p.5). MoWhile the need to generate evidence to support philanthropic funding decisions is clear, the extent to which philanthropists will use it is less certain. The utility of evidence may depend on how readily available it is to those making funding decisions, whether or not philanthropists can distinguish between the different qualities of evidence, and whether the available evidence is relevant to their question and aligns with their own tastes and preferences.Moreover, what is meant by ‘the best available evidence’ is contested, particularly in light of the differing types and weight of evidence in the social sciences , 10. GreThere is limited research on how donors use evidence to inform their philanthropy and on the barriers to and facilitators of their use of evidence. To date, much of the research in this area has concerned the extent of giving by donors rather than how they choose charities. Studies that do examine the manner in which donors choose charities usually focus on the ‘why’―namely, the donor’s motivation for choosing the charities―rather than the ‘how’, with its focus on the mechanisms by which donors choose charities.This systematic review seeks to address this gap in the research by identifying the factors that may limit or promote the use of evidence by philanthropists and by evaluating existing research on this issue. This will help support the development of mechanisms to address the barriers and scale up those factors that facilitate evidence-informed philanthropy. Our rationale is that enhanced access to and understanding of high-quality evidence in tandem with improved communications and sharing of knowledge will enable philanthropists to make better judgements which in turn will lead to ‘better and more sustainable philanthropy’ ( p.16). TTo identify, evaluate and synthesise appropriate and rigorous research, examining factors which act as barriers to or facilitators of the use of evidence by philanthropists.dx.doi.org/10.17504/protocols.io.wbsfane).This review of the barriers and facilitators to the use of evidence by philanthropists and funders was conducted according to the standards of Cochrane  and CampWe did a highly sensitive search involving electronic resources, hand searching and contacting experts and initially found nineteen studies. Each of those studies was critically appraised using GRADE CER-qual, and nine studies were included in the final data synthesis. Many of the barriers and facilitators were unique, although others were reflections of each other.This systematic review utilised both PRISMA guidelines, which stipulate a minimum standard for describing the findings of systematic reviews see Fig. .Fig. 1PABI/INFORM GlobalApplied Social Sciences Index and Abstracts (ASSIA)International Bibliography of the Social Sciences (IBSS)PAIS IndexPolicy File IndexSocial Services AbstractsSocial Science Premium CollectionWorldwide Political Science AbstractsSCOPUSOpen GreyProQuest Dissertation and Theses GlobalIn conducting a systematic review of the qualitative literature, inadequate cataloguing of qualitative research means that despite combining terms and employing precise and wide-ranging search strategies pertinent studies may still be overlooked ( p. 5). AThe authors anticipated that due to a lack of rigorous, independent research to provide an authoritative basis for our understanding of philanthropic activity , it woulPhilanthropy ImpactNew Philanthropy CapitalThe Lilly Family School of PhilanthropyTen Years’ TimeUBS PhilanthropyCharities Aid Foundation (CAF)Nonprofit QuarterlyCandid (comprising Foundation Centre and GuideStar)Association for Fundraising ProfessionalsInstitute of Fundraisingminimise publication bias, the authors utilised supplementary search methods which they blended with database searching. Supplemental search methods employed included hand searching of journals and the bibliographies of relevant articles, contacting experts and searching relevant websites including:To be eligible for inclusion, studies must have been published in English and be primary research or systematic reviews investigating the perceptions and/or experiences of philanthropists, high-net-worth individuals (HNWIs) or funders (including grant-making organisations) relating to their use of evidence. All study designs were eligible for inclusion provided they examined factors affecting the use of evidence by philanthropists; however, such factors need not have been the primary focus of those studies. Studies investigating the perceptions of professionals  as to how philanthropists (or how they perceive philanthropists to) use evidence were also eligible for inclusion. Articles were initially screened at the title, publication date and abstract level by CG using Endnote.The primary populations of interest were philanthropists, high-net-worth individuals and funders (including grant-making organisations) who make significant donations (sometimes referred to as major gifts) to fund charities or third-sector organisations . The secondary populations of interest were third-sector practitioners (such as charity CEOs), philanthropic advisors and philanthropic consultants.This review adopted the following definition of ‘philanthropist’: an individual who makes donations to charities and non-profits with the intent of addressing social problems . ‘FunderThis review defined ‘barriers’ as things or circumstances that impede the ability of philanthropists  to use evidence to inform their philanthropy or grant-making. ‘Facilitators’ are defined as any factors or conditions that enhance the ability of philanthropists  to use evidence to inform their philanthropy or grant-making. Barriers and facilitators do not need to be the primary outcome of interest of a study to be considered for inclusion.Studies were stored, screened and coded using NVIVO software, and all data were extracted by CG with a 20% random sample screened independently by PM. Any disagreements were resolved by consensus.Year of publicationAuthorTitleCountry where study was conductedStudy aimsExtracted data from the final set of included studies were captured in a data extraction table (Table S2); a further table (Table S3) captured the characteristics of the excluded studies Identified barriers to utilisation of evidenceIdentified factors of utilisation of evidenceTables S4 and S5 present the methodological limitations of the included studies as they relate to each finding, using GRADE CER-Qual methods. Table S6 captures the data from individual studies that contributed to each review finding. Table S7 is a CER-Qual Quality of Evidence Profile, while Table S8 summarises our qualitative findings. Finally, Table S9 summarises our confidence in each of the individual studies. Tables S4 to S9 are attached in Additional file The main purpose of this review was to identify limiting and promoting factors regarding the use of evidence as identified by philanthropists, funders and charity practitioners. Consequently, the review includes studies comprising a variety of research designs, namely quantitative, mixed methods and qualitative. In light of this, we conducted a thematic analysis to integrate the data, through which the main findings and theories were extrapolated and then ordered as either barriers or facilitators to form a narrative synthesis , 21. We Prior to data synthesis, the authors employed a number of critical appraisal tools to assess the credibility and rigour of the included studies and to ensure transparency in the appraisal process. However, many critical appraisal tools require the reviewers to score each of the studies against specific criteria, so studies that do not report all of the criteria will score low even though they might not merit it . Hence, http://mixedmethodsappraisaltoolspublic.pwbworks.com/w/file/fetch/127916259/MMAT_2018_criteria-manual_2018-0801_ENG.pdf).While this was first and foremost a narrative exercise, for studies that employed a qualitative research design, we conducted methodological assessment using the Joanna Briggs Institute’s Critical Appraisal Checklist for Qualitative Research . The sinThe included studies were subjected to the GRADE CER-qual assessment  to ascerThe level of confidence awarded to each study was informed by the methods of data collection and analysis that were used, the level of methodological rigour and the total number of items fulfilled on the appraisal checklists. Studies were then ranked as either high, medium or low quality. We then used our own informed judgement, taking into consideration the value of the insights derived from the individual study alongside the study’s methodology, as those “rated as ‘low quality’ because of methodological flaws or lack of reporting may nevertheless generate new insights, grounded in the data…” ( p.375).The 51 records that emerged from the supplemental hand searching were combined with 635 records which were identified through the database searching; together, these amounted to 686 records. After removing 117 duplicates, 518 studies from the database were screened at title and all 51 studies from the supplemental search were screened at title . Four hundred eighty-six studies from the database search and 32 studies from the supplemental search were excluded following scrutiny of the title and in some cases abstracts. Thirty-two studies identified through database searching were retrieved as full text, and 19 studies identified through the supplemental search were retrieved in full. Of these, a further 42 were excluded for the following reasons: not being primary research or systematic reviews focusing on the experiences of philanthropists, funding organisations, third-sector professionals, philanthropist advisors and/or consultants; or for not being primary research or systematic reviews concentrating on the barriers to and facilitators of the use of evidence. Nine studies were included in the final synthesis. None of the included studies emerged from the database searches; they were all derived from the supplemental search.The characteristics of included and excluded studies are presented in Tables S2 and S3 ; philanthropists and philanthropic advisors (one study); philanthropy advisors and consultants together with charity practitioners (one study); funders comprising trusts and foundations (two studies); philanthropy practitioners and consultants (one study); academics, funders and professionals working in the non-profit sector (one study); and academics, charities, NGOs, advisors, businesses and professionals (one study).JBI Critical Appraisal Checklist for Qualitative Research , and improved and more readily available synthesis of evidence was identified as a facilitator by one of the studies [study no. 9].Insufficient knowledge dissemination and lack of availability of and access to evidence was deemed to be a barrier by five studies , and five studies  identified knowledge dissemination, knowledge hubs and open data as