Health care decision makers often need to make decisions in limited timeframes and cannot await the completion of a full evidence review. Rapid reviews (RRs), utilizing streamlined systematic review methods, are increasingly being used to synthesize the evidence with a shorter turnaround time. Our primary objective was to describe the processes and methods used internationally to produce RRs. In addition, we sought to understand the underlying themes associated with these programs.We contacted representatives of international RR programs from a broad realm in health care to gather information about the methods and processes used to produce RRs. The responses were summarized narratively to understand the characteristics associated with their processes and methods. The summaries were compared and contrasted to highlight potential themes and trends related to the different RR programs.Twenty-nine international RR programs were included in our sample with a broad organizational representation from academia, government, research institutions, and non-for-profit organizations. Responses revealed that the main objectives for RRs were to inform decision making with regards to funding health care technologies, services and policy, and program development. Central themes that influenced the methods used by RR programs, and report type and dissemination were the imposed turnaround time to complete a report, resources available, the complexity and sensitivity of the research topics, and permission from the requestor.Our study confirmed that there is no standard approach to conduct RRs. Differences in processes and methods across programs may be the result of the novelty of RR methods versus other types of evidence syntheses, customization of RRs for various decision makers, and definition of ‘rapid’ by organizations, since it impacts both the timelines and the evidence synthesis methods. Future research should investigate the impact of current RR methods and reporting to support informed health care decision making, the effects of potential biases that may be introduced with streamlined methods, and the effectiveness of RR reporting guidelines on transparency.The online version of this article (doi:10.1186/s13643-015-0022-6) contains supplementary material, which is available to authorized users. Systematic reviews (SRs) are accepted as the gold standard in evidence-based medicine. Health care decision makers, however, are increasingly in need of evidence-based reports in limited timeframes to support informed decisions . This haDecision makers are increasingly seeking evidence to inform the policymaking process, and this requires access to high-quality evidence to inform decisions. As such, several health care organizations have turned to abbreviated systematic methods as a means of delivering evidence in a timely manner. One of the major issues with RRs, however, is that their methodologies are often not published or available outside the organization conducting the RR. To date, we have identified two publications that describe RR programs in detail ,5, whileIn September 2013, a group of three health care research organizations with a shared interest in RRs organized and facilitated an open ‘Rapid Review Methods Discussion’ at the 2013 Cochrane Colloquium in Quebec City. Among the 40 meeting registrants, academia, government, research institutions, not-for-profit organizations, and the Cochrane Collaboration were represented. The primary purpose was to exchange and share information between RR producers and users about the methods used to develop RRs and their usability and appropriateness to support informed decisions in health care. One of the key outcomes of this meeting was establishing an informal network of organizations and researchers interested in ‘rapid reviews’. Further, recognizing the growing need to better understand the methods used by rapid review producers, a number of organizations agreed to share their processes and methods. The purpose of this study, hence, was to describe the various RR programs with the aim to provide an analysis of processes and methods by highlighting themes of characteristics across with these rapid review programs. Our descriptive analysis represents the most comprehensive attempt to date to characterize a broad spectrum of RR programs and their respective methods. The discussion reflected a wide ranging set of views on what methods should be maintained and what can be sacrificed for the sake of timeliness.Following the rapid review methods discussion meeting at the 2013 Cochrane Colloquium, we applied purposive and snowball sampling techniques to form our study sample. Meeting participants were approached to share information about the methods and processes used in their RR programs. Additional RR programs were identified by the participants and this study’s coauthors. The Canadian Agency for Drugs and Technologies in Health (CADTH) led the environmental scan of international rapid review programs with contributions from the Ottawa Hospital Research Institute (OHRI) and University of Manitoba. As CADTH is an independent, not-for-profit organization funded by Canadian federal and provincial governments, we are not required to seek ethics approval to obtain information from various organizations about their practices and methods on a specific health care topic. In our correspondence with the organization, we indicated a priori that any information provided will be used in a publication, so consent to publish was not needed as the feedback was provided on a voluntary basis.A form was developed and organized into nine domains to collect information specific to methods and processes by the identified program  incorporated protocol development as part of the RR process; one respondent did not indicate if a protocol is used or not. Components specified in a protocol centered mainly on patient population(s), intervention(s), comparator(s), outcome(s) and study design(s), and the research question(s). Fifteen RR programs (51.7%) prepared protocols in conjunction with the requestor.Most RR programs  also had drafted RRs reviewed externally. Seven respondents (24.1%) stated that a decision to carry an external review depended on the type of RR report and timeline for completion, and additionally only if requested. In two instances, it was reported that the requestor regularly reviewed the draft report before being finalized. Information from industry was generally not sought, with only a handful of respondents indicating that they do this on a regular basis  or on a case-by-case basis .Twenty-four RR programs (82.8%) reported conducting internal reviews of the draft RR and a subset of programs , context and policy issues/implications of the synthesized evidence , references to review methods used , and an explanation of the strengths and limitations of review methods used . Some RR producers also included tables , graphs , and a legal disclaimer  in the final report.Based on responses from our sample, elements consistently incorporated in a RR based on the study sample are key messages or recommendations to support dissemination  disseminated their report beyond the requestor, while five (17.2%) responded that dissemination depends on the sensitivity of the topic and/or permission from the requestor. In addition, 11 RR producers 37.9%) posted the full rapid review on the Internet, with one additional producer reporting just posting a summary of the report. Three respondents indicated that the Web posting of their RR depended on the type of report produced and/or if permission was granted by the requestor. Table S3 in Additional file 7.9% postn = 16; 55.2%), clinical efficacy , cost-effectiveness and/or cost savings , safety , and to support clinical practice guideline preparation  for either a health care technology or service. Nine respondents (31.0%) also stated that research questions focused on the accuracy of diagnostic or screening tests. Some RR programs focused exclusively on questions centered on health care policy, coverage of a technology, health system interventions, health services delivery, operational efficiency, and quality improvement. Two organizations (6.9%) focused on specific health topics. More specifically, one RR program focused exclusively on questions related to HIV/AIDS and other sexually transmitted and blood borne infections, and another focused on topics related to public health programs. One RR program in Canada was focused on health and social science topics associated with suicide prevention, conceptions of masculinity, obesity, and musculoskeletal injuries.For many programs, requestors sought evidence on clinical effectiveness  to 10 years , one producer noted searching from the year 2000 onwards. Eight participants (27.6%) responded that the time period searched was based on the topic. Literature search strategies were not peer-reviewed among 14 RR producers (48.3%), and four respondents (13.8%) indicated that it was conducted depending on the report complexity and funding available. Language restrictions were imposed by the majority of RR producers in our study, where English only studies  or studies published in English and another language  were searched. Seven respondents (24.1%) did not specify whether they used language restrictions as part of their search strategy.All RR programs incorporated multiple databases and websites as data sources for their reports. Commonly searched databases included PubMed/MEDLINE, CINAHL, Embase, PsycINFO, Cochrane Library, and University of York’s Centre for Reviews and Dissemination and TRIP databases. In our study, grey literature was defined as literature that is not commercially available or indexed by major databases. Fourteen RR producers 48.3%) reported consistently searching trial registries and medical society, government regulatory, and health technology assessment websites for relevant grey literature  and for data abstraction . A few respondents stated that the number of reviewers for the study selection  and data abstraction  was predicated on the research topic.Numerous RR programs in our sample used two reviewers to select studies for inclusion , while four (13.8%) reported regularly conducting a meta-analysis and three producers (10.3%) include economic evaluations in their reports. The appropriateness of a meta-analysis in a RR would partially depend on the type of report produced. Two RR programs (6.9%) did not specify the type of evidence synthesis conducted. A few RR programs occasionally performed meta-analyses  or syntheses of the economic literature .A narrative summary was the most common method used to synthesize the evidence  indicated that they critically appraised the selected studies in their reports, while two (6.90%) did it depending on the report type and time permitted. Seven RR programs (24.1%) do not conduct a critical appraisal of studies. Similar to other forms of evidence synthesis or HTA, validated critical appraisal tools were selected according to their appropriateness for the study design (Table S4 in Additional file Most RR producers (rograms 2.1% do noBased on a sample of 29 RR programs, the study findings revealed that the definition of, and methods to conduct, RRs was more fluid and flexible compared with those established for a traditional systematic review or HTA. This phenomenon can be related in part to the novelty of RR methods versus other evidence-based approaches, tailoring of RRs to meet the decision makers’ needs, and how an organization defines ‘rapid’ since the definition impacts both the timelines and the conduct of the evidence synthesis. Central themes to factors that appear to influence the methods used by RR programs and their respective report types and dissemination are the imposed turnaround time to complete a report; resources available; the complexity and sensitivity of the research topics; and permission from the requestor. From the responses