N = 99; Mage = 5.6; 47% girls). We found that children’s reward-risk tendencies did not predict sharing behavior in a dictator-game ‘sharing’ task. However, they predicted children’s monopolizing behavior in a dictator-game ‘taking’ task and their preferences between taking home a ‘risky’ or a ‘safe’ reward in a novel prize-preference task. Overall, using a set of original pictorial scenarios to assess individual differences early on in development now provides initial evidence that bridges individual differences and decision-making domains and exposes behavioral patterns that were thus far hidden.When facing situations that involve risk and reward, some may focus on the opportunity for reward, whereas others may focus on potential risks. Here, we used an original set of pictorial scenarios to try and predict 3- to 8-year-olds’ reward-seeking and risk-avoiding behavior in three decision-making scenarios ( Any adaptive species must somehow balance between avoiding potential threats , and obtaining potential benefits . In humans, this basic psychological tension is broadly reflected in two independent neural substrates representing intrinsic motivations: Behavioral Inhibition Systems (BIS) and Behavioral Approach Systems (BAS). BIS is more sensitive to cues of punishment and loss, thus regulating avoidant behavior, while BAS is more susceptible to signals of reward, thus facilitating appetitive behavior –8.One standard assessment of BIS-BAS orientation in adulthood is with a self-report questionnaire , which eThe theoretical and pragmatic interplay between approach, avoidance, and inhibitory capacities provides significant associations between temperament in infancy and the developed adult personality , 14, 15,indirect subjective assessment, observational methods demand particular expertise, and ‘game-like’ tasks focus on specific cognitive capabilities such as inhibitory control, working memory, and attention rather than the broad BIS-BAS theoretical framework, and longitudinal studies are expensive and thus rare.This challenge is typically addressed by resorting to other measures or paradigms, such as asking caregivers to report about their children –21, obseMoreover, regarding the developmental trajectory of risk-taking behavior, a recent meta-analyses  showed tThe earliest efforts to assess temperament were carried out by Garcia-Coll et al.  and KagaIn addition to the association between temperament and risk, another related aspect would be gender. First, regarding temperament, one meta-analysis which focused on gender differences in temperament from infancy to 13-years-of-age , reportsBBB) comprises a series of original pictorial scenarios that present a protagonist facing two possible courses of action—risky & rewarding or conservative & safe. With the BBB, children choose the course of action they think a protagonist should take, and a BIS-BAS orientation score is computed. The rationale, as alluded to before, is that especially in unfamiliar scenarios in which children have little prior experience, BAS-oriented children will tend to pursue potential self-benefits, whereas BIS-oriented children will tend to avoid potential risks.Together, assuming that one’s biological, parental, cultural, and personal history converge to manifest in a dominant motivation to either approach potential benefits OR to avoid potential risks, then BIS-BAS orientation in early childhood should predict actual behavior. To address this challenge, we created a child-friendly adaptation of the widely used BIS-BAS questionnaire . The BISThe power of the BBB to predict children’s actual behavior was assessed in three distributive decision-making games that vary in their degree of familiarity to the child. The first decision-making scenario is a resource distribution task known as the Dictator game , 43. In sharing is caring”, as often stated and encouraged in kindergartens), in which children across cultures start similarly, and share about 25–30% of their endowment [Dictator-game ‘sharing’ could be considered a relatively familiar event . The ‘sharing’ and ‘taking’ scenarios may seem complementary, but recent findings with adults emphasize a general aversion to ‘taking’ from others, and that such a ‘taking aversion’ may be somewhat stronger among women [more from others  and expect BIS-oriented children to take less .The second decision-making game is a variation of the dictator game noted above and was first introduced by Eichenberger and Oberholzer-Gee –55. In tng women , 57. To ng women . Unlike one to take home with them. Notably, while children could see the content of most prizes , one prize had an opaque wrapping . In this scenario, BAS-oriented children are expected to choose a ‘risky’ prize, whereas BIS-oriented children are expected to choose one of the ‘safe’ prizes to take home with them.In the ‘sharing’ and ‘taking’ dictator games, which are dyadic tasks in nature, there could be some underlying expectation of other-regarding considerations or social norms . Thus, t‘taking’ scenario than BIS-oriented children, and will be more likely to take home with them a ‘risky’ prize in the prize-preference task. Notably, we did not have an apriori hypothesis about gender since it may be subsumed under children’s BIS-BAS orientation. Moreover, since the ratio of BIS vs. BAS-oriented children was previously found stable across ages, we did not expect age related differences in BIS-BAS orientation scores [In sum, the current research aims to assess the power of the BIS-BAS-Book  to predict children’s behavior in three decision-making scenarios. Since approach and avoid orientations are most predictive and relevant in unfamiliar or ambiguous situations , 15, ourn scores , 26. If N = 99, Mage = 5.6, SD = 1.3 years; 47 girls) were recruited from the Bloomfield Science Museum in Jerusalem, Israel. Participants were from mixed SES backgrounds, and all had signed parental permission to participate (research ethics committee #1281119). Sixteen additional children were tested but excluded due to experimenter errors. The G*Power software package (Ver 3.1.9) was used to conduct a power analysis to estimate the number of participants required for a regression model with four independent variables . Detecting a medium effect size of f2 = .15 at 80% power requires 85 participants. Our sample was ~15% larger.99 3-8-year-olds ((1) The BBB phase, in which all children completed the BBB that yielded an individual raw BIS-BAS orientation score  A Dictator-game phase, in which participants were randomly assigned to one of two dictator-games, that is, a dictator-game ‘sharing’ condition  OR a dictator-game ‘taking’ condition . (3) A Prize-preferences phase in which all children participated in the prize-preference task and chose one reward out of several to take home with them.The design consisted of three sequential phases: Content: Based on the original BIS-BAS scales [S scales , and theS scales , 65, we Protagonists: Protagonists’ characteristics, such as age and name, were identical to participants’ , and protagonists’ physical characteristics, such as gender and hair color, were also matched by using an appropriate set of illustrations. We did this to increase the likelihood that participants will provide their own tendencies rather than normative statements (as in 3rd-party judgment).Order and coding of items: We created 16 books . Each item in the BBB was scored on a 1–4 point scale to match the coding in the original BIS-BAS scales for adults .BIS-BAS Orientation Score: We based our BIS-BAS-orientation score on prior research that utilized an approach-avoidance asymmetry score [ry score , 66, 67.ry score , 65, 68,We employed ten identical erasers as resources for distribution. Each eraser was wrapped with a different color to maintain the children’s interest and participation throughout the games. In the ‘sharing’ game, the children were presented with a video of an unfamiliar, gender- and age-matched peer  and one wrapped in white paper with question marks all over . The prizes were part of what is regularly given to children as compensation for participating in studies in the Museum . PresentChildren sat in a designated quiet zone in the museum, and caregivers waited outside during the procedure while filling out a BIS-BAS questionnaire about their child. The Experimenter (E1) presented the BBB with the appropriate protagonist , and children’s verbal answers were audio-recorded for later coding.OK, now that we have finished the book, I want to show you a game … in this game, you can decide how to distribute prizes between you and another child”. E1 opened a laptop and presented a video of gender and age-matched unfamiliar peer. In the ‘sharing’ scenario, E1 placed ten rewards closer to the participant, asked participants to count the rewards, and stated, “Now, you can decide how many rewards to give to {peer’s name}”. In the ‘taking’ scenario, E1 placed ten rewards closer to the peer , asked participants to count them, and then stated, “Now, you can decide how many rewards to take from {peer’s name}.”Upon completing the BBB phase, E1 stated, “Great, now that you have completed the game, you deserve a real prize!”