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1.  Eurocan plus report: feasibility study for coordination of national cancer research activities 
Summary
The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe–wide consultation ever conducted in the field of cancer research.
Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
It is essential to include the patients’ voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench–to–bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes, becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ organizations, European institutions, Member States, industry and small and medium enterprises (SMEs), putting into practice solutions aimed at alleviating barriers to collaboration and coordination of cancer research activities in the European Union, and dealing with legal and regulatory issues. The development of an effective ECI will require time, but this entity should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co–operation between comprehensive cancer centres and basic research laboratories throughout Europe and (3) networking between funding bodies at the European level.
The European Parliament and its instruments have had a major influence in cancer control in Europe, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
Executive Summary
Cancer is one of the biggest public health crises facing Europe in the 21st century—one for which Europe is currently not prepared nor preparing itself. Cancer is a major cause of death in Europe with two million casualties and three million new cases diagnosed annually, and the situation is set to worsen as the population ages.
These facts led the European Parliament, through the Research Directorate-General of the European Commission, to call for initiatives for better coordination of cancer research efforts in the European Union. The EUROCAN+PLUS Project was launched in October 2005 as a feasibility study for coordination of national cancer research activities. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people. In this respect, the Project became the largest Europe-wide consultation ever conducted in the field of cancer research, implicating researchers, cancer centres and hospitals, administrators, healthcare professionals, funding agencies, industry, patients’ organizations and patients.
The Project first identified barriers impeding research and collaboration in research in Europe. Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain the formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
In addition, there is a shortage of leadership, a multiplicity of institutions each focusing on its own agenda, sub–optimal contact with industry, inadequate training, non–existent career paths, low personnel mobility in research especially among clinicians and inefficient funding—all conspiring against efficient collaboration in cancer care and research. European cancer research today does not have a functional translational research continuum, that is the process that exploits biomedical research innovations and converts them into prevention methods, diagnostic tools and therapies. Moreover, epidemiological research is not integrated with other types of cancer research, and the implementation of the European Directives on Clinical Trials 1 and on Personal Data Protection 2 has further slowed the innovation process in Europe. Furthermore, large inequalities in health and research exist between the EU–15 and the New Member States.
The picture is not entirely bleak, however, as the European cancer research scene presents several strengths, such as excellent basic research and clinical research and innovative etiological research that should be better exploited.
When considering recommendations, several priority dimensions had to be retained. It is essential that proposals include actions and recommendations that can benefit all Member States of the European Union and not just States with the elite centres. It is also essential to have a broader patient orientation to help provide the knowledge to establish cancer control possibilities when we exhaust what can be achieved by the implementation of current knowledge. It is vital that the actions proposed can contribute to the Lisbon Strategy to make Europe more innovative and competitive in (cancer) research.
The Project participants identified six areas for which consensus solutions should be implemented in order to obtain better coordination of cancer research activities. The required solutions are as follows. The proactive management of innovation, detection, facilitation of collaborations and maintenance of healthy competition within the European cancer research community.The establishment of an exchange portal of information for health professionals, patients and policy makers.The provision of guidance for translational and clinical research including the establishment of a translational research platform involving comprehensive cancer centres and cancer research centres.The coordination of calls and financial management of cancer research projects.The construction of a ‘one–stop shop’ as a contact interface between the industry, small and medium enterprises, scientists and other stakeholders.The support of greater involvement of healthcare professionals in translational research and multidisciplinary training.
In the course of the EUROCAN+PLUS consultative process, several key collaborative projects emerged between the various groups and institutes engaged in the consultation. There was a collaboration network established with Europe’s leading Comprehensive Cancer Centres; funding was awarded for a closer collaboration of Owners of Cancer Registries in Europe (EUROCOURSE); there was funding received from FP7 for an extensive network of leading Biological Resource Centres in Europe (BBMRI); a Working Group identified the special needs of Central, Eastern and South–eastern Europe and proposed a remedy (‘Warsaw Declaration’), and the concept of developing a one–stop shop for dealing with academia and industry including the Innovative Medicines Initiative (IMI) was discussed in detail.
Several other dimensions currently lacking were identified. There is an absolute necessity to include the patients’ voice in the establishment of priority areas in cancer research at the present time. It was a salutary lesson when it was recognized that all that is known about the quality of life of the cancer patient comes from the experience of a tiny proportion of cancer patients included in a few clinical trials. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community was evident. A top priority should be the development of translational research (in its widest form) and the development of effective and innovative cancer treatments and preventative strategies in the European Union. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
Having taken note of the barriers and the solutions and having examined relevant examples of existing European organizations in the field, it was agreed during the General Assembly of 19 November 2007 that the EUROCAN+PLUS Project had to recommend the creation of a small, permanent and neutral ECI. This should be a model structure and was widely supported at both General Assemblies of the project. The proposal is based on the successful model of the European Molecular Biology Organisation (EMBO), and its principal aims include providing a forum where researchers from all backgrounds and from all countries can meet with members of other specialities including patients, nurses, clinicians, funders and scientific administrators to develop priority programmes to make Europe more competitive in research and more focused on the cancer patient.
The ECI should assume responsibility for: stimulating innovative cancer research and facilitating processes;becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ and organizations;European institutions, Member States, industry and small and medium enterprises;putting into practice the aforementioned solutions aimed at alleviating barriers and coordinating cancer research activities in the EU;dealing with legal and regulatory issues.
Solutions implemented through the ECI will lead to better coordination and collaboration throughout Europe, more efficient use of resources, an increase in Europe’s attractiveness to the biomedical industry and better quality of cancer research and education of health professionals.
The Project considered that European legal instruments currently available were inadequate for addressing many aspects of the barriers identified and for the implementation of effective, lasting solutions. Therefore, the legal environment that could shelter an idea like the ECI remains to be defined but should be done so as a priority. In this context, the initiative of the European Commission for a new legal entity for research infrastructure might be a step in this direction. The development of an effective ECI will require time, but this should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass: (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co-operation between comprehensive cancer centres and basic research laboratories throughout Europe; (3) networking between funding bodies at the European level. Another topic deserving immediate attention is the creation of a European database on cancer research projects and cancer research facilities.
Despite enormous progress in cancer control in Europe during the past two decades, there was an increase of 300,000 in the number of new cases of cancer diagnosed between 2004 and 2006. The European Parliament and its instruments have had a major influence in cancer control, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
doi:10.3332/ecancer.2011.84
PMCID: PMC3234055  PMID: 22274749
2.  Protocol for a systematic review of the use of narrative storytelling and visual-arts-based approaches as knowledge translation tools in healthcare 
Systematic Reviews  2013;2:19.
Background
The arts are powerful, accessible forms of communication that have the potential to impart knowledge by attracting interest and developing meaningful connections. Knowledge translation aims to reduce the ‘evidence-practice’ gap by developing, implementing and evaluating strategies designed to enhance awareness and promote behavior change congruent with research evidence. Increasingly, innovative approaches such as narrative storytelling and other arts-based interventions are being investigated to bridge the growing gap between practice and research. This study is the first to systematically identify and synthesize current research on narrative storytelling and visual art to translate and disseminate health research.
Methods
A health research librarian will develop and implement search strategies designed to identify relevant evidence. Studies will be included if they are primary research employing narrative storytelling and/or visual art as a knowledge translation strategy in healthcare. Two reviewers will independently perform study selection, quality assessment, and data extraction using standard forms. Disagreements will be resolved through discussion or third party adjudication. Data will be grouped and analyzed by research design, type of knowledge translation strategy (that is, a narrative or visual-arts-based approach), and target audience. An overall synthesis across all studies will be conducted.