facilitators of the use of evidence.One study [study no. 5] reported that a paucity of measurement tools proved to be a barrier to the use of evidence, and the same study reported that the provision of appropriate measurement tools would serve to facilitate the use of evidence.All nine of the studies described at least one barrier to the use of evidence, although this was not confined to the use of evidence by philanthropists. Eight of the studies described at least one facilitator of the use of evidence. Twenty-seven unique factors were identified as barriers to the use of evidence and thirty-three factors as facilitators of the use of evidence. In a number of instances, the barriers and facilitators were reciprocal, for example:The top three barriers to the use of evidence identified by philanthropists and funders included difficulties in accessing relevant and high-quality evidence (six studies). This was illustrated by one study which pointed out that the main types of evidence relied upon by funders (such as data synthesis and scoping reviews) ‘are different to the main types of evidence they generate (e.g. impact reporting) and share with others ’ ( p.5). PrThe factors cited most frequently as facilitating the use of evidence were better knowledge transfer and improved ease of access to evidence (six studies). Recognised mechanisms for knowledge transfer included ‘peer-to-peer sharing of experience and practice’ ( p.10); pThe nine included studies comprised a range of research designs, including qualitative, quantitative and mixed methods. By conducting a thematic analysis, we took an inductive, data-driven approach, which helps with both the extraction and interpretation of the complex data. Moreover, ‘the use of thematic analysis ensures credibility as it is transparent, rational and uniform, allowing the reader to have confidence in the findings’ ( p.22). TOur review comprised nine studies describing at least one barrier or one facilitator and included one survey, two mixed-methods studies and six qualitative studies. Table All nine of the included studies described at least one barrier to the use of evidence, although this was not confined to the use of evidence by philanthropists. Eight of the included studies described at least one facilitator of the use of evidence.Difficulties in accessing evidence (six studies)Challenges in understanding the evidence (three studies)Insufficient resources (six studies)Knowledge sharing and ease of access (six studies)Professional advisors and networks (three studies)A broader definition of what counts as credible evidence and better standardisation of reporting (three studies).A number of the barriers and facilitators reported in the studies were labelled differently despite their having similar underlying constructs, for example, lack of skills and insufficient staff may be part of the same underlying problem as a lack of resources. To deal with this, we organised all of the factors into six overarching categories, comprising three barriers and three facilitators:Table S6 extrapolates the data from each study supporting each category . Hence, what motivates philanthropists to give to one particular genre of charity over another might determine the extent to which they will seek to use evidence to underpin their giving.The presumption that philanthropists seek to make pragmatic, evidence-informed decisions may not always be the case as ‘philanthropic donors are often misled by nature and by their instincts’ . It may Two key themes emerged as barriers to the use of evidence: difficulty in accessing relevant and high-quality data and a lack of understanding of that information. Further analysis revealed that the evidence sought and relied upon by philanthropists was rarely aligned with the evidence generated by the beneficiary charities. Moreover, much of the data that are generated by charities is deemed to be largely irrelevant to donors . This isAnother constraint relating to the use of evidence is the cost of obtaining relevant evidence. Few philanthropists and funders are willing to fund the cost of evaluations of interventions for example. Consequently, a number of studies, including our own, have highlighted the absence of impact measurement among TSOs. Despite the relatively transparent nature of British charity regulation, only a small minority of charities report on their impact to the Charity Commission  and a siFurther barriers relating to accessibility of evidence included a lack of scholarly research on the area in question; a lack of access to such research ; poor organisation of research; and on occasion the sheer volume of information. These problems are compounded by insufficient dissemination of high-quality and synthesised knowledge. Resource constraints emerged as an additional barrier to the use of evidence, including a lack of people, time and funding. Indeed, the cost of accessing scholarly research along with the requisite time required to ‘search for and identify relevant research’ may mean that such research is only used when it is deemed essential ( p.5). A n = 2604) of donors felt apprehensive about the impact of their donation (35 p.4), which manifested as ‘unease about determining an organization’s credibility or trustworthiness’ and ‘frustrations that some non-profits do not always explain how a charitable donation will be used’ . MoSix studies identified inadequate transfer of knowledge and difficulties accessing evidence as barriers. Inadequate infrastructure may be a contributing factor to poor transfer of knowledge, particularly the lack of any single identifiable mechanism for supporting dissemination . ConsequA number of the included studies expressed concerns that a narrow definition of what counts as credible evidence can act as an additional barrier to using evidence; however, several funders specifically raised ‘concerns about the quality of evidence’ ( p.16). ADifficulties accessing high-quality and relevant information also hinders the use of evidence. Breeze  notes thn = 2115) would donate more if they had a better understanding of the impact of their donation. One study identified syntheses of knowledge about ‘what has worked and how’ as a mechanism that facilitates the effective use of evidence and thus serves to ‘make interventions more effective and implementation stronger’  to acquiring knowledge that could help them’ ( p.5). ThThe studies in this review identified a number of factors which support the use of evidence, including signposting and the publication of links to research findings  through None of the included studies were derived from the systematic search of the data bases, rather they each emerged from the supplemental searching. Consequently, none of the included studies was subject to peer review although it should be recognised that many non-peer-reviewed papers are of high quality and vice versa . SimilarA further limitation was that the heterogeneity of study designs made it challenging to compare quality across the studies in this review. In addition, some studies used vote-counting techniques to analyse their findings, which involved counting the number of times each factor was mentioned, without any weighting of importance. This makes it difficult to determine the impact of each factor.The included studies had a range of methodological weaknesses. However, as this was intended to be a narrative review, even the one third of studies graded low quality were analysed, as we deemed them likely to offer valuable insights .We were surprised to find that even those studies that sought to make recommendations relating to the better use of evidence in philanthropy did not employ rigorous methodology .In their study, exploring the ‘Benefits of open access to scholarly research for voluntary and charitable sector organisations’, Beddoes et al.  found thTwo thirds of the studies cited challenges in accessing evidence and research, together with insufficient knowledge transfer, as barriers. Future research should therefore explore ways to enhance the transfer of knowledge and to better understand which research philanthropists and funders deem to be relevant and accessible.Four of the included studies called for broadening what constitute credible evidence; thus, research that seeks to clarify our understanding of different types and values of evidence would be welcomed..Two studies revealed the growth in the philanthropy advice market which ‘since the turn of the century’ has emerged ‘with the aim of helping philanthropists give their money away well’ ( p.6).This finding suggests that professional advisors could be a crucial conduit to wealthy donors, and thus, the quality of the advice they offer is significant. As such, some form of professional standards and accreditation for philanthropy advisors would be welcomed in the UK to ensure that the quality of advice is of a minimum standard and is reliable. Indeed, one of the included studies  reports This review has highlighted several compelling arguments for supporting and encouraging philanthropists and funders to use evidence in their decision making. If evidence-based philanthropy is to flourish, then the following steps are recommended.First, it is imperative that all philanthropy is underpinned by a commitment to ‘do no harm’ (similar to the Hippocratic oath). In January 2019, the National Council for Voluntary Organisations published a statement of ‘Charitable Ethical Principles’ which, while stopping short of a commitment to ‘do no harm’, did state that all ‘charities should proactively champion ethical behaviour and reflect and apply their charitable values in any activity they undertake’ ( p.1). HoSecond, the definition of evidence should be expanded, and funding decisions should be ‘based on a full consideration of available evidence’ ( p.9). MoIf high-quality, widely accepted, readily understood, user-friendly and reliable measures and indicators are to be available where they are most needed, philanthropy … must become more intentional about investment in developing appropriate data sources, indicators, and measures. ( p.6)National Data Strategy offers the chance to seize the new data environment, and use it to deliver better public services, and improve the economy and society for future generations’ . HIn conclusion, we theorise that the practice and impact of philanthropy is considerably enhanced by the application of the learning and knowledge that emerges from evidence-based research. Moreover, when resources are finite and not sufficient to meet the extensive demands made upon them, those responsible for deciding how funding will be allocated should endeavour to ensure that those decisions are informed by detailed consideration of all the accessible evidence .Additional file 1. Tables of Extracted Data.Additional file 2. GRADE CERQual Tables.Additional file 3. PRISMA checklist.Additional file 4. Search Strategy.Additional file 5. JBI Checklists.