. A second experimenter (E2) joined and invited the participant to come with her to choose a ‘real’ reward to take home. E2 guided the participant to a different zone in the museum and presented a basket with 12 prizes—11 were transparent, and 1 was wrapped in white paper with question marks. E2 was blind to the participant’s answers, assigned dictator-game condition, and distributive behavior in the previous phases . E2 stated: “So since you played so nice, you can choose whatever you wish to take home”. E2 mentioned the names of the various prizes so all children would be aware of the variety , and when reached the ‘risky’ prize said, “or this one… I don’t know what’s inside…”Upon completing the dictator-game phase, E1 stated, “2(96) = 3.22, p>.4), suggesting no differences in BIS-BAS orientation scores between age groups. There ratio of BIS/BAS-oriented children within each age group  was also similar and close to 1 , suggesting a relatively equal number of BIS and BAS-orientated participants per age group. No correlations were found between the BIS-BAS orientation scores obtained via the BBB and caregiver’s reports  , 26. To Χ2(40) = 3.66, p = .72), and children shared about a third of their endowment  regardless of age, gender, or BIS-BAS orientation scores  included the number of rewards shared as a dependent variable. Independent variables were direct BIS-BAS orientation score (via the BBB), indirect BIS-BAS score (via the caregiver’s report), gender, all interactions between them, and age in months as a covariate. Likelihood ratio test comparison between the full and null model (which controlled for age and gender) was non-significant (n scores .Χ2(41) = 12.61, p < .05), and yielded a two-way interaction between the direct BIS-BAS orientation score and gender (X2(1) = 6.43, p = .01), and a main effect for the direct BIS-BAS orientation score . We followed the two-way interaction with two separate GLMs per gender. For boys: Likelihood ratio test comparison between the full model (including age and direct BIS-BAS orientation score) and null model was highly significant (Χ2(21) = 11.22, p < 0.001), with a main effect for the direct BIS-BAS orientation score , suggesting that BAS-oriented boys took ~80% of others’ resources. Conversely, BIS-oriented boys took ~20%  = 0.17, p = .68), suggesting that regardless of girls’ BIS-BAS orientation score, they took ~50% of other’s resources .We used an identical analysis (GLM), which included the number of stickers taken as the dependent variable, and as predictors—direct BIS-BAS orientation score, indirect BIS-BAS score, gender, all interactions, and age in months as a covariate. Likelihood-ratio-test comparison between the full and null model (which controlled for age and gender) was significant . Whether assessed via the BBB or the caregivers, children’s BIS-BAS orientation did not predict their ‘sharing’ behavior. One explanation for the absence of findings in this regard would be that familiar contexts  do not elicit an ‘approach-avoid conflict’. Thus, habituated behavior can be expressed  regardless of individual differences in risk-reward sensitivity. If true, we should expect a relation between BIS-BAS orientation and children’s behavior in a less familiar scenario, such as the dictator-game ‘taking’. Indeed, unlike the ‘sharing’ scenario, the BBB predicted children’s behavior in the ‘taking’ game. Importantly, without accounting for individual differences, we would wrongly conclude that all children took resources to reach an egalitarian outcome . However, a new picture emerged when including individual differences: BAS-oriented boys monopolize resources from others, whereas BIS-oriented boys are far less willing to do so. Conversely, girls presented a stable egalitarian tendency regardless of their motivational orientation. These findings echo the recent findings with adults by which women were found to have a stronger ‘taking aversion’ [version’  but alsoversion’ . Here, tThe ability to predict children’s behavior in the ‘taking’ scenario is aligned with the idea that a ‘taking’ scenario may present a more salient conflict than ‘sharing’, at least for boys, for which one’s motivational orientation strongly predicted behavior. One explanation for the inability to predict girls’ behavior could be that the BBB is somewhat biased. This explanation seems unlikely given that the protagonists were gender-matched, the pictorial scenarios included a wide range of daily events, and the range of girls’ BIS-BAS scores was similar to boys’ . A seconΧ298 = 54, p = .99), as 55% chose one of the visible, ‘safe’ rewards and 45% chose the unknown, ‘risky’ reward, suggesting no initial bias towards either type of reward (see A chi-square test for children’s choices (‘safe’/‘risky’ rewards) was non-significant  = 14.3, p < .05). Three and Two-way interactions were non-significant , and only two main effects were found. The first was for the direct BIS-BAS orientation score , suggesting that BAS-oriented children are likely to choose a ‘risky’ reward above chance-level and BIS-oriented children are likely to select a ‘safe’ reward above chance level . This main effect followed the same pattern as the direct BIS-BAS orientation score but was predictive only for BIS-oriented children, who were likely to choose ‘safe’ rewards, above chance level.Likelihood Ratio Test comparison between the full and null model (which controlled for age and gender) was significant . Finally, in an unfamiliar and novel prize-preference task that did not include social interaction, both the BBB and the parental reports predicted children’s decisions. However, the BBB had an advantage in classifying children from both sides of the spectrum, i.e., high BIS-oriented children and high BAS-oriented . It is reasonable to assume that there is less ambiguity about how to behave in the presence of normative guidelines . In that case, an approach-avoid conflict would be weaker than in unfamiliar situations, wherein normative guidelines do not exist, thus allowing one’s BIS-BAS orientations to manifest predictably.Based on the idea that approach-avoid conflicts are salient, particularly in ambiguous, or unfamiliar contexts , 6, we cinitiate a ‘taking’ behavior themselves (instead of accepting offers made by others), the inclusion of motivational orientation exposed those who are willing to cause advantageous inequity, i.e., BAS-oriented boys. Notably, we had no prior hypothesis regarding gender: On the one hand, inhibitory capabilities emerge earlier among girls [Integrating the domains of individual differences and decision-making also provides new results regarding ‘taking aversion’ and risky choice preferences. First, regarding ‘taking aversion’, research on children is scarce ; yet, a ng girls , and thung girls . On the ng girls , when inSecond, regarding risky choice preferences in non-social scenarios, two sub-groups with opposite tendencies were discovered—one who strongly preferred to take home an ambiguous and ‘risky’ reward  and a second who strongly desired to take a ‘safe’ one (visible prize). Children’s prize preferences in our ecological task resonate with individual differences in novelty-seeking –77, whicnumber of questions , differences in who the questions refer to , and differences in the type of questions   and give the children the impression that the “experiment” was over. Nonetheless, using the BBB before, during, and after tasks, in a controlled manner, as well as at different time intervals, could be of great value, as some research has demonstrated the malleability of BIS-BAS orientation, across different developmental periods (e.g. between 3 to 9-years of age) , 26.who the acting agent is , what is the motivational orientation for action , and what is the type of context , may allow portraying a detailed, and theoretically coherent, description of the interplay between motivations, cognition, and behavior.Overall, by systematically examining three contexts that vary in familiarity and sociality, the current study offers initial evidence for the ability to examine individual differences in decision-making via short-term behavioral tasks. Research on individual differences should benefit from a new, theoretically driven, direct measurement suited for early childhood, providing immediate added value. For instance, as “motivational imbalance” in early childhood correlates with maladaptive behavior in the social sphere , 16, eduS1 File(DOCX)Click here for additional data file.


Text CorrectionD. immitis in the blood of dogs in the Galapagos Archipelago. However, we later realized that two earlier studies found microfilaria of D. immitis on two islands of the Galapagos Islands: Floreana and Santa Cruz.There was an error in the original publication . In the A correction has been made to Section 4. Discussion, paragraph 1:D. immitis in the blood of dogs in the Galapagos Archipelago, as previous studies targeted the detection of antibodies [27], antigens [22–26] or DNA [26]. The presence of an endemic...” has been replaced with two paragraphs, as show below,“This study represents the first report to demonstrate the direct presence of the microfilaria of D. immitis in the blood of dogs in San Cristobal Island, Galapagos. Similar studies were performed in Floreana [27] and Santa Cruz [26], which assessed the detection of antibodies [27], antigens [22–26], and DNA [26].This study represents the first report to demonstrate the direct presence of circulating microfilaria of D. immitis in the blood of dogs in the Galapagos Archipelago. Most other studies targeted the detection of antibodies [27], antigens [22–26], or DNA [26]. The presence of an endemic cycle for D. immitis depends on the presence of suitable definitive hosts (dogs), vectors (mosquitoes) and the nematodes. The presence and abundance of mosquitoes and the development of D. immitis larvae in mosquitoes are dependent on climatic factors, the most important being the temperature and availability of mosquito breeding sites . Hence, climate and weather have a significant impact on the prevalence of canine heartworm. Dirofilaria immitis L1 larvae need an average temperature higher than 15 °C to develop to L3 in the mosquitoes [53]. Additionally, a recent study demonstrated that cumulative exposure to adequate temperatures can result in the progression of larvae from microfilaria to the L3 infective stage [54]. From this point of view, the Galapagos Archipelago represents a suitable biotope for the development of the mosquito vector and of the D. immitis larvae [55]. Furthermore, sea lions spend more time on land [56], especially in the evening when mosquitoes are active [57].Our study completed the previous studies  regarding the presence of circulating microfilaria of The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.