Discussion
The findings from this research project will describe the ‘state of the science’ regarding the use of narrative storytelling and visual art as knowledge translation strategies. This systematic review will provide critical information for: (1) researchers conducting knowledge translation intervention studies; (2) nursing, medicine, and allied healthcare professionals; (3) healthcare consumers, including patients and families; and (4) decision makers and knowledge users who are charged to increase use of the latest research in healthcare settings.
doi:10.1186/2046-4053-2-19
PMCID: PMC3627614  PMID: 23514237
Knowledge translation; Narrative; Research use; Storytelling; Systematic review; Visual art
3.  Evidence-based decision-making within the context of globalization: A “Why–What–How” for leaders and managers of health care organizations 
In the globalized knowledge economy, the challenge of translating knowledge into policy and practice is universal. At the dawn of the 21st century, the clinicians, leaders, and managers of health care organizations are increasingly required to bridge the research-practice gap. A shift from moving evidence to solving problems is due. However, despite a vast literature on the burgeoning field of knowledge translation research, the “evidence-based” issue remains for many health care professionals a day-to-day debate leading to unresolved questions. On one hand, many clinicians still resist to the implementation of evidence-based clinical practice, asking themselves why their current practice should be changed or expanded. On the other hand, many leaders and managers of health care organizations are searching how to keep pace with the demand of actionable knowledge. For example, they are wondering: (a) if managerial and policy innovations are subjected to the same evidentiary standards as clinical innovations, and (b) how they can adapt the scope of evidence-based medicine to the culture, context, and content of health policy and management. This paper focuses on evidence-based health care management within the context of contemporary globalization. In this paper, our heuristic hypothesis is that decision-making process related changes within clinical/managerial/policy environments must be given a socio-historical backdrop. We argue that the relationship between research on the transfer of knowledge and its uptake by clinical, managerial and policy target audiences has undergone a shift, resulting in increasing pressures in health care for intense researcher-practitioner collaboration and the development of “integrative KT platforms” at the crossroads of different fields (the field of knowledge management and the field of knowledge translation). The objectives of this paper are: (a) to provide an answer to the questions that health professionals ask most frequently about “Why” and “How” to bridge the know-do gap, (b) to illustrate by a Canadian example how the PRO-ACTIVE program helps in closing the evidence-based practice gap.
PMCID: PMC3270906  PMID: 22312206
globalization; knowledge; know-do gap; research-practice gap; knowledge translation; knowledge sharing; evidence-based decision-making; evidence-based medicine; evidence-based health care management
4.  Transferring research to policy and practice: quo vadis? 
Introduction
Research findings are of little use if they are not used to help inform the development of policy and practice. A number of studies during the last decade have indicated the continued need to move more towards evidence-informed policy and practice, yet today there remains too little use of a common language or approach between the research and policy communities. Moreover, research that is undertaken may not be timely or relevant to the current policy making context. This presentation, therefore, will focus on the identification of barriers and facilitators to knowledge transfer to policy and practice, highlighting some examples of how knowledge transfer has been achieved.
Methods
A rapid review of literature of methods of knowledge transfer was undertaken to identify state of the art in mechanisms and approaches to bridging the gap between research and policy. Subsequently, selected policy documents and grey literature in the areas of services for older people and those with disabilities were scrutinised for exemplar mechanisms that have been used to help facilitate knowledge transfer in Europe and elsewhere.
Results
A number of different elements are key to forming successful approaches to knowledge transfer. These include better presentation of research results in brief, clear, everyday language, presenting both the strengths and limitations of different types of research, the organisation of policy dialogues to help bring researchers and policy makers together to determine feasible and policy relevant research questions, the development of a new cadre of professionals equally comfortable in both the research and policy making environments, and the use of formal assessment bodies which synthesise a range of evidence to help inform key policy making questions.
Discussion
Evidence is not just generated from research: other sources of information include media reports, representations from consumer groups and general public concerns. Knowledge transfer is thus not a linear one-time event; it requires ongoing active dialogue and exchange between researchers, policy makers and practitioners. There is potential to replicate existing mechanisms and approaches to help facilitate knowledge transfer across Europe; one key challenge, however, is to strengthen the capacity not only to conduct, but also to interpret and communicate research findings.
PMCID: PMC2707552
knowledge transfer; knowledge broking; policy syntheses; implementation
5.  Scoping review of toolkits as a knowledge translation strategy in health 
Background
Significant resources are invested in the production of research knowledge with the ultimate objective of integrating research evidence into practice. Toolkits are becoming increasingly popular as a knowledge translation (KT) strategy for disseminating health information, to build awareness, inform, and change public and healthcare provider behavior. Toolkits communicate messages aimed at improving health and changing practice to diverse audiences, including healthcare practitioners, patients, community and health organizations, and policy makers. This scoping review explores the use of toolkits in health and healthcare.
Methods
Using Arksey and O’Malley’s scoping review framework, health-based toolkits were identified through a search of electronic databases and grey literature for relevant articles and toolkits published between 2004 and 2011. Two reviewers independently extracted data on toolkit topic, format, target audience, content, evidence underlying toolkit content, and evaluation of the toolkit as a KT strategy.
Results
Among the 253 sources identified, 139 met initial inclusion criteria and 83 toolkits were included in the final sample. Fewer than half of the sources fully described the toolkit content and about 70% made some mention of the evidence underlying the content. Of 83 toolkits, only 31 (37%) had been evaluated at any level (27 toolkits were evaluated overall relative to their purpose or KT goal, and 4 toolkits evaluated the effectiveness of certain elements contained within them).
Conclusions
Toolkits used to disseminate health knowledge or support practice change often do not specify the evidence base from which they draw, and their effectiveness as a knowledge translation strategy is rarely assessed. To truly inform health and healthcare, toolkits should include comprehensive descriptions of their content, be explicit regarding content that is evidence-based, and include an evaluation of the their effectiveness as a KT strategy, addressing both clinical and implementation outcomes.
doi:10.1186/s12911-014-0121-7
PMCID: PMC4308831  PMID: 25539950
Toolkit; Knowledge translation; Practice change; Evaluation; Health
6.  The translation research in a dental setting (TRiaDS) programme protocol 
Background
It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified.
For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP). TRiaDS (Translation Research in a Dental Setting) is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation.
Methods
Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is required. Interventions are theory based and informed by evidence gathered during the diagnostic phase and by prior published evidence. They are evaluated using a range of experimental and quasi-experimental study designs, and data collection continues beyond the end of the intervention to investigate the sustainability of an intervention effect.
Discussion
The TRiaDS programmatic approach is a significant step forward towards the development of a practical, generalisable framework for knowledge translation research. The multidisciplinary composition of the TRiaDS team enables consideration of the individual, organisational and system determinants of professional behaviour change. In addition the embedding of TRiaDS within a national programme of guidance development offers a unique opportunity to inform and influence the guidance development process, and enables TRiaDS to inform dental services practitioners, policy makers and patients on how best to translate national recommendations into routine clinical activities.
doi:10.1186/1748-5908-5-57
PMCID: PMC2920875  PMID: 20646275
7.  Achieving Conservation Science that Bridges the Knowledge–Action Boundary 
Conservation Biology  2013;27(4):669-678.
There are many barriers to using science to inform conservation policy and practice. Conservation scientists wishing to produce management-relevant science must balance this goal with the imperative of demonstrating novelty and rigor in their science. Decision makers seeking to make evidence-based decisions must balance a desire for knowledge with the need to act despite uncertainty. Generating science that will effectively inform management decisions requires that the production of information (the components of knowledge) be salient (relevant and timely), credible (authoritative, believable, and trusted), and legitimate (developed via a process that considers the values and perspectives of all relevant actors) in the eyes of both researchers and decision makers. We perceive 3 key challenges for those hoping to generate conservation science that achieves all 3 of these information characteristics. First, scientific and management audiences can have contrasting perceptions about the salience of research. Second, the pursuit of scientific credibility can come at the cost of salience and legitimacy in the eyes of decision makers, and, third, different actors can have conflicting views about what constitutes legitimate information. We highlight 4 institutional frameworks that can facilitate science that will inform management: boundary organizations (environmental organizations that span the boundary between science and management), research scientists embedded in resource management agencies, formal links between decision makers and scientists at research-focused institutions, and training programs for conservation professionals. Although these are not the only approaches to generating boundary-spanning science, nor are they mutually exclusive, they provide mechanisms for promoting communication, translation, and mediation across the knowledge–action boundary. We believe that despite the challenges, conservation science should strive to be a boundary science, which both advances scientific understanding and contributes to decision making.
