Policy is a powerful tool for systematically altering healthcare access and quality, but the research to policy gap impedes translating evidence-based practices into public policy and limits widespread improvements in service and population health outcomes. The US opioid epidemic disproportionately impacts Medicaid members who rely on publicly funded benefits to access evidence-based treatment including medications for opioid use disorder (MOUD). A myriad of misaligned policies and evidence-use behaviors by policymakers across federal agencies, state Medicaid agencies, and managed care organizations limit coverage of and access to MOUD for Medicaid members. Dissemination strategies that improve policymakers’ use of current evidence are critical to improving MOUD benefits and reducing health disparities. However, no research describes key determinants of Medicaid policymakers’ evidence use behaviors or preferences, and few studies have examined data-driven approaches to developing dissemination strategies to enhance evidence-informed policymaking. This study aims to identify determinants and intermediaries that influence policymakers’ evidence use behaviors, then develop and test data-driven tailored dissemination strategies that promote MOUD coverage in benefit arrays.Guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, we will conduct a national survey of state Medicaid agency and managed care organization policymakers to identify determinants and intermediaries that influence how they seek, receive, and use research in their decision-making processes. We will use latent class methods to empirically identify subgroups of agencies with distinct evidence use behaviors. A 10-step dissemination strategy development and specification process will be used to tailor strategies to significant predictors identified for each latent class. Tailored dissemination strategies will be deployed to each class of policymakers and assessed for their acceptability, appropriateness, and feasibility for delivering evidence about MOUD benefit design.This study will illuminate key determinants and intermediaries that influence policymakers’ evidence use behaviors when designing benefits for MOUD. This study will produce a critically needed set of data-driven, tailored policy dissemination strategies. Study results will inform a subsequent multi-site trial measuring the effectiveness of tailored dissemination strategies on MOUD benefit design and implementation. Lessons from dissemination strategy development will inform future research about policymakers’ evidence use preferences and offer a replicable process for tailoring dissemination strategies.The online version contains supplementary material available at 10.1186/s43058-023-00396-5. Contributions to the literatureThis study will advance our knowledge of data-driven methods for developing and testing dissemination strategies to enhance policymakers’ use of research evidence.This is one of the first studies to examine policymakers’ perceived utility of tailored dissemination strategies.This is the first funded study examining dissemination strategy development and use for public insurance, and findings will advance efforts to improve access to evidence-based substance use treatment.This study will highlight evidence-informed decision-making behaviors across Medicaid and Children’s Health Insurance Program benefit arrays nationwide, including understudied programs in US territories.Policy is a powerful tool for systematically altering access and quality of healthcare services. But the “research to policy gap” represents a significant impediment to translating scientific knowledge about evidence-based practices (EBPs) into public policy, limiting widespread improvements in service and population health outcomes . Common The USA is in the midst of a more than 10-year opioid epidemic, driven by recent increases in fentanyl-laced drugs and inadequate access to life-saving substance use treatment . In 2021MOUD are first-line, evidence-based treatments for opioid use disorder that include buprenorphine , methadone , and naltrexone  . BuprenoNationally in the USA, there is momentum for federal policies that support access to MOUD for Medicaid/CHIP members. The Affordable Care Act identified substance use treatment as an essential health benefit and reinforced the Mental Health Parity and Addiction Equity Act requirements to remove benefit limitations on substance use treatment that are more restrictive than limits for medical/surgical benefits. Section 1006(b) of the 2018 federal Substance Use Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities (SUPPORT) Act requires all Food and Drug Administration approved MOUD be included as mandatory Medicaid state plan benefits . HoweverUS state Medicaid/CHIP agencies have flexibility in how they design and implement benefits. Benefit arrays set by Medicaid/CHIP agencies and contracted MCOs can cover MOUD while simultaneously restricting access to certain medications via utilization management policies including non-EBP medical necessity criteria and prior- and re-authorizations for certain medications. For example, 18 state Medicaid agencies require prior authorizations for injectable naltrexone, while 39 agencies require prior authorization for oral buprenorphine . “Fail fIdentifying the specific influences on and the sources of evidence from which Medicaid/CHIP and MCO policymakers derive guidance when designing benefits is critical to developing strategies that promote evidence-based MOUD coverage in insurance benefit arrays and for reducing health inequities. However, no research exists to describe key determinants of Medicaid/CHIP and MCO policymakers’ decision-making processes or strategies to improve their evidence use behaviors.Dissemination science offers an interdisciplinary approach to systematically test strategies to improve the translation of research to policy and increase access to healthcare generally and, in particular, MOUD for Medicaid and CHIP members. Dissemination science draws on theory from health services research, political science, public administration, communication, and marketing fields to investigate how EBPs can be optimally communicated to targeted adopters and implementers, such as policymakers, to inform decision-making processes , 38. DisEarly policy-focused dissemination research synthesized evidenced about the extent and types of evidence used in policymaking , 41, 42.This study will address these dissemination science knowledge deficits by conducting a US national study of Medicaid/CHIP agency and MCO policymakers’ to empirically identify key determinants, mechanisms, and preferences for evidence use. This study will solicit participation from policymakers in Medicaid/CHIP agencies across all 56 US states and territories and the more than 250 (and growing number of) contracted MCOs. We will use survey results to develop tailored dissemination strategies that promote evidence use when designing MOUD benefits (including utilization management policies) for adult and child members. Evidence use around Medicaid/CHIP MOUD benefits likely differs from evidence use for other populations and behavioral health practices. The historical politicization of Medicaid eligibility  and stigThis study aims to promote Medicaid/CHIP and MCO policymakers’ use of scientific evidence when designing MOUD benefits. The study aims and hypotheses are described below.Aim 1: Develop and administer a national survey to Medicaid/CHIP agency and MCO policymakers to identify determinants, mechanisms, and intermediary characteristics that influence their behavior seeking out, receiving, and using research evidence to define MOUD benefits.Aim 1 Rationale: Although the annual Medicaid Operations Survey collects data about Medicaid activities and priorities , these dAim 2: Empirically identify and describe subgroups of Medicaid/CHIP agencies and MCOs with distinct determinants and intermediary relationships that impact their use of evidence in MOUD benefit design.Hypothesis: Heterogenous classes (comprised of agencies/MCOs) exist with differential evidence use behaviors and intermediaries referenced when designing MOUD benefits for adults and youths.Aim 2 rationale: Medicaid/CHIP agencies are notorious for differences in structure and benefits for opioid use disorder treatment services , 57. OurAim 3: Design and assess the acceptability, appropriateness and feasibility of dissemination strategies, tailored to each latent class, to enhance evidence-informed decision-making for MOUD benefits.Hypothesis: Tailored dissemination strategies will have higher reported acceptability, appropriateness, and feasibility ratings than strategies that are not tailored to