we received, it is evident that a ‘one-size fits all’ approach may not be appropriate as RRs are produced for decision makers in an array of health care areas for different purposes and with diffing available resources and time constraints. It, therefore, seems challenging to develop a formulaic process or methodology that would be endorsed by all RR producers and users. Even so, further research may reveal particular common points of interest that would allow some standardization of the methods used to conduct specific types of RR and how to best report their results.Although our sample was not exhaustive, we sought to identify and synthesize the processes and methods used by RR programs throughout the world. Overall, our results were consistent with the findings of previous reviews on methods used to produce RRs ,6. A revRR producers are faced with a conundrum, having to meet the time-sensitive needs of decision makers, while at the same time attempting to maintain methodological rigor. This challenge has led different research groups to routinely short-cut different aspects of the traditional review methods in order to complete the evidence synthesis in the allotted time. It is understood that the streamlined methods used to produce RRs can inadvertently introduce bias into the review process. The comprehensiveness of a RR can be reduced if the literature search strategy incorporates an insufficient number of databases and languages, searches for publications are conducted within shortened timeframes and excludes the grey literature; resulting in an increased risk of missing publications of relevancy. Although potential biases in RRs have not been empirically studied, potential sources relate to the study selection and data extraction by one reviewer. As found in both our study and noted by Watt et al. , RR methRRs may be used to inform specific health care decisions in a timely manner using relevant evidence, but their appropriateness in health care and HTA merits further investigation . Legal iInterpretation and application of the findings of this study may be influenced by several limitations. Twelve of the 29 RR programs were based in Canada, and over 70% represented English-speaking jurisdictions. Our respondents, however, represented a cross section of RR programs in existence for health care decision making today. In addition, purposive sampling was employed, so the participants were not randomly selected. To help strive for comprehensiveness in our sample, RR programs from four continents, at various levels in the health care systems with diverse foci in across health sectors provided data. An additional limitation was that we were unable to distinguish any patterns between the purpose of the RR and the methods applied to produce a report. Although we inquired about the types of research questions addressed in a RR, we were unable to assess their scope according to the responses provided. Further, we were unable to explain potential reasons and causes for differences across the programs based on the information collected. This warrants further investigation.Based on discussions at the Cochrane 2013 Colloquium meeting and by having taken a more in-depth look at the methods employed by the network members, various organizations employ different measures for their program. The impact of a RR used to inform health care decisions remains unknown as few programs have measured it. Impact measurement, although complicated, should be encouraged. It would be important to capture metrics related to, for example, how often the report was used to inform a decision, policy or debate; cost savings; harms reduction; and/or how often, and in what manner it was portrayed in the media. The results of our analysis highlight the reality that RR products provide flexibility and are time sensitive. Methodological research should be undertaken to develop taxonomy of types of RRs and understand the strengths and limitations of the various forms of RRs in keeping with the volume and type of evidence identified, as well as the level of synthesis performed. How the findings are reported may impact health care decisions and understanding the extent of bias . Future The processes and methods for 29 international RR programs were reviewed and compared for greater insight on the different forms of RRs. Although numerous RRs focus on questions of clinical effectiveness, efficacy and cost-effectiveness, there is no single cohesive method to conduct a RR. In addition to the turnaround time, the resources available, the complexity and sensitivity of the research topics, and permission from the decision maker have an impact on the types of RR produced and their dissemination. Future studies should evaluate the appropriateness of the different RR methods and reporting for health care decisions, how the methods used across an array of RRs align with the PRISMA guidelines and AMSTAR tool, and the relevance of reporting guidelines for RRs to improve their transparency.


The aim of this rapid knowledge synthesis was to provide relevant research evidence to inform the implementation of a new health service in Nova Scotia, Canada: Collaborative Emergency Centres (CECs). CECs propose to deliver both primary and urgent care to rural populations where traditional delivery is a challenge. This paper reports on the methods used in a rapid knowledge synthesis project to provide timely evidence to policy makers about this novel healthcare delivery model.We used a variety of methods, including a jurisdictional/scoping review, modified systematic review methodologies, and integrated knowledge translation. We scanned publicly available information about similar centres across our country to identify important components of CECs and CEC-type models to operationalize the definition of a CEC. We conducted literature searches in PubMed, CINAHL, and EMBASE, and in the grey literature, to identify evidence on the key structures and processes and effectiveness of CEC-type models of care delivery. Our searches were limited to published systematic reviews. The research team facilitated two integrated knowledge translation workshops during the project to engage stakeholders, to refine the research goals and objectives, and to share interim and final results. Citations and included articles were categorized by whether they addressed the CEC model or component structures and processes. Data and key messages were extracted from these reviews to inform implementation.CEC-type models have limited peer-reviewed evidence available; no peer-reviewed studies on CECs as a standalone healthcare model were found. As a result, our evidence search and synthesis was revised to focus on core CEC-type structures and processes, prioritized through consensus methods with the stakeholder group, and resulted in provision of a meaningful evidence synthesis to help inform the development and implementation of CECs in Nova Scotia.A variety of methods and partnership with decision-makers and stakeholders enabled the project to address the limitations in the evidence regarding CECs and meet the challenge of identifying the best available evidence in a transparent way to meet the needs of decision-makers in a short timeframe. Health policy decision-makers are often tasked with designing and delivering complex programs and services that meet the needs of a population. Research evidence is important to inform and guide appropriate decision-making . EvidencHowever, overcoming challenges in using research evidence in policy decision-making, including finding evidence that addresses the question of interest, unclear perceived relevance to the local context, and compressed timelines for decision-making, requires focused and innovative knowledge syntheses and knowledge translation approaches . Policy While systematic reviews and rapid reviews can provide useful summaries of ‘What works?’ , the integration of evidence into decision-making remains limited . RegardlDespite the increased production of rapid reviews and projects with an integrated decision-maker involvement, there is minimal methodological guidance available for these approaches . In addiCECs were introduced in the province of Nova Scotia, Canada in 2011 in response to the challenges of access to emergency and primary care services in some rural areas of the province. The goal was to ‘keep emergency departments open, reduce patient wait times, and provide a team-based approach that offers continuity of care’ –25. CECsDefine CECs through the identification of potential structures, processes, and implementation strategies of CEC-type models in other jurisdictions.Identify scientific evidence that investigates the effectiveness of CEC-type models and their structures and processes for improving health outcomes.Our research team was engaged to:http://www.nshrf.ca) to inform this complex healthcare and service delivery problem. Challenges to informing this topic included starting with a broad question of interest and limited research evidence on the full model of care. Regardless, there was a need to inform practice. In response to these challenges, a variety of methods were adopted for the project, which permitted the synthesis of the evidence on the core components of collaborative health models and collaboration with decision-makers to refine aspects of the project focus. This approach permitted opportunities for conversations about project methods, research goals, and availability and use of research evidence.Our team worked with the government policy advisors and the Nova Scotia Health Research Foundation  , 19, incThe proposal for this project was reviewed by the Capital Health Research Ethics Board and was determined not to require ethical approval and informed consent.The rapid knowledge synthesis project was led by the members of the Nova Scotia Cochrane Resource Center. A team of methodology and content experts was recruited. Our team’s expertise included epidemiology, health sciences, literature searching, evidence synthesis, and project management. A nurse practitioner, an emergency physician, and an advanced care paramedic joined the team as content experts. A research assistant trained as an emergency department nurse assisted with scoping the literature about the model of care.What CEC-type models have been applied in jurisdictions outside of Nova Scotia?What components are included in these healthcare delivery models?How are CEC-type models assessed (e.g. what outcome measures are used)?We conducted a review of relevant practices and models in other jurisdictions in Canada to help map out the complex concept of a CEC . The objThe information from the jurisdictional/scoping review was used primarily to inform and operationalize the definition of CEC-type models to guide the scientific evidence search and synthesis rather than to inform the implementation of CECs in Nova Scotia. Initial scoping searches led to a list of 32 terms that describe healthcare delivery models similar to CECs, combining primary and emergency care in a single setting; these healthcare delivery models included, for example, ‘multidisciplinary centre’, ‘polyclinic’, ‘satellite clinic’, and ‘wellness center’. We collected information on these models by scanning publically available information online and confirming information by telephone, with site representatives. Canadian jurisdictions were selected for further exploration if they had a similar model of care and similar demographics to our Nova Scotia context.Digital resources were selected for relevant individual jurisdictions by a librarian researcher. Resources investigated included government and health department websites, individual health authority websites, research citation databases, and Google search engines . We selected relevant centres based on our CEC-type model definition, which was refined through a consultation with investigators and stakeholders. Potential centre