Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence.We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors′ attribution. In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8–35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines.Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety. Skin antisepsis has been an indispensable part of medical practice for more than a century. After a period of increased attention in the 1970s and 1980s that temporarily waned, there is now renewed interest in its role as a simple and effective measure for preventing healthcare-acquired infections.The most commonly used substances for skin antisepsis are (1) alcohols , (2) chlorhexidine, commonly available as chlorhexidine gluconate (CHG), and (3) povidone-iodine (PVI), an organic iodine complex. Among these antiseptics, alcohols are microbiologically most active but have no appreciable residual activity Among the antiseptics, CHG has attracted considerable attention through several prominent clinical studies concerning vascular catheters and surgery per se was superior to PVI per se when in fact CHG-alcohol versus PVI alone had been tested.We noticed an inconsistent interpretation of findings in some primary studies and subsequent reviews. Several articles that evaluated the efficacy of the combination of alcohols plus CHG attributed the study outcomes solely to the CHG component This apparent misinterpretation of evidence and an increasing number of recommendations that were focussing prominently or exclusively on the efficacy of the CHG component prompted us to reassess the evidence by way of systematic review. We posed the following questions: (1) What is the evidence for the efficacy of CHG alone or combination antiseptics containing it for blood culture collection, vascular catheter insertion, and surgical skin preparation? (2) How common is the attribution of efficacy from a combination of antiseptics to CHG alone in the primary literature and in systematic reviews? (3) Has this misattribution had an effect on practice recommendations and evidence-based guidelines?Exhaustive searches for primary and secondary literature were performed in three areas of skin antisepsis: (1) blood culture collection, (2) vascular catheter insertion, and (3) surgical skin preparation. For the purpose of this review, primary literature was defined as randomised clinical trials (RCTs) and non-randomised clinical studies, and secondary literature was defined as systematic reviews. Searches were performed using PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries, and a CHG product manufacturer’s website . Apart from the selection of databases, no specific limits on publication dates and language were applied. The full literature search strategy is provided in All included primary and secondary articles had to have evaluated any CHG-containing antiseptic against any other antiseptic in one of the three areas of interest. The following outcomes had to be reported: (1) for blood culture studies, the rate of blood culture contamination, (2) for vascular catheter studies, the rates of microbial catheter colonisation and/or catheter-related bloodstream infection (CR-BSI), and (3) for surgery articles, the rate of surgical site infections. The following interventions were excluded: antiseptic cloth wiping or bathing in the preoperative phase, antisepsis only during catheter maintenance but not at insertion, non-superficial skin antisepsis, and where skin antisepsis was only part of a multifactorial intervention. Further information on eligibility criteria is provided in Data were extracted on study design, antiseptics compared and their composition, main outcomes, and the authors’ interpretation of the study results. All primary (RCTs and non-RCTs) and secondary articles were rated to assess the authors’ attribution of study outcomes from CHG-containing antiseptics , while only RCTs were selected for subsequent meta-analyses (quantitative synthesis). All RCTs were appraised for risk of bias using a domain-based approach recommended by the Cochrane Collaboration Attribution was rated as “correct” if study authors recognised that the combination of both CHG and alcohol was used and therefore responsible for the outcomes. It was rated as “incorrect” if authors clearly attributed study outcomes derived from the combination of CHG and alcohol to CHG alone. It was rated as “intermediate” if there were ambiguous statements, such as when authors recognised the antiseptic properties of alcohols but also made statements suggesting that CHG alone might be responsible. It was rated as “not applicable” if CHG alone without alcohol had been used.2≥50%; p≤0.1), both fixed-effects and random-effects models were used in a sensitivity analysis.Meta-analyses to quantify the clinical efficacy of CHG compounds were performed using the RevMan software The impact of the conclusions in the primary and secondary literature on perceptions in the medical community and on practice recommendations was gleaned from a non-exhaustive survey of the tertiary literature. Tertiary literature was defined as any other articles commenting on the role of CHG in skin antisepsis, including narrative reviews, professional websites and e-mail discussion forums, clinical practice recommendations, and evidence-based guidelines.A total of 12 articles met the inclusion criteria for blood culture collection; this included 10 primary studies Correct attribution was found in seven articles (58%), ambiguous statements (intermediate ranking) in one (8%), and incorrect attribution in four (33%). Among the ones with incorrect attribution, three noted the presence of alcohol in the CHG-containing preparation but did not associate it with the efficacy of the antiseptic, while one published abstract listed and discussed CHG alone, and the presence of alcohol was found out through correspondence. Both systematic reviews recognised the importance of alcohols.Two parallel-group RCTs The Malani et al systematic review We identified several tertiary sources that contained unsubstantiated statements concerning the efficacy of CHG. A Clinical and Laboratory Standards Institute (CLSI) guideline for blood culture collection In contrast, we did not find any relevant evidence supporting the use of CHG alone prior to blood culture collection.A total of 20 articles met the inclusion criteria for vascular catheter insertion; this included 18 primary studies Judgement of attribution was not applicable to three studies, as they used aqueous CHG only. Among the remaining 17 articles, correct attribution was found in six articles (35%), ambiguous statements (intermediate ranking) in another six articles (35%), and incorrect attribution in five articles (29%). Three original articles correctly listed the presence of alcohol but did not associate it with antiseptic efficacy, while for one abstract, the presence of alcohol was found out through correspondence.Four meta-analyses were performed ; this inAdditional single-trial comparisons included (1) the combination of CHG, benzalkonium chloride and benzyl alcohol versus aqueous PVI The first systematic review Again, we found several examples in the tertiary literature that referred to CHG alone where the CHG-alcohol combination would have been relevant. A follow-up article Overall, we found strong evidence supporting the efficacy of CHG-alcohol antisepsis for catheter insertion and maintenance, particularly when compared with aqueous PVI. We also found evidence favouring aqueous CHG over aqueous PVI, but this was limited to the outcome catheter colonisation. In single trials, a CHG-containing triple combination was better than PVI-alcohol A total of 14 articles met the inclusion criteria for surgical skin antisepsis; this included 11 primary studies Among all primary and secondary articles, correct attribution to both CHG and alcohol was found in five articles (36%), ambiguous statements (intermediate ranking) in three articles (21%), and incorrect attribution in six articles (43%).Five RCTs evaluated CHG-alcohol versus aqueous PVI and were included in a meta-analysis . This shper se was superior to povidone-iodine per se.The first systematic review Again, we found examples of tertiary publications that contained unsubstantiated statements about the role of CHG. A narrative Current Concepts review on the prevention of perioperative infection As for blood cultures, we did not find any relevant evidence supporting CHG alone for pre-incisional preparation of superficial skin in surgery. In fact, aqueous CHG commonly fails US regulatory requirements for patient preoperative skin preparation We found a high proportion of primary and secondary literature and some prominent tertiary sources that attributed the efficacy of the combination of CHG and alcohol to CHG alone. The rates of incorrect attribution among the articles that we assessed ranged from 29% for catheters to 43% for surgery. The rates of incorrect and ambiguous attribution combined ranged from 42% for blood cultures to 65% for catheters. For surgery, there were more articles with incorrect (43%) than with correct attribution (36%). These conclusions were found at all levels of evidence gathering and knowledge translation, including primary clinical trials, systematic reviews, clinical practice recommendations and evidence-based guidelines.The omission of alcohols in the process of evidence assessment can be seen, for example, in the draft CDC catheter guidelines In our analyses, we found good evidence favouring CHG-alcohol combinations over aqueous PVI, the most commonly tested alternative, in all three areas of skin antisepsis. This is a comparison of two active agents against one. However, this superiority does not hold against PVI plus alcohol or other competitors combined with alcohol, either due to equivalent performance in meta-analyses (for blood cultures) or a lack of relevant studies (for catheters and surgery). For blood cultures, alcohols alone may be effective, according to another analysis Each of the three applications has different biological and functional requirements. Blood culture collection requires immediate activity at the venipuncture site, but no prolonged action. Alcohols, with their strong immediate activity that typically exceeds those of CHG and PVI by about a factor of 10 Another fact deserves consideration. Most catheter studies used the antiseptics both before insertion and during maintenance . Thus, wOur review has several limitations. First, it is partially hypothesis-driven, as indicated at the end of the Introduction section. This is unusual for systematic reviews, but nevertheless we used an explicit and rigorous systematic review methodology, including adherence to the PRISMA Statement We were unable to trace the exact origins of the CHG misattribution. However – even though this is speculative – some observations in the literature provide a few potential reasons. First, some authors may regard alcohol simply as a solvent for CHG. This is reflected by the commonly-used term “chlorhexidine in alcohol” and references to alcohol as a “base solution” for CHG. Second, alcohol may not be universally regarded as an effective antiseptic. For example, wording in the CLSI blood culture guideline Our findings have broader implications. An important scientific principle – the fact that it is generally not possible to attribute effects to only one factor when several factors have been tested together – has frequently been overlooked. The individual published analyses may have been done correctly at a technical level of evidence assessment First, it may be a matter of subjective views held by authors. If, for example, alcohol is regarded as a mere solvent for CHG, then authors are unable to draw appropriate conclusions. This means that the assessment of evidence remains susceptible to subjective influences, and this will continue to require attention in this area as well as in other subject areas. Second, this highlights the principle of biological plausibility. In the CHG example, plausibility could have been checked by what is known from microbiological studies of antiseptics Our findings also have potential implications for patient safety. When following recommendations to use “chlorhexidine”, caregivers may inappropriately use CHG on its own, in aqueous solution, as this is readily available. The clinical impact from blood cultures and vascular catheterisation may be small, because contaminated blood cultures do not directly harm patients and CHG alone appears to exert some protective effect in vascular catheterisation. However, tangible negative consequences may arise in surgery, because marked differences in surgical infection rates have been observed between different antiseptic regimens In summary, there is good evidence that CHG-alcohol is superior to aqueous PVI – an important competitor – in all three areas of skin antisepsis. However, this does not apply to competitors combined with alcohols. The perceived efficacy of CHG in skin antisepsis is often in fact based on evidence for the efficacy of the CHG-alcohol combination. In conjunction, the role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety.Table S1Results of risk of bias assessment for studies evaluating antiseptics for blood culture collection.(PDF)Click here for additional data file.Table S2Results of risk of bias assessment for studies evaluating antiseptics for vascular catheter insertion.(PDF)Click here for additional data file.Table S3Results of risk of bias assessment for studies evaluating antiseptics for surgical skin preparation.(PDF)Click here for additional data file.Text S1Eligibility criteria, literature search strategy and risk of bias assessment.(PDF)Click here for additional data file.Checklist S1PRISMA Checklist.(PDF)Click here for additional data file.