This article aims to provide a description of conceptual dimensions and psychometric properties of the tools of oral and dental health literacy.Two authors in this study conducted electronic searches in the Medline (via PubMed), and Embase databases to find relevant articles from 1990 to present day. Evaluation of the tools was carried out in two parts; general evaluation of the tools using skills introduced by Sørensen et al., and qualitative assessment of psychometric properties using COSMIN checklist.After reviewing 1839 articles on oral and dental health literacy and evaluating 33 full text articles for eligibility, 21 articles entered the study. The sample size varied from 20 to 1405 subjects and the items of each tool ranged from 11 to 99 items. Of the 21 tools examined, 16 tools were evaluated for word recognition. For the studies examined, the evaluation of COSMIN scores was often fair or good. Of the 21 tools examined, 9 tools at least in one dimension were in the category of “poor”, 19 tools were in the category of “fair”, 20 tools were in the category of “good”, and 4 tools were in the category of “excellent” in at least one dimension.The findings of this study showed that some aspects of oral and dental health literacy are being ignored in the existing tools. Therefore, the authors of present study emphasize on the necessity to design and develop a comprehensive tool and take into account two characteristics of simplicity and briefness for international use. In the twenty-first century, health literacy (HL) has been introduced as a global issue and a priority in health , 2, and Some studies point to the link between low level of OHL and lack of using preventive or therapeutic services and also understanding of health information transferred by the health care providers , 9. The Dickson-Swift et al. 2014) explained the primary tool for OHL has been derived from the HL tools. For example, the tool of Rapid Estimate of Adult Literacy in Dentistry (REALD) is an adaptation of the Rapid Estimate of Adult Literacy in Medicine (REALM), . Similar14 explaiSo far, only one systematic review has been carried out to evaluate the oral and dental health literacy tools in 2013 , which eWe report this manuscript in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA statement) guideline  Supplem.http://www.opengrey.eu/). A hand-search of relevant bibliographies was performed to identify potential studies that were excluded. The key words used in the search included; oral, dental, Health, Literacy, tool, instrument, questionnaire, Psychometric, validity, reliability. Only peer-reviewed articles that were written in English were considered. The full search strategy for each database is provided in Table A systematic library search was conducted by one of the authors (ASM) in consultation with a librarian across seven electronic databases . Gray literature sources was searched in the System for Information on Grey Literature in Europe (SIGLE) (Studies that fulfilled the following criteria were included: (1) Studies whose results have assessed one or more of the following psychometric properties: internal consistency, reliability, measurement error, content validity, face validity, structural validity, hypothesis testing, cross-cultural validity, criterion validity, or responsiveness; (2) all studies published between each database’s inception and January 2019 that have been design, develop, or psychometric to measure oral and dental health literacy; and (3) studies published in English language. Studies were excluded if they were (1) conference abstracts, systematic review and meta-analysis, and other studies that did not meet the inclusion criteria as well (2) Protocol studies related to psychometrics (Studies with no results).Search strategies were performed by two trained authors (ASM and SR). The authors were the same at all stages of the study. In the first stage, titles and abstract of the articles were evaluated. In the second stage, the full text of the articles was independently reviewed by two authors. To assess agreement between reviewers for study selection, we used the Kappa (K) statistic, which measures agreement beyond chance . A KappaThe COSMIN Risk of Bias checklist was used to assessment the methodological quality of the included studies on measurement properties. This checklist consists of several boxes, each pertaining to a specific measurement property and containing several questions/standards about the design requirements and statistical methods of the studies. For each measurement property in each study, the COSMIN item with the lowest score will indicate the overall methodological quality  , 28.In this study, the End Note software was used to organize the references. Data extraction included author, year, target population, sample size, location of the study, complete instrument name, report, time management (min), number of questions and scales, and rating. One part of the data extraction is related to the process of qualitative evaluation of the tools which is discussed below. The searches conducted From February to April 2019. The authors entered the data existed in the articles into Excel software based on the items in the data extraction section.Evaluate aspects of OHL: To examine the specific skills and competencies measured by the different tools we used the taxonomy of skills identified by Sørensen et al., 2012 in their content analysis of health literacy definitions. This process evaluates the tools based on different dimensions, including the reading dimension , interactive dimension , perceptual dimension (the ability to extract meaning from information sources), and computational dimension (the ability to perform numeric tasks and mathematic operations). The remaining dimensions includes; information search , performance , assessment , and responsibility , .Qualitative assessment of methodology and psychometric properties. To evaluate the psychometric section, the COSMIN checklist  was used . This toAt this stage, the full texts selected related to OHL tools at the screening stage were evaluated by two authors (ASM and MGH) independently, and on the basis of two factors. Differences in judgment were resolved through a consensus procedure.Supplementary material To evaluate the instruments, the strength of evidence for each was rated on a scale graded as strong, moderate, limited, conflicting or unknown. The criteria for rating were the methodological and measurement quality, the number and consistency of results among the body of research using the instrument. Strong evidence was marked by several articles with high quality methods or one published paper of an excellent quality and a report of consistency of the properties. Moderate level was characterized by several articles with fair methods or one published paper of good quality. Limited rating would characterize an instrument with one article of fair quality. Conflicting level would describe an instrument that had mixed findings. Unknown rating was for an instrument with several papers of low quality methods or simply no published paper.Two authors screened 291 articles, and the full text of 33 articles. Finally, 21 articles had the criteria to enter the study  , 37–51, The results of evaluation of COSMIN checklist are presented in Table The results of methodological quality evaluation of the tools showed that, out of the 21 tools examined, 9 tools at least in one dimension were in the category of poor, which indicated the poor quality of that area , 42, 48.Four tools, by examining seven domains, had paid the most attention to the domains in the psychometric section , 46–48, In the area of internal consistency, all tools were evaluated except for three tools , 41, 49.The results of present study showed that, the highest percentage of “excellent” and “good” quality was related to the area of internal consistency, the “fair” quality was related to the area of criterion validity, and the “poor” quality was related to the area of hypothesis testing.In this study, we attempted to examine tools that measure OHL. Based on the results of present study, the tools were different in terms of what concept of oral and dental health literacy they were measuring. They were also different in terms of items such as scoring, attention to the clinical or health dimension, target group, sample size related to the design and psychometric, and considering the dimensions of oral and dental health literacy.Based on the results of present study, most oral and dental health literacy tools merely measure the primary skills of OHL including word recognition, reading comprehension, and computation. Based on what Sørensen et al.  have conAccording to a conceptualization method by Nutbeam (2000), HL has been defined at three levels . “Basic Various approaches to literacy tools are among issues that contribute to the inadequacy of HL tools. In other words, the basis for design and development of HL tools  is either theoretical or practical, but in practice, this indicator is not measured by a fixed or definite approach or concept. These differences lead to different outcomes and provide scholars and decision makers with a wide range of comparisons and conclusions.In this study, we also found differences in the methodology, measurement and psychometric of oral and dental health literacy tools. The results showed that, there is no comprehensive tool to examine all dimensions of COSMIN checklist. None of the tools had examined or reported the areas of responsibility, measurement error, and interpretability.Health measurement tools should consider two areas of validity and reliability to ensure the accuracy of diagnosis and compliance . The resSince oral and dental health literacy tools are still being developed and designed, the relevant stakeholders including health professionals, treatment team and researchers are recommended to evaluate the tools available to synchronize them with the conceptual and scientific perspective related to their specialized goals. For an oral and dental health literacy tool that is tailored to the target group and the subject matter, it is vital to measure the domains of oral and dental health literacy.In some cases, depending on the purpose of the research, rapid estimation tools can also be useful. In most cases however, functional tools can be more effective as they provide deeper knowledge on oral and dental health literacy of target group. Whenever possible, the use of comprehensive tools (gold standard) that can cover all aspects (including content and psychometric) are useful in acquiring a deep comparative knowledge on the dimensions of oral and dental health literacy or comparison with other tools.One of the limitations of this study was that, only studies in English were included in the review. The COSMIN checklist could also be considered as another limitation of this study, as in this checklist, the validity of criteria requires a golden standard, and this is while that, there is currently no standardized tool for measuring oral and dental health literacy, and the existing studies on oral and dental health literacy are used to assess the validity of the criteria. Individual subjectivity can also play an important role in the search, data extraction and synthesis of results, so to prevent the bias, two authors were used to perform the above processes.The findings of this study showed that some aspects of oral and dental health literacy are being ignored in the existing tools. On the other hand, some areas of psychometric evaluation of the tools are not being considered, which could jeopardize the credibility of existing tools. Other findings of this study include the deficiencies in the validation methodology of the tools. Therefore, the authors of present study emphasize on the necessity to design and develop a comprehensive tool and take into account two characteristics of simplicity and briefness for international use. Because it is only then that, the tool can be used to transform oral and dental health literacy into a comprehensive and usable index for monitoring the world’s health system .Additional file 1. PRISMA 2009 Checklist.Additional file 2: Supplementary material 2. Criteria for quality rating of measurement properties.Additional file 3: Supplementary material 3. A summary of the quality of the domains examined on the basis of a checklist COSMIN for oral health assessment tools.