agency/MCO class needs and preferences.Aim 3 rationale: Dissemination strategies to effectively promote evidence-informed decision-making in Medicaid/CHIP benefits are needed. Prior research suggests that tailored dissemination strategies may be most effective for improving policymakers’ use of research , 60, butWe adhered to the Standards for Reporting Implementation Studies to describe study methods  Framework, which has demonstrated utility for investigating determinants and mechanisms across the nonlinear dissemination and implementation phases –63. In tver time .inner and outer contexts  and bridging factors  influence agency and MCO policymakers’ current and preferred processes for receiving and using evidence in policymaking across EPIS phases [inner context. On one level, it describes the nature of state Medicaid/CHIP agencies’ organizational settings where agency directors can rise through the ranks or can be politically appointed to carry out partisan agendas . Another level describes the organizational nature of MCOs. Both inner context levels consider how agency and MCO leadership, organizational characteristics, service environment , and quality and fidelity monitoring processes operate and interact to influence policymakers’ engagement in evidence-informed decision-making. The outer context includes influences at the federal  and state level  from leadership, state/federal policies , funding and contracting arrangements that impact the service environment, perceptions/stigma toward Medicaid/CHIP members, and advocacy groups that lobby for or against MOUD. Prior research on opioid use disorder treatment policy highlights the important influence that state legislators and governors have over access to care [outer context political entities to similarly influence Medicaid policymaker decisions about MOUD policies.An adapted EPIS framework Fig.  illustraS phases , 66. The to care –69, and outer context news and social media attention can influence inner context benefit design decisions. This study demonstrates how EPIS can be used to articulate multilevel, cross-context, policy relevant factors in dissemination research [Bridging factors [Innovation factors [This adapted EPIS framework considers how research , 71. Bri factors , 70 acknAim 1 will be executed as an observational cross-sectional survey design. Dissemination strategies will be pilot tested in aim 3 using a quasi-experimental design.The study will recruit Medicaid/CHIP agency staff from all 50 states, the District of Columbia, and 5 US territories  as well the more than 250 MCOs  contracted to administer benefits. Eligible participants will include agency/MCO leaders and staff whose work responsibilities include designing or influencing benefits for MOUD. Sample frames will be constructed for the eight staff types with ability to influence Medicaid/CHIP benefit and utilization management policies for MOUD: (1) Medicaid and CHIP agency Directors/Commissioners, (2) MCO executives, (3) Medicaid/CHIP agency and MCO Directors of Behavioral Health, (4) Medicaid/CHIP/MCO Directors of Policy, (5) Medicaid/CHIP/MCO Directors of Budget, (6) Medicaid/CHIP/MCO Healthcare Benefit Developers, (7) Medicaid/CHIP/MCO Pharmacy Benefit Developers, and (8) Medicaid/CHIP/MCO Utilization Management Policy Staff.A cross-sectional web-based survey will be administered to Medicaid/CHIP agency and MCO staff  to collect data on agency-level decision-making. Survey items will map to EPIS constructs to illuminate influences across outer and inner contexts. Survey items draw from existing reliable scales like the Implementation Leadership Scale , Purtle Several of the survey items have been used in prior studies examining legislators’ evidence preferences and behaviors. However, these items have not been tested with Medicaid/CHIP agency or MCO staff. To promote instrument relevance, clarity, and brevity, we will cognitively pre-test the survey with at least five different policymakers from Medicaid/CHIP agencies and/or MCOs before fielding the national survey. The cognitive pre-testing process will include conducting a phone or video call interview to verbally deliver the survey items and ask questions about each. Participants will be asked to think aloud about survey items, describe how they comprehend each item, retrieve information to respond, how confident they feel responding to specific items, and offer general impressions about the instrument . ParticiN = 791) using recruitment strategies that have been successful in prior surveys with policymakers, including the development of data frames with contact information for each stakeholder type, and by introducing the study at relevant conferences where these policymakers convene [Eligible Medicaid/CHIP agency and MCO policymakers will receive an email containing a brief study description and invitation to participate in the Qualtrics online survey. Conservatively, we estimate there are at least 2261 eligible respondents from the 56 agencies and 267 MCOs . This approximation of eligible respondents is based on estimating that each agency/MCO includes one staff member working in each of the following eight key informant roles: Medicaid/CHIP Directors or Commissioners, MCO executives, Behavioral Health Director, Policy Director and Budget Director, Healthcare Benefit Developer, Pharmacy Benefit Developer, and Utilization Management Policy Staff whose purviews include MOUD. Directors/executives will be permitted to designate a staff member to complete the survey on their behalf. Prior survey work by Grogan et al. achieved a 92% Medicaid agency response rate , 77. We  convene .Eligible policymakers will receive an email containing a brief study description and the online survey link. This email will also include the opportunity identify additional eligible policymakers via snowball sampling methods. Email messages will include a request for the recipient to provide contact information for other potentially eligible staff in their agency/MCO. They will be able to provide this contact information via email and/or by submitting the contact information via a separate weblink embedded within the email. This snowball sampling recruitment method will allow the research team to review the contact information and assess each referred staff members’ eligibility before emailing them the study description and online survey invitation. Eligible policymakers will receive up to 10 emails asking them to complete the linked survey. After the fourth email, we will conduct up to eight calls with policymakers to ensure they received the survey link, answer their questions, and encourage them to complete the survey. We will not compensate participants since state employees cannot accept such payments.Benefit policies are developed with input from Medicaid/CHIP agency and MCO leaders who set organizational priorities and the mid-level staff who use their own knowledge to draft policy language . Thus, wMedicaid/CHIP agencies are notorious for differences in structure and benefits for opioid use disorder treatment services , 57. OurA preliminary review of the literature and research team expertise in Medicaid policy was used to identify key variables from the outer context  and inner context , and intermediary types that will serve as indicators of latent classes. Given the exploratory nature of this aim, we will consider additional indicators as data are collected and analyzed.The latent class analysis will be conducted using data collected from individuals representing all respondent agencies and MCOs. Latent classes are best identified through a combination of statistical fit and conceptual interpretation , 59. A fPower calculations for LCA models are underdeveloped and unreliable , 84. HowValidation of LCA results will also depend on the proportion of the entire study sample that best fits into each identified latent class. For example, if one of the classes identified is very small, we will compare descriptive statistics for each class to identify meaningful differences between them as well as the conceptual underpinnings of each class. Descriptive summaries of each class will be presented to a small group of policymakers  to solicit their insights on the results. Their feedback will help determine if the identified latent classes really represent the different types of policymakers they have worked with throughout their careers at different Medicaid/CHIP agencies and MCOs.There are some known differences in state Medicaid policies and such differences suggest that it is likely that two or more relatively distinct latent classes could be identified. However, if meaningfully distinct latent classes of evidence use profiles for adult Medicaid and/or adolescent CHIP MOUD