Pseudomonas aeruginosa (PA). PROVE is an international, retrospective study of CFDC use in Gram-negative infections (GNI). This analysis examines outcomes by infection site and time of first CFDC dose from culture for patients with PA as of March 2023.Gram-negative (GN) bacterial resistance is a major global health problem. Cefiderocol (CFDC) is active against Eligible patients received ≥ 72 hours of CFDC as used in routine clinical practice and had a PA culture attributed to the use of CFDC. Patient characteristics, clinical course severity, and treatment patterns were assessed. Associations of infection site, carbapenem resistance (CR), CFDC susceptibility, and time of first (index) culture sample to first CFDC dose were examined with clinical cure and all-cause mortality (ACM) at 30 days. Clinical cure at the end of treatment was defined as resolution or improvement in infection signs and symptoms without evidence of later relapse.253 patients were treated with CFDC at 39 sites in the US and Europe for a primary PA infection; 30.8% were polymicrobial with other GN pathogens (Table 1). The median age was 57 years, interquartile range (IQR) 45-65; 70% were male. The most frequent comorbidities were diabetes (34.0%) and chronic pulmonary disease (20.2%). CFDC was given in an ICU setting in 72.3% with 48.6% requiring mechanical ventilation.The most common sites of infection were respiratory  of which 22 (15.3%) had secondary bacteremia (Table 1). Most (90.3%) were CR. The median time from a positive culture to start of CFDC was 5 days (IQR 3-8).Clinical cure was 63.6% and 30-day ACM was 22.5% (Table 1). Clinical cure was comparable in respiratory with and without secondary bacteremia  and was lowest in patients with skin structure infections with bacteremia (40.0%). CFDC started 3-4 days after culture had the greatest cure rate (70.8%); those started later (5-7 days) had the lowest (59.2%). 30-day ACM was also greatest for patients treated later ( > 7 days after index culture) (28.1%) and for salvage after prior treatment failure (26.7%) (Table 2).CFDC for PA is used in complex patients, most with respiratory disease. The trend of better outcomes with earlier use from culture warrants additional study.Stephen Marcella, MD, MPH, Shionogi, Inc: contracting work for Shionogi, Inc Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Bruce Friedman, MD, Shionogi: Honoraria Stefano Verardi, MD, Shionogi B.V.: Employee Laurence Gozalo, PhD, Shionogi, Inc: Analyst Christine M. Slover, PharmD, Shionogi,INC: Employee


Hand hygiene (HH) matters because it decreases pathogen transmission that can cause infection. Automatic alcohol-based hand rub (ABHR) dispensers are widely adopted in healthcare facilities as the preferred means of HH. Traditional automatic dispensers have a large supply of batteries in the dispenser housing, whereas energy-on-the-refill (EOR) is a newer power supply solution, consisting of a relatively small battery attached to a refill bottle. The objective of this study was to assess dispenser design impact on missed HH opportunities and facility workflow disruption by mitigating battery maintenance.We used date-driven discrete event simulation to evaluate the performance of three leading types of automatic dispensers in four common types of hospitals (Table 1). We analyzed up to 8 years of historical usage data and identified the usage pattern, which are used as the input traffic for our simulation model. Dispenser energy performance parameters were inputs to measure the workflow disruption of the different types of dispensers over a 6-year period in terms of battery replacements, duration of downtime, and the number of missed HH opportunities.1. This total included soap dispensers used for hand washing and ABHR dispensers that were not equipped with automated monitoring . 2. These were the dispensers used in the analysis and modeling results. 3. Total dispenses for all ABHR dispensers during the entire time range. 4. This is the average number of ABHR dispenses daily for the facility for all dispensers.The simulation results suggested that dispensers with EOR technology were free of battery failures over the entire 6 years, and thus 0 HH misses were incurred due to dead batteries . All other designs had a significant amount HH misses due to battery failures, ranging from 2,514 (± 547) to 40,522  per facility. However, the majority of HH misses were caused by empty ABHR refills. The maximum number of battery change events was 802 (± 0.60).1. Dispenser A is a traditional design with 4 “D” cell batteries in the housing and has an average dispense energy of 2.02 J/ml. Dispenser B is a traditional design with 3 “D” cell batteries in the housing and has an average dispense energy of 1.78 J/ml. Dispenser C is a new design with a “AA” battery on the refill and has an average dispense energy of 1.78 J/ml. Dispenser B is modeled at 1 dose and 2 doses because it has some ABHR formulations that can require 2 dispenses to meet the Healthcare Personnel Handwash test method antimicrobial efficacy success criteria.Differences in dispenser design, including the energy management system and usage profiles have significant impact on HH performance, which in turn can affect infection risk. By adopting the EOR system, facilities can effectively eliminate the need for battery maintenance, resulting in labor and workflow efficiencies. The EOR system significantly reduces HH disruptions and may decrease complaints by caregivers, patients and visitors. Importantly facilities should carefully study dispenser usage patterns to implement optimized policies and practices for placement and refill maintenance of ABHR dispensers to minimize overall missed HH opportunities.Nanshan Chen, n/a, GOJO Industries, Inc.: Grant/Research Support James W. Arbogast, PhD, GOJO Industries, Inc.: employee John J. McNulty, n/a, GOJO Industries, Inc.: employee Paul J. Brown, n/a, GOJO Industries, Inc.: employee Demetrius Henry, n/a, GOJO Industries, Inc.: employee Susan O'Hara, PhD, GOJO Industries, Inc.: Grant/Research Support Abedallah Al Kader, n/a, GOJO Industries, Inc.: Grant/Research Support Angela Hu, n/a, GOJO Industries, Inc.: Grant/Research Support Theodore T. Allen, PhD, GOJO Industries, Inc.: Grant/Research Support Cathy H. Xia, PhD, GOJO Industries, Inc.: Grant/Research Support


Evidence-based practice is a systematic approach to decision-making developed in the 1990s to help healthcare professionals identify and use the best available evidence to guide clinical practice and patient outcomes amid a plethora of information in often challenging, time-constrained circumstances. Today’s sports nutrition practitioners face similar challenges, as they must assess and judge the quality of evidence and its appropriateness to their athlete, in the often chaotic, time-pressed environment of professional sport. To this end, we present an adapted version of the evidence-based framework to support practitioners in navigating their way through the deluge of available information and guide their recommendations to athletes whilst also reflecting on their practice experience and skills as evidence-based practitioners, thus, helping to bridge the gap between science and practice in sport and exercise nutrition. The advancement of sport and exercise nutrition (SEN) as a recognised sub-discipline of sport and exercise science (SES) began in the late 1960s, following the pioneering work of Scandinavian scientists who investigated the role of muscle glycogen and carbohydrate availability on exercise capacity and performance . More thPractitioners must be well-versed in the four rapidly evolving disciplines that comprise SEN: exercise biochemistry and integrated metabolism, exercise physiology, nutrition, and psychology . Moreovefaster rate, with a higher proportion of investigations each year, journals are demanding stronger scientific rigour in research reporting  to improve the quality of research in the long term . It has been described as one of modern medicine’s paradigm shifts . In mediIn keeping with recent definitions of EBP in other domains of SES , we propAsk – translate athlete information into answerable outcome-based questions. 2: Acquire – find the best available evidence to answer the question. 3: Appraise – evaluate the evidence critically for validity, relevance, and applicability. 4: Apply – integrate evidence, context, and practice into professional decision-making and recommendations. 5: Audit – reflect and evaluate processes 1 through 4 and seek ways to continually improve.Evidence-based practice is commonly described as a five-step process, which we have adapted to meet the specific demands of the SEN practitioner. 1: The EBP framework for healthcare professionals, according to Straus et al., can be used in three areas of medicine: diagnosis, prognosis, and intervention . While iBefore implementing a nutritional intervention with an athlete, a nutrition assessment and consultation are required. A nutrition assessment may include an evaluation of the athlete’s diet, anthropometry and body composition, biochemical testing, a nutrition-focused clinical examination, and an audit of the athlete’s medical history . An in-dThe first step in gathering the best evidence for use in practice is to ask a question. A well-crafted question is required to ensure the practitioner does not waste time searching for the best available evidence. With the amount of information available expanding exponentially, finding the most appropriate evidence to address the athlete’s issue requires the practitioner to develop a clear understanding of the athlete’s needs and requirements , using fA practitioner’s inquiry can begin with background or foreground questions. Background questions are designed to elicit general information about the context of a situation, condition, state, or another aspect of SEN, and must be answered before posing a foreground question. Depending on a practitioner’s academic training, competent practitioners should be able to answer most background questions. Therefore, this review will concentrate on foreground questions, which focus on specific knowledge that gathers the best evidence to solve an athlete’s issue. The EBP framework can use the PICO model to generate foreground questions, which stands for “population,” “intervention,” “counter-intervention,” and “outcome.”The practitioner must be explicit about the characteristics of the population to which their question refers. The question may want to consider some of the following information: age , gender, menstrual status , ethnicity, and training status, as each have the potential to influence the relevance of the evidence required to inform their nutritional intervention , 27–30.The practitioner must be specific about the main intervention, independent factor, or variable in their question. For this review, the intervention is focused on a dietary treatment  or condition ; however, other examples include, but are not limited to, an exposure , or issue in which the practitioner is interested —the more specific the description of the intervention, the narrower the search.When formulating a question, the practitioner may include an alternative to compare to the intervention; however, this is not always necessary. For example, if the intervention is a dietary supplement, the comparison could be a no-treatment group masked by using a placebo or a blinded control group; however, this would not be implied in the question. Using the practitioner’s background knowledge to develop their question, the comparison could be a common dietary practice used in this context or the “standard” approach. A practitioner, for example, might want to assess the outcomes of a popular dietary treatment  