descriptions were assessed by two researchers with conflicts resolved through a consultation among the research team. We contacted centres with particular relevance to the Nova Scotia context (i.e. had a similar model of urgent and primary care in one setting and similar population demographic characteristics). We clarified our understanding of individual jurisdictional practices, as described through web presences, with centre representatives by telephone. Information from telephone contact was integrated into the data extraction. We compiled a comprehensive set of 320 distinct elements potentially relevant to CECs, which were grouped into 24 searchable component domains. The subsection, ‘Important topics relevant to CECs’ lists the 24 components searched. This scoping activity defined important considerations for CEC-type models and directed our topics for searching the evidence and evidence synthesis. During this process, we iteratively refined an operational definition of a CEC, which was unavailable prior to this exercise. The final operationalization of a CEC is outlined in the subsection, ‘Definition of a Collaborative Emergency Centre’.Here is a list of topics identified as important for informing implementation of CECs, including the evidence of effectiveness of CEC-type models, and relevant structures and processes.Full CEC-type models*Original topic of interest: Hours of access to emergency or primary care servicesHealth care professional staff available in an emergency careHealth care professional staff available in a primary health careCollaborative practices in emergency or primary health care deliveryTele-health or teleconsultationDiagnostic services available in emergency or primary health care*Prioritized component topics:* Structure of emergency services (i.e. triage)Structure of primary care services Emergency protocols or use of standing ordersDestination and transfer planService infrastructureAmbulatory clinic servicesIn-patient beds availableFormal community health needs assessmentHealth promotion & prevention servicesSpecific governance structureFormal program evaluationSpecific program funding structureSpecific funding structure for health professionalsCommunity awareness campaignsRecruitment and retention programsAffiliation with an educational institutionInvolvement in conducting researchNon-Prioritized component topics*Revised literature searches and evidence synthesis occurred for five of the six prioritized components. The full CEC model remained a priority item despite a lack of evidence. Lack of a manageable, comprehensive search strategy for diagnostic services meant that this component could not be efficiently searched or synthesized within this rapid knowledge synthesis. A CEC-type centre focuses on the delivery of health care services including access to both primary care and emergency care through a seamless collaborative team approach.Primary care encompasses access to health promotion, wellness, chronic disease management, illness and injury prevention, and diagnosis and treatment of illness and injury.Access to emergency care includes initial emergency stabilization of life-threatening conditions, response to  the majority of urgent conditions and those conditions of lesser urgency.As operationalized by clinical stakeholders and policy decision-maker partners: A health care provider must be available on-site, and has a formal supportive relationship with other professional(s) or institution(s) elsewhere through telephone or technological means.We used an integrated KT approach, engaging clinical and policy decision-makers, to help refine our evidence summary questions and interpret findings relevant for CECs in Nova Scotia. This was executed through two half-day workshops with selected local stakeholders, including individuals from groups relevant to CECs in Nova Scotia and able to provide policy, operations, administration, and healthcare provider perspectives. This included 19 representatives from the Department of Health and Wellness, primary healthcare practitioners , emergency care practitioners , and members of the Cumberland County Health Authority involved in the development and/or functioning of the first implemented CEC . WorkshoA first stakeholder workshop was held once the project was underway in which CEC-model components identified in the jurisdictional/scoping review were presented. The goals of the stakeholder workshop were to discuss methods for evidence synthesis in general; to discuss the objectives and approach of our specific project; to refine definitions and priorities within the project; and to discuss key findings, key messages, and dissemination plans. The revised goals developed within the first workshop were (1) to define CECs through the identification of potential structures, processes, and implementation strategies of CEC-type models; and (2) to identify scientific evidence investigating the effectiveness of CEC-type models and their structures and processes.The set of 24 structures and processes, identified in the jurisdictional/scoping review, were presented at the first workshop. Stakeholders identified the components that they felt were most important for the model being implemented in the province. Prioritized components were identified through a consensus exercise: sheets of paper with individual structures and components were placed on the wall of the meeting room; everyone receiving an equal number of small dot stickers; attendees placed their dot stickers next to the structure or processes they considered most important; results were tallied and six structures and processes were clearly identified as the most important to consider, in addition to the overall concept of a CEC. These were prioritized as having critical importance to the functioning and local implementation of a CEC. A subsequent evidence synthesis was focused on these components .Comprehensive literature searches in peer-reviewed and grey literature were executed for each prioritized component (structures/processes). Given the broad nature of this review project and the limited time available to summarize the findings from all prioritized research questions, the primary goal was to identify recent, high-quality systematic reviews relevant to CECs and CEC-type models and each prioritized structure or process. Therefore, search strategies were first conducted with an established filter, if available  ) was conThe effectiveness of CEC-type models compared to traditional healthcare delivery models, andThe effect of specific CEC-type model structures or processes.The objectives of the rapid evidence synthesis were to describe the following:Effectiveness of CECs: For the overall question about the effectiveness of CEC-type models of healthcare delivery on health outcomes, we identified and screened 1,723 unique citations as title and abstract records and excluded 1,678 records. At the full text level, we screened 45 results available electronically; none of these met our criteria for inclusion in our summary of evidence. Zero reviews or studies were identified that assessed the effectiveness of CEC-type models as a complete concept. We identified 12 grey literature sources potentially providing evidence on the effect of CEC-type models of care delivery. Following thorough assessment, these 12 grey literature documents were also excluded.Effect of Structures/processes: To overcome the obstacle of a lack of evidence for ‘CECs’ from our initial database and grey literature search, we searched for evidence on the processes and structures identified in the jurisdictional/scoping review and prioritized by the researchers, content experts, decision-makers, and stakeholders in the first integrated KT workshop. The new search strategy included terms to capture the prioritized component parts and structures and processes for CEC-type models with the goal to gather evidence about the feasibility and potential effect of the component parts of such model.We imported citations identified in the searches into Endnote X4 reference management software , removedAn information specialist developed and executed comprehensive literature searches for systematic reviews on five of the six prioritized CEC structures and processes. PubMed, EMBASE, CINAHL, and The Cochrane Library  were searched between 15 August and 20 September 2011 for each prioritized structure or process question. Full search strategies for database searches for prioritized structures and processes are available on request. No date limits were set. One prioritized structure, ‘having a comprehensive set of diagnostic services available in primary or emergency care’, was not included in the knowledge synthesis as we were not able to develop a manageable, comprehensive search strategy for this concept.Four thousand five hundred sixty-six unique citations were identified and screened as title and abstract records. Four thousand two hundred fifty-three records were excluded in stages 1 and 2. In stage 3, we retrieved and screed 313 full text articles, excluding 258. Fifty-five systematic reviews were included in our summary of evidence. A range of 2–19 systematic reviews were identified for each of the prioritized CEC structures/processes Author conclusionsReview quality Quality of evidence includedData items extracted from the included studies: There was insufficient homogeneous data to allow quantitative synthesis of results. Instead, the content experts developed key messages and synthesized overall messages from the data extracted from the systematic reviews and studies included in the synthesis for the prioritized CEC structures and processes. They used worksheets developed to extract key messages on the effectiveness of each prioritized CEC structure or process. Content experts flagged any records that they felt were not fully relevant to the specific structure or process, or which they believed were not generalizable to our local Nova Scotian context; these studies were discussed by the review team and excluded by a consensus decision. A minimum of two content experts looked at each data table and extracted the messages. The review team compared the results and assessed them for consistency. Twenty-eight key messages were identified from the evidence assessed in our review. This included a range of 2–7 (median =5) key messages extracted for each of the prioritized searches. Examples of key messages are provided in subsection, ‘Examples of key messages’.There is good evidence from systematic reviews to support Nurse Practitioners working in primary care and in the ED with regard to patient satisfaction and compliance, with care at least equivalent to a physician-in-training.This review captured limited evidence from systematic reviews on the role of paramedics in the ED or primary care.There is limited but promising evidence from systematic reviews on the benefit of tele-consultation.Cost-effectiveness of these novel approaches is unknown.A growing number of CEC-type models are in operation across Canada and the world; Nova Scotia has the opportunity to share our experiences and to lead.Selected examples of key messages extracted from the included systematic reviews and studies identified through a comprehensive search of the published literature. Key messages and the data tables were discussed at a second stakeholder workshop. A checklist of structures and processes of CECs was provided to stakeholders to inform future implementation of new CECs.Feedback was collected from stakeholders on their satisfaction with the project scope and findings in the form of a brief anonymous survey collected on paper at the end of the workshop. Stakeholders were asked to comment on the project following the final presentation. Comments included ‘Excellent work compiling available research’, ‘Very informative for decision-making’, ‘It was collaborative with stakeholders’, and also ‘We need to better define our questions so we can have the