benefit are not found, such a result would be an insightful finding in and of itself. For example, a lack of distinct latent classes would indicate that evidence dissemination strategies could be developed for broad audiences of policymakers rather than needing to develop multiple tailored strategies for different groups of policymakers. Then, the outcomes of such strategies could be examined across multiple states. Thus, a finding of distinct latent classes or no latent classes will provide meaningful insights into evidence use behaviors for Medicaid/CHIP policymakers.Using latent class predictors identified in aim 2, we will design adult  and child  class-specific policy dissemination strategies with the common aims of (1) facilitating evidence exchange between agency and MCO policymakers and research-driven intermediaries and (2) promoting the uptake of evidence-based MOUD benefits. Thus, dissemination strategies will serve as new bridging factors to share evidence between outer context entities and inner context policymakers .Dissemination strategies require clearly defined sources, messages, channels, and audiences , 90 and α = 0.85, 4 items), appropriateness , and feasibility  have demonstrated discriminant content validity and structural validity [We will identify one agency/MCO from each latent class to participate in the pilot study testing tailored dissemination strategies. At least two latent classes are expected to be identified in aim 2. We expect that fourteen individuals from agencies/MCOs represented in each of those classes will participate in the pilot study. Each participating agency/MCO will be assigned strategies tailored to their class  and strategies tailored to the other classes . Participants will complete a brief survey evaluating the acceptability (satisfaction with content/delivery), appropriateness , and feasibility (practicability for using presented evidence when designing MOUD benefits)  of each validity .d = 1.00. Descriptive statistics will characterize the overall perceptions of each dissemination strategy and we will explore between agency differences and between stakeholder type differences in strategy ratings.Although inferential statistics are not appropriate for pilot studies –96, grouThis study will illuminate key determinants, mechanisms, and intermediaries influencing policymakers’ evidence-based decision-making behaviors and preferences when designing benefits for MOUD, shedding light on the “black box” policymaking processes in Medicaid/CHIP benefit arrays –54. ThisThe methodology proposed in this study will also yield generalizable findings about Medicaid/CHIP agencies and MCOs on a national level. This is critical since the external validity of many Medicaid studies is limited due to heterogeneity in agency structures and policies , 57. StuSurvey methods introduce the potential for non-response bias if individuals who do not respond to the survey differ in meaningful ways from those who do participate. To reduce nonresponse, the research team will make several attempts to solicit participation and secure survey responses. We have already conducted preliminary informational interviews with multiple Medicaid policymakers to discuss the best approaches to introduce the study survey and generate participation from their peers; these suggestions will inform the development of all outreach materials. To address nonresponse issues, we will create a category for each variable and attempt to model non-response/missing data as an additional category of indicators used in the LCA. This will enable us to explicitly model missing data as a category for each indicator rather than having the LCA simply “ignore” any missing variables.Self-reported survey data can also invite recall and social desirability biases. However, these survey methods are established, practical approaches for obtaining data on policymakers’ evidence-informed decision-making behaviors , 98. AltIt is important to note that the SUPPORT Act requirement for Medicaid agencies to include all MOUD in their benefit arrays is set to expire in 2025 . It is uResearch on effectively translating scientific evidence into policy is necessary to resolve long-standing health disparities, including in accessing high quality substance use treatment. It is not enough for researchers to publish scientific findings in peer reviewed journals; new strategies for communicating evidence with policymakers are needed to bridge the research to policy gap. This study offers an opportunity to generate practical dissemination strategies that are responsive to policymaker needs, as opposed to designing strategies that are designed for theoretical impact . The resAdditional file 1.


Over the past decade, an industry has emerged around Clinical Practice Guideline (CPG) development in healthcare, which has increased pressure on guideline-producing organisations to develop CPGs at an accelerated rate. These are intended to improve the quality of care provided to patients while containing healthcare costs and reducing variability in clinical practice. However, this has inadvertently led to discrepancies in CPG recommendations between health organisations, also challenging healthcare providers who rely on these for decision-making and to inform clinical care. From a global perspective, although some countries have initiated national protocols regarding developing, appraising and implementing high-quality CPGs, there remains no standardised approach to any aspect of CPG production.A scoping review of the literature and document analysis were conducted according to Joanna Brigg’s Institute methodology for scoping reviews. This comprised two qualitative methods: a comprehensive review of the literature  and a document analysis of all national and international guideline development processes .A set of clear principles and processes were identified as crucial to CPG development, informing the planning, implementation and dissemination of recommendations. Fundamentally, two common goals were reported: to improve the quality and consistency of clinical practice (patient care) and to reduce the duplication or ratification of low-grade CPGs.Consultation and communication between CPG working parties, including a wide range of representatives  is essential. Further research is required to establish the feasibility of standardising the approach and disseminating the recommendations. In the last 20 years, the number of Clinical Practice Guidelines (CPGs) produced for healthcare has risen exponentially . CPGs arOver the past decade, an industry around CPG development has increased efforts by guideline-producing organisations to develop CPGs at an escalated rate , 7. To fVarious problems with guideline development processes have been reported in the past, which impede their optimal use and impact at the point of care . In 2003Since then, approaches to CPG development have made significant strides in refining and describing the requirements for high quality CPGs , 14, altIn an effort to ensure CPGs are robust and reliable as intended, a range of ‘next stage’ approaches to CPG development have emerged in recent years, all of which focus on optimising methodological transparency , 19. WhiEvidence suggests that increased collaboration between local, organisational and regional CPG working parties may improve the quality of health services on a global scale . SimilarThis review aimed to explore evidence underpinning the processes and principles of health-related CPG development, including handbooks and methodological guidance publications. Although evidence exists on specific health organisations’ approach to CPG development, exploration of their principles and processes may inform the development of a standardised approach that is acceptable to healthcare providers and health organisations worldwide, and CPGs that present best practice recommendations based on the latest evidence.