versus the common dietary approach  on key performance outcomes for their athlete see .The outcome to a question refers to what the practitioner is trying to achieve, measure, improve, or affect. A practitioner’s question may include multiple outcomes. Suppose all the outcomes are not included in a single study; in that case, the practitioner may need to formulate several questions, change the question’s outcome each time, and evaluate more evidence. For example, a practitioner may want to know how a diet intervention impacts performance, metabolism, and its associated side effects. Although these outcomes may be included in the same study, the practitioner may need to search across multiple studies to find the appropriate evidence.via lower hierarchy tiers, starting with un-pooled, well-designed RCTs (Level 3). While well-designed RCTs provide a level of robustness for internal validity and thus increased certainty that the outcomes are caused by the intervention, due to the high levels of controls implemented, this may reduce the practical relevance of the results. If there is insufficient evidence to fully answer a practitioner’s question using Level 1–3 evidence, the practitioner may need to consult other lower-tier evidence such as less well-controlled trials and observational research (Level 4), case studies/reports (Level 5), and “expert opinion” (Level 6). When considering the effectiveness of an intervention, caution should be used when evaluating lower tiers of evidence due to the lack of controls and the potential for bias. However, they can provide practical insights that are often unattainable with well-controlled studies, such as undertaking more extended intervention periods  or studying an intervention within its real-world context .Once the PICO question has been developed, the practitioner should consider acquiring the best available scientific literature as their foundation and triangulating this information with relevant grey literature and professional experience. The quality of scientific evidence often relates to its susceptibility to bias based on study design and is commonly organised into tiers of evidence see . For intGrey literature is used to describe all materials and research that are produced outside of commercial and academic publishing channels and encompasses evidence derived from pre-appraised research such as research reviews, reputable sports nutrition organisation websites, podcasts, blogs, conference proceedings, and social media posts . When leProfessional experience refers to knowledge gained from working with athletes and within specific professional settings . Although experience-based anecdotes from the field generally are the least objective and most susceptible to bias , there avia platforms such as ResearchGate and, in some cases, Twitter.The methods used to search for scientific and grey literature are similar and typically consist of three key steps . Before Once all the available evidence has been collected, it must be appraised by the practitioner before being used to inform the decision-making process. This is more important than ever given the increasing availability of scientific publications, which can vary in terms of scientific rigour, as well as the increased accessibility of non-scientific opinions and anecdotal evidence, fuelled by the growth of social media platforms and alternative media . When evaluating research findings, the hierarchies of evidence framework can be used to rank each piece of evidence based on its probability of bias, providing the practitioner with a measure of certainty that can be placed in their recommendations see . As a reAlthough high-level evidence is considered less susceptible to bias, the practitioner should still critically appraise the quality of the data and the appropriateness of this evidence to their PICO question. For example, systematic reviews can be evaluated using the AMSTAR tool , which cWhile the hierarchical approach to evidence appraisal prioritises high-level evidence, practitioners are encouraged not to overlook lower-tier evidence, which may provide important evidence of the appropriateness, likelihood of acceptance, and feasibility that is often overlooked or difficult to implement in highly controlled RCTs. For example, although case studies are seen as lower-tier evidence due to their low levels of control, they provide important insight into the feasibility and practical application of specific interventions and often provide unique insight into highly niche population groups such as elite athletes. Using the work of Stellingwerff  as an exGiven that evidence from grey literature often bypasses traditional peer-review processes, the quality of this evidence will vary greatly and is highly susceptible to bias. As a result, a thorough appraisal of grey literature is critical before this evidence is used to inform the decision-making process. The AACODS checklist  and QualAfter acquiring and appraising the available evidence relevant to their question, the practitioner’s decision to apply the evidence must be guided by their professional experience and understanding of the athlete . AccordiField expertise refers to understanding the context of the environment or organisation where the intervention will be applied . The praThe practitioner faces the challenge of communicating their knowledge into practical health and performance solutions for athletes and key stakeholders with varying levels of sports nutrition knowledge and availability to receive information. This necessitates adjusting the delivery of knowledge based on the individual and scenario. Although intended for sports scientists, the knowledge translation framework developed by Bartlett and Drust serves as an important tool for assisting the practitioner in effectively communicating their recommendations to athletes and relevant stakeholders . We beliUnderstanding the athlete requires a consideration of their needs, values, preferences, behaviours, and adjusting the nutritional strategy to accommodate these aspects. When implementing any nutritional strategy, the practitioner must keep in mind that the activity is carried out primarily through a set of behaviours that are formed by, among other factors, the athlete’s unique characteristics outlined above. According to Michie et al. , all behMichie et al.  recommenFor practitioners who are still establishing field expertise and getting to know their athletes, there is an elevated risk of “analysis paralysis,” yet they are expected to make quick decisions based on a multitude of contextual factors that will influence their intervention. In such cases, they should seek relevant guidance from more experienced mentors and colleagues in their professional communities of practice. Furthermore, the practitioner should not be concerned about deviating from a specific behaviour change strategy or nutritional intervention if it is not accomplishing the intended goal. This flexibility in decision-making, known as “context-responsiveness,” has been demonstrated to improve outcomes in other areas of healthcare .To keep pace with the evolving landscape of SEN, the practitioner must stay current with the latest relevant scientific literature while continuously adapting to changes in the sporting environment. Of equal importance is the practitioner’s agile commitment to their respective athlete’s ever-evolving goals, values, preferences, and behaviours. To maintain adherence to EBP principles and develop skills and knowledge in the fast-paced, ever-changing profession of SEN, practitioners must regularly reflect on the methods, applications and outcomes experienced in the field. Finding the time and self-discipline to self-audit can be challenging for many practitioners. However, those who fail to do so risk slowing their pace of professional development; continuing with ineffective approaches for engaging with Steps 1–5 of EBP; and leaning on cognitive biases, often to the detriment of their athlete when it comes to providing timely, relevant, and accurate advice. A series of questions for practitioners to self-audit their execution of the EBP steps, highlighting areas for improvement and continuous development when using the EBP framework, is provided in According to Kahneman , a NobelIt is generally accepted that there are two theoretical models of reflection, which are iterative and vertical reflection. Iterative reflection refers to a particular experience that elicits reflection, resulting in new understandings and the intention to act differently. Vertical reflection refers to reflecting in various depths, such as descriptive, intermediate, and critical . Kim proTo give accurate reflections of practice, practitioners must keep a detailed record of the nutritional interventions applied and their corresponding outcomes. Furthermore, as data collection technology advances, it is becoming easier to obtain accurate data in the field ; hence, There are concerns that the rise of EBP could render some practitioners unduly reliant on the necessity for a scientific reference before considering a nutritional intervention, thus diminishing their inherent ability to draw on their professional experience. There is a natural tendency to regard scientific evidence as the criterion starting point that shapes decision-making within EBP. However, the triangulation of the science with the other two cornerstones  is the only way to confidently subscribe to EBP in its purest form. The scientific process is undoubtedly paramount for producing evidence with the least amount of bias that serves to influence practice; however, practitioners must remember that such evidence is merely an abstraction until it is applied to the complex, often highly uncontrolled environment of an athlete’s reality . This isContrary to this concern, delivering a nutritional intervention that triangulates professional experience and client values with scientific evidence naturally drifts further away from the definitive literature as the recommendations become increasingly personalised to the athlete. Furthermore, if no clear evidence exists to support a nutritional intervention, the practitioner should act based on their professional judgement rooted in their understanding of the fundamental principles of SEN, current literature, experiential evidence, and ongoing, in-practice experimentation. Professional judgement can be strengthened by maintaining a detailed record of the athlete, the nutritional intervention, and associated outcomes. With advancements in data collection technology, such as wearables and real-time monitoring, collecting meaningful data from the field is becoming more accessible . In an ibest strategy; instead, there are only appropriate-at-the-time strategies once the three cornerstones of EBP have been given equal consideration. Notably, what constitutes as best is highly subjective and varies in tandem with the athlete’s needs, training objectives, evidence, and continuous reflections. Thus, practitioners should avoid idealising their approaches and instead, in the words of the late Professor Kevin Tipton, remain “sceptical but open-minded” .In the fast-paced, often time-pressed world of professional sport, our SEN-adapted framework of EBP is designed to serve as a guide, encouraging practitioners to collect the best available evidence and combine it with their professional judgement (refined through continuous reflections) and understanding of the athlete , 47, as AR, MH, and LB drafted, critically reviewed, revised the manuscript for important intellectual content, contributed to the manuscript revision, and read and approved the submitted version. All authors contributed to the article and approved the submitted version.