Logrando que la Ciencia de la Conservación Trasponga la Frontera Conocimiento-Acción
Resumen
Hay muchas barreras para utilizar ciencia para informar a la política y práctica de la conservación. Los científicos de la conservación que desean producir ciencia relevante para el manejo deben equilibrar esta meta con el imperativo de demostrar novedad y rigor en su ciencia. Los tomadores de decisiones que buscan que sus decisiones se basen en evidencias deben equilibrar el deseo de conocimientos con la necesidad de actuar a pesar de la incertidumbre. La generación de ciencia que informe efectivamente a las decisiones de manejo requiere que la producción de información (los componentes del conocimiento) sea sobresaliente (relevante y oportuna), creíble (autoritativa, verosímil y confiable) y legítima (desarrollada mediante un proceso que considera los valores y perspectivas de todos los actores relevantes) a la vista tanto de investigadores como de tomadores de decisiones. Percibimos tres retos clave para quienes desean generar ciencia de la conservación que logre estas tres características de la información. Primero, las audiencias científicas y de manejo pueden tener percepciones contrastantes sobre la relevancia de la investigación. Segundo, la credibilidad se puede lograr a costa de la relevancia y legitimidad a la vista de los tomadores de decisiones y tercero, los diferentes actores pueden tener percepciones conflictivas sobre los que constituye información legítima. Resaltamos cuatro marcos institucionales que pueden facilitar que la ciencia informe al manejo: organizaciones de frontera (organizaciones ambientales que trasponen la frontera entre la ciencia y el manejo), investigadores científicos insertados en agencias de manejo de recursos, vínculos formales entre tomadores de decisiones y científicos en instituciones enfocadas a la investigación, y programas de capacitación para profesionales de la conservación. Aunque estos no son los únicos métodos para generar ciencia que traspone fronteras, ni son mutuamente excluyentes, proporcionan mecanismos que promueven la comunicación, traslación y mediación para trasponer la frontera conocimiento-acción. Consideramos que no obstante los retos, la ciencia de la conservación debería pugnar por ser una ciencia de frontera, que incrementa el entendimiento científico y contribuye a la toma de decisiones.
doi:10.1111/cobi.12050
PMCID: PMC3761186  PMID: 23574343
boundary organizations; boundary science; decision making; environmental management; implementation gap; scientific uncertainty; ciencia de frontera; incertidumbre científica; manejo ambiental; organizaciones de frontera; toma de decisiones; vacío de implementación
8.  Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments 
PLoS Medicine  2013;10(7):e1001489.
Background
The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address.
Methods and Findings
We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria—most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.
Conclusions
By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The development process for new drugs is lengthy and complex. It begins in the laboratory, where scientists investigate the causes of diseases and identify potential new treatments. Next, promising interventions undergo preclinical research in cells and in animals (in vivo animal experiments) to test whether the intervention has the expected effect and to support the generalization (extension) of this treatment–effect relationship to patients. Drugs that pass these tests then enter clinical trials, where their safety and efficacy is tested in selected groups of patients under strictly controlled conditions. Finally, the government bodies responsible for drug approval review the results of the clinical trials, and successful drugs receive a marketing license, usually a decade or more after the initial laboratory work. Notably, only 11% of agents that enter clinical testing (investigational drugs) are ultimately licensed.
Why Was This Study Done?
The frequent failure of investigational drugs during clinical translation is potentially harmful to trial participants. Moreover, the costs of these failures are passed onto healthcare systems in the form of higher drug prices. It would be good, therefore, to reduce the attrition rate of investigational drugs. One possible explanation for the dismal success rate of clinical translation is that preclinical research, the key resource for justifying clinical development, is flawed. To address this possibility, several groups of preclinical researchers have issued guidelines intended to improve the design and execution of in vivo animal studies. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the authors identify the experimental practices that are commonly recommended in these guidelines and organize these recommendations according to the type of threat to validity (internal, construct, or external) that they address. Internal threats to validity are factors that confound reliable inferences about treatment–effect relationships in preclinical research. For example, experimenter expectation may bias outcome assessment. Construct threats to validity arise when researchers mischaracterize the relationship between an experimental system and the clinical disease it is intended to represent. For example, researchers may use an animal model for a complex multifaceted clinical disease that only includes one characteristic of the disease. External threats to validity are unseen factors that frustrate the transfer of treatment–effect relationships from animal models to patients.
What Did the Researchers Do and Find?
The researchers identified 26 preclinical guidelines that met their predefined eligibility criteria. Twelve guidelines addressed preclinical research for neurological and cerebrovascular drug development; other disorders covered by guidelines included cardiac and circulatory disorders, sepsis, pain, and arthritis. Together, the guidelines offered 55 different recommendations for the design and execution of preclinical in vivo animal studies. Nineteen recommendations addressed threats to internal validity. The most commonly included recommendations of this type called for the use of power calculations to ensure that sample sizes are large enough to yield statistically meaningful results, random allocation of animals to treatment groups, and “blinding” of researchers who assess outcomes to treatment allocation. Among the 25 recommendations that addressed threats to construct validity, the most commonly included recommendations called for characterization of the properties of the animal model before experimentation and matching of the animal model to the human manifestation of the disease. Finally, six recommendations addressed threats to external validity. The most commonly included of these recommendations suggested that preclinical research should be replicated in different models of the same disease and in different species, and should also be replicated independently.
What Do These Findings Mean?
This systematic review identifies a range of investigational recommendations that preclinical researchers believe address threats to the validity of preclinical efficacy studies. Many of these recommendations are not widely implemented in preclinical research at present. Whether the failure to implement them explains the frequent discordance between the results on drug safety and efficacy obtained in preclinical research and in clinical trials is currently unclear. These findings provide a starting point, however, for the improvement of existing preclinical research guidelines for specific diseases, and for the development of similar guidelines for other diseases. They also provide an evidence-based platform for the analysis of preclinical evidence and for the study and evaluation of preclinical research practice. These findings should, therefore, be considered by investigators, institutional review bodies, journals, and funding agents when designing, evaluating, and sponsoring translational research.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001489.
The US Food and Drug Administration provides information about drug approval in the US for consumers and for health professionals; its Patient Network provides a step-by-step description of the drug development process that includes information on preclinical research
The UK Medicines and Healthcare Products Regulatory Agency (MHRA) provides information about all aspects of the scientific evaluation and approval of new medicines in the UK; its My Medicine: From Laboratory to Pharmacy Shelf web pages describe the drug development process from scientific discovery, through preclinical and clinical research, to licensing and ongoing monitoring
The STREAM website provides ongoing information about policy, ethics, and practices used in clinical translation of new drugs
The CAMARADES collaboration offers a “supporting framework for groups involved in the systematic review of animal studies” in stroke and other neurological diseases
doi:10.1371/journal.pmed.1001489
PMCID: PMC3720257  PMID: 23935460
9.  Women's Access and Provider Practices for the Case Management of Malaria during Pregnancy: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(8):e1001688.
Jenny Hill and colleagues conduct a systematic review and meta-analysis of women’s access and healthcare provider adherence to WHO case-management policy of malaria during pregnancy.
Please see later in the article for the Editors' Summary
Background
WHO recommends prompt diagnosis and quinine plus clindamycin for treatment of uncomplicated malaria in the first trimester and artemisinin-based combination therapies in subsequent trimesters. We undertook a systematic review of women's access to and healthcare provider adherence to WHO case management policy for malaria in pregnant women.
Methods and Findings
We searched the Malaria in Pregnancy Library, the Global Health Database, and the International Network for the Rational Use of Drugs Bibliography from 1 January 2006 to 3 April 2014, without language restriction. Data were appraised for quality and content. Frequencies of women's and healthcare providers' practices were explored using narrative synthesis and random effect meta-analysis. Barriers to women's access and providers' adherence to policy were explored by content analysis using NVivo. Determinants of women's access and providers' case management practices were extracted and compared across studies. We did not perform a meta-ethnography. Thirty-seven studies were included, conducted in Africa (30), Asia (4), Yemen (1), and Brazil (2). One- to three-quarters of women reported malaria episodes during pregnancy, of whom treatment was sought by >85%. Barriers to access among women included poor knowledge of drug safety, prohibitive costs, and self-treatment practices, used by 5%–40% of women. Determinants of women's treatment-seeking behaviour were education and previous experience of miscarriage and antenatal care. Healthcare provider reliance on clinical diagnosis and poor adherence to treatment policy, especially in first versus other trimesters (28%, 95% CI 14%–47%, versus 72%, 95% CI 39%–91%, p = 0.02), was consistently reported. Prescribing practices were driven by concerns over side effects and drug safety, patient preference, drug availability, and cost. Determinants of provider practices were access to training and facility type (public versus private). Findings were limited by the availability, quality, scope, and methodological inconsistencies of the included studies.
Conclusions
A systematic assessment of the extent of substandard case management practices of malaria in pregnancy is required, as well as quality improvement interventions that reach all providers administering antimalarial drugs in the community. Pregnant women need access to information on which anti-malarial drugs are safe to use at different stages of pregnancy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria, a mosquito-borne parasite, kills about 600,000 people every year. Most of these deaths occur among young children in sub-Saharan Africa, but pregnant women and their unborn babies are also vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia, miscarriages, and preterm births, and kills about 10,000 women and 100,000 children each year. Since 2006, the World Health Organization (WHO) has recommended that uncomplicated malaria (an infection that causes a fever but does not involve organ damage or severe anemia) should be treated with quinine and clindamycin if it occurs during the first trimester (first three months) of pregnancy and with an artemisinin-based combination therapy (ACT) if it occurs during the second or third trimester; ACTs should be used during the first trimester only if no other treatment is immediately available because their safety during early pregnancy has not been established. Since 2010, WHO has also recommended that clinical diagnosis of malaria should be confirmed before treatment by looking for parasites in patients' blood (parasitology).