“What is known about approaches to clinical guideline development in healthcare? To achieve this aim, two specific objectives were identified:• Establish the various principles applied to clinical guideline development; and• Determine the processes by which this occurs.This review aimed to elicit information on what is known about clinical practice guideline development in healthcare. Our review question was: To address the objectives above, we employed two complementary qualitative research methods: the first comprised a scoping review of the literature, and the second included document analysis of all national and international guideline processes regarding CPG development. Although different, both methods are considered interrelated qualitative approaches for conducting thematic data analysis and interpretation .Two methodological approaches guided the scoping review. First, the Joanna Briggs Institute (JBI) methodology for conducting scoping reviews , which pOriginal articles, reviews and health-related CPG documents from inter-governmental and non-governmental organisations were included if they met the inclusion criteria.The review was not limited to a specific healthcare population. All health organisations and disciplines within healthcare were included in this review.Given the review was designed to elicit information about intercollegiate guideline networks and other approaches relevant to clinical guideline development, we considered documents that provided a definition or description of CPG development relevant to the health industry.We considered all literature relevant to clinical guideline development.We considered all open-access literature published between 2000–2022. Health-related policy and government documents, reviews and primary research articles written in English were considered for inclusion. Additional literature and health-related CPG documents were also sought from health-related organisational websites.We attempted to identify records that defined or discussed approaches to health-related CPG development. Following a cursory search, date parameters were set between 2000–2022, as seminal work on guideline development was noted during this timeframe. Records were included if they identified key stakeholders of health-related clinical guideline development networks, mapped CPG processes or discussed key principles of CPG development. Documents were excluded if they were not published in English or relevant to the review question and objectives. Following screening, available full texts were retrieved, reviewed and tabulated by author one see Fig. .Fig. 1PRIn accordance with the JBI approach, we employed a three-step search strategy. First, a preliminary search was conducted in Cumulative Index to Nursing and Allied Health Literature (CINAHL), a broad database that indexes high-quality literature relevant to nursing and allied health, health research, healthcare and health education. The search terms used were health* AND  AND . This preliminary search was followed by an analysis of the keywords in the title and abstract of retrieved documents and the index terms used to describe the documents. We identified the following search terms, which were added to the initial search terms applied: “clinical care process specifications”, “caremaps” and “practice guidelines”. Suitable MeSH or Subject headings were not identified.Second, we conducted a database search using all identified keywords in CINAHL, Scopus and PubMed. Third, a manual search through the reference lists of all identified documents was conducted for additional relevant documents. The first author also researched health-related websites for policy or government documents relating to CPG development. This was conducted by entering various combinations of the original search terms in Google, followed by a manual search for references to CPGs in the articles retrieved during the initial search. The following CPG developers were identified: “Health and Medical Research Council of Australia (NHMRC)”, The Joanna Briggs Institute (JBI)”, “American Agency for Healthcare Research and Quality (AHRQ)”, “Guidelines International Network (GIN)”, UK National Institute of Health and Care Excellence (NICE)” and the “Scottish Intercollegiate Guidelines Network (SIGN)”.Given the diversity and multidisciplinary nature of the data, quality appraisal was performed initially by categorising the sources of data into two different groups. The first group comprised peer-reviewed articles, the second group included data sourced from all other documents . We considered the sources in the first group to be of higher quality, given that the documents were subjected to peer review. This was performed by author one, who assessed each article's methodological quality for inclusion against the JBI CASP checklist. Articles that scored > 6 out of ten were deemed high quality and included in the review.Data extraction was undertaken in three stages by the first author. First, key information from each text was obtained. This included author(s) names, publication date, country, record type, aim(s) and key concepts or principles presented in the results. Second, thematic analysis was conducted on the first data set (which comprised peer-reviewed articles) following Braun and Clarke’s six-stage guide to thematic analysis . This waSix articles were included in this review, and five health-related organisational documents, which collectively presented current information on various approaches to CPG development in healthcare. Of these, perspectives and approaches were included from Australia, Canada, the United Kingdom (UK), Asia, South Africa, Scotland and the United States of America (USA). All articles discussed, to some extent, processes by which guideline development groups function, collaborate and work through the guideline development process. Similarly, all documents explained the processes and methods used in CPG development , was consistently reported to include individuals from professional, organisational, regional and national levels , 37. IntClinical guideline development was reported across all articles to involve both a technical process (searching and appraising evidence-based research) and a social process (translating evidence-based research into CPGs) , 25, 37.Specific guideline development processes were commonly reported as a series of steps or phases that mapped the pathway from CPG development to dissemination. This included: identifying the need for and scope of the CPG, recruitment of an interdisciplinary working group and engaging with key stakeholders, searching for evidence, developing best practice recommendations, external review and consultation, dissemination and implementation of recommendations , 34, 35.Group decision-making was generally reported as a formal process for reaching group consensus , involviAn aspect consistently reported across all articles was the need to consider conflicts of interest (COI), given that financial, intellectual and other investments in all areas of healthcare could lead to biased judgement regarding the scope or topic of focus. Conflicts of interest were also noted to arise during the guideline development process, potentially introducing substantial bias in the final recommendation . SimilarOne national and five international health-related documents were examined to extract definitions and other relevant information regarding approaches to CPG development –11, 36. There was international consensus that guideline development groups should be multidisciplinary, gender and geographically balanced, representing all those likely to use the intended clinical guideline  , 11, 36.CPG development was described by two organisations as a set of critical principles that presented the best available evidence with resource constraints in mind, taking into account the anticipated end users or groups most likely to be affected by the recommendations , 11. Sim• Guidelines should be outcomes focused and involve a cycle of interdependent activities: Planning and development, dissemination, implementation and evaluation.• Guidelines should be flexible and capable of adapting to varying local and global audiences.• Guidelines should be based on the best available evidence and include a statement about the strength of recommendations.• Guidelines should demonstrate essential qualities such as validity, reliability, clinical applicability, flexibility and clarity.• Guidelines should be continually revised to maintain currency and update in light of new evidence or intelligence.• Collaboration between local and national agencies, inter-governmental organisations and relevant expert opinion  is preferential.Each of the six documents included in this review individually outlined a set of core principles considered essential for developing CPGs. When compared, the attributes underpinning good CPG development were identified, and the following summations were made:Combined word frequencies in all documents indicated that good principles of CPG development primarily relied on multidisciplinary collaboration, communication and a standardised approach see Fig. .Fig. 2ThAll documents, to some degree, referred to CPG development as a process of identifying and implementing interventions (including practices) to optimise the best possible health outcomes for consumers –11. This• Planning and defining the scope of the guideline.• Formation of an inter-disciplinary, and where possible inter-organisational, guideline development panel.• Defining the purpose of the guideline and intended target audience.