The COVID-19 pandemic has placed the use of evidence for policy-making high up on the international agenda. To fight the pandemic, Governments around the world have publicly stressed the need to draw on evidence by engaging scientific advisors and advisory bodies . At the To assess different institutional responses in terms of the evidence-policy-society nexus and to learn lessons on how to build equity-centred, agile and responsive evidence-informed decision-making mechanisms, WHO convened its first Global Evidence-to-Policy Summit  in late At the Summit, WHO Director-General, Tedros Adhanom Ghebreyesus , was joistrengthening collaboration, information sharing and networking at country, regional and global levels to reduce duplication of efforts in evidence generation and widely increase access to the benefits of research evidence;moving away from siloed approaches and establishing integrated systems to leverage multisectoral and multidisciplinary approaches, beyond research;creating and/or enhancing national structures and evidence advisory bodies that swiftly respond to decision-makers’ requirements for evidence;creating and/or scaling-up innovative mechanisms that allow decision-makers to keep abreast of large amounts of rapidly changing evidence, such as living evidence syntheses; andraising public trust in evidence to improve pandemic response efforts and accelerate the achievement of the 2030 Agenda and SDGs.WHO’s Evidence-Informed Policy Network (EVIPNet) , a long-The Summit culminated in the launch of the EVIPNet Call for Action , developinstitutionalizing structures, such as the EVIPNet knowledge translation platforms, which serve as institutional knowledge intermediaries that are agile and can rapidly respond to societal and decision-makers’ needs, while drawing on different forms of contextualized, actionable evidence;developing and adhering to high-quality norms and standards that promote rigorous, transparent and systematic evidence-to-policy-society mechanisms and rely on equity-oriented, inclusive and multisectoral participation of all stakeholders;strengthening national and international capacity, including sustainable funding, to empower countries and international actors in evidence-to-policy-society processes, while enhancing legitimacy and building trusted relationships across the evidence ecosystem between researchers, policy-makers and the society; andstriving to ensure that global public goods, such as relevant, timely and high-quality global evidence syntheses and locally adaptable guidelines, are available and easily accessible, especially in emergency situations.Senior leaders of key stakeholder and partner institutions–including the Asian Development Bank, Cochrane, the Evidence Commission, UNICEF Innocenti, among others–expressed strong support for the Call for Action and committed to joining the new Coalition of Partners to foster sustainable evidence-to-policy-society systems.Mobilizing evidence for better decision-making is certainly not a novel field. Yet, the COVID-19 pandemic has put the spotlight on the importance of evidence. It has ‘stress-tested’  the evid


The disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.high and LAMP3low expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.We retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3Compared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.LAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response. DespiPrevious basic and clinical studies have analyzed chronic HBV infection’s characteristics, natural history, and immunological pathogenesis , 6, 7. CRecent studies have provided a new perspective on immunological markers as therapeutic agents for chronic liver diseases. Lysosome-associated membrane glycoprotein 3 (LAMP3) is a glycosylated membrane protein located on the 3q chromosome , 17. As 22.1We collected three independent transcriptional profiles from the GEO database, including the liver samples of healthy control and patients with CHB. Furthermore, as a representative of non-viral hepatitis, one RNA-seq dataset of patients with nonalcoholic steatohepatitis (NASH) was also used for validation in other hepatitis. 2.2high and LAMP3low expression groups. DEGs  between these two groups were extracted and analyzed using R 4.1.2  for Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment Analysis (GSEA).According to the median counts of LAMP3 expression, patients with CHB were divided into LAMP32.3Pearson correlation analysis were applied to evaluate the genes related to LAMP3 expression. The associations of LAMP3 expression with the adaptive immune response-related genes were analyzed by the “cor.test” function of R studio. The “ggcatterstats” function in the “ggstatplot” package generated the dot plot. Finally, the analyzed results were visualized in Glue modules by Cytoscape 3.9.1.2.4We collected liver tissues of 27 patients with CHB and 5 healthy controls  to validate the bioinformatic results. The detailed information of all participants showed in 2.5Subsequently, immunohistochemistry (IHC) was performed using primary antibody anti-LAPM3  to validate the expression in our cohort. Five fields (×200) were randomly selected and captured for analysis in each sample. The number of cells in the portal tract  was quantified.2.6high and LAMP3low expression groups were analyzed by the Mann–Whitney U test. Two paired p < 0.05 was assumed significant statistically.All statistical analysis was completed by SPSS 20.0  and R 4.1.2 . The differences of transcriptional levels between control and CHB patients, or LAMP333.1In total, three GEO RNA-seq profiles  were used to compare the transcriptional expression of LAMP3 between patients with CHB and healthy controls. 3.2high and LAMP3low) according to the median expression levels of LAMP3. DEGs between LAMP3high and LAMP3low subgroups were then analyzed. Biological processes and molecular functions in GO enrichment showed that the upregulated DEGs were mainly associated with T cell activation, cell response to chemokine, cytokine, and chemokine receptor binding  into two groups , aspartate aminotransferase (AST), and direct bilirubin (DBIL) , the overexpression of LAMP3 substantially increased the lipid accumulation of hepatocytes , in our Furthermore, in other viral infections, e.g., hepatitis C virus and human papillomavirus, LAMP3 is also specifically induced as a classical interferon-stimulated gene , 23. MorWe also analyzed the biological mechanism of LAMP3 participation in HBV infection. The GEO database was analyzed, and we found that the upregulated LAMP3 expression in HBV-infected patients mainly participated in T cell activation and adaptive immune response. Previous studies showed that LAMP3 was primarily expressed in DC cells, and LAMP3 participated in major histocompatibility complex class II-restricted antigen presentation and the processing of exogenous antigens . LAMP3 iCurrently, research on the interaction between LAMP3+ DCs and T cells is mainly focused on the tumor field, which might provide a basis for the understanding that LAMP3 participates in T cell activation and immune regulation during HBV infection. For example, in hepatocellular carcinoma, LAMP3+ DCs were positively correlated with the infiltration of exhausted CD8+ T cells and Tregs . In gast5in vivo and in vitro experiments. Second, the validation sample in this study was a cross-sectional cohort. In the future, we need to explore the application value of LAMP3 in HBV treatment.Although no previous studies have reported on the association of LAMP3 with HBV infection, our study adds knowledge to this research gap. Our results revealed that the increased LAMP3 expression could enhance T cell activation and adaptive immune regulation. However, this study had several limitations. First, our explanation of the role of LAMP3 in HBV infection was based on pre-existing data from the GEO database and verified by our cohort; however, we did not confirm the function of LAMP3 in HBV infection by conducting The original contributions presented in the study are included in the article/This study was approved by the Ethical Committees of Peking University People’s Hospital (no. 2021PHB122). The patients/participants provided their written informed consent to participate in this study.ZW, XW and BF contributed to conception and design of the study. RJ, FL and HR performed the experiments. LW, HC, and BF analyzed and interpreted of data. ZW and XW wrote the first draft of the manuscript. BF made critical revision of the manuscript for important intellectual content. All authors contributed to manuscript revision, read, and approved the submitted version.


Racial/ethnic discrimination indicates the stereotyped or unkind conduct of superiority towards other persons based on their race or skin color. The UK General Medical Council published a statement supporting zero-tolerance approach to racism in the workplace. We aimed to systematically review racial discrimination in surgery and answer the following questions: (1) Does racial/ethnic discrimination in surgery exist in citations from the last 5 years. (2) If yes, are ways suggested to reduce racial/ethnic discrimination in surgery?The systematic review was performed in compliance with the PRISMA guidelines along AMSTAR 2. A 5-year literature search was carried out on PubMed for articles published from 1/1/2017 to 01/11/2022. Search terms were ‘racial discrimination and surgery’, ‘racism OR discrimination AND surgery’, ‘racism OR discrimination AND surgical education’. The retrieved citations were quality assessed by MERSQI and evidence graded by GRADE.A total of 9116 participants responded with a mean of 1013 (SD = 2408) responses per citations reported in 9 studies from a final list of 10 included citations. Nine studies were from USA and 1 from South Africa. There was evidence of racial discrimination in the last 5 years and the results were justified on strong scientific evidence constituting the basis for evidence grade I. The second question’s answer was ‘yes’ which was defendable on moderate scientific recommendation and thereby establishing the basis for evidence grade II.There was sufficient evidence for the presence of racial discrimination in surgical practice in the last 5 years. Ways to decrease racial discrimination in surgery exist. Healthcare and training systems must increase the awareness of these issues to eliminate the harmful effect on the individual as well as on the level of the surgical team performance. The existence of the discussed problems must be managed in more countries with diverse healthcare systems. The term “racism” refers to prejudice defining that one person feels superior over another. Racial discrimination indicates the stereotyped or unkind conduct towards other persons based on their race or skin color . It was A previous study scrutinized in details stress neurobiology and mental aftermath of racial discrimination . Racial/A.Does racial/ethnic discrimination in surgery exist in citations from the last 5 years?B.Are ways suggested to reduce racial/ethnic discrimination in surgery?Based on both psychological and physical harmful stress responses towards unethical conduct, we aimed to study if racial discrimination still exists in surgical practice. Therefore, our research questions were as follows:A systematic review was performed in compliance with the PRISMA  guidelines  along AMA 5-year literature search was carried out on PubMed for articles published from 1/1/2017 to 01/11/2022 . MERSQI generates a potential range from 5 to 18 scores depending on the dimensions’ correspondence with the content of the citation. At present, a range from 9 to 13.5 scores was produced depending on the dimensions’ degree of correspondence to each of the 10 citations.The retrieved citations were available in full text. Quality assessment of the citations was applied using The Medical Education Research Study Quality Instrument (MERSQI) which contains 10 items that reflect 6 domains of study quality including study design, sampling, type of data, validity, level of data analysis, and outcomes . Each diOur method for identifying and evaluating data has been reported in line with assessing the methodological quality of systematic reviews (AMSTAR 2). There was a good compliance with Amstar 2 tool. Reporting ‘’yes’’ in 11 criteria and ‘’partial yes’’ in one. The 4 ‘’no’’ were related to meta-analysis, which was not applicable in this study.Quality of evidence for the evidence grading was based on criteria for using GRADE , comprisEvidence grade I: strong scientific evidence based on at least 2 studies with high evidential value or a systematic review/meta-analysis with high evidential value.Evidence grade II: moderate scientific