The DECIDE framework was developed to support evidence-informed health system decisions through evidence summaries tailored to health policymakers. The objective of this study was to determine policymakers’ perceptions regarding the criteria in the DECIDE framework and how best to summarise and present evidence to support health system decisions.We conducted an online survey of a diverse group of stakeholders with health system decision experience from 15 countries and the World Health Organization. We asked about perceptions of criteria relevant to making health system decisions, use of evidence, grading systems, and evidence summaries.We received 112 responses (70% response rate). Most respondents had healthcare (85%) and research (79%) experience. They (99%) indicated that systematic consideration of the available evidence would help to improve health system decision-making processes and supported the use of evidence from other countries (94%) and grading systems (81%). All ten criteria in the DECIDE framework were rated as important in the decision-making process. Respondents had divergent views regarding whether the same (38%) or different (45%) grading systems should be used across different types of health decisions. All components of our evidence summary were rated as important by over 90% of respondents.Survey respondents were supportive of the DECIDE framework for health system decisions and the use of succinct summaries of the estimated size of effects and the quality of evidence. It is uncertain whether the findings of this survey represent the views of policymakers with little or no healthcare and research experience. The project’s objective is to develop and evaluate communication strategies to support evidence-informed decisions by building on the work of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group [http://www.gradeworkinggroup.org] and the Cochrane Applicability and Recommendations Methods Group [http://www.armg.cochrane.org]. As part of the DECIDE project, we have developed a framework for communicating evidence to inform decisions about health systems [http://www.decide-collaboration.eu/WP5/Strategies/Framework].Decisions regarding health systems are often political processes involving a number of policymakers and other key stakeholders. There is a need to support these decisions with the best available evidence, however, the effects of health system interventions are often uncertain and stakeholders may have a low level of medical and research literacy. The Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence (DECIDE) project is a collaborative research project funded by the European Commission’s Seventh Framework Programme . SURE is a related collaborative research project with the objective of developing and evaluating strategies for improving access to and use of research evidence in health policy development in Africa. These countries were included as we had sufficient networks linked to the DECIDE and SURE projects to provide the necessary referrals to potential participants. Inclusion criteria for survey participants included people responsible for health system decisions and stakeholders with an interest in and experience with health system decisions, such as delivery, governance and financial arrangements, and strategies for implementing health system changes. This could include public officials, managers, health workers, and representatives of special interest groups, international organizations, non-governmental organisations, donor countries, or the general public. Our partners in the DECIDE and SURE projects from each country and other personal contacts helped us to identify 10 to 20 people who were not involved with the DECIDE collaboration in each of the 15 countries and within WHO, with the aim of obtaining 10 completed questionnaires from each. We prepared an online survey (in English only) using the LimeService online platform [https://www.limeservice.com/]  group of policymakers from different countries, with a wide range of experience with different types of health policy and management decisions and with different perspectives. Our sampling frame included the nine DECIDE partner countries , the World Health Organization (WHO), and six SURE  partner countries, namely Cameroon, Ethiopia, Mozambique, Zambia, Uganda, and South Africa [To determine current use and perceived importance of the DECIDE criteria in health system decision-making, we asked participants to provide an example of a health system decision with which they had been involved or were familiar. Participants were asked to rate whether each of the ten criteria in the DECIDE framework , adverse (undesirable) effects, resource use (cost), value for money, impacts on equity, implementability (feasibility), and acceptability) had been considered as part of this healthcare decision on a 3-point scale . If a given criterion had not been considered, they were asked whether they considered it relevant, and also to state any other criteria they considered relevant. The opportunity to make optional comments was provided. Participants were also asked to rate the importance  of each of the ten criteria, with optional comments if desired.To determine perceptions on the use of evidence in health system decisions, we asked participants about their use of 1) evidence from other countries; 2) systematic reviews to inform their health system decision; and 3) evidence grading systems. Specifically, we asked whether they believed that evidence grading systems should be the same or different for health system decisions, compared to clinical decisions. We also assessed the perceptions of participants as to the contents of summaries of evidence. These summaries, based on the best available evidence, should be concise yet include all of the key information needed to inform a health system decision. We asked participants to rate the importance of including certain types of information (components) in these summaries, namely: effect sizes, confidence intervals, numbers of studies, and the quality of the evidence. Participants also provided information on their research, healthcare, and decision-making experience.versus SURE partner countries) and across groups with different types of experience (with versus without research training or experience).Participants were contacted by email and asked to complete the online survey. Initial contacts were made by our partners in each country or directly by us. Non-responders received reminders via email at two and four weeks after the initial invitation. We summarised the results using frequencies and percentages, and collated provided comments. Our primary analysis focused on implications for our evidence to health system decisions framework and evidence summaries. We explored potential differences in responses across participants from different countries (DECIDE We received 112 responses (70% response rate) to the online survey. Of these, 84 responses (75%) were complete and 28 (25%) were partially complete. We received 23 responses (46% response rate) from the six SURE countries, 84 responses (93% response rate) from the nine DECIDE partner countries, and five responses (50% response rate) from WHO. Table We asked participants to describe a recent healthcare decision with which they had been involved or had the opportunity to follow closely. One hundred and two respondents 91.1%) had such an example and 10 (8.9%) respondents imagined a current or recent decision. Figure .1% had sRespondent ratings on the importance of the ten criteria are summarised in Figure Most respondents agreed that a system of grading evidence would either definitely (59.7%) or probably 33.3%) improve health system decision-making processes Table . When as3.3% imprversus SURE partner countries) or experience (with compared to without research training or experience).Overall, there was relatively little variation in the responses. Nonetheless, we explored potential differences in responses across participants from different countries and across groups with different types of research experience (Additional file We received 112 responses to an online survey from a diverse, international group of policymakers, managers, their support staff and other stakeholders to better understand their perceptions of the ten criteria in the DECIDE framework for going from evidence to health system decisions. We also obtained their perceptions of the components of summaries of evidence. Our respondents had a high level of professional healthcare and research experience and training and had worked in a wide range of levels and organizations. This may be due to the way in which they were identified, or a greater interest among those policymakers with clinical or research experience to participate in the survey. Our sample of policymakers was not intended to be representative of included countries, but was rather to obtain a diverse range of views from respondents.Respondents had generally considered all ten criteria in the DECIDE framework in their own healthcare decisions and consistently rated these criteria as important or probably important to decision-making. In earlier work, Guindo and colleagues identified a range of healthcare decision criteria and criteria-based decision-making tools used in empirical studies of health system decisions – the most frequently cited criteria were equity and fairness, efficacy/effectiveness, stakeholder interests and pressures, cost effectiveness, strength of evidence, and safety . In our Most respondents agreed that a system of grading evidence would improve health system decisions; however, there was considerable disagreement as to whether these grading systems should be uniform across clinical and health system decisions. This is consistent with the ongoing debate in the literature on the application of the GRADE approach to a range of decisions ,12. WhilEffectively communicating complex information through summaries has been proven in the use of the GRADE summary of findings table ,19 and SThe strengths of this survey were a good response rate from a diverse range of countries, backgrounds, levels of decision-making, and organisations. The fact that 25% of the surveys were partially completed may have been due to survey length. The comparatively lower response rate from SURE partner countries means results are likely biased towards higher-resource settings, limiting their applicability to resource-constrained settings. One significant limitation of the survey was the relatively high level of healthcare and research experience amongst respondents; only four respondents had no healthcare or research experience. This is probably not representative of health policymakers in general and potentially limits the generalizability of our findings. Nonetheless, the fact that the criteria included in the DECIDE framework were regarded as important for decision-making by these respondents provides further support for their inclusion in a framework for going from evidence to health system