What makes a biochemist? Here, we introduce the Biochemical Literacy Framework (BCLF) comprised seven key skills: critical thinking, self‐management, communication, information literacy, visual literacy, practical skills and content knowledge. This BCLF is intended to facilitate further consultation and discussion towards defining the context and qualities of a biochemist. When developing meaningful curricula, institutions must engage with the desired disciplinary attributes of their graduates. Successfully employed in several areas, including psychology and chemistry, disciplinary literacies provide structure for the development of core competencies‐pursuing progressive education. To this end, we have sought to develop a comprehensive blueprint of a graduate biochemist, providing detailed insight into the development of skills in the context of disciplinary knowledge. The Biochemical Literacy Framework (BCLF) aspires to encourage innovative course design in both the biochemical field and beyond through stimulating discussion among individuals developing undergraduate biochemistry degree courses based on pedagogical best practice. Here, we examine the concept of biochemical literacy aiming to start answering the question: What must individuals do and know to approach and transform ideas in the context of the biochemical sciences? The BCLF began with the guidance published by relevant learned societies – including the Royal Society of Biology, the Biochemical Society, the American Society for Biochemistry and Molecular Biology and the Quality Assurance Agency, before considering relevant pedagogical literature. We propose that biochemical literacy is comprised of seven key skills: critical thinking, self‐management, communication, information literacy, visual literacy, practical skills and content knowledge. Together, these form a dynamic, highly interconnected and interrelated meta‐literacy supporting the use of evidence‐based, robust learning techniques. The BCLF is intended to form the foundation for discussion between colleagues, in addition to forming the groundwork for both pragmatic and exploratory future studies into facilitating and further defining biochemical literacy. ASBMBAmerican Society for Biochemistry and Molecular BiologyBCLFBiochemical Literacy FrameworkBSCSBiological Sciences Curriculum StudiesNUSNational Union of StudentsQAAQuality Assurance AgencyRSBRoyal Society of BiologyThe modern employment market means that graduates must be freethinking and adaptable , prepariFor undergraduate biochemistry students, biochemistry is simply the context in which key skills and attributes are learnt and developed. There is little concrete restriction on the topics taught in an undergraduate biochemistry degree – paving the way for institutions to play to their strengths and produce engaging teaching around ‘hot topics’ at the forefront of research. However, in contrast to some current teaching practice at undergraduate level, skills should be taught in the context of disciplinary content knowledge , 4. SkilTeaching skills in the context of disciplinary knowledge could support evidence‐based design for learning within programmes, focusing on the interconnections of biochemical knowledge, fostering lifelong learning skills and developing confident curious open‐minded biochemists ready to integrate and participate in society. Individuals who are highly literate in the biochemical sciences can draw upon their skill set to apply themselves to new challenges as they desire with little constraint.High‐quality science education sustains a dynamic scientific community able to address global problems, and encourages an increased scientific literacy in the general population , 9. WithBybee  and ShamOther disciplines have undertaken more advanced investigations into both best pedagogic practices, and literacy within their speciality – in particular, we have referred to existing research in chemistry, biology and psychology , 18, 19 In these disciplinary frameworks, scientific literacy has been positioned as being underpinned by disciplinary literacy . It is iWhen examining these literacies, we learnt that there is unlikely to be a ‘one‐size‐fits‐all’ approach with such a diverse and multidisciplinary topic as biochemistry, with both chemistry and biology remaining active areas of pedagogic discussion , 21, 22 et al. [There are several existing concept inventories for the biochemical sciences, most notably the work of Loertscher et al.  on identThe overall aim of when formulating the BCLF was to construct a clear framework of the capabilities composing ‘Biochemical Literacy’. We aimed to achieve this through two objectives: firstly, collating the key capabilities embedded within guidance published by learned societies relating to the development of undergraduate Biochemical Sciences programmes, and identifying themes within and across documentation; and secondly, identifying literature relevant to each theme, utilising systematic literature searching techniques in order to provide clarity and depth to the framework.The BCLF could prove invaluable in assisting the production of higher quality courses by initiating discussion among those developing biochemical degree courses, in particular regarding pedagogic best practices as the foundation of the curriculum. There are several pedagogical approaches implicitly supported by the framework due to their alignment with the idea of teaching skills in the context of content knowledge , 30. TheThe data for this study consisted of guidance documents published by the scholarly, statutory and specialist organisations: the QAA, RSB, the Biochemical Society, Advance HE (previously known as the Higher Education Academy) and the American Society for Biochemistry and Molecular Biology (ASBMB). These represent the main sources of reference for the creation and content of undergraduate biochemistry courses in UK Higher Education Institutions and are all available in the public domain. Each of these documents has undergone development and/or validation processes as detailed in Table Additional material was identified when referring to the bibliographies of guidance provided by relevant organisations, before finally additional scholarly guidance were identified through a series of searches utilising the online databases PubMed, ERIC and Google Scholar. Only literature written in the English Language where the full text was available, or obtainable within the study time frame through interlibrary requests were included.Thematic analysis provided both the overarching concepts, and much of the detail present in the BCLF. The data were coded inductively, identifying key words common to all documentation beginning with the UK QAA subject benchmark statement for the biosciences  then movCritical thinkingCommunicationSelf‐managementInformation literacyVisual literacyPractical skillsContent knowledgeBuilding on our interpretation of literacy, we begin to explore it in the context of the biochemical discipline. Defining the skills and foundational knowledge underpinning disciplinary literacy is complex and multifaceted  due to tThe grouping of these skills is almost immaterial beyond assisting clarity of communication – what matters is how they interact, that is their connections together with the discussion they elicit when designing and planning a course of learning. These connections are illustrated in Fig. Rigorous, well‐evidenced and inquiry‐based evaluation is fundamental to ‘thinking like a scientist’ , 37, 38.This self‐improving cycle of ‘scientific thinking’ is supported by the general principles of ‘critical thinking’ , 44, 45.et al. [Critical thinking has been discussed by several within the Scholarship of Teaching and Learning in relation to the biosciences , 47. Howet al.  who exam, 50Determining connections to make evidenced‐based conclusions whilst utilizing evaluation and amalgamation of information To a biochemist, critical thinking could be considered as an independent, controlled, self‐monitored and self‐improving process forming the foundation for all other skills , 44, 48.We have illustrated this in Fig. Critical thinking, like many other skills, cannot be learnt easily and must be practised regularly to form the habits of mind necessary , 51, 52.Graduates in biochemistry are encouraged to come to evidence‐based conclusions and thus must be able to use sources of information effectively to inform their decision. This does not mean that every biochemist will come to the same conclusion; however, they should be able to defend their position whilst recognising the transient nature of knowledge, using evidence gathered through thorough critical analysis of information assembled efficiently from a variety of relevant and robust sources. Facilitating this process is information literacy, the subcomponents (including interactions) of which are illustrated in Fig. Individuals in any discipline benefit greatly from drawing upon established knowledge to inform their actions both at work and in their personal lives , 48, 63.Being able to locate information competently is essential to allow individuals to inform and expand their learning. A modern graduate must be able to confidently use the tools available to them (linking with technology skills) to learn from a wide range of materials , 62.A literature search begins the information retrieval process, employing a variety of techniques discussed elsewhere , 66, andAs illustrated in Fig. Information can come in many forms, and sources are not restricted to written information. Interpreting information communicated in external representations such as graphs and infographics draws upon ‘visual literacy’. As in information literacy, a critical approach to interpreting external representations of information facilitates building a meaningful understanding of knowledge .et al. [Offerdahl et al.  argued tet al. , 67. Theet al. . The relet al. . Thus, vDuring use of information, an understanding and avoidance of plagiarism through citation and awareness of intellectual property is vital. Plagiarism at graduate level is a contentious issue that often makes the national news. In addition, only 40% of UK higher and further education students surveyed by the National Union of Students (NUS) in 2012 considered their knowledge of intellectual property to be sufficient to support them in their future career .In the modern world, with its technological advances and cross‐disciplinary work, good communication and collaboration skills are essential. Good communication facilitates change, through collaborations borne out of mutual understanding, and thus is applicable whilst learning, throughout a career and in life. All of the biochemical course guidance places an emphasis on these skills, as critical for the graduate biochemist – regardless of their postgraduate choices , 71.Communication encompasses a wide range of skills, including the use of language (such as appropriate use of discipline‐specific nomenclature), listening skills  and usinThere are several skills underpinning self‐management as illustrated in Fig. Effective self‐management may help in avoiding stress by controlling and directing aspects of learning, as in project management, drawing upon time management skills such as prioritisation and planning. Without organisational and self‐management skills, an individual may struggle to engage fully in the self‐directed learning critical to remaining up‐to‐date in a discipline , 84.Individuals with good self‐management skills may be considered more proficient in their laboratory skills where timing and organisation is essential. These skills are often necessary to complete a biochemistry course with