basis: a study with high evidential value and at least 2 studies with moderate evidential valueEvidence grade III: low scientific evidence: a study with high evidential value or at least 2 studies with moderate evidence valueEvidence grade IV: insufficient scientific evidence: 1 study with moderate evidence and/or 2 at least 2 studies with low evidential valueWe assessed the risk of bias in a blind manner and the quality estimates were completed by the two authors, separately. If the assessments did not agree, we adjusted and averaged the scores of the two quality assessors. The means were by visual binning divided into 4 classes, but we discarded classes of low or insufficient scientific evidence in our result. Thereby, we regarded that we filled the GRADE’s criteria for consideration of an individual study’s risk of bias or quality to estimate the study’s suitability for establishing a basis for the ratings about its strength to contribute to the body of evidence of the findings in this systematic review. Thereafter, we controlled for accumulated risk of bias by calculating and grading the body of evidence after the quality-assessment outcome according to PRISMA’s recommendations.Descriptive statistics like Pearsons r and Spearmans rho were computed by IBM SPSS version 26.After a careful selection procedure, a final 10 citations were included in our systematic review. A total of 9116 participants responded with a mean of 1013 (SD = 2408) responses per citations reported in 9 citations. Nine studies came from USA and 1 from South Africa. Altogether, 8 cross-sectional studies, 1 prospective cross-over trial cluster-randomized study as well as 1 retrospective cross-sectional analysis were included in the results –23. The Hu et al.  indicateSudol et al.  revealedyes. The answer is justified on Evidence grade I, that is, strong scientific evidence based on 2 studies with high evidential value. In other words, Hu et al. [To answer the question if racial/ethnic discrimination in surgery existed and still exists in the last 5 years, the answer is u et al.  and Sudou et al.  constituPillado et al.  studied Khubchandani et al.  evaluateSmith et al.  stated tEven though considerable effort has reached the training physicians to educate them to be conscious of their own bias and also to be conscious about “embedded stereotypes” that exist and persist in the medical education in order to make meaningful changes, there are still work to do. The authors finish with the words: “Identifying and then confronting existing representation trends in images used in plastic-surgery education is one controllable, yet powerful technique that can make plastic surgeons leaders in the pursuit of an anti-racist medical culture.”.The question: Are ways suggested to reduce racial/ethnic discrimination in surgery.can be answered with yes on a moderate scientific basis according to conditions for Evidence grade II requiring one study  with higRacial/ethnic discrimination in surgery exists in citations from the last 5 years. During these 5 years more than 50% of all general surgery residents reported some form of mistreatment, the highest prevalence and severity existed among racial/ethnic-minority female physicians, explicitly among underrepresented minority (URM) physicians. Racial/ethnic-minority females with racial/ethnic microaggressions were likely to report physician burnout , 22. BurThe British Medical Association, surveyed 2030 UK doctors from different specialties and medical students on their experience of racism in the medical profession . Twenty-Overall, surgical residents who are discriminated, abused, or harassed at least a few times per month were most likely to have symptoms of burnout and suicidal thoughts . PrimaryThe Association of Surgeons in Training in the UK created a new council role as equality and diversity officer, followed by other associations such as The British Orthopedic Trainee Association. One of the roles of the equality and diversity officers is to work on raising the awareness towards surgical training amongst underrepresented groups and to promote excellence in surgical training for the benefit of patients and trainees irrespective of race, gender, disability, sexual orientation, and religion. We believe the first step to work against such misconduct is to encourage victims to speak up and to seek guidance, when escalation takes place and formal report will be needed. We believe that each case should be studied, and offenders need to understand the potential consequences of such misconduct in forms of being suspended or losing license to practice. These suggestions for consequences of serious misconduct need support from different institutions and healthcare systems. In agreement, the UK General Medical Council published a statement supporting zero-tolerance to racism in the workplace.To reduce racial/ethnic discrimination in surgery, wrongdoers can be confronted by means of restorative justice  which isAnother remedy to deal with racism is to educate the surgical staff to fully understand the life experiences of surgical residents as well as to care about providers holistically, and to scrutinize the roots of distress of provider discrimination on surgical care delivery, along with supervising resident’s mental-health wellbeing to avoid burnout and/or attrition . IndividWe discussed race/ethnic discrimination’s negative health and psychological influence, as racial bias diminishes empathy, increases distrust, and reduced referral rates for specialty care for persons of color , 34. It p < 0.01, 2-tailed and rs [p = 0.02 and significant. Most problems with interrater reliability were connected with restriction of alternative for study design and response rate while surveys were most often distributed electronically. Our median overall MERSQI score was 11 and mean 11.3 (range from 9 to 13.5 out) and Cook et al.’s [Self-report is most used to quantify experiences of racial discrimination. Potential limitations consist of self-ratings, although self-ratings are recommended for assessments of personality traits. As with any questionnaire, participants may deliver the answers they believe they should. On one hand, we do not know if subjective intuitions satisfactorily represent factual events. On the other hand, the private experience is likely to be more closely related to the own brain compared with that of an observer. Yet, one strength of Likert scales is claimed to be their capacity to show how strongly a participant feels about something. This, therefore, gives more details than a simple yes or no answer and, thus, do not provide in-depth replies and are easy to analyze statistically. A previous study  evaluated and rs  = 0.71; Most of the studies about racial discrimination in surgery during the last 5 years were performed in USA. Therefore, we lacked reports from the European healthcare systems or from the UK despite the continuous increase of racial/ethnic diversity in Europe. Future research should focus on disclosure of hotspots in surgery and its subspecialities where racial/ethnic discrimination is frequent. Consequently, a standardized pathway for reporting misconduct escalation should be developed with the support of trainees’ associations and healthcare institutions to guide victims of racial discrimination and encourage them to speak up to create mentally healthier surgeons with a brighter future in clinical practice.There was sufficient evidence for the presence of racial discrimination in surgical practice in the last 5 years. Ways to decrease racial discrimination in surgery exist. Healthcare and training systems must increase the awareness of these issues to eliminate the harmful effects on the individual level as well as on the surgical team performance. The discussion of the mentioned interpersonal complications needs to be extended to numerous countries with diverse healthcare systems.


Data continue to accumulate indicating that many systematic reviews are methodologically flawed, biased, redundant, or uninformative. Some improvements have occurred in recent years based on empirical methods research and standardization of appraisal tools; however, many authors do not routinely or consistently apply these updated methods. In addition, guideline developers, peer reviewers, and journal editors often disregard current methodological standards. Although extensively acknowledged and explored in the methodological literature, most clinicians seem unaware of these issues and may automatically accept evidence syntheses  as trustworthy.A plethora of methods and tools are recommended for the development and evaluation of evidence syntheses. It is important to understand what these are intended to do (and cannot do) and how they can be utilized. Our objective is to distill this sprawling information into a format that is understandable and readily accessible to authors, peer reviewers, and editors. In doing so, we aim to promote appreciation and understanding of the demanding science of evidence synthesis among stakeholders. We focus on well-documented deficiencies in key components of evidence syntheses to elucidate the rationale for current standards. The constructs underlying the tools developed to assess reporting, risk of bias, and methodological quality of evidence syntheses are distinguished from those involved in determining overall certainty of a body of evidence. Another important distinction is made between those tools used by authors to develop their syntheses as opposed to those used to ultimately judge their work.Exemplar methods and research practices are described, complemented by novel pragmatic strategies to improve evidence syntheses. The latter include preferred terminology and a scheme to characterize types of research evidence. We organize best practice resources in a Concise Guide that can be widely adopted and adapted for routine implementation by authors and journals. Appropriate, informed use of these is encouraged, but we caution against their superficial application and emphasize their endorsement does not substitute for in-depth methodological training. By highlighting best practices with their rationale, we hope this guidance will inspire further evolution of methods and tools that can advance the field.The online version contains supplementary material available at 10.1186/s13643-023-02255-9. Evidence syntheses are commonly regarded as the foundation of evidence-based medicine (EBM). They are widely accredited for providing reliable evidence and, as such, they have significantly influenced medical research and clinical practice. Despite their uptake throughout health care and ubiquity in contemporary medical literature, some important aspects of evidence syntheses are generally overlooked or not well recognized. Evidence syntheses are mostly retrospective exercises, they often depend on weak or irreparably flawed data, and they may use tools that have acknowledged or yet unrecognized limitations. They are complicated and time-consuming undertakings prone to bias and errors. Production of a good evidence synthesis requires careful preparation and high levels of organization in order to limit potential pitfalls . Many auGiven their potential impact on people’s lives, it is crucial for evidence syntheses to correctly report on the current knowledge base. In order to be perceived as trustworthy, reliable demonstration of the accuracy of evidence syntheses is equally imperative . ConcernPublication of methodological studies that critically appraise the methods used in evidence syntheses is increasing at a fast pace. This reflects the availability of tools specifically developed for this purpose –6. Yet mThese reports, while not widely acknowledged, suggest there are pervasive problems not limited to evidence syntheses that evaluate specific kinds of interventions or include primary research of a particular study design  . SimilarSeveral international consortiums of EBM experts and national health care organizations currently provide detailed guidance Table . They drNotably, Cochrane is the largest single producer of evidence syntheses in biomedical research; however, these only account for 15% of the total . The WorMany authors are familiar with the evidence syntheses produced by the leading EBM organizations but can be intimidated by the time and effort necessary to apply their standards. Instead of following their guidance, authors may employ methods that are discouraged or outdated 28]. Suboptimal methods described in in the literature may then be taken up by others. For example, the Newcastle–Ottawa Scale (NOS) is a commonly used tool for appraising non-randomized studies . Many auEditorials about unreliable or misleading systematic reviews highlight several of the intertwining