research assist us to make operational level decisions’. When asked, ‘In your opinion, how useful will information provided today be for decision-making with regard to Collaborative Emergency Centres?’, 100% of participants responded ‘somewhat useful’ or ‘very useful’.http://www.nshrf.ca/sites/default/files/cec_rapid_knowledge_synthesis_short_report_2012.pdf) and (http://www.nshrf.ca/sites/default/files/cec_rapid_knowledge_synthesis_full_report_2012.pdf) (accession date 14 November 2012).Three reports were produced an executive summary (2 pages), a short report (16 pages) , and a fBetter Care, Sooner report by helping to address issues of emergency department overcrowding and long wait times to see general practitioners [We encountered several challenges in this project that are not atypical of initiatives to apply research evidence to policy decision-making. These included a broad proposed question on a complex healthcare delivery topic, and no direct research evidence was available. The establishment of CECs in Nova Scotia sought to fulfill a key commitment of the itioners  and to fitioners –40. The Our approach to meet these challenges was to clarify the operationalization of the healthcare delivery model, to break the model into component parts to search for evidence, and to prioritize structures and processes with stakeholders for the evidence summary. This approach could be useful to inform development and implementation of other unique, complex, or multicomponent healthcare services. Initial scoping searches led to a list of names and terms that describe healthcare delivery models similar to CECs. We worked with local content experts to identify the most useful evidence for our context. This helped to provide the best evidence available for the policy issue at hand. Consensus of key clinical stakeholders and health policy decision-makers on a definition of CECs to clarify the scope for communication was an important outcome for the project. The subsequent evidence synthesis was based on research evidence obtained from the revised search.Due to the complexity of the topic of interest and time constraints, our research team applied a rapid review approach with goals of transparency and practical relevance in mind. The rapid knowledge synthesis project used systematic and transparent methods that minimize potential bias. We streamlined the search and selection procedures by using an accelerated process, and focused on systematic review evidence when available, and studies published in the English language. We used similar methods to the ‘rapid review’ approach described by Khangura et al. , althougIn addition to summarizing the available evidence, this project developed researcher/policy decision-maker relationships and provided a local example of the potential value of using research evidence to inform decision-making. Including integrated KT components added to our timeline, however, we think that this was an important part of our project. Two factors that substantially increase the likelihood of health policy related research being used to inform policy are engagement between researchers and policy makers and timeliness of delivery of information . We usedAn important limitation of our project was that we did not comprehensively evaluate practical application of our evidence synthesis approach and did not assess the impact of the stakeholder interactions and evidence report. Future researchers should consider a parallel investigation that evaluates the usefulness and impact of policy-related evidence synthesis projects and decision-maker interactions on decision-making and the implementation of health services.The information and framework provided by our knowledge synthesis informed subsequent research projects evaluating CECs in our region. Ongoing research is assessing the impact of CECs and effect of specific healthcare delivery components, guided by our review. Policy decisions in our region, and other Canadian jurisdictions, are waiting for the results of these evaluations.Through participating in this first rapid knowledge synthesis, our research centre further developed existing and new relationships with provincial health policy decision-makers and clinicians. By working directly with these stakeholders, we were able to address limitations in the available evidence and identify areas where further knowledge was prioritized. This is one example of a rapid review project with a goal of providing useful and timely research evidence for decision-makers. We based our approach on available guidance and attempted to follow principles of transparency, limiting bias, and integrated KT. However, there remains a need for future studies to evaluate rapid review methods and to assess the effectiveness of different approaches to increase decision-makers’ use of research evidence.


To assess correlation between liver or spleen stiffness measurement by transient elastography (TE) and hepatic venous pressure gradient (HVPG) in patients with chronic liver disease as well find optimal and rule in/rule out cut-offs for prognosis of clinically significant (CSPH) and severe (SPH) portal hypertension.In this prospective study patients with different chronic liver diseases were included. TE was performed at the same day prior to HVPG measurement. HVPG was measured using catheter tip occlusion technique. Based on HVPG, patients were categorized into groups of CSPH and SPH. Cut-off values were established by applying ROC curve analysis.r = 0.75 and r = 0.62, respectively. Accuracy to detect CSPH was 88.7 % for liver stiffness of 17.4 kPa and 77.7 % for spleen stiffness of 47.6 kPa. Accuracy to detect SPH was 83.1 % for liver stiffness of 20.6 kPa and 77.7 % for spleen stiffness of 50.7 kPa. Liver stiffness <11.4 kPa could rule out CSPH with 55.2 % specificity and >21.9 kPa rule in CSPH with 74.4 % sensitivity. Liver stiffness <12.1 kPa could rule out SPH with 50.0 % specificity and >35 kPa rule in SPH with 58.2 % sensitivity.The study included 107 consecutive patients referred for HVPG measurement or transjugular liver biopsy. Successful spleen TE was performed in 99 of the patients. Liver and spleen TE strongly correlated with HVPG, Liver and spleen stiffness correlate with HVPG and could be used to predict CSPH or SPH. Spleen elastography was not superior to liver elastography in predicting portal hypertension. Portal hypertension is a common and important finding in patients with progressive liver disease of any etiology, leading to further complications and decreased patient survival , 2. DireWe performed a single center prospective study in the Gastroenterology Department at the Hospital of Lithuanian University of Health Sciences . Patients with different chronic liver diseases, who were referred for HVPG measurement or/and transjugular liver biopsy, were included in the study. As HPVG is an independent prognostic indicator in patients with chronic liver disease –7, patieThe routine clinical , hematological (complete blood count) and biochemical , alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin) measurements were performed at the same day prior to HVPG measurement. Abdominal ultrasonography was performed to exclude multiple focal liver lesions.Liver stiffness using FIBROSCAN®  device was measured on the same day before HVPG measurement. Patients were in fasting state. Procedure was performed in accordance with manufacturer’s recommendations. Interquartile range/median <30 % and success rate >60 % was considered as good quality criteria for TE. We performed 10 successful measurements for each patient. Liver elastography was unsuccessful in 10 patients (5.9 %), who were excluded from study.Assessment of spleen stiffness was performed by the same methodology used for liver elastography. The quality criterion  for spleen stiffness was the same as for liver stiffness. If typical elastography picture could not be found using FIBROSCAN device, exact point for spleen stiffness measurement was found using Toshiba Xario 200 ultrasound device .HVPG was measured in fasting state. None of the patients have received medications affecting portal pressure before HVPG measurement. The standard criteria for HVPG measurement was applied . HPVG waStatistical analysis was performed using SPSS 20.0. Kolmogorov – Smirnov test was used to check data normality. For descriptive statistics frequencies, means, medians and standard deviations were calculated. HVPG scores were compared with liver and spleen stiffness expressed in kPa using non-parametric Spearman correlation. Based on HVPG, patients were categorized into groups with and without CSPH or into those with and without SPH. Comparisons between patients with and without CSPH or SPH were made using Mann–Whitney Test. Areas under the receiver operating characteristic (AUROC) curve were calculated and points for best specificity and sensitivity established, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated. P-values less than 0.05 were considered to be statistically significant.The demographic and clinical characteristics of the patients are represented in Table p < 0.001) and for spleen TE . Comparisons between patients with and without CSPH or SPH was made using Mann–Whitney Test. The test revealed that there are statistically significant differences in liver and spleen stiffness between patients with and without CSPH or with and without SPH  for liver TE and 0.846 (p < 0.001) for spleen TE. AUROC curve for HVPG ≥ 12 mmHg was 0.915 (p < 0.001) for liver TE and 0.869 (p < 0.001) for spleen TE. AUROC curve values were higher for liver elastography than for spleen elastography and higher for CSPH than for SPH.The AUROC curves for each HVPG category are presented in Figs. Liver and spleen TE cut-off values for different HVPG categories were established and specificity, sensitivity, positive predictive value, negative predictive value and accuracy were calculated Table . To incrUp to date, several studies that evaluated liver elastography for prediction of clinically significant portal hypertension have been published , 13–17. Few studies investigated liver TE in SPH, where AUROC curve was found to be between 0.79 and 0.92 , 19, 20.Studies analyzing correlation of spleen stiffness measured by transient elastography with HVPG are still scarce. Colechia et al. found strong correlation between spleen stiffness and HVPG r – 0.88) . The mar8 . The mOur data show that liver and spleen elastography correlate well with HVPG, however liver stiffness has better correlation coefficient and AUROC than spleen elastography. We expected that spleen elastography might be more accurate than liver elastography for evaluation of HVPG subgroups because it reflects dynamic component of portal hypertension. Insufficient accuracy of spleen TE could be partially explained by influence of various shunts, arising during progression of portal hypertension. Taking into account other drawbacks of spleen elastography such as decreased success of spleen TE performance, missing cut-off points with 100 % specificity or sensitivity and less standardized procedure, it appears to suggest little benefit in clinical practice and no significant advantage over liver elastography. The wide variation of liver transaminases in our patients cohort could lead to higher transient elastography values and consequently to higher cut-off, as noted in different studies analyzing correlation of TE with liver fibrosis . HoweverOur study revealed that both liver and spleen stiffness measured by transient elastography correlate with hepatic venous pressure gradient. However, spleen elastography has no advantage in comparison to standard liver elastography for prediction of clinically significant or severe portal hypertension. Liver stiffness <11.4 kPa could rule out and >21.9 kPa rule in clinically significant portal hypertension. Liver stiffness <12.1 kPa could rule out and >35 kPa rule in severe portal hypertension.


Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder of childhood. Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in approximately 80% of JMML patients. Distinct clinical features have been reported to be associated with specific gene mutations. The advent of genomic studies and recent identification of novel genetic mutations in JMML are important not only in diagnosis but also in the management and prognosis of the disease. Herein, we present 2 patients with JMML harboring different mutations, NRAS and c-CBL, respectively, with distinct clinical features and different therapeutic approaches. Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder that accounts for 2%-3% of all pediatric leukemias ,2,3,4,5.Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL, the genes involved in the RAS-MAPK pathway, are found in approximately 80% of these patients . The advIn the past, the only known curative therapy for JMML was hematopoietic stem cell transplantation (HSCT), but recently it was reported that some patients have clinical improvement and long-term survival without any treatment ,14,15,16A 9-month-old male was admitted with complaints of fever, bloody diarrhea, and recurrent lower respiratory tract infections of 3 months in duration. His physical examination was normal. The complete blood count analysis was as follows: hemoglobin of 9.4 g/dL, white blood cells of 39.7x109/L (with neutrophil predominance), and platelets of 185x109/L. Immunological and serological testing excluded immunodeficiency and viral infections. Bone marrow aspiration showed myeloid lineage predominance with slight dysmyelopoiesis. Cytogenetic analysis of the bone marrow sample revealed a normal karyotype and a negative result for the BCR/ABL fusion gene. During follow-up, he began to suffer from diarrhea, febrile episodes, and painful vasculitic skin lesions with no infectious origin. Mild thrombocytopenia, monocytosis, and myeloid precursors on peripheral blood smear appeared 6 months after his first admission. Analysis of hemoglobin electrophoresis revealed increased hemoglobin F (23%). Diagnosis of JMML was made according to the current WHO diagnostic criteria . The genA 17-month-old female presented with fever, failure to thrive, and recurrent respiratory tract infections of a few months in duration. She was 71 cm tall (<3rd percentile), weighed 7.5 kg (<3rd percentile), and had an occipitofrontal head circumference of 43 cm (<3rd percentile). Physical examination revealed broad forehead, mild hypertelorism, short upturned nose, prominent philtrum, mild retrognathism, pallor, petechiae, hepatomegaly , and splenomegaly . The complete blood count analysis showed leukocytosis (53.7x109/L), monocytosis (11.1x109/L), anemia (Hb: 8.9 g/dL), and thrombocytopenia (platelets: 46x109/L). Peripheral blood smear showed a leukoerythroblastic picture, dysplastic monocytes, and monocytosis (23%). Bone marrow examination revealed cellular smears with myeloid hyperplasia, features of dysmyelopoiesis, and presence of 3% blasts. Cytogenetic studies of the patient revealed a normal karyotype with absence of the BCR/ABL fusion gene, monosomy 7, or any other chromosomal abnormality. Hemoglobin F level was 3%. JMML was diagnosed according to the WHO criteria [JMML is clinically a heterogeneous disease . AlthougPatient 1 was found to have NRAS mutation. RAS proteins are small GTP-binding signaling molecules that control cell proliferation, survival, and differentiation . The actMutations causing alteration in the structure of CBL protein have recently been associated with various myeloid malignancies, including JMML ,27,28. PIn conclusion, JMML is phenotypically and genotypically a heterogeneous disease. Despite the aggressive clinical course observed in most patients, some patients may have a mild clinical course. Recent developments in identifying molecular lesions have revealed the importance of genotype-phenotype correlation in this disease, which is critical for tailoring the management. Every patient with a possible diagnosis of JMML should be screened for underlying molecular lesions.


Many of the world’s life threatening diseases  could be prevented by eliminating life-style habits such as tobacco use, unhealthy diet, physical inactivity and excessive alcohol use. Incorporating evidence-based research on methods to change unhealthy lifestyle habits in clinical practice would be equally valuable. However gaps between guideline development and implementation are well documented, with implications for health care quality, safety and effectiveness. The development phase of guidelines has been shown to be important both for the quality in guideline content and for the success of implementation. There are, however, indications that guidelines related to general disease prevention methods encounter specific barriers compared to guidelines that are diagnosis-specific. In 2011 the Swedish National board for Health and Welfare launched guidelines with a preventive scope. The aim of this study was to investigate how implementation challenges were addressed during the development process of these disease preventive guidelines.Seven semi-structured interviews were conducted with members of the guideline development management group. Archival data detailing the guideline development process were also collected and used in the analysis. Qualitative data were analysed using content analysis as the analytical framework.The study identified several strategies and approaches that were used to address implementation challenges during guideline development. Four themes emerged from the analysis: broad agreements and consensus about scope and purpose; a formalized and structured development procedure; systematic and active involvement of stakeholders; and openness and transparency in the specific guideline development procedure. Additional factors concerning the scope of prevention and the work environment of guideline developers were perceived to influence the possibilities to address implementation issues.This case study provides examples of how guideline developers perceive and approach the issue of implementation during the development and early launch of prevention guidelines. Models for guideline development could benefit from an initial assessment of how the guideline topic, its target context and stakeholders will affect the upcoming implementation. Non-communicable diseases, such as cancer, cardiovascular disease and diabetes are responsible for 60% of all deaths globally, killing roughly 35 million people each year. The WHO estimates that over a third of all cancer cases and up to 80% of heart disease, stroke, and type 2 diabetes cases could be prevented by eliminating known risk factors, such as tobacco use, unhealthy diet, physical inactivity and the harmful use of alcohol . With evOne way to facilitate the use of evidence in clinical practice is the development of clinical practice guidelines, hereafter referred to simply as ‘guidelines’. Guidelines are defined as “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options” . The prihttp://www.guideline.gov/), national programs (Scottish Intercollegiate Guidelines Network) and societies  .Our analysis of the development of the Disease Prevention Guidelines shows that implementation challenges were identified and addressed by guideline developers. Several of these activities and approaches i could be condensed into four themes: 1) Broad agreements and consensus about scope and purpose; 2) Systematic and active involvement of stakeholders; 3) Formalized and structured development procedure; and 4) Openness and transparency in the specific guideline development procedure. Two additional factors were perceived as influencing developers’ choices for addressing implementation issues; the preventive guideline scope and guideline developers workload. Table Archival data state that the need for disease preventive guidelines was initially raised as a political initiative, based on national public health policy. This policy was launched by the Swedish Parliament in 2002 and specifically targeted the role and responsibility of the health service providers to improve their performance in health promotion . In paraRespondents described how hearings and spoken agreements with a broad range of interest groups  were used to identify and settle on a feasible focus and objectives for the Disease Prevention Guidelines. The developers considered these collaborations and agreements to be a significant component for implementation success, as they prompted a readiness, both among guideline developers and among target users, on what the guidelines may come to imply.“The goal was to reach consensus over the country about which areas these guidelines should address as early as possible in the process. To direct health care in a top-down manner on how they should work. But guidelines are after all a soft law, there is no support in the  law. The NBHW cannot give penalties to health providers who do not adhere to the guidelines. If we do not collaborate with the users – in a broad sense – from the very beginning, clinical guidelines will stay on the bookshelves. If we fail to narrow them down and to have a realistic scope the main objective also fails, to reduce disparities across the country and the differences in the various groups of the population access to care.” .Steering documents and respondents described how different actors were involved in the process during different stages of the development process Figure . AccordiThe Disease Prevention Guideline development involved 70 individuals organized in six operative groups: the guideline development management group (6), a prioritization group (25) and four expert groups (39). The expert groups were staffed based on their expertise in prevention and one or more of the four life-style areas. Expertise in the fields of scientific methodology, health economics, ethics and communication/linguistics were also made available to the guideline development group.Health professionals, experienced in disease prevention in clinical settings, were involved in the process of prioritizing. The task of the prioritizing group was to rank recommended practices from 1 (highly recommended) to 10 (not recommended) based on the severity of the condition, efficacy of the method, and cost-effectiveness. With the goal of involving a variety of stakeholders, the developers tried to obtain wide representation in the prioritization group, equal gender representation, and accordingly engaged professionals from different parts of the country, professional groups and knowledge areas. A majority were also trained researchers. The meetings with the prioritization group were organized to facilitate active participation with a decision process described as an adopted Delphi-method.The purpose of involving many people in the development process was associated with the implementation challenge. The network activities aimed to create broad agreements about the advantages and demarcations of disease preventing guidelines, as early as possible in the process. Secondly collaborations aimed to raise awareness about the upcoming guidelines and to engage influential actors in the early stages of guideline development. Finally, by including representatives of many different stakeholder groups the developers hoped to predict and plan for a wider range of implementation barriers.Throughout the development process influential organizations and networks  were involved through hearings, interviews, and piloting trials.“By collaborating with the health professional groups and the national network of health-promoting hospitals and incorporating them in our development process, in defining the main purpose and what lifestyle areas we should include and which we had to exclude, we aimed to plant a seed of change that would have the opportunity to develop as the guidelines developed. The initial efforts to identify the relevant health questions are crucial for implementation. And that starts on day one of the guideline development, with hearings and broad discussions. We thought ‘implementation’ from the very beginning.” .Respondents also described difficulties with involving the target population in the guideline development process. Traditionally, NBHW utilized patient/consumer organizations to recruit target populations . However, in the case of the development of Disease Prevention Guidelines, recruitment was difficult due to the focus on prevention. Respondents indicated that the target populations’ perspective was, to some extent, advocated by the health professionals serving in the prioritization group.During the final stages of guideline development, potential target users were involved in regional seminars and referral rounds where stakeholder views and preferences were sought. These views and preferences led to changes in the final version of the guidelines. Respondents described how stakeholder groups  raised different considerations regarding the future use of the guidelines. For example, stakeholders asked which health professional groups  would be responsible for the interventions recommended in the guidelines. Developers chose not to provide detailed answers about application of the guidelines, as they felt this was the most appropriate response in light of health providers’ independence from national governance. Respondents also argued that this standpoint stimulated local engagement and responsibility for the implementation of the guidelines.The NBHW guideline development model outlines a formalized procedure for preparing and completing the development of guidelines. Respondent comments underscored the need for a proscribed process and described how the definition of key guideline concepts required a systematic, preparatory procedure, where the basic concepts and terms were thoroughly scrutinized and defined. Respondents attributed the clarity of scope, purpose and concepts as important for encouraging target user’s motivation, understanding and future accuracy in guideline usage.