their assessment deadlines and laboratory skill elements, and however, not all students will enter at the same level; therefore, self‐management skills must also be explicitly developed , 83.Self‐improvement is also a factor of self‐management, and as shown in Fig. Research suggests that directly training students to manage and use feedback productively can lead to an increase in students' self‐reported feedback literacy . FeedbacMaking judgements about the quality of workManaging emotion in response to feedbackTaking meaningful action on feedbackThere are three key elements to appreciating feedback purpose and processes and thus increasing feedback literacy: , 92MakiAll the elements of feedback literacy should be considered when aiming to facilitate biochemical literacy as without the capacity to identify actions to improve, students may stagnate in their learning.There are many practical elements underpinning the biochemical sciences . These aThe biochemical graduate benefits from good laboratory skills – these skills underpin drug discovery, diagnostic services and the development of consumer goods  . LaboratThe exact laboratory skills a biochemical graduate should have at their disposal are likely to change frequently with advances in analytical techniques. However, the literate graduate would be confident enough in their laboratory practices to adapt, with appropriate training, to new methods and equipment. These laboratory skills are likely to draw upon technological skills, psychomotor skills, creativity and critical thinking skills in order to support the most adaptable and versatile graduates.The capability for adaption is key in this technologically fast moving era . AdaptioOnline information seeking has been shown to be without depth in the ‘Google Generation’ (born post‐1993), and therefore, appropriate levels of technological skills should not be assumed in undergraduates – these are skills that can be, and need to be taught , 107. TeWe have focused little on defining exact technology skills required for the biochemical graduate – this is because, like biochemical literacy, technological literacy is underpinned by cognitive skills we earlier grouped under ‘critical thinking’ . This fuAn understanding of research methods and methodology facilitates the understanding of scientific processes by enabling the development of connections as well as supporting the logical analysis of information , 111. A When testing a hypothesis, consideration must be given to ethics at all levels. Ethics promote truth and minimise error – for example by prohibiting fabrication, falsification or misrepresentation of data , 113. EtLinking with practical laboratory skills are data management skills. Data management is required on several scales as a biochemist – from the physical organisation of stored samples, and the maintenance of a laboratory book to large data sets and meta data. The appropriate transformation, analysis and interpretation of experimental data using either/both qualitative and quantitative techniques involve the use of good numeracy skills , 115.Numeracy skills are vital for on‐the‐go calculations in the laboratory environment; therefore, these skills must also be taught and reinforced. To facilitate analysis of data, the use of statistical programmes and spreadsheets is beneficial – again linking with technological skills.Grouped under research methods and methodology are the health and safety considerations that must underpin testing and laboratory skills. These are vital for the undergraduate biochemist to participate in laboratory‐based learning tasks, as well as for the graduate biochemist in a research or specimen analysis role. The fundamental idea of ‘risk assessment and minimising risk’ learnt in the laboratory applies widely in workplaces across industry sectors, with consideration given not just to one’s own health and safety, but the health and safety of others too. A variety of teaching methods can be used to educate in health and safety , 117, buBiological knowledge is complex, progressing alongside scientific advances and giving rise to a dynamic and changing discipline. Much of taught knowledge is conceptual rather than specific, and these concepts are illustrated with examples to enhance perspective and comprehension . To undeDue to the unique viewpoint biochemists utilise, biochemistry requires a strong foundation in chemistry; chemical principles relate to important biochemical concepts, therefore enabling more complete understanding and deeper study. Not all students enter university with the same grounding in chemistry, thus ensuring the basics are embedded early in courses (though these do not have to be in chemistry‐specific modules/courses ) is vitaBiochemistry uses chemical knowledge and techniques to understand and solve biological problems, focusing on biological processes within and related to living organisms. ‘Science is not a body of information to be mastered, but rather a way to construct new knowledge’ . For exaSeveral key concepts are mentioned in each course content guidance document examined – we have identified and categorised these for clarity during discussions in Fig. Each of the guidance documents referred to five key concepts – homeostasis, biochemical reactions, structure and function, evolution and information storage. These five key concepts are not categorical and interact with each other – for example, the structure of a molecule determines its function, which may be as a catalyst in a biochemical reaction. The subconcepts were chosen from the guidance to give an indication of the scope of the key concept; however, teaching should highlight the interactions to provide a more comprehensive and authentic understanding of biochemical knowledge , 123. FuThe term ‘scientific literacy’ has been in use for many decades, with several definitions. Scientific literacy is the ability to ‘make use of scientific knowledge in real‐world situations’ , that isThe seven skills  of the biochemically literate individual proposed here are not intended to be an unchangeable, rigid framework for curriculum design. Their interaction and connections are far more important than the categories in which they have been placed for clarity of communication. This is intended to support the creation of evidence‐based programmes of learning – focusing on the interconnections of biochemical knowledge, fostering lifelong learning skills and developing confident curious open‐minded biochemists. We intend that this proposed framework be utilised as the basis of discussion and innovation when developing biochemical curricula constructed around the idea of ‘skills in the context of disciplinary content knowledge’.Future work will include the exploration of academic, student and industry definitions of biochemical literacy  with the particular aim to validate the current proposal in line with the other disciplines discussed. Additionally, responses to the proposed BCLF will be invited to explore where further work might be directed.The authors declare no conflict of interest.DLE, IGB, NEW, AET, SGB and SLT involved in the conceptualisation. DLE performed the data curation, resources and investigation, and involved in the project administration and visualisation. IGB, NEW, SGB, SLT and AET involved in the funding acquisition. DLE, IGB, NEW and AET performed the methodology. IGB and NEW involved in the supervision. DLE, IGB, NEW and SGB wrote original draft preparation. DLE, IGB, NEW, SGB and SLT reviewed and edited the manuscript.


Lipid rafts are membrane microdomains with heterogeneous and highly dynamic small regions (10–200 nm) rich in sterols and sphingolipids. These unique membrane regions are involved in many crucial biological functions, including the formation of signaling platforms, coalescence of membrane receptors, and amplification of intracellular signaling. Mounting evidence has shown that microbial pathogens, including bacteria, viruses, and parasites, employ these lipid rafts for cellular internalization. Conversely, the engagement of immunological synapses into lipid rafts activates antigen-presenting cells and modulates the T cell response, thus magnifying the host defense against infection. Since pathogens can exploit lipid rafts for cellular interaction via direct contact or virulence factors, disruption or restriction of membrane raft formation can block infection. The five articles presented in this Research Topic collection highlight the current state of knowledge on the interaction of pathogens and their virulence factors with host cell lipid rafts and their roles in infection and disease progression.Boesze-Battaglia et al. demonstrate that when macrophages were treated with Cdt encoded by Aggregatibacter actinomycetemcomitans, a host cell protein, cellugyrin (synaptogyrin-2), relocates from the detergent-soluble membrane fraction to cholesterol-rich microdomains. Although cellugyrin is not required for Cdt binding to the cell surface, it is essential for its internalization and the induction of pro-inflammatory cytokines. They also demonstrate that Cdt interacts with cellugyrin in a complex that includes Derlin-2, a protein involved in endoplasmic reticulum-associated degradation. Their results provide an important finding that cellugyrin is critical to Cdt translocation and toxicity in human macrophages.Lipid rafts provide membrane platforms for microbial virulence factors and promote their intracellular delivery. Several gram-negative bacteria encode cytolethal distending toxins (Cdts) that contribute to bacterial persistence and invasiveness, which exacerbate disease. These toxins bind to membrane rafts and are internalized and trafficked to target host molecules, resulting in cell cycle arrest, cytokine production, and/or cell toxification. Chen et al. employ a cell-based model to investigate the role of membrane cholesterol platforms in Clostridium difficile infection and show that the binding of surface layer proteins to the host cell membrane efficiently triggers caspase-1-dependent inflammasome activation. Depletion of cellular cholesterol abrogates the inflammasome activation induced by C. difficile, indicating that C. difficile colonization of the intestinal epithelium is cholesterol dependent. The results of this study may, therefore, answer the clinically relevant question of why statin use reduces the risk of C. difficile infection.Colonization is an essential initial step in bacterial pathogenesis. Colonization of the host intestinal epithelium and subsequent multiplication in the gut require the contributions of numerous bacterial surface proteins. Listeria monocytogenes, a facultative intracellular pathogen, has been used as a model microorganism to study microbe-host interactions for several decades. Tsai and Chen focus on the role of membrane rafts in the interplay between Listeria monocytogenes and host cells. This review summarizes three important issues: (i) the interaction of listeriolysin O with cholesterol-rich microdomains, (ii) the roles of lipid rafts in Listeria internalization, and (iii) the roles of lipid rafts in Listeria cell-to-cell spread. They emphasize the significance of lipid rafts and raft-associated molecules in the interplay between L. monocytogenes and host cells at different interfaces. The review highlights the importance of the recent findings that lipid rafts are involved in the pathophysiology of L. monocytogenes infection.Fecchi et al. report an updated review focus on lipid rafts, which play pivotal roles in coronavirus entry via endocytosis and in the regulation of autophagy. They discuss the close interplay between lipid rafts and autophagy and reveal that lipid rafts can regulate