Why Was This Study Done?
Prompt diagnosis and treatment of malaria in pregnancy in regions where malaria is always present (endemic regions) is extremely important, yet little is known about women's access to the recommended interventions for malaria in pregnancy or about healthcare providers' adherence to the WHO case management guidelines. In this systematic review and meta-analysis of qualitative, quantitative, and mixed methods studies, the researchers explore the factors that affect women's access to treatment and healthcare provider practices for case management of malaria during pregnancy. A systematic review uses predefined criteria to identify all the research on a given topic. Meta-analysis is a statistical method for combining the results of several studies. A qualitative study collects non-quantitative data such as reasons for refusing an intervention, whereas a qualitative study collects numerical data such as the proportion of a population receiving an intervention.
What Did the Researchers Do and Find?
The researchers identified 37 studies (mostly conducted in Africa) that provided data on the range of healthcare providers visited, antimalarials used, and the factors influencing the choice of healthcare provider and medicines among pregnant women seeking treatment for malaria and/or the type and quality of diagnostic and case management services offered to them by healthcare providers. The researchers explored the data in these studies using narrative synthesis (which summarizes the results from several qualitative studies) and content analysis (which identifies key themes within texts). Among the studies that provided relevant data, one-quarter to three-quarters of women reported malaria episodes during pregnancy. More than 85% of the women who reported a malaria episode during pregnancy sought some form of treatment. Barriers to access to WHO-recommended treatment among women included poor knowledge about drug safety, and the use of self-treatment practices such as taking herbal remedies. Factors that affected the treatment-seeking behavior of pregnant women (“determinants”) included prior use of antenatal care, education, and previous experience of a miscarriage. Among healthcare providers, reliance on clinical diagnosis of malaria was consistently reported, as was poor adherence to the treatment policy. Specifically, 28% and 72% of healthcare providers followed the treatment guidelines for malaria during the first and second/third trimesters of pregnancy, respectively. Finally, the researchers report that concerns over side effects and drug safety, patient preference, drug availability, and cost drove the prescribing practices of the healthcare providers, and that the determinants of provider practices included the type (cadre) of heathcare worker, access to training, and whether they were based in a public or private facility.
What Do These Findings Mean?
These findings reveal important limitations in the implementation of the WHO policy on the treatment of malaria in pregnancy across many parts of Africa and in several other malaria endemic regions. Notably, they show that women do not uniformly seek care within the formal healthcare system and suggest that, when they do seek care, they may not be given the appropriate treatment because healthcare providers frequently fail to adhere to the WHO diagnostic and treatment guidelines. Although limited by the sparseness of data and by inconsistencies in study methodologies, these findings nevertheless highlight the need for further systematic assessments of the extent of substandard case management of malaria in pregnancy in malaria endemic countries, and the need to develop interventions to improve access to and delivery of quality case management of malaria among pregnant women.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001688.
Information is available from the World Health Organization on malaria (in several languages) and on malaria in pregnancy; the 2010 Guidelines for the Treatment of Malaria are available; the World Malaria Report 2013 provides details of the current global malaria situation
The US Centers for Disease Control and Prevention also provides information on malaria; a personal story about malaria in pregnancy is available
Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy
The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy and provides links to the consortium's publications and an online library on malaria in pregnancy
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1001688
PMCID: PMC4122360  PMID: 25093720
10.  Engaging national organizations for knowledge translation: Comparative case studies in knowledge value mapping 
Background
Government sponsors of research and development, along with their funded investigators, are increasingly tasked with demonstrating evidence of knowledge use by nontraditional audiences. This requires efforts to translate their findings for effective communication. For technology-related knowledge, these audiences include clinicians, consumers, manufacturers, public policy agencies, and knowledge brokers. One potentially efficient approach is to communicate research findings through relevant national organizations. However, this requires an understanding of how such organizations view and treat research knowledge, which can be determined through knowledge-value mapping. Do knowledge values differ between national organizations representing different audiences? Can a deeper understanding of knowledge values help sponsors, investigators, and organizations better communicate research findings to stakeholders?
Methods
A series of comparative case studies on knowledge-value mapping were derived through interviews with spokespersons for six national organizations. The semi-structured interviews followed a 10-item questionnaire to characterize different ways in which each organization engages with research-based knowledge. Each participating organization represents a particular stakeholder group, while all share a common interest in the research subject matter.
Results
Each national organization considers the value of the research knowledge in the context of their organization's mission and the interests of their members. All are interested in collaborating with researchers to share relevant findings, while they vary along the following dimensions of knowledge engagement: create, identify, translate, adapt, communicate, use, promote, absorptive capacity, and recommendations for facilitation.
Conclusions
The principles of knowledge translation suggest that investigators can increase use by tailoring the format and context of their findings to the absorptive capacity of nonscholars. Greater absorption should result in higher levels of knowledge awareness, interest, and use, which can then be documented. National organizations and their members, in turn, can strive to optimize their absorptive capacities regarding the state of the sciences. This combination will ensure the highest possible return on public investment in research activities. This knowledge-value mapping study concludes that national organizations are appropriate channels for communicating research findings and for meeting statutory requirements and general expectations for generating and documenting knowledge use.
doi:10.1186/1748-5908-6-106
PMCID: PMC3180429  PMID: 21910866
11.  Impact of clinical and health services research projects on decision-making: a qualitative study 
Background
This article reports on the impact assessment experience of a funding program of non-commercial clinical and health services research. The aim was to assess the level of implementation of results from a subgroup of research projects (on respiratory diseases), and to detect barriers (or facilitators) in the translation of new knowledge to informed decision-making.
Methods
A qualitative study was performed. The sample consisted of six projects on respiratory diseases funded by the Agency for Health Quality and Assessment of Catalonia between 1996 and 2004. Semi-structured interviews to key informants including researchers and healthcare decision-makers were carried out. Interviews were recorded, transcribed verbatim and analysed on an individual (key informant) and group (project) basis. In addition, the differences between achieved and expected impacts were described.
Results
Twenty-three semi-structured interviews were conducted. Most participants indicated changes in health services or clinical practice had resulted from research. The channels used to transfer new knowledge were mainly conventional ones, but also in less explicit ways, such as with the involvement of local scientific societies, or via debates and discussions with colleagues and local leaders. The barriers and facilitators identified were mostly organizational (in research management, and clinical and healthcare practice), although there were also some related to the nature of the research as well as personal factors. Both the expected and achieved impacts enabled the identification of the gaps between what is expected and what is truly achieved.
Conclusions
In this study and according to key informants, the impact of these research projects on decision-making can be direct (the application of a finding or innovation) or indirect, contributing to a more complex change in clinical practice and healthcare organization, both having other contextual factors. The channels used to transfer this new knowledge to clinical practice are complex. Local scientific societies and the relationships between researchers and decision-makers can play a very important role. Specifically, the relationships between managers and research teams and the mutual knowledge of their activity have shown to be effective in applying research funding to practice and decision-making. Finally the facilitating factors and barriers identified by the respondents are closely related to the idiosyncrasy of the human relations between the different stakeholders involved.
doi:10.1186/1478-4505-11-15
PMCID: PMC3660213  PMID: 23663364
Informed decision-making; Qualitative research; Research impact; Respiratory diseases; Payback model
12.  Supporting collaborative use of the diabetes population risk tool (DPoRT) in health-related practice: a multiple case study research protocol 
Background
Health policy makers have stated that diabetes prevention is a priority; however, the type, intensity, and target of interventions or policy changes that will achieve the greatest impact remains uncertain. In response to this uncertainty, the Diabetes Population Risk Tool (DPoRT) was developed and validated to estimate future diabetes risk based on routinely collected population data. To facilitate use of DPoRT, we partnered with regional and provincial health-related decision makers in Ontario and Manitoba, Canada. Primary objectives include: i) evaluate the effectiveness of partnerships between the research team and DPoRT users; ii) explore strategies that facilitate uptake and overcome barriers to DPoRT use; and iii) implement and evaluate the knowledge translation approach.