“The concepts of health promotion or disease prevention were not very distinctly defined among us when the development of the Disease Prevention Guidelines was initiated. And if we were not clear about these basic concepts in the very beginning, we acknowledged the obvious risk that the guidelines would not be used as we or the literature we based the recommendations on intended. So we put a lot of energy and resources in defining the concepts and scope of the guidelines.” .Procedures for searching, assessing evidence and formulating recommendations were described in the model and in the final version of the Disease Prevention Guidelines and published on the NBHW website. A plan for evaluating and updating guidelines was provided with the final version of the guidelines. The guideline developers identified the use of systematic, transparent and scientifically sound methods as an essential factor for implementation, affecting future guideline users’ perception of the reliability and trustworthiness of the Disease Prevention Guidelines. Respondents stated that for some conditions/interventions there was a significant lack of evidence for appropriate grading approaches (according to GRADE). This problem was addressed through a formalized consensus procedure where existing evidence was complemented with proven, clinical experience.“It is easier to develop guidelines with a medical scope since they often include a higher amount of studies that fit our questions as developers, compared to guidelines with a preventive scope. It is more difficult when we do not have a good scientific basis and we have no health economic data. It is a flaw. Then it may be based on estimates, which is not optimal. We have handled the shortcomings of scientific data through developing a consensus process. We had a need to formalize and systematize proven experience in any sense.” .Respondents also described how the structured and rigorous guideline development process was demanding for the members of the guideline development groups. Respondents expressed that that it was a challenge to educate the participating experts and health professionals on the development model and follow it through.Several of the respondents described efforts to provide a rich description of Disease Prevention Guidelines development methods, as well as providing evidence and the health economic evaluations to clarify the basis for recommendations. The recommendations were linked to references and the background material and the final guideline document was published on the NBHW website. Respondents felt that these considerations were important for increasing transparency and reliability in the development process. Respondents also critiqued their own performance in the development process concerning ambiguous instructions to involved experts and health professionals. Respondents felt, that this issue provide some explanation for the delay in guideline completion. The process took five years and was delayed approximately ten months in relation to the original completion deadline.Communications and linguistics experts edited the final document to strengthen clarity and reduce ambiguities. Recommendations were described in summary form and included brief advice, counselling or qualified counselling as methods for changing lifestyle. The recommendations included a brief description of counselling methods, with more detailed descriptions given in a supplement. The guideline developers stated that it was very difficult to keep a balance between being clear and specific and being general enough to preserve the independence of the Swedish regional health care providers.The respondents underscored the value of the regional conferences as a means for addressing implementation challenges in the last phase of the guideline development process. In these conferences, regional health care providers and guideline developers met and openly assessed the implications of the Disease Prevention Guidelines. Some of the respondents stated that the regional conferences increased the health care providers’ awareness and responsiveness to the final version of the guidelines. Resource implications and potential implementation barriers were presented by health care providers during the final phases of the development process. By asking health care managers to assess consequences and resource implications of guideline implementation  they hoped to influence the target users to use of the Disease Prevention Guidelines at local, regional and national levels. Thanks to these regional considerations, a chapter detailing financial and organizational consequences of guideline implementation was presented, discussed and included in the final version of the Disease Prevention Guidelines.“The NBHW concluded that the guidelines required  changes in terms of human resources, steering documents, organization and reallocation of resources, education and skills and interaction with stakeholders within and outside the health sector.” (text extracted from the Disease Prevention Guidelines).Respondents also discussed how guideline developers  were asked to state their competing interests. Information about all members of the guideline development group was documented in the initial phase of the Disease Prevention Guidelines process and one member was excluded from the process based on the possibility of editorial dependence. The respondents felt these efforts to ensure editorial independence, increased guideline credibility, which in turn would enhance guideline implementation.Respondents described the process of disease prevention guideline development as challenging and explorative and a pioneering journey. The focus on prevention, challenged various components of the established model for guideline development at NBHW, being that is was a new type of guideline (preventive) that covered a large field and several topics . The generic characteristics of these prevention guidelines also created challenges relating to the multidisciplinary audience of guideline users and target population. Respondents described the process of defining the intended users and target population  as long and complex. Specific attention was given to this issue and criteria for identifying the target population were developed and piloted through the health-promoting hospitals network in Sweden.The long and complex process of guideline development was largely undertaken by the 3–4 people in the guideline development management group. Towards the end of the process, the workload increased and respondents described this last phase of development as intense and very demanding. Some respondents concluded that the strained work conditions led to a decreased focus on implementation and guideline applicability, thereby challenging developers’ ability to plan ahead in the process.Several key issues influencing the success or failure of guideline implementation are settled already during the guideline development process. It is therefore urgent to address these issues when planning for guideline development. Several basic features  have been shown to play an important role in guideline usage ,22, whicThis case study provides an in-depth look at the possibilities to address implementation challenges during development of prevention guidelines. Several activities and approaches for enhancing the achievement of guideline intentions were identified. Four areas for achieving guideline development success included: broad agreements and consensus about scope and purpose of the guidelines, a formalized and structured development procedure, systematic and active involvement of stakeholders, and openness and transparency in the guideline development process. In addition, the early involvement of the target audience and the involvement of a broad group of stakeholders made hypothetical trials and discussions of guideline implementation possible. This was one aspect of the development process that seemed to be especially important for prevention guidelines. To increase trustworthiness and the quality of the guidelines, rigorous and transparent methods were used for sourcing, prioritizing and incorporating information on health economics and ethics.The NBHW’s main task is to develop guidelines and recommendations in a credible way and, through collaborations, transparency and support, to stimulate implementation. However, the NBHW is restricted in its influence, due to a limited mandate as a government agency among rather autonomous county councils and municipalities in the Swedish health care system.To be used, it has been argued that clinical guidelines need to be established and integrated as a part of other health care quality improvement processes . This reFurther, this strategy of broad agreement may have contributed to raised awareness and motivation among guideline target users  in a way that boosts health care organizational readiness to alter their course in the direction of the Disease Prevention Guidelines. This strategy is supported by similar research. For example, Cabana et al.  identifiThe NBHW used its standard guideline development model with small adjustments to fit the prevention focus. The unusually complex development process that respondents found frustrating might reflect difficulties that come with matching public health interventions to the prevailing medical evidence system ,40,41.The involvement of patients or other target populations in guideline development is supported by WHO, the Guidelines International Network and AGREE ,22,52. HOur results are based on a single case study of prevention guideline development in a specific national context. There might be other aspects that need to be considered in other contexts and other ways of achieving a more conscious focus on implementation issues and preparations for implementation.This case study provides examples of how guideline developers perceive and approach the issue of implementation at an early stage in the life-cycle of prevention guideline development. The study also identifies characteristics of the process of developing guidelines with a preventive or public health focus. These include the complexity of addressing implementation issues in this area and the need for a decision model when addressing research not based on RCTs. The prevention focus influenced how implementation challenges were perceived and addressed. We conclude that guideline developers could benefit from including an assessment of what the specific focus areas  of guidelines may imply for their future use and how these areas impact the support needed for guideline implementation. Another question that should be explored in future research relates to how scientific evidence from the field of public health and preventive medicine should be operationalized and assessed in the guideline development process.It seems obvious that societies would benefit from utilizing available knowledge for addressing major threats to global health and innovative ways for improving life-style practices of large populations. But the path from evidence to changed health practice is an uneven one. Prevention guidelines might aid this process, but clinical guidelines will reach their potential only if they are known, adopted and used by their target groups. By illustrating how specific implementation challenges were perceived and addressed throughout different phases of guideline development, this study can provide some ideas for how to improve guideline development and support the implementation of preventive actions in health systems and health care practices.