• Reviewing the literature and developing recommendations for practice.• Stakeholder consultation  and peer review.• Presentation and publication of the CPG.• Dissemination and implementation.• Evaluation and ongoing revision.Formulation of a set of key processes for undertaking CPG development activities was established using iterative comparison and evaluation, which resulted in eight core processes consistently reported as essential to CPG development:The thematic analysis results identified five common processes for CPG development: Planning, consultation, implementation, evaluation and dissemination see Fig. .Fig. 3ThTo date, there has been no exploration or evaluation of the varying approaches to CPG development worldwide. Yet, clinicians, consumers and healthcare organisations rely on these to guide clinical practice. The findings of this review identify the core principles and processes that can be used when developing CPGs, including the underpinning ethical and value-based activities that should guide the decisions of national and international guideline committees.This review intended to present a clear overview of what is known to date about various approaches to CPG development in healthcare and the implications of this on health services, care providers and clinical outcomes. As a result, a set of clear principles and processes were identified as crucial to guideline development activities, which inform the planning, dissemination and implementation of CPGs. Fundamentally, all documents included in this review articulated two common goals: to improve the quality and consistency of clinical practice (patient care) and to reduce the duplication or ratification of low-grade CPGs. Unequivocally, clinicians want to provide patients with evidence-informed care. To achieve this, they require guidelines that reflect the evolving body of scientific evidence in combination with clinical expertise and patient preferences. This parallels evidence-based practice (EBP). Yet, in many areas across the health sector, knowledge translation and inconsistency in both policy and practice continues to hamper the closure of the evidence-practice gap in healthcare , 38. To Globally, a surge in publications around CPG development indicates the increasing interest and research focus on facilitating EBP. It also confirms a rise in the number of CPGs developed for local, regional and system-level use . These aAn international team of guideline developers and researchers, known as the AGREE collaboration , sought to address this issue by creating a generic instrument, initially labelled the AGREE and then later amended to the AGREE II, which was designed to assess the rigour of guideline development processes . HoweverAt the core of this review, the requirement for consultation and communication between parties and collaboration from a wide range of representatives  were highlighted as essential. These concepts resonate with other well-established national and global guideline development working parties , 42, 43,This review has some limitations. There are possibly other guideline development organisations  that may not have published principles or processes for CPG development yet provide clear guidance on these aspects for end users. As such, they were not identified during the search and screening process. There may also be other published literature to support the findings of this review that were not sourced. However, the broad inclusion criteria for this scoping review ensured all records (both published and web-based) were considered for inclusion and were not limited to document type.Our review aimed to elicit information on what is known about CPG development in healthcare. From the records included in this review, there is strong concordance as to the key principles and processes of CPG development: Establish a multidisciplinary guideline development group, have a wide range of experts from both local and regional contexts, identify the problem and develop recommendations that are applicable and transferrable across sites and health systems, collaborate and consult with persons both in and external to the guideline development group. While these key principles and processes are both useful to health service providers and decision-makers in healthcare contexts, there remains ongoing inconsistency in clinical practice and quality of care between health organisations around the world, excessive duplication of low-grade CPGs also wastes resources and the efforts of care providers who rely on CPGs to inform their decision-making and clinical practice. To address this persistent issue, further research is required to establish the feasibility of standardising the approach and resultant recommendations made to CPGs.


Leishmania (Mundinia)enriettii is a species commonly found in the guineapig, Cavia porcellus. Although it is a dermotropic species,there is still an uncertainty regarding its ability to visceralise duringLeishmania life cycle.L. enriettii (strainL88) to visceralise in lungs, trachea, spleen, and liver of C.porcellus, its natural vertebrate host. Here, we investigated the ability of C. porcellus, animals were experimentallyinfected for viscera removal and PCR typing targeting hsp70gene. Animals were infected sub-cutaneously in the nose and followed for 12 weeksusing histological (hematoxilin-eosin) and molecular tools (polymerase chainreaction-restriction fragment length polymorphism - PCR-RFLP). To isolateparasite from L.enriettii, we performed additional in vivoexperiments. During 6th week PI, the parasite was isolated from the spleenconfirming previous histopathological and PCR observations. Histological analysis revealed intense and diffuse inflammation with thepresence of amastigotes in the trachea, lung, and spleen up to 12 weekspost-infection (PI). Molecular analysis of paraffin-embedded tissuesdetected parasite DNA in the trachea and spleen between the 4th and 8thweeks PI. At the 12th PI, no parasite DNA was detected in any of the organs.To confirm that the spleen could serve as a temporary site for Leishmania enriettii (strain L88) was able to visceralisein the trachea, lung, and spleen of C. porcellus. Leishmania enriettii is a parasite belonging to the subgenusMundinia,,Cavia porcellus. Othermembers of this subgenus include Leishmania (M.)macropodum,Leishmania (M.) martiniquensis,Leishmania (M.) orientalisLeishmania (Mundinia) sp. (Ghanaisolate).Mundinia,Leishmania and Viannia subgenera.,,Culicoidesspp.).,L. enriettii is yet to bedetermined, although Lutzomyia monticula has been suggested.L. enriettii strains in theState of Paraná, Brazil. It did not detect the parasite in the wild reservoirsreinforcing the role of C. porcellus as a the main, if not the only,domestic host.An interesting feature of the members of this subgenus is their ability to infectnon-phlebotomine vectors, such as ceratopogonids  is its ability to specifically infect guinea pigs.C. porcellus, L. enriettii causes a severeulcerated cutaneous lesion (CL) that heals over time. For this reason, C.porcellus was used as a model for CL for many years.,L. enriettii did notuse salivary glands extracts (SGE) until recent biological and immunopathologicalstudies.,Lutzomyia longipalpis SGEs modulated the infection by preventing theattraction of monocytes and CD163 macrophages throughout the course of infection. After12 weeks post-infection (PI) regardless the use of SGEs, the CL lesions healedspontaneously. Early and recent reports,,,,L. enriettii to visceralisein guinea pigs after several inoculation routes. It was, however, unknown if thisphenomenon is permanent or transient requiring fast transmission to vector(s).Several research groups have been studied L. enriettii, there are severalaspects of infection that still need to be better elucidated. In our previous study, wereported the proinflammatory features of L. enriettii infection in theskin.L. enriettii, we provide a more detailed study on theimmunopathological aspects in different organs using molecular and histologicalapproaches in C. porcellus viscera.Over the 75 years since the discovery of Histology evaluations - Trachea, lung, liver, and spleen wererecovered from our previous study.5promastigotes of L. enriettii reference strain (MCAV/BR/1945/L88)in 0.1 mL of phosphate-buffered saline (PBS) supplemented with 1/2 salivary gland ofL. longipalpis. Animals (n = 12) were followed for 12 weeks andeuthanised with an overdose of ketamine and xylazine (500 mg/kg and 100 mg/kg) atweeks four (n = 3), eight (n = 3), and 12 (n = 3). Negative controls included threeanimals euthanised at weeks four, eight, and 12. Tissue fragments were fixed in a10% buffered formalin solution, pH 7.2 for 