Methods
This protocol reflects an integrated knowledge translation (IKT) approach and corresponds to the action phase of the Knowledge-to-Action (KtoA) framework. Our IKT approach includes: employing a knowledge brokering team to facilitate relationships with DPoRT users (objective 1); tailored training for DPoRT users; assessment of barriers and facilitators to DPoRT use; and customized dissemination strategies to present DPoRT outputs to decision maker audiences (objective 2). Finally, a utilization-focused evaluation will assess the effectiveness and impact of the proposed KtoA process for DPoRT application (objective 3). This research design utilizes a multiple case study approach. Units of analyses consist of two public health units, one provincial health organization, and one provincial knowledge dissemination team whereby we will connect with multiple regional health authorities. Evaluation will be based on analysis of both quantitative and qualitative data collected from passive (e.g., observer notes) and active (e.g., surveys and interviews) methods.
Discussion
DPoRT offers an innovative way to make routinely collected population health data practical and meaningful for diabetes prevention planning and decision making. Importantly, we will evaluate the utility of the KtoA cycle for a novel purpose – the application of a tool. Additionally, we will evaluate this approach in multiple diverse settings, thus considering contextual factors. This research will offer insights into how knowledge translation strategies can support the use of population-based risk assessment tools to promote informed decision making in health-related settings.
doi:10.1186/1748-5908-9-35
PMCID: PMC3998044  PMID: 24655716
Diabetes population risk tool; Diabetes; Knowledge translation; Knowledge-to-action; Partnership; Knowledge broker; Public health; Risk tool; Chronic disease
13.  A self-evaluation tool for integrated care services: the Development Model for Integrated Care applied in practice 
Purpose
The purpose of the workshop is to show the applications of the Development Model for Integrated Care (DMIC) in practice. This relatively new and validated model, can be used by integrated care practices to evaluate their integrated care, to assess their phase of development and reveal improvement areas. In the workshop the results of the use of the model in three types of integrated care settings in the Netherlands will be presented. Participants are offered practical instruments based on the validated DMIC to use in their own setting and will be introduced to the webbased tool.
Context
To integrate care from multiple providers into a coherent and streamlined client-focused service, a large number of activities and agreements have to be implemented like streamlining information flows and adequate transfers of clients. In the large range of possible activities it is often not clear what essential activities are and where to start or continue. Also, knowledge about how to further develop integrated care services is needed. The Development Model for Integrated Care (DMIC), based on PhD research of Mirella Minkman, describes nine clusters containing in total 89 elements that contribute to the integration of care. The clusters are named: ‘client-centeredness’, ‘delivery system’, ‘performance management’, ‘quality of care’, ‘result-focused learning’, ‘interprofessional teamwork’, ‘roles and tasks’, ‘commitment’, and ‘transparant entrepreneurship’ [1–3]. In 2011 a new digital webbased self-evolution tool which contains the 89 elements grouped in nine clusters was developed. The DMIC also describes four phases of development [4]. The model is empirically validated in practice by assessing the relevance and implementation of the elements and development phases in 84 integrated care services in The Netherlands: in stroke, acute myocardial infarct (AMI), and dementia services. The validation studies are recently published [5, 6]. In 2011 also other integrated care services started using the model [7]. Vilans developed a digital web-based self-evaluation tool for integrated care services based on the DMIC. A palliative care network, four diabetes services, a youth care service and a network for autism used the self-evaluation tool to evaluate the development of their integrated care service. Because of its generic character, the model and tool are believed to be also interesting internationally.
Data sources
In the workshop we will present the results of three studies in integrated diabetes, youth and palliative care. The three projects consist of multiple steps, see below. Workshop participants could also work with the DMIC following these steps.
One: Preparation of the digital self-evolution tool for integrated care services
Although they are very different, the three integrated care services all wanted to gain insight in their development and improvement opportunities. We tailored the digital self-evaluation tool for each specific integrated care services, but for all the basis was the DMIC. Personal accounts for the digital DMIC self-evalution survey were sent to multiple partners working in each integrated care service (4–16 partners).
Two: Use of the online self-evaluation tool each partner of the local integrated care setting evaluated the integrated care by filling in the web-based questionnaire. The tool consists of three parts (A-C) named: general information about the integrated care practice (A); the clusters and elements of the DMIC (B); and the four phases of development (C). The respondents rated the relevance and presence of each element in their integrated care practice. Respondents were asked to estimate in which phase of development their thought their service was.
Three: Analysing the results
Advisers from Vilans, the Centre of excellence for long-term care in the Netherlands, analysed the self-evolution results in cooperation with the integrated care coordinators. The results show the total amount of implemented integrated care elements per cluster in spider graphs and the development phase as calculated by the DMIC model. Suggestions for further development of the integrated care services were analysed and reported.
Four: Discussing the implications for further development
In a workshop with the local integrated care partners the results of the self-evaluation were presented and discussed. We noticed remarkable results and highlight elements for further development. In addition, we gave advice for further development appropriate to the development phase of the integrated care service. Furthermore, the professionals prioritized the elements and decided which elements to start working on. This resulted in a (quality improvement) plan for the further development of the integrated care service.
Five: Reporting results
In a report all the results of the survey (including consensus scores) and the workshops came together. The integrated care coordinators stated that the reports really helped them to assess their improvement strategy. Also, there was insight in the development phase of their service which gave tools for further development.
Case description
The three cases presented are a palliative network, an integrated diabetes services and an integrated care network for youth in the Netherlands. The palliative care network wanted to reflect on their current development, to build a guiding framework for further development of the network. About sixteen professionals within the network worked with the digital self-evaluation tool and the DMIC: home care organisations, welfare organizations, hospice centres, health care organisations, community organizations.
For diabetes care, a Dutch health care insurance company wished to gain insight in the development of the contracted integrated care services to stimulate further development of the services. Professionals of three diabetes integrated care services were invited to fill in the digital self-evaluation tool. Of each integrated care service professionals like a general practitioner, a diabetes nurse, a medical specialist, a dietician and a podiatrist were invited. In youth care, a local health organisation wondered whether the DMIC could be helpful to visualize the results of youth integrated care services at process- and organisational level. The goal of the project was to define indicators at a process- and organisational level for youth care services based on the DMIC. In the future, these indicators might be used to evaluate youth care integrated care services and improve the quality of youth care within the Netherlands.
Conclusions and discussion
It is important for the quality of integrated care services that the involved coordinators, managers and professionals are aware of the development process of the integrated care service and that they focus on elements which can further develop and improve their integrated care. However, we noticed that integrated care services in the Netherlands experience difficulties in developing their integrated care service. It is often not clear what essential activities are to work on and how to further develop the integrated care service. A guiding framework for the development of integrated care was missing. The DMIC model has been developed for that reason and offers a useful tool for assessment, self-evaluation or improvement of integrated care services in practice. The model has been validated for AMI, dementia and stroke services. The latest new studies in diabetes, palliative care and youth care gave further insight in the generic character of the DMIC. Based on these studies it can be assumed that the DMIC can be used for multiple types of integrated care services. The model is assumed to be interesting for an international audience. Improving integrated care is a complex topic in a large number of countries; the DMIC is also based on the international literature. Dutch integrated care coordinators stated that the DMIC helped them to assess their integrated care development in practice and supported them in obtaining ideas for expanding and improving their integrated care activities.
The web-based self-evaluation tool focuses on a process- and organisational level of integrated care. Also, the self assessed development phase can be compared to the development phase as calculated by the DMIC tool. The cases showed this is fruitful input for discussions. When using the tool, the results can also be used in quality policy reports and improvement plans. The web-based tool is being tested at this moment in practice, but in San Marino we can present the latest webversion and demonstrate with a short video how to use the tool and model. During practical exercises in the workshop the participants will experience how the application of the DMIC can work for them in practice or in research. For integrated care researchers and policy makers, the DMIC questionnaire and tool is a promising method for further research and policy plans in integrated care.
PMCID: PMC3617779
development model for integrated care; development of integrated care services; implementation and improvement of integrated care; self evaluation
14.  Evaluation of a health systems knowledge translation network for Africa (KTNET): a study protocol 
Background
Despite the increasing investment in health-related research in Sub-Saharan Africa, a large gulf remains between what is known and what is practiced in health systems. Knowledge translation programs aim to ensure that a wide range of stakeholders are aware of and use research evidence to inform their health and health-care decision-making. The purpose of this study is to provide insight into the impacts on capacity building for knowledge translation and knowledge translation activities by a coalition of eight research groups in Africa.
Methods/design
We will use a mixed methods approach. Key informant interviews and document reviews will be employed to evaluate changes in knowledge translation capacity and to evaluate the effects of knowledge translation on potential users of research. Quarterly teleconferences will be done to evaluate the impacts of knowledge translation activities on users of research. Using website tracking, we will be able to explore the influence of knowledge translation networking and dynamics of the knowledge translation network.