Several laparoscopic approaches to the adrenal gland have been described. We prefer the lateral transabdominal approach. The aim of this study is to evaluate prospectively the presence of any anatomical and dynamic changes in the spleen after laparoscopic transperitoneal left adrenalectomy (LTLA), which can cause an increased risk of early and late complications.We have evaluated 21 patients before and 6 months after surgery in order to verify the possible presence of a wandering spleen. A clinical and instrumental follow-up  were performed. During US protocol, in supine, right lateral, and orthostatic position, the longitudinal and anteroposterior diameter of the spleen and the resistive index within 3 cm of the origin of the splenic artery in three different measurements averaged were measured. MR protocol evaluated, in supine and right lateral position, the splenic volume and its distances from the diaphragm dome and the lateral margin of the costal arch.p Values calculated for each parameter were not statistically significant. Our results confirm the absence of any anatomical and dynamic changes in the spleen after LTLA.The most common complications after laparoscopic adrenalectomy are well known and widely described. Our experience does not exclude the occurrence of a wandering spleen, but allows us to state that a rightful mobilization of the pancreaticosplenic block can avoid this event, and in agreement with other authors, the presence of a wandering spleen remains an isolated complication. The laparoscopic approach for adrenalectomy was first described by Gagner . Since iThe most accepted route to the adrenal gland is the laparoscopic transperitoneal approach, with the patient placed on hyperextended lateral flank , 4. On tn = 6), Conn’s syndrome (n = 4), pheochromocytoma (n = 6), nodular cortical hyperplasia (n = 4), and metastatic lung cancer (n = 1) . Statistical significance was taken to be a p value less than 0.05.From January 2008 to July 2013, we treated 71 patients with adrenal diseases in our Department. During the same period, 43 laparoscopic procedures were performed and of these we evaluated only the 21 laparoscopic left adrenalectomies, 9 males (42.86 %) and 12 females (57.14 %) with a mean age of 52.05 years (range 17–73).The characteristics of the patients are shown in Table A total of 21 LTLA were followed during the study period. Intraoperative and postoperative outcomes are summarized in Table p = 0.531). Neither anteroposterior diameter of the spleen (p = 0.394) nor the resistive index (p = 0.454) was significantly different in these reports. Also MR outcomes showed no difference between pre- and postoperative averages of splenic volume (p = 0.849), distance from its lateral margin to costal arch (p = 0.428), and its distance from diaphragm dome (p = 0.080). These results confirm the absence of any anatomical and dynamic changes in the spleen after LTLA (Table During the US protocol, no significant difference in the pre- and postoperative longitudinal diameter of the spleen was observed ( p = 0.39 nor the Since its introduction in 1992 , 12–16. The unique case of alteration of the spleen assessment after LTLA was described by Corcione et al. . He obse


Sexual activity before competition has been considered as a possible cause for reduced performance since ancient Greece and Rome. Recently, the hypothesis that optimal sport performance could be influenced by a variety of factors including sexual activity before competition has been investigated. However, few scientific data are available, with the exception of anecdotal reports of individual experiences. The present systematic review focused on the current scientific evidence on the effects of sexual activity on sport performance regardless of sport type. Data were obtained following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, using PubMed/MEDLINE, ISI/Web of Science, the Cochrane Collaboration Database, Cochrane Library, Evidence Database (PEDro), Evidence Based Medicine (EBM) Search review, National Guidelines, ProQuest, and Scopus, all searched from inception further, to broaden the search, no time filter nor language restriction have been applied. Also, the gray literature was mined using Google Scholar. Only relevant scientific articles reporting outcomes of athletic performance after sexual activity were considered. The impact of sexual activity before a sport competition is still unclear, but most studies generally seem to exclude a direct impact of sexual activity on athletic aerobic and strength performance. The most important aspect seems to be the interval from the time of the sports competition that affects negatively the performance if it is shorter than 2 h. There are possible negative effects from some possible concurrent wrong behaviors such as smoking or alcohol abuse. There are no investigations about the effect of masturbation in this context. There is a need to clarify the effects of sexual activity on competition performance. The present evidence suggests that sexual activity the day before competition does not exert any negative impact on performance, even though high-quality, randomized controlled studies are urgently needed. In ancient times, abstinence was considered the best method to ensure athletic performance and communion between body and spirit. Roman and Greek educators believed that great sacrifices could sustain success. This is probably the main reason why many coaches support the importance of sexual abstinence before sports competition , Evidence Based Medicine (EBM) Search review, National Guidelines, ProQuest, and Scopus. We used a string made up of the following key words with proper Boolean connectors: coitus, sexual intercourse, sexual activity, sexual climax, orgasm, masturbation, abstinence, sports, competition, exercise, physical activity, strength, speed, endurance, and performance. Truncated words with wild card option and Medical Subject Headings (MeSH) terms were used when appropriate. The platform “Primo Central Ex Libris UNO per tutti” was used.The current systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines , to avoid any bias. Disagreement was assessed using κ statistics, and resolved through discussion; a third reviewer (NLB) was involved if necessary.All manuscripts initially considered relevant by title and abstract were eligible for inclusion. The full text of the manuscripts was obtained to ascertain whether they satisfied the following inclusion criteria, detailed according to the PICO standard:P (population): athletes ;I (intervention/exposure): having sexual activity before a competition/match;C (comparison): studies comparing athletes reporting sexual activity vs. athletes not having sexual intercourse before a competition/match, where such comparison has been performed;O (outcome): impact of sexual activity on performance.Other inclusion criteria concerned the design , language , and time filter (none applied).In addition, to broaden our research, the references section of the selected articles was searched by hand to try and identify other relevant articles. Also, target journals were hand-searched. Further, to identify as many potentially relevant manuscripts as possible, a gray literature search using Google Scholar was performed. Finally, a search of theses and dissertations databases was performed.The search strategy is detailed in Table Two reviewers were contents experts (LS and GG), and one reviewer (NLB) was an experienced biostatistician/epidemiologist. The contents experts only assessed potential publications with respect to the appropriateness of the research questions tested. The biostatistician only evaluated the appropriateness of the methods employed. Disagreement was resolved by consensus.http://clinicalevidence.bmj.com/x/set/static/ebm/learn/665072.html).The strength of the body of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) evidence system  and 10 min (p < 0.01) during the recovery phase of a morning test 2 h after sexual activity. These differences disappeared during the recovery phase of the afternoon stress test performed approximately 10 h after sexual intercourse  or concentration (archery or pistol shooting) sports. Some coaches support the role of relaxation in improving coordination and peak athletic performance.The impact of sexual activity in sport, especially before sport competition, has been studied for the last 60 years. Many questions relate to athletes' performance, and several are not yet solved. Considering that top sports competition is undertaken by young adults, and therefore the expectancy of success is high, it is not surprising that the prospect that decreased athletic performance from sexual activity has been the object of interest by governing bodies, officials and coaches (Catania and White, The idea of a possible benefit of abstinence before sports competition is ancient, based on anecdotal evidence, and not sufficiently supported by the recent scientific literature. Only one study Fisher,  promotesFrom the present review, the major area of controversy concerns the principal aspect of the sexual intercourse and therefore if it can be considered correct on not, in terms of sports performance, to permit to have sexual intercourse before the sport competition. While some coaches continue to highlight the importance of abstinence, the literature does not support this belief. From the present review, only low powered studies of relatively poor scientific design have investigated the impact of sexual activity using specific tests to evaluate the effects on aerobic power and strength (Boone and Gilmore, At present, there has been little methodologically well-performed research on this topic. Also, given the variety of sports, and their different metabolic and situational differences, generalization is not possible. Most studies seem to have focused on male athletes: at present, there is a growing population of female athletes, and it is unclear whether gender differences could be evident. Finally, the attitude to sexual activity changes according to different cultures, countries and religions: this is a further variable that should be investigated.From the present review, doubts remain regarding the possible negative impact of sexual activity the night before competition. This aspect is considered important in sports, but there is insufficient evidence of the possible specific detrimental effect on the sports performance. In addition, no exhaustive data are available about the possible impact of the sexual activity on different kinds of sports, in terms of endurance or resistance performance, or in terms of team or individual sports. There are few scientifically sound data about the effect masturbation (Catania and White, LS conceived, designed and wrote the paper; GG revised the final version of the paper; JP and NB revised and contributed to improve the statistical analysis and approach of the systematic review. NM continuously supervised the manuscript. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Mosquito habitat-association studies are an important basis for disease control programmes and/or vector distribution models. However, studies do not explicitly account for incomplete detection during larval presence and abundance surveys, with potential for significant biases because of environmental influences on larval behaviour and sampling efficiency.Anopheles larvae in Ethiopia to evaluate the effect of six factors previously associated with larval sampling  on larval presence and detectability. Comparisons were made between: (i) a presence-absence logistic regression where samples were pooled at the site level and detectability ignored, (ii) a success versus trials binomial model, and (iii) a presence-detection mixture model that separately estimated presence and detection, and fitted different explanatory variables to these estimations.Data were used from a dip-sampling study for Riparian vegetation was consistently highlighted as important, strongly suggesting it explains larval presence (−). However, depending on how larval detectability was estimated, the other factors showed large variations in their statistical importance. The presence-detection mixture model provided strong evidence that larval detectability was influenced by sunshine and water temperature (+), with weaker evidence for algae (+) and water depth (−). For larval presence, there was also some evidence that water depth (−) and pH (+) influenced site occupation. The number of dip-samples needed to determine if larvae were likely present at a site was condition dependent: with sunshine and warm water requiring only two dips, while cooler water and cloud cover required 11.Environmental factors influence true larval presence and larval detectability differentially when sampling in field conditions. Researchers need to be more aware of the limitations and possible biases in different analytical approaches used to associate larval presence or abundance with local environmental conditions. These effects can be disentangled using data that are routinely collected  by employing a modelling approach that separates presence from detectability.The online version of this article (doi:10.1186/s12936-016-1308-4) contains supplementary material, which is available to authorized users. Anopheles mosquito larval presence or abundance to a suite of environmental factors related to the water body, such as depth [Accurately estimating site-specific mosquito larval abundance is central to vector control strategies for identifying breeding habitat characteristics , 2, deteas depth –8, tempeas depth , 9, algaas depth , 11, ripas depth , 10. Desas depth  or specias depth , 13, temas depth  and wateas depth , 15. YetThere is a need to incorporate more relevant biological detail into our modelling of malarial mosquito ecology . One relIn this study, data were used from a dip sampling survey in Ethiopia to examine if observations were confounded by imperfect detection, and determine if different environmental variables influenced larval presence compared to detection probability. First, as a comparison to previous studies, the data were analysed using the most common approach : i.e., aTwenty-six sampling sites in both artificial and natural water habitats were chosen in farming and grazing lands near to lake Abaya and Chamo in Ethiopia [Additional file Anopheles  or non-Anopheles (n = 676). Anopheles larvae were stored in 78 % ethanol for later morphological confirmation and showed that misclassification in the field was extremely low (~0.3 %). Of the Anopheles, 118 could be further classified, with 117 being from the Anopheles gambiae sensu lato species complex and one as Anopheles garnhami. There was large within-site variation in the number of larvae sampled during dipping, with 14 of the 23 sites where Anopheles larvae were found recording at least one dip during sampling that contained no Anopheles larvae .Larvae were identified in the dipper at the time of collection as Anopheles larvae: i.e., water pH, depth and temperature, as well as the presence of algae, amount of riparian vegetation and sun/shading on the water (see references above). Although other factors likely regulate Anopheles presence, the study specifically focussed on these variables for three reasons: (1) the aim was not to exhaustively determine the variables linked to Anopheles presence, but rather to demonstrate how different statistical models can change the interpretation of the importance of different variables, (2) to show how presence and detectability can be confounded, factors were used that varied in their probability of being related to these two processes , and (3) by limiting the search to factors that have been previously identified in at least one study as being potentially important, this avoided many of the problems associated with the exponential growth of the number of possible models during model selection [Site factors were measured at each visit that included water and local environmental variables previously linked to the presence or abundance of election .Anopheles larval survival; [For water variables, a portable water chemistry meter  was used to record water pH (±0.01) and water temperature (±0.5 °C) at each site following the manufacturer’s instructions. In addition, water depth (±0.5 cm) at the location of each dip sample was measured. Dip sampling was restricted to areas within sites with water depths of <200 mm in slow flowing or still water because this range of water depths may influence egg laying  in addiAnopheles based on particular explanatory variables. This method assumes that if larvae are present you will find them at least once during sampling, and thus does not account for detectability. The second model form  is also a logit-link binomial GLMM, but it incorporates information about the number of samples taken at each site and the number of dips in which larvae were found at each site; i.e., the response variable for each site contains two pieces of information, the number of dips taken  and the number of dips that contained larvae (‘successes’). Unlike the first model form, this allows for a range of probabilities in the response variable from 0 to 1. One consequence of this when examining larval-habitat associations is that the model will report relationships between not only factors related to larval presence, but also to the number of dip samples at each site containing larvae. Thus, the proportion of samples containing larvae at each site will be a function of factors related to presence/absence and detectability or abundance. Although results from such analyses may include explanatory variables that are related to detectability, they are unable to separate which factors are correlated to presence and/or detectability.Three modelling approaches were compared. The first two model forms represent methods that have been previously used in larval habitat-association studies , with thAnopheles larvae once detection was accounted for.The third model form (presence-detection mixture) explicitly separates factors relating to presence at a site from those of detectability. This essentially involves combining the first two model forms in a way that disentangles these key elements that determine whether larvae are found when sampling a water body: the probability of observing larvae in a scoop becomes the product of true presence  × detection probability . This means that by explicitly estimating detection probability based on the multiple samples taken at each site, the true presence can be derived from the field observations , the effect size of explanatory variables of interest were examined by using two commonly used approaches for model selection: multi-model inference using the likelihood framework  and stepPresence-detection models—the third model form—were implemented in a Bayesian hierarchical framework in JAGS  called There were clear differences between the predictions of the presence–absence and success-trial GLMMs that reflected the different information contained in their response variables. For the presence–absence model, there was strong evidence that riparian vegetation had a negative effect on larval presence (−) Table . There wThere was overwhelming support for modelling separate presence and detection components in a mixture model compared to the equivalent success-trial GLMM . This was based on separating the three variables identified in the success-trial GLMM analyses (riparian vegetation + sunshine + depth) into the different components of the mixture model: presence (riparian vegetation) and detection (sunshine + depth).The results from the full model  make it clear that sunshine + water temperature played a key role in detectability Fig. , while rBecause detectability was strongly influenced by sunshine on the water surface and water temperature Fig. , the numMosquito habitat-association studies aim to identify factors linked to larval presence or abundance as the basis for control programmes or distribution models , 10. HowThere were some clear differences in the results from the three analytical approaches. The first approach, and the one most commonly used (presence-absence logistic regression ), assumeThe second approach  used the same data, but retained the success versus trials sampling information within the response variable. Here, the explanatory variable explains not only larval presence at the site, but also the proportion of dips at a site that contain larvae. So it makes sense that the results retain the main effect identified in the first analysis for larval presence (riparian vegetation) and include additional effects that are likely to explain the proportion of dips at a site that contain larvae . This illustrates the importance of understanding the analytical method used when comparing habitat-association studies, as the results from these two methods contain different information despite using the same sample data. Interestingly between the first and second analysis, water depth went from being a factor with some support to a factor with strong support. This suggested that water depth operates on both presence and detection, with the success-trial analysis combining these effects. This interpretation is somewhat supported by the negative effects of depth on both presence and detection in the mixture model Table . The varThe final modelling approach explicitly modelled presence and detection separately, in a way that allowed explanatory variables to influence these estimates. Here some of the patterns from previous analyses are repeated: i.e., riparian vegetation explaining larval presence and sunshine explaining detection probability. Water depth and pH were again highlighted as being of likely importance to larval site presence. Interestingly, water temperature was a very strong predictor of larval detectability, while in the previous analyses temperature showed no indication of being important. Table Riparian vegetation had a clear negative relationship with larval presence Anopheles species prefer sun-exposed and shallow water bodies, although whether this is because of direct effects on larval development or indirectly through habitat quality is unknown [Many  unknown . The res unknown , this pr unknown  that mig unknown , 15 thatAnopheles live and often feed [A. gambiae larvae are more likely to dive to the bottom for food under conditions of lower surface food availability [Factors highlighted as influencing detection almost certainly operate through their impact on larval behaviour. Conventional dipping methods sample near the water surface  and, thuten feed , meaningten feed , 39, sinlability . In addiA. gambiae, but also between-species and between-life-stage comparisons [These results clearly show that detectability needs to be accounted for when undertaking mosquito larval surveys, especially if the density of larvae is low. Although the analyses focus on a presence–absence survey, detectability issues will also influence abundance estimates. Because environmental factors influence detection in different ways, and these factors are not uniform within the environment, systematic biases may emerge if they are not included when modelling habitat associations and species distributions. This has implications not only for studies of parisons , 4, 8 whAttempts to deal with incomplete detection are partly incorporated into current sampling protocols, with multiple samples collected at each site. This approach will be reasonably effective if enough sampling at each site is undertaken. However when mosquito abundance falls to low levels, the amount of effort to confirm site occupancy increases exponentially . Thus, a