decisions.versus different systems for grading evidence, further clarification of the included criteria, the need for additional criteria, and the perceptions of policymakers and stakeholders who do not have a research or health professional background.This survey confirmed the relevance of the criteria that we had identified and incorporated in the DECIDE framework for health system decisions and suggests that the framework is likely to be helpful for informing health system decisions. Further development and evaluation of the framework will be based on practical applications of the framework to health system and population health decisions and user testing . Facets Health system decision-making requires careful consideration of a multitude of variables, such as the magnitude of the problem, the size of benefits and adverse effects, feasibility and acceptability, as well as resource and equity implications. Surveyed individuals supported the use of systems to grade the quality of evidence for health system decisions, but there was disagreement as to whether uniform or different grading systems should be used for health system and clinical decisions. Communication of evidence to policymakers and stakeholders involved in health system decisions should employ succinct summaries of measures of effect and the quality of evidence in clear and simple language.DALY: Disability-adjusted life years; DECIDE: Developing and evaluating communication strategies to support informed decisions and practice based on evidence; GRADE: Grading of recommendations assessment development and evaluation; HRP: Special programme of research development and research training in human reproduction; NNT: Number needed to treat; SUPPORT: Supporting policy relevant reviews and trials; SURE: Supporting the use of research evidence for policy in African health systems; UNDP: United nations development programme; UNFPA: United nations population fund; WHO: World health organization.The authors declare that they have no competing interests.All the named authors contributed to the survey design and content. JPV and ADO administered the survey and JPV conducted the analysis. JPV and ADO prepared the initial draft of the manuscript and all authors contributed to and approved the final version of the manuscript. This manuscript represents the views of the named authors alone. All authors read and approved the final manuscript.2 tests; none were significant at the P <0.05 level.Participant responses on quality of evidence and components of evidence summaries, stratified by research experience and country of origin. Differences in responses by respondent research experience and country of origin were tested using χClick here for file


The importance of basing health policy and health care practices on the best available international evidence  and on translating knowledge or evidence into action  is increasingly being emphasized across all health sectors inmost countries. Evidence-based healthcare is a process that identifies policy or clinical questions and addresses these questions by generating knowledge and evidence to effectively and appropriately deliver healthcare in ways that are effective, feasible, and meaningful to specific populations, cultures, and settings. This evidence is then appraised, synthesized, and transferred to service delivery settings and health professionals who then utilize it and evaluate its impact on health outcomes, health systems, and professional practice. Many of the common theories that address this translational process place it apart from the evidence-based practice cycle and most recognise only two translational gaps. This paper seeks to clarify the nature of evidence-based healthcare and translation science and proposes a reconceptualization that both brings together these two dominant ideas in modern healthcare and asserts the existence of a third fundamental gap that is rarely addressed the gap between knowledge need and discovery. The challenges related to facilitating the cycle of scientific discovery through to the widespread adoption of a healthcare innovation have become of central concern to individuals and communities who seek or need healthcare; health professionals; policy makers; the funders of health services. Indeed, the interface between identifying knowledge needs for health improvement, pure scientific bench research, clinical trial based research, and, ultimately, the implementation of the results of research into some form of pragmatic outcome is a growing source of ongoing angst in both the research and clinical communities. It is a vital enterprise that, if achieved successfully, has the potential to result in dramatic improvements in global health outcomes. Whilst the translation of evidence into action is the raison d'être of the evidence-based practice movement, so, too, is it the core interest of translation science. Clarifying the nature and components of these two seemingly different  fields of endeavour and reconceptualizing this complementarity is important in advancing health policy and practice towards improving the health of people globally.Nursing in central to the delivery of healthcare and an increasingly major contributor to the evidence-based practice movement broadly and the achievement of evidence-based practice in healthcare settings. Although the origins of evidence-based practice are in medicine, nursing is increasingly playing a role, particularly with respect to aligning practice with evidence at the point of care. Nurse scientists, therefore, are well positioned to take a leadership role in the field of translational science.There are a number of models that attempt to represent the components of evidence-based healthcare to facilitate understanding, analysis, improvement, and/or the replacement of the process as it is currently conceived, purported and practiced, for example, the Ace Star Model of Knowledge Transformation ; the fivThe JBI Model is developmental and, building on frameworks that have evolved, was constructed out of experience within the evidence-based practice field; the emerging international work of the Joanna Briggs Institute and the international Collaborating Centers of the Joanna Briggs Collaboration; involvement in disseminating, implementing and evaluating evidence-based guidelines in clinical settings; an examination of the scientific and professional literature.Evidence-based practice can be conceptualized as clinical decision making that considers the best available evidence; the context in which the care is delivered; client preference; and the professional judgment of the health professional. The JBI model of evidence-based healthcare depicts the four major components of the evidence-based healthcare process as:healthcare evidence generation;evidence synthesis;evidence/knowledge transfer;evidence utilization.Each of these components is modelled to incorporate their essential elements, and the achievement of improved global health is conceptualized as both the goal or endpoint of any or all of the model components and the raison d'être and driver of evidence-based healthcare .Evidence-based healthcare is described as a cyclical process that derives questions, concerns, or interests from the identification of global healthcare needs by clinicians or patients/consumers and then proceeds to address these questions by generating knowledge and evidence to effectively and appropriately meet these needs in ways that are effective, feasible, and meaningful to specific populations, cultures, and settings. This evidence is then appraised, synthesized, and transferred to service delivery settings and health professionals who then utilize it and evaluate its impact on health outcomes, health systems, and professional practice.The term “evidence” is used in the model to mean the substantiation or confirmation that is needed in order to believe that something is true . Health Central to the JBI understanding of evidence-based practice is that health professionals will use research evidence together with the context of care, patient/client values and preferences, and the experience, expertise, and clinical judgment of the health professional. Using all of this information, health professionals are in a position to make evidence informed decisions.The model is premised on the belief that global health issues are both the driver and reason for evidence-based practice. The US Institute of Medicine (IOM) describes global health as “the goal of improving health for all people in all nations by promoting wellness and eliminating avoidable disease, disability, and death” . For theThe JBI model assumes that the raison d'être of the research enterprise is to address unmet needs for knowledge; that is, to identify and address concerns that arise out of the experiences of patients/clients, the users of healthcare, healthcare professionals, and families, carers, and communities to generate evidence that will effectively and appropriately meet these identified needs . The model asserts that evidence may derive from experience, expertise, inference, deduction, or the results of rigorous inquiry but recognizes that “the results of well-designed research studies grounded in any methodological position are seen to be more credible as evidence than anecdotes or personal opinion” . HoweverEvidence synthesis is the evaluation or analysis of research evidence and opinion on a specific topic to aid in decision making in healthcare. Although the science of evidence synthesis has developed most rapidly in relation to the meta-analysis of numerical data linked to theories of cause and effect, the further development of theoretical understandings and propositions of the nature of evidence, and its role in healthcare delivery and the facilitation of improved global health is identified as an important element of this component of the model. Similarly, the increasing, ongoing interest and theoretical work on methods of synthesizing evidence from diverse sources are depicted as an element of evidence synthesis.The third element of evidence synthesis is the operationalization of methods of synthesis through the systematic review process. This element in the model is grounded in the view that evidence of feasibility, appropriateness, meaningfulness, effectiveness, and economics are legitimate foci for the systematic review process; and that diverse forms of evidence  can be appraised, extracted, and synthesized .There are three elements of synthesis in the model: theories that underpin synthesis, synthesis methodologies and the systematic review of evidence.This component of the model relates to the act of transferring evidence (knowledge) to individual health professionals, health facilities, and health systems globally by means of journals, other publications, guidelines, electronic media, education and training, and decision support systems. Evidence transfer is seen to involve more than disseminating or distributing information and should include careful development of strategies that