Discussion
We have adopted the dynamic knowledge transfer model and the Landry framework to come up with a framework for this study so as to explore the capacity of producers and users of research to generate, disseminate, and use research findings, while highlighting their strengths and weaknesses. This information will be useful for guiding implementers that seek to build capacity on knowledge translation so as to promote the utilization of research findings for informing programs, practice, and policy.
doi:10.1186/s13012-014-0170-4
PMCID: PMC4274690  PMID: 25423876
Health systems; Knowledge translation; Evidence-based practice; Africa
15.  Knowledge Translation Tools are Emerging to Move Neck Pain Research into Practice 
Development or synthesis of the best clinical research is in itself insufficient to change practice. Knowledge translation (KT) is an emerging field focused on moving knowledge into practice, which is a non-linear, dynamic process that involves knowledge synthesis, transfer, adoption, implementation, and sustained use. Successful implementation requires using KT strategies based on theory, evidence, and best practice, including tools and processes that engage knowledge developers and knowledge users. Tools can provide instrumental help in implementing evidence. A variety of theoretical frameworks underlie KT and provide guidance on how tools should be developed or implemented. A taxonomy that outlines different purposes for engaging in KT and target audiences can also be useful in developing or implementing tools. Theoretical frameworks that underlie KT typically take different perspectives on KT with differential focus on the characteristics of the knowledge, knowledge users, context/environment, or the cognitive and social processes that are involved in change. Knowledge users include consumers, clinicians, and policymakers. A variety of KT tools have supporting evidence, including: clinical practice guidelines, patient decision aids, and evidence summaries or toolkits. Exemplars are provided of two KT tools to implement best practice in management of neck pain—a clinician implementation guide (toolkit) and a patient decision aid. KT frameworks, taxonomies, clinical expertise, and evidence must be integrated to develop clinical tools that implement best evidence in the management of neck pain.
doi:10.2174/1874325001307010582
PMCID: PMC3805983  PMID: 24155807
Knowledge translation; neck pain; tools; implementation.
16.  A Collaborative Quality Improvement Model and Electronic Community of Practice to Support Sepsis Management in Emergency Departments: Investigating Care Harmonization for Provincial Knowledge Translation 
JMIR Research Protocols  2012;1(2):e6.
Emergency medicine departments within several organizations are now advocating the adoption of early intervention guidelines for patients with the signs and symptoms of sepsis. This proposed research will lead to a comprehensive understanding of how diverse emergency department (ED) sites across British Columbia (BC), Canada, engage in a quality improvement collaborative to lead to improvements in time-based process measures and clinical outcomes for septic patients in EDs. To address the challenge of sepsis management, in 2007, the BC Ministry of Health began working with emergency health professionals, including health administrators, to establish a provincial ED collaborative: Evidence to Excellence (E2E). The E2E initiative employs the Institute for Healthcare Improvement (IHI) model and is supported by a Web-based community of practice (CoP) in emergency medicine. It aims to (1) support clinicians in accessing and applying evidence to clinical practice in emergency medicine, (2) support system change and clinical process improvement, and (3) develop resources and strategies to facilitate knowledge translation and process improvement. Improving sepsis management is one of the central foci of the E2E initiative. The primary purpose of our research is to investigate whether the application of sepsis management protocols leads to improved time-based process measures and clinical outcomes for patients presenting to EDs with sepsis. Also, we seek to investigate the implementation of sepsis protocols among different EDs. For example: (1) How can sepsis protocols be harmonized among different EDs? (2) What are health professionals’ perspectives on interprofessional collaboration with various EDs? and (3) What are the factors affecting the level of success among EDs? Lastly, working in collaboration with the BC Ministry of Health as our policy-maker partner, the research will investigate how the demonstrated efficacy of this research can be applied on a provincial and national level to establish a template for policy makers from other jurisdictions to translate knowledge into action for EDs. This research study will employ the IHI model for improvement, incorporate the principles of participatory action research, and use the E2E online CoP to engage ED practitioners (eg, physicians, nurses, and administrators, exchanging ideas, engaging in discussions, sharing resources, and amalgamating knowledge) from across BC to (1) share the evidence of early intervention in sepsis, (2) adapt the evidence to their patterns of practice, (3) develop a common set of orders for implementing the sepsis pathway, and (4) agree on common indicators to measure clinical outcomes. Our hypothesis is that combining the social networking ability of an electronic CoP and its inherent knowledge translation capacity with the structured project management of the IHI model will result in widespread and sustained improvement in the emergency and overall care of patients with severe sepsis presenting to EDs throughout BC.
doi:10.2196/resprot.1597
PMCID: PMC3626155  PMID: 23611816
Knowledge translation; continuous quality improvement; emergency medicine; sepsis
17.  From policy to practice: implementing frontline community health services for substance dependence–study protocol 
Background
Substance abuse is a worldwide public health concern. Extensive scientific research has shown that screening and brief interventions for substance use disorders administered in primary care provide substantial benefit at relatively low cost. Frontline health clinicians are well placed to detect and treat patients with substance use disorders. Despite effectiveness shown in research, there are many factors that impact the implementation of these practices in real-world clinical practice. Recently, the Ministry of Health and Social Services in Quebec, Canada, issued two policy documents aimed at introducing screening and early intervention for substance abuse into frontline healthcare clinics in Quebec. The current research protocol was developed in order to study the process of implementation of evidence-based addiction treatment practices at three primary care clinics in Montreal (Phase 1). In addition, the research protocol was designed to examine the efficacy of overall policy implementation, including barriers and facilitators to addictions program development throughout Quebec (Phase 2).
Methods/Design
Phase 1 will provide an in-depth case study of knowledge translation and implementation. The study protocol will utilize an integrated knowledge translation strategy to build collaborative mechanisms for knowledge exchange between researchers, addiction specialists, and frontline practitioners (guided by the principles of participatory-action research), and directly examine the process of knowledge uptake and barriers to transfer using both qualitative and quantitative methodologies. Evaluation will involve multiple measures, time points and domains; program uptake and effectiveness will be determined by changes in healthcare service delivery, sustainability and outcomes. In Phase 2, qualitative methods will be utilized to examine the contextual facilitators and barriers that frontline organizations face in implementing services for substance dependence. Phase 2 will provide the first study exploring the wide-scale implementation of frontline services for substance dependence in the province of Quebec and yield needed information about how to effectively implement mandated policies into clinical practice and impact public health.
Discussion
Findings from this research program will contribute to the understanding of factors associated with implementation of frontline services for substance dependence and help to inform future policy and organizational support for the implementation of evidence-based practices.
doi:10.1186/s13012-014-0108-x
PMCID: PMC4159513  PMID: 25138688
Substance dependence; Screening; Brief interventions; Frontline health services; Implementation; Knowledge translation; Policy; Organizational change
18.  Translational Science and Evidence-Based Healthcare: A Clarification and Reconceptualization of How Knowledge Is Generated and Used in Healthcare 
Nursing Research and Practice  2012;2012:792519.
The importance of basing health policy and health care practices on the best available international evidence (“evidence-based health care”) and on translating knowledge or evidence into action (“translation science” or “translational research”) 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.
doi:10.1155/2012/792519
PMCID: PMC3306933  PMID: 22474583
19.  Developing a framework for transferring knowledge into action: a thematic analysis of the literature 
Objectives
Although there is widespread agreement about the importance of transferring knowledge into action, we still lack high quality information about what works, in which settings and with whom. Whilst there are a large number of models and theories for knowledge transfer interventions, they are untested meaning that their applicability and relevance is largely unknown. This paper describes the development of a conceptual framework of translating knowledge into action and discusses how it can be used for developing a useful model of the knowledge transfer process.
Methods
A narrative review of the knowledge transfer literature identified 28 different models which explained all or part of the knowledge transfer process. The models were subjected to a thematic analysis to identify individual components and the types of processes used when transferring knowledge into action. The results were used to build a conceptual framework of the process.
Results
Five common components of the knowledge transfer process were identified: problem identification and communication; knowledge/research development and selection; analysis of context; knowledge transfer activities or interventions; and knowledge/research utilization. We also identified three types of knowledge transfer processes: a linear process; a cyclical process; and a dynamic multidirectional process. From these results a conceptual framework of knowledge transfer was developed. The framework illustrates the five common components of the knowledge transfer process and shows that they are connected via a complex, multidirectional set of interactions. As such the framework allows for the individual components to occur simultaneously or in any given order and to occur more than once during the knowledge transfer process.