autophagy by interacting with autophagosomes and autophagy-related proteins. During co-evolution with their natural hosts, viruses have developed the ability to hijack autophagic mechanisms to their advantage by using them for immune evasion or exploiting autophagosomes as a replicative niche. Their review addresses the current knowledge regarding the interaction of coronaviruses with lipid rafts and autophagic pathways, which may be useful for developing novel potential targets to block coronavirus infection.Pathogens hijack membrane rafts to gain access into host cells, and the destruction of raft compartments decreases pathogen infectivity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19) and the cause of the ongoing global pandemic since the December of 2019. Accumulating evidence has revealed that reducing the abundance of lipid rafts significantly decreases SARS-CoV-2 infection. The spike protein, located on the viral envelope, binds to angiotensin converting enzyme 2 (ACE2), which is localized to lipid rafts. Thus, ACE2 plays an essential role in initiating viral entry into host cells. Since ACE2 is a raft-associated protein, disruption of the raft architecture by treating cells with methyl-β-cyclodextrin (MβCD) or statins, the most common agents used to disrupt lipid rafts, may be an ideal strategy to reduce SARS-CoV-2 infection. Two reviews of the literature address the issue of “lipid raft therapy” for the treatment of coronavirus infections. First, Sviridov et al. present an ideal solution for developing an antiviral treatment by targeting multiple stages of the viral lifecycle and co-morbidities of SARS-CoV-2 infection. They proposed that lipid rafts are the main sites for the initial binding, internalization, and cell-to-cell transmission of SARS-CoV-2. Most importantly, lipid rafts also play key roles in host immune responses, the dysregulation of which is characteristic of severe COVID-19. The common co-morbidities of COVID-19 including severe inflammation and coagulopathy. Lipid rafts are involved in the regulation of inflammatory response and platelet function, thereby targeting lipid rafts is an effective therapeutic approach to mitigate inflammation and attenuate platelet function. In addition, MβCD can be employed to deliver compounds with limited solubility to cells, such as Remdesivir. However, some agents of lipid raft therapy may possess side effects, which require careful attention. In summary, this review concludes the potential use of “lipid raft therapy” for COVID-19, which has several advantages over other treatment strategies, including (i) the targeting of multiple steps of infection and co-morbidities of COVID-19, (ii) its insensitivity to viral mutation and thus its potential applicability for both the current pandemic and future pandemics, (iii) its safety, broad spectrum activity, and ability to be rapidly repurposed for COVID-19 treatment, and (iv) its potential either as a standalone therapy or in combination with other therapies. Therefore, pharmaceutical agents that reduce cellular cholesterol and thus dissociate membrane rafts are a promising therapeutic strategy to treat emerging viral infections.Second, As such, this themed collection provides updates on the latest research into the functions of lipid rafts in microbial pathogenesis. Understanding the interactions between microbial pathogens and lipid rafts may provide crucial insights into the mechanisms of infectious diseases and aid in the development of novel therapeutic strategies to prevent or ameliorate the diseases caused by these pathogens.C-HL drafted the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.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.


To investigate how many traditional Chinese medicine (TCM) guidelines adopted a grading system and the differences among them, and the distribution of level of evidence used to support TCM recommendations.A comprehensive search of relevant guideline webpages and literature databases were undertaken from inception to August 2018 to identify guidelines including TCM interventions. Two independent reviewers extracted the information about grading systems and recommendations.One hundred forty-two TCM guidelines were included, among which, 68 (47.9%) adopted a total of eight grading systems. The definitions, letters, and codes among these systems varied significantly. A total of 1284 recommendations were extracted from included TCM guidelines. More than 60% recommendations were based on a low and very low level of evidence (level C:33.4% and level D: 30.2%). Only 7.8% recommendations were rated as strong recommendation (grade I), while 76.2% recommendations were rated as conditional recommendation (grade II).Various grading systems were used in TCM guidelines, which might confuse guideline users. The low proportion of high level of evidence in TCM recommendations might downgrade the confidence to TCM interventions. China is the only country where western medicine and traditional Chinese medicine (TCM) are practiced alongside each other at every level of the healthcare system. and traditional Chinese treatments account for about 40% of the total . Over thWhen guideline panels, especially evidence-based guideline panels decide to recommend an interventional or diagnostic option for guidelines users, they must make judgments about the quality of evidence and strength of recommendations based on the evidence related to the specific context and other factors. The quality of evidence reflects the extent to which confidence in an estimate of the effect is adequate to support a particular recommendation , 5. The The quality of evidence and strength of recommendations are necessary as they could help to communicate a clear message, so as to help guideline users, readers and stakeholders to understand recommendations quickly and concisely, and more and more international guidelines organizations, such as Scottish Intercollegiate Guidelines Network (SIGN), National comprehensive cancer network (NCCN), National Institute for Health and Care Excellence (NICE) and WHO are applying a grading system to rate the quality of evidence and strength to their recommendations. However, the grading systems adopted by different guideline organizations varied in the definitions, letters, and codes , for exaLimited studies have focused on the varied grading systems in guidelines. Holger J, et al.  investigChinese Guideline Clearinghouse and PubMed were searched as an international database, and Wanfang Data Knowledge Service Platform, VIP Online Publishing Platform, China National Knowledge Infrastructure (CNKI) and SinoMed were searched as domestic databases for TCM guideline. Search terms in electronic databases included “guidelines”, “statement”, “recommendations”, “traditional medicine”, “traditional Chinese medicine”, and “Chinese herbal medicine”. Additional file The including criteria were as follows: (1) complete guideline text is available in English or Chinese, and (2) guideline contains recommendations regarding TCM interventions. If a guideline had updates, only the most recent version would be assessed. The following literature was excluded: duplicate guidelines, guidelines for patients, editorials, translations of guidelines, secondary or multiple publications and short summaries. We also excluded “de novo” or adaptations of external guidelines, as they did not generate their own recommendations.For each included TCM guideline, two reviewers will independently extract the following information by using a standard form: 1) characteristic information: guideline organizations , year of publication, journal, publication type , scope of guideline  and funding information, classified into four categories: industry, government, academic association and not reported; 2) grading systems information including: any form of grading systems used for rating the level of evidence and/or strength of recommendations, and the codes, letters, numbers, and symbols of the grading system were also extracted when available; 3) recommendation information: the exact recommendations of each TCM guideline were extracted and standardized into treatment or diagnostic categories. The Consensus was reached by discussing when recommendations were not obvious in guidelines, and disagreements were settled by discussing with a third author (Y.D.L).Chest [The proportion of different levels of evidence and strength of recommendations in TCM guidelines was estimated and compared among subgroups. Considering various grading systems might be used to evaluate the level of evidence and strength of recommendations, a composite grading system was generated to represent all recommendations according to a study published in Chest .The level of evidence was classified into four categories: grade A (high), the evidence used for supporting the recommendation was based on randomized controlled trials without important limitations, or meta-analysis; grade B (moderate), evidence behind the recommendation was based on randomized controlled trials with important limitations, or upgraded observational studies; grade C (low), evidence for recommendation was based on non-randomized studies, cohort or case-control studies, case series; and grade D (very low), the recommendation was made by expert opinion.The strength of recommendation was adapted into three categories: level I (strong recommendation), recommendation can apply to most patients in many circumstances; level II , the best action may differ depending on circumstances or patients’ or societal values; and level UG, insufficient evidence on which to formulate a recommendation.The following subgroup analyses were conducted to compare the difference of level of evidence and strength of recommendations in TCM guidelines including: 1) year of publication (e.g. 2003–2007 vs. 2008–2012 vs. 2013–2016 vs. 2017–2018); 2) type of recommendation (treatment vs. diagnosis); 3) form of publication ; and source of funding (any funding vs. not reporting).P < 0.05 denoted statistical significance. All tests were two-sided. Statistical analyses were conducted using SPSS version 19.0 .Statistic tests of significance might not be necessary as we included the entire cohort of TCM guidelines. Instead, we performed a descriptive analysis using the calculation of the percent distributions of recommendations among quality of evidence and strength of recommendations. Agreement between each reviewer’s data extraction was tested by using a two-way ANOVA with single-rater two-way intra-class correlation coefficients (ICCs). According to Landis and Koch , the degWe yielded 2380 records from databases, guideline websites and manual searches after excluding duplicated records, of which 166 records were considered to be potentially relevant; after selection, a total of 142 TCM guidelines were satisfied the inclusion criteria  TCM guidelines published in 2008–2012  TCM guidelines developed by Chinese medical institute and 197% (n = 28) developed by China Academy of TCM. 86.6% (n = 123) TCM guidelines focused on diagnosis and treatment. In terms of funding, 53.5% (n = 76) TCM guidelines were supported by the government, and 19.7% (n = 28) funded by medical association, however, none TCM guidelines reported the conflicts of interest statement. The ICC value for data extraction process was 0.87, 95% confidence interval 0.83 to 0.90, indicating a good agreement between reviewers.Table In the 142 TCM guidelines, 52.1% did not adopt any grading system, eight grading systems were found in the rest 47.9% TCM guidelines. Table A total of 1284 recommendations were extracted from 142 included guidelines. Of recommendations with levels of evidence, more than 