48 hours. Paraffin blocks were cut in amicrotome (3-4 μm) and mounted on slides prior to routine histological analysis(hematoxylin-eosin - HE). Histological slides were qualitatively analysed underlight microscopy as previously reported.Parasite detection in paraffin tissues - Paraffin-embedded tissuesamples  were subjected to DNA extractionhsp70 gene .In vivo experiments - For visceralisation confirmation, sixexperimental animals were divided in two groups including: (1) two negative controlsinoculated with (PBS+SGE) and (2) four animals infected with L.enriettii. Guinea pigs were infected intradermally with 105L. enriettii promastigotes in PBS + SGE from L.longipalpis as previously reported.Parasite recovery and typing - Tissue fragments from trachea,lungs, liver, and spleen were seeded in NNN-Schneider’s medium and incubated at26ºC. Cultures were followed until appearance of promastigoteforms. Positive cultures were expanded for DNA extraction and polymerase chainreaction (PCR) typing using hsp70 gene as above. The ~1,300-bpfragment was subjected to digestion with HaeIII (New England) andrestriction profiles were analysed in a 4% agarose gel.Ethical considerations - This work was approved by the EthicsCommittee for Animal Use (CEUA), Oswaldo Cruz Foundation (FIOCRUZ) (LW-24/19). Youngmale C. porcellus were bred according to the InternationalStandards for the Breeding and Use of Laboratory Animals,Histopathological evaluation - Histopathological changes in thetrachea, lung, spleen, and liver of infected animals were analysed at the 4th, 8th,and 12th weeks PI using HE. Negative controls with uninfected animals did not showany histological alterations  (L88 strain ofL. enriettii), trachea (Tra) (4th week PI) and spleen (4th and8th weeks PI). At 12 weeks PI, no DNA was detected in the organs  was similar tothose caused by typical viscerotropic species in hamsters’ liver.,L.infantum, where only chronic interstitial pneumonitis with notablethickening of the interalveolar septa were noted.L. enriettii can visceralise andcause immunopathological events in trachea, lungs, and spleen up to 12 weeks PI.While our previous paperConsistent with previous observations, we detected amastigote forms of hsp70 gene has beensuccessfully used as a tool for discriminating L. martiniquensisand L. orientalis.L. enriettii fromtrachea to spleen in the first 8 weeks PI. After two months, it disappears from thetrachea and increases its presence in the spleen. No parasite DNA was found at 12weeks PI suggesting a possible clearance of the parasite in the organs. However,this result is conflicting with the histopathological findings that showedamastigote forms in the tissues during this period. This also does not correlatewith what occurs in the skin of the same animals, whose lesions reached their peakat 6 weeks PI and are completely healed at 12 weeks.,,To confirm this, paraffin-embedded tissues were assayed for the presence of parasiteDNA using molecular tools. Recently, L. enriettii can reach theviscera, cause severe histopathological alterations that decrease, but notcompletely disappear, for example, in the skin 8-12-weeks PI. It is interesting tonotice that under our controlled experimental conditions the animals were apparentlyactive and did not have any clinical signs.,,L.enriettii is yet to be determined.Based on our data, it is likely that Leishmaniainfantum (viscerotropic) can cause cutaneous lesions in Honduras,Central America.Leishmania donovani, another viscerotropic species, can causeunusual dermal lesions after therapeutic failure known as Post-kala-azar dermalLeishmaniasis (PKDL).Leishmania amazonensis(dermotropic). It was isolated from lymph nodes from dogs showing symptoms of caninevisceral leishmaniasis, similar to that caused by L. infantum,L. martiniquensis, another member of theMundinia subgenus, causes not only LV, but also CL inHIV-positive patients.L. enriettii showed adual profile being able to cause dermotropic and viscerotropic lesions under ourexperimental conditions in its main host C. porcellus.Leishmaniasis comprises a wide spectrum of clinical manifestations including diseasescaused by dermotropic and viscerotropic species. Depending on the region,intraspecies tropism variations may occur. For example, in vivo infection targeting the spleen as a possible source forparasite isolation and observed the same pattern of lesion development as reportedelsewhere at four-eight weeks PI.,To confirm our previous histological and molecular findings, next we performed anLeishmania enriettii (strain L88) visceralised in C.porcellus causing severe lesions in lungs, trachea, and spleen. Despitethe clinical cure of the skin lesion, the parasite was not eliminated from thetissues during the 12 weeks PI as judged by the histological studies. In contrast tothe infected field-collected guinea pigs, L. enriettii underlaboratory conditions did not cause any clinical sign to them. This finding is ofepidemiological importance, since those animals may be potential sources for vectorinfection facilitating parasite maintenance and spreading in the environment. Thisphenomenon warrants further investigation to address the role of apparentlycutaneous healed animals in L. enriettii transmission.


It was possible to prepare a Standard Operating Procedure for Surgical Count, train the nursing team, carry out educational intervention for surgical teams.there was an improvement in complying with the standardized procedure at the first moment and worsening in the period related to the pandemic. New efforts began again, including a self-instructive online course combined with first-time strategies. It is an essential practice for intraoperative patient safety, considering that, although it is a rare event, retained surgical item (RSI) at the end of surgery is an event that can have serious implications.Counting items, such as needles, compresses and instruments, in the operative field should include the review of fields, hampers and garbage men so that the count of items offered has no discrepancy with the number found at the end. Standardized procedures for surgical counting should be widely disseminated and rigorously complied with between teams, including registration, conference by at least two people  and at least two moments (when items are included in the field and at the end of surgery). For discrepant counts, before closing the operative wound, after a second count, a radiograph can be performed to identify the item in the cavity.Currently, manual counting is the main one performed in most hospitals, and needles are known to be the least counted items.The JBI has published a document that gathers the best evidence for surgical counting. The Evidence Summary Operating Room: Surgical Counts presents recommendations with the respective levels of evidence, based on the principle that there should be high priority for developing more effective and standardized procedures, for preventing the event of forgetfulness/RSI, considering not only the computerization of the process, but human aspects, such as a multidisciplinary approach, construction of standardized institutional procedures and perioperative team training-4. Multidisciplinary engagement is a significant challenge, since, for successful counting, the entire surgical team must be involved, and nursing professionals have a leading role in favor of patient safety with the safe execution of the counting process. Nursing-led initiatives can not only optimize processes related to surgical counting, but also ensure that personal factors related to surgical professionals or institutional, such as availability of time between surgeries, printouts for records and other resources for counting, interfere minimally with the success of a care instruction for this practice-6. An evidence-based guideline should guide the nursing practice of surgical counting, in order to ensure patient and professional safety. The present study brings as guiding question strategies to implement and maintain assets and with good Standard Operating Procedures compliance for evidence-based best practices.Although there is evidence available in the literature for best practices, it is still a challenge for surgical centers to ensure the correct counting of surgical itemsTo report the implementation and maintenance of an evidence-based Standard Operating Procedure for surgical counting performed at a teaching hospital.This is a report of an evidence implementation project for surgical counting, carried out in a university hospital, initiated in December 2017, and subsequent cycles for better performance of the implemented standardized procedure and maintenance of better results. The university hospital has two operating rooms, a central one