Conclusion
Our framework provides a foundation for gathering evidence from case studies of knowledge transfer interventions. We propose that future empirical work is designed to test and refine the relevant importance and applicability of each of the components in order to build more useful models of knowledge transfer which can serve as a practical checklist for planning or evaluating knowledge transfer activities.
doi:10.1258/jhsrp.2009.008120
PMCID: PMC2933505  PMID: 19541874
20.  National policy development for cotrimoxazole prophylaxis in Malawi, Uganda and Zambia: the relationship between Context, Evidence and Links 
Background
Several frameworks have been constructed to analyse the factors which influence and shape the uptake of evidence into policy processes in resource poor settings, yet empirical analyses of health policy making in these settings are relatively rare. National policy making for cotrimoxazole (trimethoprim-sulfamethoxazole) preventive therapy in developing countries offers a pertinent case for the application of a policy analysis lens. The provision of cotrimoxazole as a prophylaxis is an inexpensive and highly efficacious preventative intervention in HIV infected individuals, reducing both morbidity and mortality among adults and children with HIV/AIDS, yet evidence suggests that it has not been quickly or evenly scaled-up in resource poor settings.
Methods
Comparative analysis was conducted in Malawi, Uganda and Zambia, using the case study approach. We applied the ‘RAPID’ framework developed by the Overseas Development Institute (ODI), and conducted a total of 47 in-depth interviews across the three countries to examine the influence of context (including the influence of donor agencies), evidence (both local and international), and the links between researcher, policy makers and those seeking to influence the policy process.
Results
Each area of analysis was found to have an influence on the creation of national policy on cotrimoxazole preventive therapy (CPT) in all three countries. In relation to context, the following were found to be influential: government structures and their focus, donor interest and involvement, healthcare infrastructure and other uses of cotrimoxazole and related drugs in the country. In terms of the nature of the evidence, we found that how policy makers perceived the strength of evidence behind international recommendations was crucial (if evidence was considered weak then the recommendations were rejected). Further, local operational research results seem to have been taken up more quickly, while randomised controlled trials (the gold standard of clinical research) was not necessarily translated into policy so swiftly. Finally the links between different research and policy actors were of critical importance, with overlaps between researcher and policy maker networks crucial to facilitate knowledge transfer. Within these networks, in each country the policy development process relied on a powerful policy entrepreneur who helped get cotrimoxazole preventive therapy onto the policy agenda.
Conclusions
This analysis underscores the importance of considering national level variables in the explanation of the uptake of evidence into national policy settings, and recognising how local policy makers interpret international evidence. Local priorities, the ways in which evidence was interpreted, and the nature of the links between policy makers and researchers could either drive or stall the policy process. Developing the understanding of these processes enables the explanation of the use (or non-use) of evidence in policy making, and potentially may help to shape future strategies to bridge the research-policy gaps and ultimately improve the uptake of evidence in decision making.
doi:10.1186/1478-4505-9-S1-S6
PMCID: PMC3121137  PMID: 21679387
21.  WHO Essential Medicines Policies and Use in Developing and Transitional Countries: An Analysis of Reported Policy Implementation and Medicines Use Surveys 
PLoS Medicine  2014;11(9):e1001724.
Kathleen Holloway and David Henry evaluate whether countries that report having implemented WHO essential medicines policies have higher quality use of medicines.
Please see later in the article for the Editors' Summary
Background
Suboptimal medicine use is a global public health problem. For 35 years the World Health Organization (WHO) has promoted essential medicines policies to improve quality use of medicines (QUM), but evidence of their effectiveness is lacking, and uptake by countries remains low. Our objective was to determine whether WHO essential medicines policies are associated with better QUM.
Methods and Findings
We compared results from independently conducted medicines use surveys in countries that did versus did not report implementation of WHO essential medicines policies. We extracted survey data on ten validated QUM indicators and 36 self-reported policy implementation variables from WHO databases for 2002–2008. We calculated the average difference (as percent) for the QUM indicators between countries reporting versus not reporting implementation of specific policies. Policies associated with positive effects were included in a regression of a composite QUM score on total numbers of implemented policies. Data were available for 56 countries. Twenty-seven policies were associated with better use of at least two percentage points. Eighteen policies were associated with significantly better use (unadjusted p<0.05), of which four were associated with positive differences of 10% or more: undergraduate training of doctors in standard treatment guidelines, undergraduate training of nurses in standard treatment guidelines, the ministry of health having a unit promoting rational use of medicines, and provision of essential medicines free at point of care to all patients. In regression analyses national wealth was positively associated with the composite QUM score and the number of policies reported as being implemented in that country. There was a positive correlation between the number of policies (out of the 27 policies with an effect size of 2% or more) that countries reported implementing and the composite QUM score (r = 0.39, 95% CI 0.14 to 0.59, p = 0.003). This correlation weakened but remained significant after inclusion of national wealth in multiple linear regression analyses. Multiple policies were more strongly associated with the QUM score in the 28 countries with gross national income per capita below the median value (US$2,333) (r = 0.43, 95% CI 0.06 to 0.69, p = 0.023) than in the 28 countries with values above the median (r = 0.22, 95% CI −0.15 to 0.56, p = 0.261). The main limitations of the study are the reliance on self-report of policy implementation and measures of medicine use from small surveys. While the data can be used to explore the association of essential medicines policies with medicine use, they cannot be used to compare or benchmark individual country performance.
Conclusions
WHO essential medicines policies are associated with improved QUM, particularly in low-income countries.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The widespread availability of effective medicines, particularly those used to treat infectious diseases, has been largely responsible for a doubling in the average global life expectancy over the past century. However, the suboptimal use (overuse and underuse) of medicines is an ongoing global public health problem. The unnecessary use of medicines (for example, the use of antibiotics for sore throats caused by viruses) needlessly consumes scarce resources and has undesirable effects such as encouraging the emergence of antibiotic resistance. Conversely, underuse deprives people of the undisputed benefits of many medicines. Since 1977, to help optimize medicine use, the World Health Organization (WHO) has advocated the concept of “essential medicines” and has developed policies to promote the quality use of medicines (QUM). Essential medicines are drugs that satisfy the priority needs of the human population and that should always be available to communities in adequate amounts of assured quality, in the appropriate dosage forms, and at an affordable price. Policies designed to promote QUM include recommendations that medicines should be free at the point of care and that all health care professionals should be educated about the WHO list of essential medicines (which is revised every two years) throughout their careers.
Why Was This Study Done?
Surveys of WHO member countries undertaken in 2003 and 2007 suggest that the implementation of WHO policies designed to promote QUM is patchy. Moreover, little is known about whether these policies are effective, particularly in middle- and low-income countries. For most of these countries, it is not known whether any of the policies affect validated QUM indicators such as the percentage of patients prescribed antibiotics (a lower percentage indicates better use of medicines) or the percentage of patients treated in compliance with national treatment guidelines (a higher percentage indicates better use of medicines). Here, the researchers analyze data from policy implementation questionnaires and medicine use surveys to determine whether implementation of WHO essential medicines policies is associated with improved QUM in low- and middle-income countries.
What Did the Researchers Do and Find?
The researchers extracted data on ten validated QUM indicators and on implementation of 36 policy variables from WHO databases for 2002–2008 and compared the average differences for the QUM indicators between low- and middle-income countries that did versus did not report implementation of specific WHO policies for QUM. Among 56 countries for which data were available, 27 policies were associated with improved QUM. Four policies were particularly effective, namely, doctors' undergraduate training in standard treatment guidelines, nurses' undergraduate training in standard treatment guidelines, the existence of a ministry of health department promoting the rational use of medicines, and the provision of essential medicines free to all patients at point of care. The researchers also analyzed correlations between how many of the 27 effective policies were implemented in a country and a composite QUM score. As national wealth increased, both the composite QUM score of a country and the reported number of policies implemented by the country increased. There was also a positive correlation between the numbers of policies that countries reported implementing and their composite QUM score. Finally, the implementation of multiple policies was more strongly associated with the composite QUM score in countries with a gross national income per capita below the average for the study countries than in countries with a gross national income above the average.
What Do These Findings Mean?
These findings show that between 2002 and 2008, the reported implementation of WHO essential medicines policies was associated with better QUM across low- and middle-income countries. These findings also reveal a positive correlation between the number of policies that countries report implementing and their QUM. Notably, this correlation was strongest in the countries with the lowest per capita national wealth levels, which underscores the importance of essential medicines policies in low-income countries. Because of the nature of the data available to the researchers, these findings do not show that the implementation of WHO policies actually causes improvements in QUM. Moreover, the age of the data, the reliance on self-report of policy implementation, and the small sample sizes of the medicine use surveys may all have introduced some inaccuracies into these findings. Nevertheless, overall, these findings suggest that WHO should continue to develop its medicine policies and to collect data on medicine use as part of its core functions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001724.