identify target audiences—such as clinicians, managers, policymakers and consumers—and methods to package and transfer information that is understood and used in decision making. The model therefore depicts three major elements of evidence/knowledge transfer—education and training, information delivery, and the transfer of evidence though organizational and team systems. .This component of the model relates to the implementation of evidence into practice, as is evidenced by practice and/or system change. It identifies three elements: evaluating the impact of the utilization of evidence on the health system, the process of care and health outcomes; practice change; embedding evidence through system/organizational change.The JBI Model of evidence-based healthcare adopts a pluralistic approach to the notion of evidence whereby the findings of qualitative research studies are regarded as rigorously generated evidence and other text derived from opinion, experience, and expertise is acknowledged as forms of evidence when the results of research are unavailable. Pearson and Jordan  say “WhiThe Agency for Healthcare Research and Quality (AHRQ) in the United States report to congress stated that, “the ultimate goal (of AHRQ) is research translation—that is, making sure that findings from AHRQ research are widely disseminated and ready to be used in everyday healthcare decision making.” In 1999, AHRQ published its first Translating Research into Practice (TRIP) initiative. The purpose of the TRIP initiative was to generate new knowledge about approaches that promote the utilization of rigorously derived evidence to improve patient care. The Agency's goal was to enhance the use of research findings, tools, and scientific information that would work in diverse practice settings, among diverse populations, and under diverse payment systems . The neeKnowledge translation has been seen as the process from basic discovery (basic/laboratory science) to intervention development  , 17, knoMode 1 and Mode 2 knowledge have been used to describe different ways of knowledge generation. Whereas “Mode 1 relates to the traditional paradigm of scientific discovery” .The notion of translation gaps in the research-into-action cycle is common in all of the work in progress internationally, and Pearson and Jordan  suggest The first gap relates to the gap between “knowledge needs”  and the work undertaken by scientists and researchers during the “discovery” process. Within this gap there can be an integrated approach to topic selection, where there is active collaboration between those conducting the research and the end users of research . This gap is a vital component of translational research and is well addressed by very few groups, a notable exception being the National Institute for Health Research in the UK, with its associated Clinical Research Networks and its community engagement program “INVOLVE.”The second commonly identified gap relates to the gap between what is referred to here as “discovery research”  and “clinical research” . This gap is the most commonly addressed gap on the international stage with significant work being undertaken in many countries; but for most, this is where translational research begins and ends.The third translation gap, that of translating research into practice, is rarely represented by strong programs in most countries, although some have recently ventured into this realm, notably in cardiology and metabolic/human nutrition centers.Translating knowledge into action within healthcare is a complex, evolving, and dynamic process. While various models have been described, an accepted standard approach has yet to be widely adopted. Regardless of the model used, it is clear that three main gaps exist:the gap between the need for knowledge and the discovery of that new knowledge;the gap between the discovery of new knowledge and the clinical application of that knowledge;the gap between the clinical application and the development of routine clinical actions or policy.Pearson and Jordan , PearsonPearson et al.  assert tThe gap between the need for knowledge and discovery (gap 1) equates with the elements in the JBI Model that focus on the state of global health and the generation of knowledge through the conduct of basic or discovery-oriented research. Applying the findings of discovery research to the “real-world” (gap 2) through the conduct of clinical research  is also a component of evidence generation. Evidence synthesis, transfer, and utilization in the JBI model represent the processes that most adequately address the gap between clinical application and clinical or policy action (gap 3).Although evidence-based healthcare is gaining acceptance globally, it is complex, sometimes misunderstood, and frequently maligned. The sources of evidence accessed by practitioners, regardless of its nature—numerical, qualitative, or anecdotal—or its focus—feasibility, appropriateness, meaningfulness, or effectiveness—influences healthcare practice in all disciplines. Research evidence that is rigorously generated, regardless of design, demands due consideration of its quality prior to its utilization in the clinical environment. Evidence that is generated through the conduct of clinical trials; epidemiology; observational studies; qualitative studies; and action-oriented research are essential in addressing the knowledge and evidence needs of individuals and communities and of clinical and policy decision makers .The JBI model of evidence-based healthcare emphasizes the need for the generation, synthesis, transfer, and utilization of evidence derived from diverse research approaches; has been constructed to facilitate reasoning and critique about evidence-based healthcare and its role in improving global health, within a logical conceptual framework.Translation science  is as complex and as frequently misunderstood as evidence- based healthcare. The dominant view of translation science overly emphasises the translation of the results of “basic,” “bench,” or discovery research into clinical application through the conduct of clinical trials—an enterprise that is now well entrenched in most advanced economies. We contend that translation is much more than the conduct of clinical trials to test discoveries. It begins with translating the questions that arise out of the need for knowledge in the “real world” into discovery research (addressing what we describe as gap 1); translating the findings of discovery research into clinical or policy application through clinical or policy research (addressing what we describe as gap 2); translating the findings of clinical or policy research into action at the clinical or policy level (addressing what we describe as gap 3). Integrating these three translation gaps into a model of evidence based health appears, to us, to clarify and reconceptualize the complexities of improving health outcomes through translating knowledge into action.


A wandering spleen occurs when there is a laxity of the ligaments that fix the spleen in its normal anatomical position.This is a case report of a wandering spleen with horseshoe kidney in a 29-year-old male admitted with acute lower abdominal pain and vomiting to emergency department of Shariati hospital in Isfahan province. Sonographic examination showed a homogeneous 21 × 15 × 8 cm mass in the lower part of the abdomen and pelvis associated with a horseshoe kidney. Laparotomy confirmed the clinical and ultrasound findings.The association of horseshoe kidney with a wandering spleen in this case may be due to an embryological anomaly. Wandering spleen is displacement of the spleen from its normal location due to a loss or weakening of ligaments that hold the spleen in the left upper quadrant . Van HorA 29-year-old man with acute lower abdominal pain and vomiting was admitted to the emergency department of Shariati hospital in Isfahan province. The physical examination revealed that there is a large tender and mobile mass in hpogastric region. An abdominal distension was noticed too . He was afebrile (36.9°C) with normal blood pressure (123/82 mm Hg) but with tachycardic (112 beats per minute). White blood cell count, hemoglobin level, platelets count and urinary analysis were normal. A plain abdominal radiographic examination showed marked colonic gaseous distension present in the left upper quadrant.Sonographic examination showed a homogeneous 21 × 15 × 8 cm mass in the lower part of the abdomen and pelvis with echogenicity that was consistent with normal spleen tissue while the normal splenic bed in the left upper abdomen was empty. The left kidney was atrophic measuring 85 mm in length which is showing increased parenchymal echogenisity. Right kidney was also enlarged to 129 mm in length. The lower poles of both kidneys were deviated medially suggesting a horseshoe kidney. No sign of hydronephrosis or stone was detected in the kidneys. Laparotomy examination confirmed the clinical and ultrasound findings. The enlarged spleen mass in the lower part of the abdomen and pelvis had a 720 degree torsion around a 25-cm long splenic pedicle with a horseshoe kidney. The spleen had no holding ligaments. Although a detorsion of the spleen was attempted, there was no success since the pedicle had become fibrotic. There were varicose dilatations in the veins surrounding the pedicle of the spleen. The splenic artery was double tied and excised.Then the splenectomy completed by double tying and excising the vein as well. The excised spleen had 843 g weight. , C, D. TThis was the first report on a wandering spleen associated with horseshoe kidney in an adult man. Embryologically, the spleen originates from the mesenchymal remnant of the dorsal mesogastrium at the left upper quadrant of the abdomen. During this process, the spleen establishes its peritoneal connections with the left kidney and stomach by the splenorenal and gastrosplenic ligaments . When thVan Horne described a case of wandering spleen for the first time in 1667 while performing an autopsy . The cauClinically, patients may present with normal complaints, such as occasional nausea, vomiting or mild cramp-like pain due to splenic congestion or intermittent torsion and spontaneous detorsion , 7. BecaSurgical treatments include splenectomy and splenopexy. For many years, the preferred treatment was to remove the spleen surgically, initially by conventional laparotomy and more recently by laparoscopy . The firThe wandering spleen usually is located in an anterior abdominal position and is more exposed to an abdominal impact in accidents. On the other hand, it should not be denied that misplaced spleen sometimes can be the possible reason behind wrong diagnosis in cases that experience traumatic injuries. Wondering spleen is also at risk of iatrogenic traumatic injuries during surgical or endoscopic manipulation of the colon, stomach, pancreas and other abdominal organs in such cases. An increased awareness of this condition may help in reducing the incidence of mortality in emergency departments.