with ten operating rooms and an outpatient unit with four rooms, and it serves fifteen surgical specialties, with highly complex procedures.The report is divided into the evidence implementation project and four other cycles after implementation, related to maintaining improvements.. Considering that, at the time, there were no service statistics on cases and no institutional guidelines for surgical counting, a sample of open surgeries was audited to estimate possible failures in counting and to schedule the first intervention to implement a standardized evidence-based procedure. The following steps were collected from institutional records, mainly from the VigHosp hospital surveillance system.The implementation project was reported in detail in another publicationFor the first step, in which the surgeries were audited, and for subsequent data collection, the research was presented to the institution’s Research Ethics Committee, assessed and approved prior to collection.The hospital routine did not require the counting of instruments or needles, and surgeons, at the time, could “dismiss” the surgical count. The printed forms used were not suitable for counting recording. Errors and near misses were not recorded as adverse events in the hospital system, and the nursing team was not yet familiar with the system and did not understand the responsibility of the records or their relevance. Discrepant counts were rarely recorded, even in medical records, and radiography was not requested – the team was unaware of this “possibility”.The implementation project had a diagnostic step, followed by an intervention step and an intervention assessment step, with a total duration of six months, between December 2017 and March 2018.. At this step, JBI tools were used, such as the JBI Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP), an audit and feedback tool. A team was selected for the project, data collection was carried out from the initial audit of open surgeries and process failures were assessed. The team consisted of four nurses involved in collecting data, carrying out the necessary interventions and assessing the best practices implemented in a new audit cycle with the same criteria used in the first moment. For the audit steps, interviews with technicians and nurses, medical records and participant observation were used. The audit criteria were: 1. The nurse in charge is informed when there is a discrepant count; 2. Fields for incorrect count logging include pertinent event details; 3. A nurse reviews the incorrect count record; 4. There is follow-up of incorrect counting case; 5. A standardized counting approach is strictly performed; 6. A multidisciplinary approach for the surgical team is used for counting; 7. Yields between people in the operating room are limited, to ensure the same team during surgery and on most counts; 8. Reconciliation of surgical count is done before the patient leaves the operating room.The diagnostic step corresponds to a baseline audit, for which eight audit criteria were developed to assess the surgical counting process steps at the institution. The criteria were taken from a summary of evidence for best practices in surgical counting from the JBI. When implementing the SOP, banners were made and quick face-to-face meetings were held with all teams, who received pamphlets about the practice. In March 2018, another audit cycle was conducted with the same criteria. In this cycle, the incorporation of technologies that facilitate surgical counting, such as bar code readers, was also attempted, but there was no success due to institutional reasons.Thirty open surgeries were audited in a period of one month, with several specialties. A matrix was listed containing barriers and strategies to be used to improve the indicators, using the JBI GRiP. The results were discussed with the heads of the surgical specialties, and an evidence-based SOP was developed for surgical counting in the hospital. The SOP was prepared by the researchers, together with nurses from the unit who were involved in the implementation project, using the JBI Evidence Summary as a reference. The SOP underwent adaptations by the elaboration group to the reality of the sector, in order to make it feasible with the available resourcesThere was low compliance with best practices in five criteria , and no surgery had a full-room counting SOP, as it did not include radiography. There was only one case of communication to the student-counting nurse. In 53% (16) surgeries, there was interaction between the surgeon and the technician for the surgical count. The only criterion considered with high strength was 7, with 77% (n=23).Sistematização da Assistência de Enfermagem Perioperatória).The main barriers to surgical counting identified were lack of knowledge by the team on the relevance of counting, resistance to changing a practice and inadaptation of forms to records. To improve the records, adaptations were made in the form of the Systematization of Perioperative Nursing Care , greater theoretical workload and short videos with simulated case discussions based on cases from the hospital itself. Operating room, obstetric center and medical team professionals were invited to participate. There was low number of medical professionals and nursing professionals at the obstetric center. Moreover, there were brief interventions with the nursing team to discuss the cases found with each new notification. The online course was made available on the platform, being included in the admission training for the unit, and a version was included in the institution’s patient safety course, mandatory for residents and new professionals.From the beginning of the previous cycle, in August 2021 until the month of March 2022, there was no record of forgetting compresses or discrepant counts – near misses.. Regardless of manual or computerized instrument count, team training, considering the multidisciplinary surgical team, is decisive for the event avoidability-2. Furthermore, the dissemination of a culture of surveillance and notification is decisive for monitoring errors and near misses and for directing interventions.Current evidence of higher recommendation to avoid RSI events involves more light, behavioral technologies than harsh technologiesThis project aimed to implement in the service best practices of surgical counting to promote safety for professionals and patients. It was observed that, although the initial efforts and their positive results, the maintenance of efforts is of paramount importance. Personnel renewal should be considered and, in the case of a university hospital, this is a very relevant factor due to the participation of students and residents in the surgery, renewing the team periodically. Although the JBI methodology recommends more periodic follow-up audits using the same baseline audit criteria, the main indicators of the need to reinforce SOP compliance in the present study were the error and near miss records. The outcomes towards which efforts are directed are key indicators of the need for strategies to maintain implementation results; however, the application of the same audit criteria allows more accuracy to identify which points in the process are more flawed and need more attention.One of the positive results was the SOP preparation for hospital surgical counting. Even with decades of existence, until the beginning of this project, the hospital did not have a SOP like this. The relevance of SOP lies not only in improving safety, but in influencing the training of medical and nursing students and residents, who are potential disseminators of evidence-based practice learned beyond the hospital walls.Another positive result was the reformulation of the SAEP registration form. The current instrument is the third version and is suitable for recording all events from needle, compress and instrument counts to discrepant counts., 4, 5, 6. To this end, institutional documents must be prepared in order to standardize the time to carry out the counts, the form of registration, actions to be taken in discrepant count and the relevant flows involved.Evidence for surgical counting is currently available and there are many discussions and efforts towards implementing best practices. In the study presented here, it is not possible to directly state the percentage of reduction of near misses found, since the practice of notification was encouraged, which was not carried out before. However, the research team, over the course of that year, was able to verify that the educational intervention improved the outcomes of compliance with the protocol, improved count records, improved the investigation of discrepant counts and the use of intraoperative