60% based on level C and D evidence   and high level of evidence (grade A), instead, recommendations from any funding got a higher proportion in grade B and C level of evidence  and lower proportion in grade D level of evidence (24.6% vs 45.9%).Our results showed that eight evidence grading systems were used in 47.8% TCM guidelines, while the rest 52.1% did not sue any evidence grading system. For the eight evidence grading systems, the different codes, letters, and level of evidence are likely to lead to confuses and even misunderstanding for guideline users when using TCM guidelines.The definitions to the eight grading systems also varied a lot, for example, the GRADE system graded the quality of evidence according to bias which might decrease the confidence of included studies, that is to say, even RCTs might be at low quality of evidence if they were at high risk of bias . On the Besides, the codes from the eight grading systems were very different Table , for exaConsidering different grading systems would generate different results of level of evidence and strength of recommendation, which could contribute to challenges of implementing of TCM guidelines, therefore a standardized and well-recognized grading system is needed for TCM guidelines. A study evaluated the effect of presenting a recommendation in a clinical practice guideline using different grading systems to determine to what extent the system used changes the clinician’s eventual response to a particular clinical question, they found the clinician’s decision to use a therapy was influenced most by the GRADE system . It woulSome international guideline organizations such as SIGN and AHRQ had realized the importance of reaching consensus to standardized grading system and began to adopt the GRADE system in their new guidelines. The GRADE system was developed by GRADE working group in 2000, which has been adopted by more than 100 national and international organizations . SimilarAnother important issue is that we found more than 50% of TCM guidelines did not adopt any grading system. This could limit the application of TCM guidelines in practice. It is almost a consensus among international guideline organizations that a unique systematic approach to grade evidence and strength of recommendations can minimize bias, aid interpretation and promote the implementation of guidelines , as gradNormally, the higher the quality of evidence, the more likely a strong recommendation can be made . HoweverThe conflicts of interest in guidelines, which defines as any interest held by an expert that may affect or reasonably be perceived to affect the expert’s objectivity and independence in providing advice, can influence the level of evidence and strength of recommendations . WHO divSubgroup analyses indicated that the proportion of the high level of evidence from TCM guidelines published in CSCD journals was not better than in non-CSCD journals. This might indicate that the peer review process in CSCD journals is probably not more rigorous than in non-CSCD journals. This is surprising because CSCD journals are required to meet more criteria, compared to those in non-CSCD journals.Addressing the limitations of existing TCM guidelines, a standardized grading system developed by multidisciplinary experts is needed. Using the same grading system and codes will make TCM guidelines more understandable. Moreover, informing TCM recommendations underlying the evidence-based approach, as well as using systematic reviews to support recommendations will make TCM guidelines more trustworthy.Our overall findings have some strengths. Firstly, this study is the first to examine the evidence type and grading systems of recommendations in TCM guidelines. Secondary, each grading system has been appropriately compared according to their codes and definitions, which provided clear information about the differences among them. Thirdly, and subgroups analyses were conducted to detect the variation of different groups among level of evidence and strength of recommendation. Nonetheless, our study has several limitations. We included TCM guidelines in journals and books, but we may have missed guidelines published in other forms such as web page, which might understate the performance of TCM guidelines. Second, our study could not establish the causality between the poor performance and the characteristics of TCM guidelines. Besides, the evidence level of each recommendation was appropriately re-classified according to evidence type by evaluators, which might lead to some bias to interpret the quality of TCM guidelines.Various grading systems were used in TCM guidelines, which might confuse guideline users. The low proportion of high level of evidence in recommendations could downgrade the confidence to TCM interventions. A standardized grading system should be established in TCM guidelines. And more high level of evidence should be used to enhance the confidence of recommendations and promote the dissemination and implementation of TCM guidelines.Additional file 1. Search strategies for TCM guidelines.Additional file 2. The characteristic information of included TCM guidelines.


Escherichia coli, which causes > 80% of UTIs.Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor’s association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions.The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI.While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed ClinicalTrials.govNCT01776021.Clinical trial registration number: The online version contains supplementary material available at 10.1186/s12866-021-02106-4. E. coli (UPEC) is responsible for more than 80% of UTIs and has been the focus of many research studies ) for the cranberry group at week 0; Column C: the average abundance (in cpm) for the cranberry group at week 24; Column D: the average abundance for the placebo group at week 0; Column E: the average abundance for the placebo group at week 24; Column F: the log2 ratio of the fold-change over 24 weeks in the cranberry group to the fold-change over 24 weeks in the placebo group, where a positive value indicates a pathway/gene family increased after 24 weeks in the cranberry group relative to the placebo group; Column G: the p-value of the Wilcoxon rank sum test comparing the fold-changes after 24 weeks between cranberry and placebo group individuals; Column H: the Benjamini-Hochberg adjusted p-value .Additional file 3. Flavonifractor sp. 54 gene annotations, including those that were defined as OTU41-characteristic genes. Definitions for columns are found in the first tab.Additional file 4. De-identified sample metadata, which includes sample ID, study arm, anonymous patient ID, and visit information.Additional file 5. FASTA format file containing representative sequences for OTUs in this study, including OTU41.Additional file 6. The unfiltered raw count OTU table generated by UPARSE for all sequenced samples.Additional file 7. The OTU table with sample and OTU filtering, rarefied to 5000 reads/sample, which was used in downstream analysis.Additional file 8: Figure S1. Additional analysis of diversity using 16S data. a) Shannon diversity index, a measure of ɑ-diversity, is not significantly different between cranberry and placebo cohort (p > 0.5) b) β-diversity of longitudinal samples from the same subject is significantly lower than that between samples from different subjects (p = 1.6 × 10− 20); c) β-diversity of samples from the placebo cohort versus those from the cranberry cohort do not differ significantly; p = 0.51).Additional file 9: Figure S2. Analysis of WMS data confirms that cranberry beverage consumption does not change overall gut microbiome composition. a) WMS-based taxonomic profiles displaying the phylum-level composition of the microbial population indicate that the composition did not change over time or due to cranberry consumption. The sample order was sorted by the relative abundance of Firmicutes. b) The species richness, based on WMS data, did not change significantly with cranberry beverage consumption. c) A comparison of all samples at the 16S OTU level, using principal coordinate analysis (PCoA) based on Bray-Curtis dissimilarities, indicated that the samples from the cranberry cohort did not cluster into a specific group, and the trajectories from week 0 to week 24 (shown by arrows) were scattered, indicating no common shift in microbial composition after 24 weeks of cranberry or placebo treatment. The first two principal components (PCo1 and PCo2) accounted for 14.8 and 10.8% of the variability, respectively.Additional file 10: Figure S3. Log2 fold changes of OTUs of Escherichia coli (OTU117), Bifidobacterium sp. , and Akkermansia muciniphila (OTU19). None were significantly different between cranberry and placebo study arms.Additional file 11: Figure S4. Additional analyses further confirm the difference in abundance of the Flavonifractor species represented by OTU41 between the cranberry and placebo cohorts, validating our 16S-based OTU-level analysis. WMS read mapping to the OTU41 16S V4 regions confirms that OTU41 differs significantly between the cranberry and placebo cohorts (p = 0.03).Additional file 12: Figure S5. The relative abundance of OTU66, the OTU most closely related to Flavonifractor plautii, did not change significantly after cranberry beverage consumption (p = 0.43).Additional file 13: Figure S6. OTU41 consists of two major oligotypes, 183G and 183A. a) 183G was found in approximately two-thirds of the sequence assigned to OTU41, while 183A was found in approximately one-third, with very minor amounts of 183 T. Both 183G and 183A alleles were represented in women from both study arms at weeks 0 and 24. b) Both major oligotypes of OTU41 behave consistently with the overall behavior of OTU41, trending upwards in placebo and downwards in cranberry consumption.Additional file 14: Figure S7. 16S rRNA V4 region phylogeny containing OTUs from our study, along with sequences extracted from the reference genomes used in the comparative genomics analysis (shown in green). OTU41 and Flavonifractor sp. 54 are indicated in bold. Taxonomic assignments for OTUs are shown in brackets, with their confidence value in parentheses. These reference genomes also showed close relationships to OTUs found across our study, indicating the species they represent are also present in study participants, though their relative abundances were unchanged by cranberry or placebo consumption.Additional file 15: Figure S8. WMS alignment results of genes from two cobalamin synthesis operons in the Flavonifractor sp. 54 assembly. a) Genomic ANI to Flavonifractor sp. 54 vs. gene alignment coverage of each gene. b) Genomic breadth of coverage (in % of genome) vs. gene alignment coverage. c) Average genomic depth of sequencing vs. gene alignment coverage. These results suggest that our choice of a 75% gene coverage threshold for gene presence was conservative as OTU41-containing samples with low OTU41 abundance and/or sequencing depth tended to not meet this threshold despite modest evidence for these genes being present.Additional file 16: Figure S9. Oligotyping entropy profile for OTU41. X axis is the position in the alignment to OTU41 consensus sequence. Y axis is the Shannon Entropy of each position in the sequences that were clustered into OTU41. Position 183 was the only position in the OTU41 alignment that was above an entropy of 0.4. The background highlights the major oligotypes based on the top 6 most entropic positions, which represent the G and A alleles at position 183.Additional file 17: Table S1. 16S rRNA sequences included in phylogenetic analysis. Table S2. Whole genomes included in comparative analysis.