Spleen can have a wide range of anomalies including its shape, location, number, and size. Although most of these anomalies are congenital, there are also acquired types. Congenital anomalies affecting the shape of spleen are lobulations, notches, and clefts; the fusion and location anomalies of spleen are accessory spleen, splenopancreatic fusion, and wandering spleen; polysplenia can be associated with a syndrome. Splenosis and small spleen are acquired anomalies which are caused by trauma and sickle cell disease, respectively. These anomalies can be detected easily by using different imaging modalities including ultrasonography, computed tomography, magnetic resonance imaging, and also Tc-99m scintigraphy. In this pictorial essay, we review the imaging findings of these anomalies which can cause diagnostic pitfalls and be interpreted as pathologic processes. Spleen is an intraperitoneal organ located in the left upper quadrant with a smooth serosal surface. Its normal position is provided by two fatty ligaments: the gastrosplenic ligament, which connects the greater curvature of the stomach to the ventral aspect of the spleen, and the splenorenal ligament between the left kidney and the spleen, attaching the spleen to the posterior abdominal wall. The splenic hilum is directed anteromedially and includes splenic artery and six or more branches of the splenic vein. Splenic size changes according to the age and weight. Configuration of the spleen is also variable according to the indentations of the organs including stomach, colon, pancreas, and kidney which are in close relation to the spleen –4.The fetal spleen is lobulated, and these lobules normally disappear before the birth. Lobulation of the spleen may persist into adult life and be typically seen along the medial part of the spleen. A persisting lobule results in a variation in shape of the spleen . But somThe notches and clefts of the spleen are other congenital shape anomalies which are located on the diaphragmatic surface and especially superior border of the adult spleen. These are remnants of the grooves that originally separate the fetal lobules. Clefts occasionally may reach 2-3 cm in length and may cause misinterpretations as a splenic laceration in patients with abdominal trauma , 2 Figu. PersistAccessory spleen, in other words supernumerary spleens, splenunculi, or splenules, results from the failure of fusion of the primordial splenic buds in the dorsal mesogastrium during the fifth week of fetal life. Incidence of accessory spleen in the population is 10%–30% of patients in autopsy series and 16% of patients undergoing contrast enhanced abdominal CT. Although the most common location for an accessory spleen is splenic hilum 75%)  and panc%  and paWandering or ectopic spleen is a rare entity in which the spleen is located outside of its normal location. Its reported incidence in several large series of splenectomies is less than 0.5% and mainly detected in children and women between 20 and 40 years of age. The reason for the wandering spleen is the laxity or maldevelopment of the supporting splenic ligaments, and the spleen can be found in any part of the abdomen related to the length of the vascular pedicle.Wandering spleen may be incidentally detected or may cause different degrees of abdominal pain related to acute, chronic, and intermittent torsion of the vascular pedicle. Ultrasonography and CT are the most used methods for diagnosis. Imaging findings of wandering spleen are the absence of the spleen in its normal position and a mass located anywhere in the abdomen or pelvis with enhancement pattern of a normal splenic tissue . In casePolysplenia and asplenia typically occurs in association with situs ambiguous which is also known as heterotaxia. Situs ambiguous with asplenia (Ivemark syndrome), also referred to as right isomerism or bilateral right sidedness, is characterized by ambiguous location of the abdominal organs and congenital absence of most or all of normal splenic tissues. Greater prevalence of reported cases is in males, and congenital heart disease is present in most or all cases. Most affected individuals often die within the first year of their life because of related severe congenital heart disease and immunodeficiency related to absence of the spleen.Situs ambiguous with polysplenia, also referred to as left isomerism or bilateral left sidedness, is a complex congenital syndrome associated with multiple highly variable cardiovascular and visceral anomalies and is more common in females. Splenic number can vary from two to six and diameter from 1 cm to 6 cm. Location of the spleens may be either in the left or right side of the upper quadrant. Other abdominal anomalies coexisting with polysplenia include a right-sided stomach, a midline or left-sided liver, malrotation of the intestine, a short pancreas, absence of gallbladder, and inferior vena cava anomalies. The most common and characteristic inferior vena cava (IVC) anomaly is interruption of the infrahepatic portion of the IVC with azygos continuation . RadioloSplenosis is an acquired anomaly of the spleen which occurs in case of splenic trauma or splenectomy. Heterotopic autotransplantation and implantation of the splenic tissue can be located anywhere in the peritoneal cavity and even in extraperitoneal locations and other unusual locations including pleural cavity, lung, pericardium, pelvis, and subcutaneous tissues. Splenosis is often numerous and variable in size and shape. Thoracic splenosis requires a simultaneous splenic and left diaphragmatic injury that causes pleural or peripheral pulmonary nodule(s). Although both accessory spleen and splenosis are ectopic splenic tissues, their microscopic architecture, arteries supplying them, and origins are different. Accessory spleen which is a congenital anomaly has normal splenic tissue histology and is supplied by the branches of the splenic artery. However, splenosis is an acquired condition, has a distorted microscopic architecture, and is supplied by surrounding vessels. Splenosis is mostly asymptomatic and found incidentally on US, CT, and MRI examinations . With thOn the other hand, a functioning splenic tissue is a desired condition in case of splenectomy to maintain normal immunological function and eliminate the aged blood cells. But in a patient who had splenectomy for hypersplenism, a preservable splenic tissue is an undesired condition that may cause recurrent disease –13. Adults with small spleen usually have homozygous sickle cell disease which causes chronic splenic infarction. The spleen can be densely calcified and small on radiographs and CT . SplenicThere are also diagnostic pitfalls in assessing anatomical variations of spleen including splenic notches and clefts mimicking splenic laceration as mentioned before, an accessory liver lobe mimicking an accessory spleen or an intra-abdominal tumor, and a wandering accessory spleen mimicking an intra-abdominal mass. A gastric diverticulum located on the greater curvature may also mimic an accessory spleen when totally filled with oral contrast medium . Accessory liver lobe is a very rare anatomic variation in which accessory liver tissue attaches to the normal liver tissue by a bridge of hepatic tissue, a mesentery, or a stalk . This raA wandering accessory spleen is another extremely rare entity in which an accessory spleen has a long vascular pedicle with a normally located spleen . AlthougIn conclusion, knowing imaging findings of splenic variations and anomalies is important to avoid diagnostic pitfalls and misinterpretations.


Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence.We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies  where the evidence for the use of chemotherapy is very different . Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed.Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy.Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence. Clinical practice guidelines are important for interpreting and translating research evidence for clinical practice and medical decision making. As stated by the Institute of Medicine “guidelines are systematically defined and evidence-based statements that reduce undesirable practice variation by discouraging use of services of questionable value while encouraging use of services with proven efficacy” Here we aimed to examine systematically guidelines produced by professional societies and organizations in the fields of cancer and gynecological oncology and evaluate in depth guidelines that address the use of chemotherapy in advanced stage gynecological malignancies, including breast, ovarian, cervical and endometrial cancer. All these malignancies are common We constructed a database of gynecological and cancer societies and organizations that might provide guidelines for chemotherapy in advanced gynecological malignancies. We considered societies and organizations that were international , intercontinental (including two or more countries in a continent), or national belonging to one of the top 20 countries with the highest human development index We performed internet searches in Google and Yahoo (completed in June 2009). Initially we made 624 different searches with each engine and the first 100 results for each search were scrutinized. The 624 searches pertain to all the possible combinations of 8 subject matter terms , three terms for type of entity , and 26 terms for geographic identifiers . Whenever we came across a URL referring to a potentially pertinent society or organization, we searched the entire directory. All the links in these websites were further searched in order to reach any additional pertinent societies or organizations. We recorded both organizations with accessible webpages, as well as those whose presence was mentioned in some URL, but either their link was not functional (not working or under construction) or they did not have a webpage that we could identify.Available websites from eligible societies and organizations were scrutinized for any sort of clinical practice guidelines on any subject matter (last update June 2009). Whenever there was availability to perform an electronic search within the website, we used the terms “guidelines” or “recommendations” or “position statements” in English. For non-English websites, we translated these terms into the language the website used. We could do this in all languages except for 4 Japanese, 1 Swedish, 1 Finnish, 1 Danish and 2 Dutch organizations.www.guideline.gov), Guidelines International Network (G-I-N) (www.g-i-n.net), National Institute for Health and Clinical Excellence (NICE) (www.nice.org.uk), National Library of Health (www.library.nhs.uk), New Zealand Guidelines Group (NZGG) (www.nzgg.org.nz), Guidelines Advisory Committee (GAC) (www.gacguidelines.ca), Australian National Health and Medical Research Council (NHMRC) (www.nhmrc.gov.au) and the Scottish Intercollegiate Guidelines Network (SIGN) (www.sign.ac.uk) in order to identify additional potentially eligible guidelines. Finally, we also searched PubMed with the strategy (guidelines OR recommendations OR position statement) AND  AND (cancer OR carcinoma OR neoplasm OR neoplasia).Additionally, we perused some standard websites containing information and/or links to guideline-related information, including the National Guidelines Clearinghouse (NGC) , specialty setting , and whether it provided any clinical practice guidelines on any topic, regardless of whether the guidelines had been developed by the specific society/organization or some other source and similarly whether they provided any eligible guideline addressing chemotherapy for one or more of the eligible malignancies. Whenever any eligible guidelines were available, we recorded whether recommendations were freely accessible through the website and whether they provided separate information developed by the society/organization itself or a link to another society/organization's guidelines.We recorded the exact wording and documentation regarding the chemotherapy question from all the eligible guidelines that mentioned anything on chemotherapy of advanced or recurrent breast, ovarian, cervical and endometrial cancer. For cervical cancer we separately recorded statements for stages III–IVa and stage IVb since treatment and chemotherapy response differs between these stages For each eligible guideline we addressed whether it provided grading for the levels of evidence (and how this had been assessed) and the strength of recommendations. We recorded aspects of the production and implementation process for the guideline, including involvement of multidisciplinary teams, search strategies, reported funding, reported conflicts of interest, implementation plans, and use of specific indicators to assess actual uptake. In addition, we recorded the date of publication of the guidelines and the date of publication of the most recent cited randomized trial or meta-analysis. We addressed the utilization of randomized evidence within the guidelines by recording whether guidelines cited within their reference list any randomized trials and meta-analyses pertinent to the chemotherapy question and, if so, how many; and whether they made a comment on the need for more randomized trials to provide sufficient guidance.We also analyzed the outcomes discussed in the guidelines. We addressed whether the guidelines provided any statement regarding each of the following aspects of the effects of chemotherapy: overall survival, disease-free interval or progression-free survival, response rate, recurrence rate, symptoms relief, quality of life, toxicity profile and cost.Finally, for each guideline and each type of advanced stage malignancy, we recorded the position on whether chemotherapy should be used or not. We classified guidelines as “in favor” or “against”, if they clearly supported or clearly opposed, respectively, the use of chemotherapy. We also recorded whether guidelines in favor of chemotherapy were unequivocal about its overall favorable benefit-risk ratio or offered any caveats.We evaluated whether guidelines for the different malignancies differed among themselves in the use of grading, aspects of the production and implementation process, timeliness, utilization of randomized evidence, outcomes discussed, and stance towards use of chemotherapy. Group comparisons for categorical variables used Fisher's exact test and group comparisons for continuous variables used Mann-Whitney U test and analysis of variance. All analyses were conducted in STATA SE version 10.0. P-values are two-tailed.Internet searches identified 220 societies/organizations. Additional searches performed in Pubmed and standard guideline websites identified 4 more societies (1 and 3 respectively) that provided any sort of clinical practice guidelines. Of the 224 entities, 105 were named “society”, 51 “association”, 8 “organization” and 60 had other names . There were 26 international, 77 intercontinental, and 153 national entities covering a diverse array of countries and a range of specialties . Nine ofSixty-nine entities (31%) provided any sort of guidelines in their websites . For fifTwenty entities provided any sort of guideline for chemotherapy in advanced or recurrent gynecological cancer . Among tA little over half of the guidelines covering the use of chemotherapy in advanced gynecological malignancies addressed the level of evidence available for the recommendations; nonetheless no uniformity existed regarding the systems for grading the level of evidence with 5 different systems being utilized . FurtherKey aspects regarding the guideline production and implementation process did not significantly differ among analyzed guidelines. More than 60% of the guidelines were stated to have been developed by multidisciplinary teams of experts and only 1 guideline regarding endometrial cancer was developed by experts from one medical field only (obstetricians/gynecologists), while in the remaining guidelines it was unclear what experts exactly were involved. A specific search strategy for the development of the guideline was provided in less than 40%. None of the guidelines reported industry-related funding, but often there was no statement about who had potentially funded the guidelines; moreover, conflicts of interest statements from panel members were available in less than half of the guidelines. Finally, only few of the guidelines provided an implementation plan of the guidelines beforehand or reported that specific indicators were considered in order to assess their actual uptake .The number of randomized trials cited within the guidelines significantly differed among the malignancies tested (p<0.001) . Almost Statements regarding overall survival were provided in most guidelines with no significant difference for the discussion of this outcome for the different malignancies . ConversNone of the analyzed guidelines for these advanced stage gynecological malignancies were against using chemotherapy in these patients. All guidelines seemed to endorse explicitly or implicitly the use of some chemotherapy, at least in some settings and patients. No major caveats were raised for breast, ovarian, and stage III–IVa cervical cancer Our evaluation identified over 200 cancer and gynecological societies and organizations that operate at international or national level. This is an impressive number and it offers a picture of flourishing professional activity. Many of these organizations have very extensive membership, organize large meetings, and have substantial influence upon their members, subscribers, and visitors to their websites The analyzed guidelines did not differ across malignancies in terms of their adoption of levels of evidence, grading of recommendations, and aspects of production and implementation process, or timeliness. Their performance in this regard on average is comparable to guidelines from other fields The guidelines that we analyzed differed substantially across malignancies in the extent of utilization of randomized evidence . This is not surprising, given that there are far more randomized trials and meta-analyses performed for advanced breast and ovarian cancer than for cervical and endometrial cancer. The conduct of randomized trials may be encouraged in fields where results of chemotherapy have been favorable (breast and ovarian cancer), while investigators may feel less enthusiastic to perform more trials in fields where chemotherapy has shown equivocal results with no clear benefits . Most of the analyzed guidelines cited at least one randomized trial. It has been observed across diverse fields that utilization of randomized evidence has increased in guidelines over time Even though the benefits of chemotherapy vary a lot among the malignancies that we analyzed, all of the guidelines explicitly or implicitly endorsed the use of chemotherapy for all malignancies. This is fully justified for breast, ovarian and possibly stage III–IVa cervical cancer, where the available evidence shows that chemotherapy has substantial benefits Furthermore, outcomes such as secondary effectiveness measures and toxicity profile were addressed more frequently in breast and ovarian cancer, whereas cervical and endometrial cancer guidelines totally omitted statements regarding quality of life and costs of chemotherapy and were less likely to discuss also these other outcomes. Reporting of these issues is important for one to adopt or decline the use of specific treatments. Especially in tumors in which chemotherapy does not appear to offer clear benefit in terms of overall survival, secondary effectiveness outcomes, toxicity, quality of life and cost may be the only data available to justify or not its use. Omission of statements regarding these outcomes in these malignancies may mislead conclusions and may explain the generally favorable stance of the guidelines towards chemotherapy even for advanced cervical and endometrial cancer.One may argue that scientific societies may sometimes have considerable conflicts that pose obstacles in creating objective guidelines. For example, if professionals benefit from administering specific interventions to patients, their societies may not be unbiased enough to recommend that patients should not be treated with specific interventions . The ubiquitous recommendation of chemotherapy for all the examined types of cancers (regardless of whether it is effective or not) raises such concerns. An unbiased, intersocietal and interprofessional collaborative approach may be useful in this regard.Some limitations of our work should be discussed. First, for 32 entities we could not find access to a website. However, it is not very likely that these entities would have guidelines of their own, let alone high-quality ones. Second, it is possible that some entities may not have published guidelines on chemotherapy, if they deemed that chemotherapy is ineffective and thus not worth addressing. However, we found a similar number of guidelines for tumors where chemotherapy is very effective and for those where it is more controversial. Third, there are no established validated searches for unearthing professional societies and organizations and some of them may have been missed by our searches. However, given the multiple layers of our search, it is unlikely that prominent entities were missed.In conclusion, our evaluation suggests that guidelines from professional gynecological and cancer societies and organizations have substantial room for improvement. Recommendations should be based on solid scientific evidence with balanced discussion of all potential benefits, harms and costs of the proposed interventions.