factors that may contribute to continued publication of unreliable evidence syntheses: shortcomings and inconsistencies of the peer review process, lack of endorsement of current standards on the part of journal editors, the incentive structure of academia, industry influences, publication bias, and the lure of “predatory” journals –48. At tOver time, the generalized acceptance of the conclusions of systematic reviews as incontrovertible has affected trends in the dissemination and uptake of evidence. Reporting of the results of evidence syntheses and recommendations of CPGs has shifted beyond medical journals to press releases and news headlines and, more recently, to the realm of social media and influencers. The lay public and policy makers may depend on these outlets for interpreting evidence syntheses and CPGs. Unfortunately, communication to the general public often reflects intentional or non-intentional misrepresentation or “spin” of the research findings –52 News Many authors and peer reviewers are volunteer health care professionals or trainees who lack formal training in evidence synthesis , 53. InfIn the following sections, we highlight methodological concepts and practices that may be unfamiliar, problematic, confusing, or controversial. In Part 2, we consider various types of evidence syntheses and the types of research evidence summarized by them. In Part 3, we examine some widely used (and misused) tools for the critical appraisal of systematic reviews and reporting guidelines for evidence syntheses. In Part 4, we discuss how to meet methodological conduct standards applicable to key components of systematic reviews. In Part 5, we describe the merits and caveats of rating the overall certainty of a body of evidence. Finally, in Part 6, we summarize suggested terminology, methods, and tools for development and evaluation of evidence syntheses that reflect current best practices.A good foundation for the development of evidence syntheses requires an appreciation of their various methodologies and the ability to correctly identify the types of research potentially available for inclusion in the synthesis.Systematic reviews have historically focused on the benefits and harms of interventions; over time, various types of systematic reviews have emerged to address the diverse information needs of clinicians, patients, and policy makers  SystematBoth Cochrane , 59 and There is consensus on the importance of using multiple study designs in evidence syntheses; at the same time, there is a lack of agreement on methods to identify included study designs. Authors of evidence syntheses may use various taxonomies and associated algorithms to guide selection and/or classification of study designs. These tools differentiate categories of research and apply labels to individual study designs . A familiar example is the Design Tree endorsed by the Centre for Evidence-Based Medicine . Such toSuboptimal levels of agreement and accuracy even among trained methodologists reflect challenges with the application of such tools , 72. ProThese concerns suggest that available tools and nomenclature used to distinguish types of research evidence may not uniformly apply to biomedical research and non-health fields that utilize evidence syntheses  , 76. MorAn alternative to these tools and nomenclature involves application of a few fundamental distinctions that encompass a wide range of research designs and contexts. While these distinctions are not novel, we integrate them into a practical scheme see Fig.  designedApplication of these basic distinctions may avoid some of the potential difficulties associated with study design labels and taxonomies. Nevertheless, debatable methodological issues are raised when certain types of research identified in this scheme are included in an evidence synthesis. We briefly highlight those associated with inclusion of non-randomized studies, case reports and series, and a combination of primary and secondary studies.When investigating an intervention’s effectiveness, it is important for authors to recognize the uncertainty of observed effects reported by studies with high RoB. Results of statistical analyses that include such studies need to be interpreted with caution in order to avoid misleading conclusions . Review Nonetheless, certain design features of NRSI  may help to distinguish stronger from weaker ones. Cochrane recommends that authors of a review including NRSI focus on relevant study design features when determining eligibility criteria instead of relying on non-informative study design labels , 80 ThisCorrectly identified case reports and case series can contribute evidence not well captured by other designs ; in addiSynthesis of combined evidence from primary and secondary studies may provide a broad perspective on the entirety of available literature on a topic. This is, in fact, the recommended strategy for scoping reviews that may include a variety of sources of evidence . However, except for scoping reviews, the synthesis of data from primary and secondary studies is discouraged unless there are strong reasons to justify doing so.Combining primary and secondary sources of evidence is challenging for authors of other types of evidence syntheses for several reasons . AssessmWe suggest that journal editors require authors to identify which type of evidence synthesis they are submitting and reference the specific methodology used for its development. This will clarify the research question and methods for peer reviewers and potentially simplify the editorial process. Editors should announce this practice and include it in the instructions to authors. To decrease bias and apply correct methods, authors must also accurately identify the types of research evidence included in their syntheses.The need to develop criteria to assess the rigor of systematic reviews was recognized soon after the EBM movement began to gain international traction , 89. SysThese tools are often interchangeably invoked when referring to the “quality” of an evidence synthesis. However, quality is a vague term that is frequently misused and misunderstood; more precisely, these tools specify different standards for evidence syntheses. Methodological standards address how well a systematic review was designed and performed . RoB assWe direct attention to the currently recommended tools listed in Table AMSTAR  was in uSystematic reviews that include randomized and/or non-randomized studies as evidence can be appraised with AMSTAR-2 and ROBIS. Other characteristics of AMSTAR-2 and ROBIS are summarized in Table Interrater reliability has been shown to be acceptable for AMSTAR-2 , 11, 102A good understanding of what is required to satisfy the standards of AMSTAR-2 and ROBIS involves study of the accompanying guidance documents written by the tools’ developers; these contain detailed descriptions of each item’s standards. In addition, accurate appraisal of a systematic review with either tool requires training. Most experts recommend independent assessment by at least two appraisers with a process for resolving discrepancies as well as procedures to establish interrater reliability, such as pilot testing, a calibration phase or exercise, and development of predefined decision rules , 106. ThThe standards of AMSTAR, AMSTAR-2, and ROBIS have been used in many methodological studies and epidemiological investigations. However, the increased publication of overviews or umbrella reviews and CPGs has likely been a greater influence on the widening acceptance of these tools. Critical appraisal of the secondary studies considered evidence is essential to the trustworthiness of both the recommendations of CPGs and the conclusions of overviews. Currently both Cochrane  and JBI Barriers to the uptake of AMSTAR-2 and ROBIS include the real or perceived time and resources necessary to complete the items they include and appraisers’ confidence in their own ratings . ReportsAuthors of overviews and CPGs report results of AMSTAR-2 and ROBIS appraisals for each of the systematic reviews they include as evidence. Ideally, an independent judgment of their appraisals can be made by the end users of overviews and CPGs; however, most stakeholders, including clinicians, are unlikely to have a sophisticated understanding of these tools. Nevertheless, they should at least be aware that AMSTAR-2 and ROBIS ratings reported in overviews and CPGs may be inaccurate because the tools are not applied as intended by their developers. This can result from inadequate training of the overview or CPG authors who perform the appraisals, or to modifications of the appraisal tools imposed by them. The potential variability in overall confidence and RoB ratings highlights why appraisers applying these tools need to support their judgments with explicit documentation; this allows readers to judge for themselves whether they agree with the criteria used by appraisers , 108. WhTheoretically, we would expect an association of AMSTAR-2 with improved methodological rigor and an association of ROBIS with lower RoB in recent systematic reviews compared to those published before 2017. To our knowledge, this has not yet been demonstrated; however, like reports about the actual uptake of these tools, time will tell. Additional data on user experience is also needed to further elucidate the practical challenges and methodological nuances encountered with the application of these tools. This information could potentially inform the creation of unifying criteria to guide and standardize the appraisal of evidence syntheses .Complete reporting is essential for users to establish the trustworthiness and applicability of a systematic review’s findings. Efforts to standardize and improve the reporting of systematic reviews resulted in the 2009 publication of the PRISMA statement  with itsThe original PRISMA statement fostered the development of various PRISMA extensions Table . These iThe 2009 PRISMA standards  for repoMisunderstanding of the roles of these tools and their misapplication may be widespread problems. PRISMA 2020 is a reporting guideline that is most beneficial if consulted when developing a review as opposed to merely completing a checklist when submitting to a journal; at that point, the review is finished, with good or bad methodological choices. However, PRISMA checklists evaluate how completely an element of review conduct was reported, but do not evaluate the caliber of conduct or performance of a review. Thus, review authors and readers should not think that a rigorous systematic review can be produced by simply following the PRISMA 2020 guidelines. Similarly, it is important to recognize that AMSTAR-2 and ROBIS are tools to evaluate the conduct of a review but do not substitute for conceptual methodological guidance. In addition, they are not intended to be simple checklists. In fact, they have the potential for misuse or abuse if applied as such; for example, by calculating a total score to make a judgment about a review’s overall confidence or RoB. Proper selection of a response for the individual items on AMSTAR-2 and ROBIS requires training or at least reference to their accompanying guidance documents.Not surprisingly, it has been shown that compliance with the PRISMA checklist is not necessarily associated with satisfying the standards of ROBIS . AMSTAR-Choice of an appropriate tool for the evaluation of a systematic review first involves identification of the underlying construct to be assessed. For systematic reviews of interventions, recommended tools include AMSTAR-2 and ROBIS for appraisal of conduct and PRISMA 2020 for completeness of reporting. All three tools were developed rigorously and provide easily accessible and detailed user guidance, which is necessary for their proper application and interpretation. When considering a manuscript for publication, training in these tools can sensitize peer reviewers and editors to major issues that may affect the review’s trustworthiness and completeness of reporting. Judgment of the overall certainty of a body of evidence and formulation of recommendations rely, in part, on AMSTAR-2 or ROBIS appraisals of systematic reviews. Therefore, training on the application of these tools is essential for authors of overviews and developers of CPGs. Peer reviewers and editors considering an overview or CPG for publication must hold their authors to a high standard of transparency regarding both the conduct and reporting of these appraisals.Many authors, peer reviewers, and editors erroneously equate fulfillment of the items on the PRISMA checklist with superior methodological rigor. For direction on methodology, we refer them to available resources that provide comprehensive conceptual guidance , 60 as wTo