The World Health Organization does not recommend dilatation and sharp curettage (D&C) for the surgical treatment of miscarriage during the first trimester because this may cause Asherman’s syndrome due to endometrial damage; therefore, suction remains the primary treatment option. While manual vacuum aspiration (MVA) has been widely used since the 1990s outside Japan, the use of an MVA device (Women’s MVA system) was approved in Japan in October 2015. Here, we examined the efficacy of the MVA kit in women surgically treated for miscarriage.This retrospective cohort study was conducted between 2014 and 2018 at the International University of Health and Welfare Hospital in Japan. Women who underwent surgical treatment for miscarriage within 12 weeks of pregnancy were identified and enrolled in the study. A total of 404 women were included who underwent the following procedures: 121 D&C, 123 electric vacuum aspiration (EVA), and 160 MVA. For each participant, the duration of surgery, amount of bleeding, amount of anesthetic used, incomplete abortion requiring repeat procedures, and intraoperative/postoperative complications were evaluated.p = 1.00). The amount of anesthetic used was not significantly different among all groups. Bleeding of ≥ 100 mL was confirmed in three (2.4%), one (0.8%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.50). Incomplete abortion was identified in three (2.4%), two (1.6%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.61). However, severe intraoperative/postoperative complications were not observed in any group.The duration of surgery was 13.7 ± 7.2, 11.2 ± 4.2, and 6.9 ± 4.3 min in the D&C, EVA, and MVA groups, respectively (Surgical treatment for miscarriage performed using the MVA kit has safety and efficacy similar to those of conventional methods, such as D&C and EVA. The World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) recommend the use of suction for abortion as well as treatment of miscarriage during the first trimester from the perspective of safety, efficacy, and lower risk of endometrial damage, such as Asherman’s syndrome. These guidelines do not recommend the use of dilatation and sharp curettage (D&C); therefore, suction has become the mainstream treatment in Western countries, and manual vacuum aspiration (MVA) has been widely used since the 1990s. However, D&C is still performed in Japan in > 50% of cases [In October 2015, an MVA device, called the Women’s MVA system, was approved for use in Japan and is being used in routine clinical practice. We introduced the use of the MVA kit at our hospital in June 2016 and have performed surgical treatments for miscarriage during the first trimester using the MVA kit only.In the present study, we examined the efficacy and safety of MVA kit for the surgical treatment of miscarriage occurring during the first trimester.This retrospective cohort study was conducted between January 2014 and December 2018 at the International University of Health and Welfare Hospital in Tochigi, Japan. The study was approved by the Ethics Committee of the International University of Health and Welfare Hospital . We excluded patients with contraindications to suspected ectopic pregnancy , suspected molar pregnancy, and suspected completed spontaneous abortion . Women who underwent surgical treatment for miscarriage within 12 weeks of pregnancy were identified and enrolled in the study. Participants were randomized to one of the three study groups. We performed D&C alone between January 2014 and March 2015, electric vacuum aspiration (EVA) alone between April 2015 and May 2016, and MVA alone from June 2016 for the surgical management of early miscarriage at our hospital. All patients provided written and oral informed consent for the procedure and study participation after proper explanation of the risks and benefits of the procedure. In each case of surgical treatment for miscarriage, the duration of surgery, amount of bleeding, amount of anesthetic used, incomplete abortion requiring repeat procedures, and intraoperative/postoperative complications were evaluated.Study participants were divided into three groups according to the treatment: D&C group, patients treated with D&C alone; EVA group, patients treated with EVA alone; and MVA group, patients treated with the MVA kit alone.Surgery was performed using the J.A.M.W. placenta forceps and J.A.M.W. uterine curettes  in the D&C group, Atom Vacuum Extractor VP-450  in the EVA group, and Women’s MVA system MVA kit  in the MVA group. For nulliparous cases, the cervical canal was dilated prior to surgery using a Lamicel osmotic dilator . For all groups, we used intravenous anesthesia (15 mg of pentazocine and 1–1.5 mg of 1% propofol/kg of body weight). Additional 10–20 mg of propofol was administered if patients complained of intraoperative pain. In the D&C and EVA groups, we confirmed the position of the uterus and uterine cavity using a uterine probe and sequentially dilated the cervical canal using a J.A.M.W. cervical dilator . In the D&C group, we used J.A.M.W. placenta forceps and J.A.M.W. uterine curettes according to the gestational age . We extracted the uterine contents using J.A.M.W. placenta forceps and performed curettage with J.A.M.W. uterine curettes.In the EVA group, we selected a metal catheter depending on the gestational age and suctioned the uterine contents with a pressure of − 400 to − 600 mmHg. After examination using a probe in the MVA group, the cervical canal was dilated to the diameter of the cannula equivalent to the gestational age  using a dilator , and the cannula was inserted into the fundus of the uterus. Subsequently, the double valve of the aspirator was closed, the plunger was removed to create a vacuum within the syringe (approximately pressure: −610 mmHg), and the uterine contents were suctioned after connecting with the inserted cannula. Surgery was performed in all patients under the guidance of transabdominal ultrasonography. Methylergometrine maleate was injected intramuscularly after confirming the complete removal of the uterine contents to complete the procedure, and all patients were administered oral methylergometrine maleate for 5 days postoperatively.t-test and chi-squared test were performed for statistical analysis, and P- values of < 0.05 were considered statistically significant.Student’s Study participants included 404 women who underwent surgical treatment for miscarriage within 12 weeks of pregnancy at our hospital between January 2014 and December 2018. Among these, 121 patients were included in the D&C group, 123 in the EVA group, and 160 in the MVA group.p = 0.44). The mean gestational age was 8.3 ± 1.3, 8.5 ± 1.4, and 8.4 ± 1.4 weeks in the D&C, EVA, and MVA groups, respectively (p = 0.84). Patient backgrounds were not significantly different among the groups (Table p = 1.00). The amount of propofol used was 9.6 ± 4.7, 9.0 ± 3.4, and 8.8 ± 2.5 mL in the D&C, EVA, and MVA groups, respectively (p = 0.76). Further, bleeding of ≥ 100 mL occurred in three (2.4%), one (0.8%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.50). Incomplete abortion was identified in three (2.4%), two (1.6%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.61). Surgical performance was not significantly different among the three groups ; thereby, indicating the efficacy of MVA . In thesSeveral studies have compared MVA and D&C. Verkuyl et al. conducted a randomized study including 357 patients with incomplete miscarriage prior to 18 weeks of gestation and showed that MVA was associated with significantly less bleeding and pain and a shorter duration of surgery than D&C. However, there was no significant difference in the incidences of uterine perforation and septicemia [Regarding the efficacy of MVA from the perspective of endometrial protection, Gilman et al. examined the occurrence of Asherman’s syndrome in 1,580 patients treated for miscarriage during the first trimester and confirmed Asherman’s syndrome in 6 out of 483 (1.2%) patients treated with D&C alone or with D&C and EVA. However, no cases of Asherman’s syndrome were reported in patients treated with MVA . A studyAnother study describing the advantages of MVA reported that it is silent (because it does not require electricity), can be performed as an outpatient procedure, and involves single-use equipment, which eliminates the need to clean and disinfect surgical tools; thereby, reducing the risk of infection .In Japan, induced abortion during the first trimester is performed using D&C in 33% of cases and using D&C and EVA with a metal suction tube in 47% of the cases . D&C is Surgical treatment for miscarriage performed using the MVA kit is as safe and efficacious as conventional methods such as D&C and EVA.