The World Health Organization provides information about essential medicines; its latest lists of essential medicines are available on the Internet; information about WHO policies to improve the quality use of medicines is also available (in several languages)
The International Network for the Rational Use of Drugs designs, tests, and disseminates effective strategies to improve the way drugs are prescribed, dispensed, and used, particularly in resource-poor countries
The essentialdrugs.org website helps health care professionals, researchers, and policy makers obtain and discuss current information on essential drugs, policy, program activities, education, and training (available in several languages); the website is run by Satellife, which aims to use technology to connect health workers in resource-limited countries to each other and to up-to-date clinical and public health content
doi:10.1371/journal.pmed.1001724
PMCID: PMC4165598  PMID: 25226527
22.  How funding agencies can support research use in healthcare: an online province-wide survey to determine knowledge translation training needs 
Background
Health research funding agencies are increasingly promoting evidence use in health practice and policy. Building on work suggesting how agencies can support such knowledge translation (KT), this paper discusses an online survey to assess KT training needs of researchers and research users as part of a Canadian provincial capacity-building effort.
Methods
The survey comprised 24 multiple choice and open-ended questions including demographics, interest in learning KT skills, likelihood of participating in training, and barriers and facilitators to doing KT at work. More than 1,200 people completed the survey. The high number of responses is attributed to an engagement strategy involving partner organizations (health authorities, research institutes, universities) in survey development and distribution. SPSS was used to analyze quantitative results according to respondents’ primary role, geographic region, and work setting. Qualitative results were analyzed in NVivo.
Results
Over 85 percent of respondents are interested in learning more about the top KT skills identified. Research producers have higher interest in disseminating research results; research users are more interested in the application of research results. About one-half of respondents require beginner-level training in KT skills; one-quarter need advanced training. Time and cost constraints are the biggest barriers to participating in KT training. More than one-half of respondents have no financial support for travel and almost one-half lack support for registration fees. Time is the biggest challenge to integrating KT into work.
Conclusions
Online surveys are useful for determining knowledge translation training needs of researchers, research users and ultimately organizations. In this case, findings suggest the importance of considering all aspects of KT in training opportunities, while taking into account different stakeholder interests. Funders can play a role in developing new training opportunities as part of a broad effort, with partners, to build capacity for the use of health research evidence. Survey results would ideally be complemented with an objective needs assessment based on core competencies, and should be acted on in a way that acknowledges the complexity of knowledge translation in healthcare, existing training activities, and the expertise stakeholders already have but may not refer to as knowledge translation.
doi:10.1186/1748-5908-9-71
PMCID: PMC4060070  PMID: 24906229
Knowledge translation; Evidence-based decision making; Health research capacity building; Health research funder; Evidence use
23.  Evidence-informed decision-making by professionals working in addiction agencies serving women: a descriptive qualitative study 
Background
Effective approaches to the prevention and treatment of substance abuse among mothers have been developed but not widely implemented. Implementation studies suggest that the adoption of evidence-based practices in the field of addictions remains low. There is a need, therefore, to better understand decision making processes in addiction agencies in order to develop more effective approaches to promote the translation of knowledge gained from addictions research into clinical practice.
Methods
A descriptive qualitative study was conducted to explore: 1) the types and sources of evidence used to inform practice-related decisions within Canadian addiction agencies serving women; 2) how decision makers at different levels report using research evidence; and 3) factors that influence evidence-informed decision making. A purposeful sample of 26 decision-makers providing addiction treatment services to women completed in-depth qualitative interviews. Interview data were coded and analyzed using directed and summative content analysis strategies as well as constant comparison techniques.
Results
Across all groups, individuals reported locating and using multiple types of evidence to inform decisions. Some decision-makers rely on their experiential knowledge of addiction and recovery in decision-making. Research evidence is often used directly in decision-making at program management and senior administrative levels. Information for decision-making is accessed from a range of sources, including web-based resources and experts in the field. Individual and organizational facilitators and barriers to using research evidence in decision making were identified.
Conclusions
There is support at administrative levels for integrating EIDM in addiction agencies. Knowledge transfer and exchange strategies should be focussed towards program managers and administrators and include capacity building for locating, appraising and using research evidence, knowledge brokering, and for partnering with universities. Resources are required to maintain web-based databases of searchable evidence to facilitate access to research evidence. A need exists to address the perception that there is a paucity of research evidence available to inform program decisions. Finally, there is a need to consider how experiential knowledge influences decision-making and what guidance research evidence has to offer regarding the implementation of different treatment approaches within the field of addictions.
doi:10.1186/1747-597X-6-29
PMCID: PMC3224771  PMID: 22059528
Substance use; knowledge translation; evidence-informed decision-making; research utilization
24.  Knowledge exchange in the Pacific: The TROPIC (Translational Research into Obesity Prevention Policies for Communities) project 
BMC Public Health  2012;12:552.
Background
Policies targeting obesogenic environments and behaviours are critical to counter rising obesity rates and lifestyle-related non-communicable diseases (NCDs). Policies are likely to be most effective and enduring when they are based on the best available evidence. Evidence-informed policy making is especially challenging in countries with limited resources. The Pacific TROPIC (Translational Research for Obesity Prevention in Communities) project aims to implement and evaluate a tailored knowledge-brokering approach to evidence-informed policy making to address obesity in Fiji, a Pacific nation challenged by increasingly high rates of obesity and concomitant NCDs.
Methods
The TROPIC project draws on the concept of ‘knowledge exchange’ between policy developers (individuals; organisations) and researchers to deliver a knowledge broking programme that maps policy environments, conducts workshops on evidence-informed policy making, supports the development of evidence-informed policy briefs, and embeds evidence-informed policy making into organisational culture. Recruitment of government and nongovernment organisational representatives will be based on potential to: develop policies relevant to obesity, reach broad audiences, and commit to resourcing staff and building a culture that supports evidence-informed policy development. Workshops will increase awareness of both obesity and policy cycles, as well as develop participants’ skills in accessing, assessing and applying relevant evidence to policy briefs. The knowledge-broking team will then support participants to: 1) develop evidence-informed policy briefs that are both commensurate with national and organisational plans and also informed by evidence from the Pacific Obesity Prevention in Communities project and elsewhere; and 2) collaborate with participating organisations to embed evidence-informed policy making structures and processes. This knowledge broking initiative will be evaluated via data from semi-structured interviews, a validated self-assessment tool, process diaries and outputs.
Discussion
Public health interventions have rarely targeted evidence-informed policy making structures and processes to reduce obesity and NCDs. This study will empirically advance understanding of knowledge broking processes to extend evidence-informed policy making skills and develop a suite of national obesity-related policies that can potentially improve population health outcomes.
doi:10.1186/1471-2458-12-552
PMCID: PMC3444395  PMID: 22830984
Policy; Obesity; Knowledge exchange; Knowledge broker; Pacific
25.  Effective continuing professional development for translating shared decision making in primary care: A study protocol 
Background
Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the healthcare professional and the patient. SDM is the essential element of patient-centered care, a core concept of primary care. However, SDM is seldom translated into primary practice. Continuing professional development (CPD) is the principal means by which healthcare professionals continue to gain, improve, and broaden the knowledge and skills required for patient-centered care. Our international collaboration seeks to improve the knowledge base of CPD that targets translating SDM into the clinical practice of primary care in diverse healthcare systems.
Methods
Funded by the Canadian Institutes of Health Research (CIHR), our project is to form an international, interdisciplinary research team composed of health services researchers, physicians, nurses, psychologists, dietitians, CPD decision makers and others who will study how CPD causes SDM to be practiced in primary care. We will perform an environmental scan to create an inventory of CPD programs and related activities for translating SDM into clinical practice. These programs will be critically assessed and compared according to their strengths and limitations. We will use the empirical data that results from the environmental scan and the critical appraisal to identify knowledge gaps and generate a research agenda during a two-day workshop to be held in Quebec City. We will ask CPD stakeholders to validate these knowledge gaps and the research agenda.
Discussion
This project will analyse existing CPD programs and related activities for translating SDM into the practice of primary care. Because this international collaboration will develop and identify various factors influencing SDM, the project could shed new light on how SDM is implemented in primary care.
doi:10.1186/1748-5908-5-83
PMCID: PMC2988066  PMID: 20977774

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