enable their uptake, Table Issues involved in meeting the standards for seven review components  If that is not possible, the search should be updated close to the time of completion . DiffereAMSTAR-2 requires authors to provide references for any studies excluded at the full text phase of study selection along with reasons for exclusion; this allows readers to feel confident that all relevant literature has been considered for inclusion and that exclusions are defensible.The design of the studies included in a systematic review  should not be equated with appraisal of its RoB. To meet AMSTAR-2 and ROBIS standards, systematic review authors must examine RoB issues specific to the design of each primary study they include as evidence. It is unlikely that a single RoB appraisal tool will be suitable for all research designs. In addition to tools for randomized and non-randomized studies, specific tools are available for evaluation of RoB in case reports and case series  and singImplications of the RoB assessments must be explicitly discussed and considered in the conclusions of the review. Discussion of the overall RoB of included studies may consider the weight of the studies at high RoB, the importance of the sources of bias in the studies being summarized, and if their importance differs in relationship to the outcomes reported. If a meta-analysis is performed, serious concerns for RoB of individual studies should be accounted for in these results as well. If the results of the meta-analysis for a specific outcome change when studies at high RoB are excluded, readers will have a more accurate understanding of this body of evidence. However, while investigating the potential impact of specific biases is a useful exercise, it is important to avoid over-interpretation, especially when there are sparse data.Syntheses of quantitative data reported by primary studies are broadly categorized as one of two types: meta-analysis, and synthesis without meta-analysis Table . Before Systematic reviews that employ meta-analysis should not be referred to simply as “meta-analyses.” The term meta-analysis strictly refers to a specific statistical technique used when study effect estimates and their variances are available, yielding a quantitative summary of results. In general, methods for meta-analysis involve use of a weighted average of effect estimates from two or more studies. If considered carefully, meta-analysis increases the precision of the estimated magnitude of effect and can offer useful insights about heterogeneity and estimates of effects. We refer to standard references for a thorough introduction and formal training –167.There are three common approaches to meta-analysis in current health care–related systematic reviews Table . AggregaLess familiar and more challenging meta-analytical approaches used in secondary research include individual participant data (IPD) and network meta-analyses (NMA); PRISMA extensions provide reporting guidelines for both , 118. InSeveral items in AMSTAR-2 and ROBIS address meta-analysis; thus, understanding the strengths, weaknesses, assumptions, and limitations of methods for meta-analyses is important. According to the standards of both tools, plans for a meta-analysis must be addressed in the review protocol, including reasoning, description of the type of quantitative data to be synthesized, and the methods planned for combining the data. This should not consist of stock statements describing conventional meta-analysis techniques; rather, authors are expected to anticipate issues specific to their research questions. Concern for the lack of training in meta-analysis methods among systematic review authors cannot be overstated. For those with training, the use of popular software  guideline  and methFamiliarity with AMSTAR-2 and ROBIS makes sense for authors of systematic reviews as these appraisal tools will be used to judge their work; however, training is necessary for authors to truly appreciate and apply methodological rigor. Moreover, judgment of the potential contribution of a systematic review to the current knowledge base goes beyond meeting the standards of AMSTAR-2 and ROBIS. These tools do not explicitly address some crucial concepts involved in the development of a systematic review; this further emphasizes the need for author training.We recommend that systematic review authors incorporate specific practices or exercises when formulating a research question at the protocol stage, These should be designed to raise the review team’s awareness of how to prevent research and resource waste , 130 andReport of an overall certainty of evidence assessment in a systematic review is an important new reporting standard of the updated PRISMA 2020 guidelines . SystemaHistorical systems for rating evidence are based on study design and usually involve hierarchical levels or classes of evidence that use numbers and/or letters to designate the level/class. These systems were endorsed by various EBM-related organizations. Professional societies and regulatory groups then widely adopted them, often with modifications for application to the available primary research base in specific clinical areas. In 2002, a report issued by the AHRQ identified 40 systems to rate quality of a body of evidence . A critiRecognition of the shortcomings of hierarchical rating systems raised concerns that misleading clinical recommendations could result even if based on a rigorous systematic review. In addition, the number and variability of these systems were considered obstacles to quick and accurate interpretations of the evidence by clinicians, patients, and policymakers . These iGRADE offers a consistent and sensible approach for two separate processes: rating the overall certainty of a body of evidence and the strength of recommendations. The former is the expected conclusion of a systematic review, while the latter is pertinent to the development of CPGs. As such, GRADE provides a mechanism to bridge the gap from evidence synthesis to application of the evidence for informed clinical decision-making , 190. WeIn GRADE, use of “certainty” of a body of evidence is preferred over the term “quality.”  CertaintThis process results in assignment of one of the four GRADE certainty ratings to each outcome; these are clearly conveyed with the use of basic interpretation symbols Table  192]. N. N192]. GRADE’s developers acknowledge some subjectivity is involved in this process . In addiOutcomes important to the individuals who experience the problem of interest maintain a prominent role throughout the GRADE process . These oThe GRADE approach is applicable irrespective of whether the certainty of the primary research evidence is high or very low; in some circumstances, indirect evidence of higher certainty may be considered if direct evidence is unavailable or of low certainty . In factTheoretically, application of GRADE should improve consistency of judgments about certainty of evidence, both between authors and across systematic reviews. In one empirical evaluation conducted by the GRADE Working Group, interrater reliability of two individual raters assessing certainty of the evidence for a specific outcome increased from ~ 0.3 without using GRADE to ~ 0.7 by using GRADE . HoweverSimply invoking “the GRADE approach” does not automatically ensure GRADE methods were employed by authors of a systematic review (or developers of a CPG). Table Nevertheless, GRADE is prone to misapplications , 208, whOther caveats pertain to application of a GRADE certainty of evidence rating in various types of evidence syntheses. Current adaptations of GRADE are described in Additional File The expected culmination of a systematic review should be a rating of overall certainty of a body of evidence for each outcome reported. The GRADE approach is recommended for making these judgments for outcomes reported in systematic reviews of interventions and can be adapted for other types of reviews. This represents the initial step in the process of making recommendations based on evidence syntheses. Peer reviewers should ensure authors meet the minimal criteria for supporting the GRADE approach when reviewing any evidence synthesis that reports certainty ratings derived using GRADE. Authors and peer reviewers of evidence syntheses unfamiliar with GRADE are encouraged to seek formal training and take advantage of the resources available on the GRADE website , 212.Accumulating data in recent years suggest that many evidence syntheses  are not reliable. This relates in part to the fact that their authors, who are often clinicians, can be overwhelmed by the plethora of ways to evaluate evidence. They tend to resort to familiar but often inadequate, inappropriate, or obsolete methods and tools and, as a result, produce unreliable reviews. These manuscripts may not be recognized as such by peer reviewers and journal editors who may disregard current standards. When such a systematic review is published or included in a CPG, clinicians and stakeholders tend to believe that it is trustworthy. A vicious cycle in which inadequate methodology is rewarded and potentially misleading conclusions are accepted is thus supported. There is no quick or easy way to break this cycle; however, increasing awareness of best practices among all these stakeholder groups, who often have minimal (if any) training in methodology, may begin to mitigate it. This is the rationale for inclusion of Parts 2 through 5 in this guidance document. These sections present core concepts and important methodological developments that inform current standards and recommendations. We conclude by taking a direct and practical approach.Inconsistent and imprecise terminology used in the context of development and evaluation of evidence syntheses is problematic for authors, peer reviewers and editors, and may lead to the application of inappropriate methods and tools. In response, we endorse use of the basic terms Table  defined We also propose a Concise Guide Table  that sumTo encourage uptake of best practices, journal editors may consider adopting or adapting the Concise Guide in their instructions to authors and peer reviewers of evidence syntheses. Given the evolving nature of evidence synthesis methodology, the suggested methods and tools are likely to require regular updates. Authors of evidence syntheses should monitor the literature to ensure they are employing current methods and tools. Some types of evidence syntheses  are not included in the Concise Guide; for these, authors are advised to obtain recommendations for acceptable methods by consulting with their target journal.We encourage the appropriate and informed use of the methods and tools discussed throughout this commentary and summarized in the Concise Guide Table . HoweverIn line with our main objective, the suggested tools in the Concise Guide address the reliability of evidence syntheses; however, we recognize that the utility of systematic reviews is an equally important concern. An unbiased and thoroughly reported evidence synthesis may still not be highly informative if the evidence itself that is summarized is sparse, weak and/or biased . Many inAlternatively, the frequency of “empty” and inconclusive reviews published in the medical literature may relate to limitations of conventional methods that focus on hypothesis testing; these have emphasized the importance of statistical significance in primary research and effect sizes from aggregate meta-analyses . It is bWe look forward to others’ ideas and proposals for the advancement of methods for evidence syntheses. For now, we encourage dissemination and uptake of the currently accepted best tools and practices for their development and evaluation; at the same time, we stress that uptake of appraisal tools, checklists, and software programs cannot substitute for proper education in the methodology of evidence syntheses and meta-analysis. Authors, peer reviewers, and editors must strive to make accurate and reliable contributions to the present evidence knowledge base; online alerts, upcoming technology, and accessible education may make this more feasible than ever before. Our intention is to improve the trustworthiness of evidence syntheses across disciplines, topics, and types of evidence syntheses. All of us must continue to study, teach, and act cooperatively for that to happen.Additional file 2A. Overviews, scoping reviews, rapid reviews and living reviews.Additional file 2B. Practical scheme for distinguishing types of research evidence.Additional file 4. Presentation of forest plots.Additional file 5A. Illustrations of the GRADE approach.Additional file 5B. Adaptations of GRADE for evidence syntheses.Additional file 6. Links to Concise Guide online resources.