Movement Disorder SocietyRecently, the American Academy of Neurology published an evidence-based guideline for the pharmacological treatment of chorea in Huntington’s disease. Although the progress in medical care because of the implementation of criteria of evidence-based medicine is undisputed, the guideline classifies the level of evidence for drugs to reduce chorea based on anchors in the Unified Huntington’s Disease Rating Scale-Total Motor Score chorea sum score, which were chosen arbitrarily and do not reflect validated or generally accepted levels of clinical relevance. Thus, the guideline faces several serious limitations and delivers clinical recommendations that do not represent current clinical practice; these are reviewed in detail, and arguments are presented why these recommendations should not be followed. To remedy the lack of evidence-based recommendations and provide guidance to a pragmatic symptomatic therapy of chorea in HD, a flow-chart pathway that follows currently established clinical standards based on expert opinion is presented. © 2013  Recently, the American Academy of Neurology (AAN) published an evidence-based guideline for the pharmacological treatment of chorea in Huntington’s disease (HD).A fundamental problem of the guideline is the assignment of “levels of importance” for different amplitudes of change in the UHDRS-TMS chorea sum score. These levels are used as anchors in the analysis, which classifies responses to therapy on which clinical recommendations in this guideline are based. A “2 to < 3-point” decrease in the UHDRS-TMS chorea sum score is classified as “moderately important,” whereas a “>3-point” decrease is considered “very important.” These cutoffs are arbitrarily chosen and do not reflect validated or generally accepted levels of clinical relevance for a change in the UHDRS-TMS chorea sum score. Seven subitems of different body regions contribute to the UHDRS-TMS chorea sum score. Thus, a mean improvement of just 1 point in less than 50% of the areas assessed could result in a “very important” change. Considering that chorea may not be the most relevant symptom of HD and that patients often do not seem to suffer from it,Several specific recommendations for the use of drugs in treating chorea were given, which need a critical comment—these are presented in the “Caveat” sections below. In addition, a pragmatic approach to treating chorea in patients with HD, based on expert opinion, is presented in the form of a stepwise decision tree outlined in a flow chart .The recommendation to use riluzole to treat chorea, which is referred to even in the abstract of the guideline, is not clinically established.4The uncritical use of tetrabenazine in doses of “up to 100 mg/day,” as recommended in the guideline, also is not clinically established practice.8In addition, the use of amantadine 300–400 mg/day), which is recommended in the first sentence of the guideline’s recommendation section right after tetrabenazine and before riluzole, requires a comment. The use of amantadine to treat chorea is highly controversial among experts, as recently revealed by a questionnaire obtained from HD experts: clinicians who had used amantadine described its benefit as small and transient; a minority considered it useful as monotherapy or adjunctive therapy, whereas a smaller but not insignificant number of respondents considered its use inappropriate for the treatment of chorea, and several cited inexperience with its use.00 mg/dayIn conclusion, the guideline in its current form may be misleading and does not provide reference to treatment recommendations by experts or to standards established in common clinical practice.In part, this may be due to the fact that, in the process applied during the development of this AAN guideline, results of secondary endpoints from randomized clinical trials primarily designed to answer other questions were included. Although this may be useful for scientific discussion, clinical conclusions from these results may be biased and should not be directly translated into clinical guidelines. Accordingly, a recent Cochrane review applying criteria of evidence-based medicine concluded that no statement can be made regarding the best medical practice for the control of motor and nonmotor symptoms in HD.11In this context, it should be considered that treatment recommendations in diseases with lower prevalence often lack the necessary clinical trials to document effects of clinically well-established therapies, as required by current evidence-based medicine criteria. Thus, expert opinions may be preferable to obtain meaningful guidelines.Yet how can meaningful, less disputed recommendations be established and provide a readily accessible reference for clinical practice? Recently, a pragmatic pathway for treating chorea in HD was developed based on a questionnaire that was presented to 52 HD experts mainly from North America and Europe, as mentioned above.This pathway will lead to satisfactory alleviation for most patients with clinically disturbing chorea who require treatment. It is important to bear in mind that treatment of chorea should aim to reduce involuntary movements, not to abolish them. Side effects, such as sedation and a negative impact on cognitive functioning, should always be assessed for and carefully monitored. Patients who respond inadequately to the suggested interventions should be referred to HD specialists. Currently, effective treatment of chorea should follow expert advice and not evidence-based guidelines in order to avoid side effects and potential harm to patients.Dr. Reilmann has provided consulting services, advisory board functions, clinical trial services, quantitative motor analyses, and/or lectures for Novartis, Teva, Siena Bitoech, Neurosearch Inc., Medivation/Pfizer, Lundbeck, Ipsen, Wyeth, ISIS Pharma, Link Medicine, Prana Biotechnology, the Cure Huntington’s Disease Initiative Foundation USA, MEDA, Temmler Pharma, and AOP Orphan Pharmaceuticals AG. He serves on the Advisory Board of the “Jacques and Gloria Gossweiler Foundation,” he has several responsibilities in the European Huntington’s Disease Network . and he serves as Global Coordinating Principle Investigator of clinical trials. Dr. Reilmann has received grant support from the High-Q-Foundation, the Cure Huntington’s Disease Initiative Foundation (CHDI), the Deutsche Forschungsgemeinschaft (DFG), and the European Huntington’s Disease Network (EHDN).


Evidence-based medicine (EBM) is considered as one of the greatest inventions in modern medicine, advocating the use of the best available valid evidence, in line with clinical expertise and patients’ preference, to provide the best patient care. The philosophy probably has existed since the earliest age of medicine, but it was not until 1972 when Professor Archie Cochrane introduced the concept in one of his book, after which it was developed into a practical methodology by a group of scientists in the late 1980s and early 1990s. The work of EBM in Indonesia was first initiated in the early 2000s by conducting a series of intensive trainings at various medical teaching centres all over Indonesia. Most of the pioneers of EBM dissemination in Indonesia are paediatricians. Since then, teaching activities have been flourishing, leading to the formal incorporation of EBM into medical curricula in some medical schools. Collaborations with similar centres in Europe and Asia have a positive impact. Efforts are also being made in promoting the application of EBM principle in daily practice, such as in ward rounds, journal readings, and case discussions, both in undergraduate and postgraduate education settings. The term and practice of EBM have become very familiar for most health professionals in Indonesia, although occasionally it is misinterpreted in a narrow perspective, seeing evidence as the single factor determining health care. However, the implementation of EBM in clinical practice sometimes is hampered by the scarcity of relevant valid evidence like those happening in the field of paediatric endocrinology. This requires the transition of EBM practice in the future, in which health professionals do not merely act as evidence users but also play roles as evidence producers by conducting more patient-oriented research relevant to actual health problems. This is indeed very important, since most of the evidence available comes from studies in Western countries. Indonesian Clinical Epidemiology and Evidence-based Medicine (ICE-EBM) Network which currently has more than 30 member institutions has an important role in the acceleration of evidence-based practice in Indonesia.


Health authorities in several countries have decided that the health care services should be evidence-based. Recent research indicates that evidence-based practice may be more successfully implemented if the interventions overcome identified barriers.The present study aimed to examine factors influencing the implementation of evidence-based practice among nurses in a large Norwegian university hospital.Cross-sectional data was collected from 407 nurses during the period November 8 to December 3, 2010, using the Norwegian version of Developing Evidence-based Practice questionnaire (DEBP). The DEBP included data on various sources of information used for support in practice, on potential barriers for evidence-based practice, and on self-reported skills on managing research-based evidence. The DEBP was translated into Norwegian in accordance with standardized guidelines for translation and cultural adaptation.Nurses largely used experienced-based knowledge collected from their own observations, colleagues and other collaborators for support in practice. Evidence from research was seldom used. The greatest barriers were lack of time and lack of skills to find and manage research evidence. The nurse’s age, the number of years of nursing practice, and the number of years since obtaining the last health professional degree influenced the use of sources of knowledge and self-reported barriers. Self-reported skills in finding, reviewing and using different sources of evidence were positively associated with the use of research evidence and inversely related to barriers in use of research evidence.Skills in evidence-based practice seem to reduce barriers to using research evidence and to increase use of research evidence in clinical practice. Evidence-based practice requires making professional decisions based on systematically gathered evidence drawn from research and from experience and on the patients’ desires and needs in a specific situation . Public et al.[Complex and often unpredictable conditions within the organization determine whether an implementation process for evidence-based nursing practice is successful ,9. Flodget al. conducteIt is unclear which individual factors must be present for practice to be evidence-based. Individual factors are influenced by the fact that the individual nurse is working in a context with others, so that colleagues, organizational and cultural factors influence the practice . ImplemeResearch shows that measures for implementing evidence-based practice are more likely to succeed if they overcome identified barriers . The BARThe BARRIERS to Research Utilization Scale has been criticized because it solely identifies the barriers to the use of research and does not identify the degree to which nurses use other sources of information to support practice in relation to the definition of evidence-based practice . ClinicaGathering evidence to be used in practice requires systematic methods and not arbitrary Internet searches. How nurses rate their own skills in finding, assessing and using evidence seems to be an important factor to consider in implementing evidence-based practice. In Norway, health authorities have decided that the health care services should be evidence-based.The present study aimed to identify the sources of knowledge on which nurses base their practice, barriers they consider hinder evidence-based practice and the skills they identify in finding, reviewing and using research-based evidence. Further, we wanted to determine whether the self-reported skills in finding, reviewing and using research in practice were associated with a) the sources of knowledge that were reported to be used and b) the reported barriers to evidence-based practice.We carried out a cross-sectional survey at Haukeland University Hospital in Bergen, Norway. This hospital treats nearly 600,000 patients and trains about 2000 health care workers each year . The surThe questionnaires were distributed to the nurses at work with an attached reply envelope. Each unit selected a contact person who took responsibility for collecting data. They were informed about the aims of the study and that the study was anonymised and that participation was voluntary. The designated contact persons further disseminated information about the study to the nurses at their respective units by e-mail as well as at information meetings. Completed questionnaires were collected at each unit. A person other than the investigator opened the envelopes and delivered the questionnaires for data processing. The study was approved by the ombudsperson of the Haukeland University Hospital as well as the head of the Department of Research and Development. A pseudo number was made to ensure that data could not directly be traced back to any respondent. The link between the pseudo number and personal identification number was stored separately on a secured server at the hospital.et al.[The self-reported Developing Evidence-based Practice Questionnaire was developed by Gerrish et al. for mappet al.. Gerrishet al. procedurThe Norwegian version of the questionnaire includes 50 pre-structured questions and 4 open-ended questions. The pre-structured questions that were answered by using a five-point Likert scale. The open-ended questions were beyond the scope of the current study. The Questionnaire is divided into 5 sections. Section 1 consists of 22 questions about the use of sources of knowledge for support in practice, rated from never (1) to always (5). The sources of knowledge are divided into five dimensions, (1) own experience covered by items 1–5, (2) social interaction covered by items 6–8, (3) internal sources of knowledge covered by items 9–14, (4) research evidence covered by items 15–19 and (5) external sources of knowledge covered by items 20–22. Sections 2–4 include 20 statements on possible barriers to evidence-based practice. Respondents rated the statements in sections 2 and 3 from strongly agree (1) to strongly disagree (5). In contrast, section 4 has a positive value for affirmative responses, from always (1) to never (5). Section 5 includes 8 questions about skills in finding, reviewing and using research-based evidence. The responses range from complete beginner (1) to expert (5). The questionnaire ends with questions on demographic variables such as the nurse’s age, sex, current educational level and number of years of nursing practice.P values were two-sided, and values below 0.01 were considered statistically significant. To handle missing values in regression models, we used the method of list-wise deletion. Continuous variables were reported as means (SD) and categorical variables as counts (percentage).We used PASW for Windows version 18.0  for statistical analysis. Due to multiple testing, all P value for trend was estimated by incorporating the background variables as linear terms in the regression models. P values were reported with and without adjustment for age, number of years of nursing practice, number of years since obtaining last health professional degree, as well as current educational level.To examine the associations of various background variables with variables on sources of knowledge, we used linear regression models. Variables on sources of knowledge were continuous  and constructed by aggregating response items within each of the five dimensions: own experience, social interaction, internal source of knowledge, external source of knowledge, and research evidence. Background variables selected for the analyses were categorical and included nurse’s age, number of years of clinical practice, and number of years since obtaining last health professional degree. The To examine the associations of self-reported skills in finding, reviewing and using research evidence with the use of specific sources of knowledge and evidence, we used chi-square tests. Variables on the use of specific sources of knowledge and evidence were recoded into 3 categories  and included two separate response items on finding research-based evidence, two separate response items on assessing research-based evidence, and two separate response items on using research-based evidence to change practice. Similar analyses were performed for the association between self-reported skills in evidence-based practice and reported barriers.Of the 661 nurses invited to participate, 407 (62%) returned completed questionnaires. The mean age of the respondents was 37.4 (range 22–63) years. The respondents had a mean 11.3 (range 0–40) years of nursing practice. The mean number of years since obtaining last health professional degree was 7.5 (range 0–37). The population characteristics are displayed in Table The ranking of sources of information showed that the five most frequently used sources in supporting clinical practice were: 1) information learned about each patient as an individual, 2) knowledge based on personal experience, 3) information obtained from hospital policy and protocols, 4) information obtained from experienced nurses, and 5) information obtained from discussion with physicians  insufficient time to find research reports, 2) insufficient time to find organizational information (such as guidelines and protocols), 3) lack of confidence in assessing the quality of research, 4) difficulty in understanding English-language publications and 5) insufficient time at work to implement changes in practice .The use of research was significantly associated with self-reported skills in finding and reviewing research-based evidence and implementing it in practice , “Research reports are not easy to find”, “I find it difficult to understand research reports”, “I do not feel confident in judging the quality of research reports” , “I do not feel confident about beginning to change my practice”  and “I lack authority in the work to change practice” .Furthermore, self-reported skills in evidence-based practice were significantly associated with barriers for evidence-based practice Table . ParticiP < 0.001, not shown in tables). This trend was similar for the number of years since obtaining the last health professional degree .Younger nurses and nurses with fewer years of practice generally reported greater barriers to changing practice based on the “best” evidence than respondents of average age . This trend was also statistically significant for the number of years of nursing practice and the number of years since obtaining the last health professional degree .Nurses who disagreed or strongly disagreed with the following statements “I do not know how to find appropriate research reports”, “I do not feel confident in assessing the quality of research reports” and “I find it difficult to identify the implications of research findings for my own practice” were younger than nurses who agreed or strongly agreed with the statements (all Figure The results showed that nurses mainly used experience-based knowledge for use in practice rather than evidence gained from research journals. Insufficient time was the greatest barrier to finding and reviewing research literature. However, skills in evidence-based practice influenced the use of knowledge sources as well as how the nurses assessed barriers to evidence-based practice.et al.[et al.[Articles published in medical, nursing and other research journals were the least frequently used sources of information. This result is in accordance with other studies -25. A suet al., who fouet al.,28. Expeet al.. A revieet al.. Estabrol.[et al. found thl.[et al.,30. The l.[et al.. A prerel.[et al..This study and others ,32 show et al.[In accordance with other studies ,35, the et al. investigIn contrast, a culture that supports the implementation of research in practice is considered a strong motivational factor for using research-based evidence . FindingMost responding nurses rated their skills in evidence-based practice as being beginner/novice. Previous studies ,32,38 haThis study found that skills in evidence-based practice were statistically significantly associated with the sources of information used. Nurses who reported higher skills in evidence-based practice used research papers more often than nurses with lower skills. This suggests that an implementation process should include courses in evidence-based practice for nurses .Similarly, skills were statistically significantly associated with how the barriers to the use of research-based evidence were assessed, also after being adjusted for age. Nurses with better skills reported fewer barriers to evidence-based practice. Research is not used in isolation but is influenced by factors at the individual level, collaboration between multidisciplinary groups, management and organizational structure . A recenThis was a cross-sectional study which describes a nurse population in a specific time period. Although it may indicate possible associations, more studies should be conducted to confirm our findings. Furthermore, our results may not be representative for nurses in general, but biased towards nurses in units where the management implements evidence-based practice. Finally, the Developing Evidence-based Practice Questionnaire is relatively new and has to date only been used in a few studies for assessing factors influencing the development of evidence based practice. Our results could therefore not be directly compared to other studies.This study showed that experience-based knowledge was a more frequent source of information in clinical practice than research-based evidence. Insufficient time was the main barrier to using research-based evidence, in contrast to workplace culture which was the least reported barrier. Nurse’s age, the number of years of practice and the number of years since obtaining the last health professional degree were associated with the sources of information used and the barriers to implementing evidence-based practice. The responding nurses rated their skills in managing evidence as poor. Higher skills in managing evidence were associated with the sources of evidence used.The results from this study might be a base for systematic facilitation where the purpose is to help and support nurses to overcome reported barriers and to increase skills in evidence-based practice. A prerequisite for a successful facilitation process is that leaders support nurses to participate in working groups to achieve research utilization in nursing practice.The authors declare that they have no competing interests.MWN, SH and AD contributed to the design of the study, the acquisition, interpretation and analysis of the data, as well as drafting and critically revising the manuscript. RMN and AD contributed to the process of analysis and interpretation of finding and critically revising the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/367/prepub