radiography in the investigation.Another initiative with a strategy similar to the present implementation project achieved a 50% reduction in the number of incorrect and discrepant counts.As a positive point, we highlight the change in culture that counting is a waste of time and the empowerment of nursing technicians to stop failures in the process. Emergency surgeries have the highest failure rate, however the study’s surgical center only attends to elective surgeries, and the hospital does not have an emergency service, 7-8.There are still barriers in the service to requesting intraoperative radiography, with some professionals trying to avoid wasting time for the next surgery. However, it is clear to all nursing that it is not an option not to follow the SOP guidelines. Some professionals still try to dispense with counting instruments, claiming it is not an important step, and counting sharps has lower compliance. There is an incentive for the presence of a nurse in the room at the end of the surgery, since it is known that the presence of nurses increases SOP compliance and reduces noise and distractions. During the follow-up period (December 2017 to March 2022), the hospital was unable to include technologies to improve the surgical counting process, such as the use of bar codes, scanners, radiofrequency detectors, although they are new technologies in several countries, and there is already evidence for their use, or even electronic medical records for recording intraoperative activities, 6, 9. Although errors and near misses have been reported, it is not possible to take the number of notifications as an absolute value for the number of cases in the outliers, considering that item recount takes place several times a week with reconciliation and few cases are reported. The reported cases of discrepant counts were only those where there was no reconciliation or where there were difficulties in counting with the surgical team. Finally, the feedback of the results to the teams can be cited as a limitation of this study, since the return of notified cases is made only to the head of each specialty involved, and there is no wide dissemination of cases, case studies, discussions and dissemination of statistical data. The discussion of cases is of paramount importance to complete the educational process, 10.As limitations of this study, it is considered not including radiology professionals in the training steps, although there are international recommendations for them to be includedWith the project of implementation and maintenance of a standardized procedure based on evidence, it was possible to collaborate with the SOP elaboration for surgical counting in the hospital, adapt the forms, train the nursing team, carry out educational interventions for the surgical teams, foster the culture of surgical counting for patient safety and empower nursing technicians to take a leading role in the process. Additionally, the dissemination of this work, the result of years of collective efforts, can contribute to motivating improvement processes in other surgical centers and expanding the safety culture among operating room professionals.Surgical counting should be implemented as a best practice in an evidence-based operating room and international guidelines. The initial phase of implementing evidence-based best practices struggled at a time when there was no routine, no written guidelines, and no culture focused on the relevance of surgical counting and event recording. The JBI methodology for implementing best practices based on evidence was instrumental in initiating and guiding this reported process.With the implementation project and the SOP assessment and maintenance cycles, there was a change in the service’s culture, with broad awareness and promotion of critical thinking, in addition to mere instrumentation.There was an improvement in SOP compliance at the first moment and worsening in the period related to the pandemic. New efforts have resumed, including self-instructing online course coupled with first-time strategies.


Dirofilaria immitis is a parasitic nematode endemic in the Mediterranean countries, which causes cardiopulmonary dirofilariosis in wild and domestic animals. Despite being recognized hosts of D. immitis, wild carnivores such as wolves and foxes are frequently disregarded when considering a potential role in the transmission of these zoonotic nematodes. In Portugal, studies available regarding D. immitis circulation are scarce, likely underestimating its relevance. To add knowledge on this, we sought to assess Iberian wolves (Canis lupus signatus) and red foxes (Vulpes vulpes) from northern Portugal for D. immitis antigenemia and microfilaremia.Blood samples from 42 Iberian wolves and 19 red foxes were collected, during 2010–2012, in Peneda-Gerês National Park. Antigenemia was searched for by rapid antigen detection test kits (Uranotest Dirofilaria ®). Microfilaremia was assessed by polymerase chain reaction (PCR). Nucleic acids were extracted from blood using QIAamp® DNA Mini Kit (Qiagen), and DNA was screened for the presence of microfilaria using a conventional PCR targeting the 5.8S-internal transcribed spacer 2–28S regions, followed by bidirectional sequencing, Basic Local Alignment Search Tool analysis and phylogenetic analysis.D. immitis antigenemia. Nevertheless, two wolves were positive for D. immitis microfilaremia  as revealed by PCR and confirmed by bidirectional sequencing.Three red foxes had antigenemia, with an occurrence of 15.8% , while showing no evidence for the presence of microfilaremia. No wolf samples presented evidence for Dirofilaria microfilaremia in wolves does not necessarily correlate to an endangerment of the infected animal's health, positive individuals can act as a reservoir for further infection if the intermediate mosquito hosts are present. To the best of our knowledge, one single study had reported that wolves were suitable Dirofilaria hosts, but microfilaremia have never been reported.Although  Dirofilaria immitis  is a parasitic nematode, which causes cardiopulmonary dirofilariasis in wild and domestic canines and felines, and also pulmonary dirofilariasis in humans ), Acanthocheilonema reconditum (578 bp), Brugia malayi (615 bp), Brugia pahangi (664 bp), Brugia timori (625 bp), Dirofilaria immitis (542 bp), Dirofilaria repens (484 bp), Mansonella ozzardi (430 bp) and Onchocerca volvulus (470 bp). For all reactions, a total of 5 μl of genomic DNA was added to 12.5 μl Xpert Fast Hotstart Mastermix (2×) with dye , 5.5 μl of deionized sterile water and 1 μl (10 μM) of each of the DIDR-F1 and DIDR-R1 primers in a 25-μl final volume of the reaction mixture. The reactions were carried out in an automatic DNA thermal cycler 100 , including negative and positive controls . The PCR amplification products were visualized by Xpert Green DNA Stain direct  fluorescence after electrophoresis in a 1.5% agarose gel at 100 V for 40 min. To confirm species identification, all amplicons of expected size were sequenced bidirectionally for genetic characterization. Briefly, amplicons were purified with GRS PCR & Gel Band Purification Kit , and bidirectional sequencing was performed by Sanger method, using the respective primers. Sequences were manually corrected using the BioEdit Sequence Alignment Editor v 7.1.9 software package, version 2.1 , and further analyses were performed by comparison with the sequences available in the NCBI (GenBank) nucleotide database (http://blast.ncbi.nlm.nih.gov/Blast). Phylogenetic analysis was performed using MEGA version 6.0 software [O. volvulus, D. immitis and D. repens obtained from GenBank were used for the phylogenetic analysis. Maximum likelihood (ML) method was applied. The ML bootstrap values were estimated using 1000 replicates with Tamura 3‐parameter as the correction model, estimated as the best substitution model by MEGA version 6.0 software. We deposited the 5.8S-ITS2-28S of D. immitis sequences recovered in this study in GenBank.To detect microfilaremia, DNA was extracted from blood using the QIAamp® DNA Mini Kit , using an automated QIAcube nucleic acid extractor . DNA was stored at − 20 °C until further analysis. A negative extraction control was processed along with each batch of 12 samples. DNA specimens were initially screened for the presence of microfilaria by using a conventional PCR targeting the 5.8S-internal transcribed spacer (ITS) 2–28S regions of the genome. Briefly, pan-filarial primer pair − DIDR-F1 and DIDR-R1 − amplifying products with distinct molecular weights were used to differentiate nine filarial species, namely D. immitis infection, out of the 61 wild carnivores screened by rapid antigen detection, three had D. immitis antigen circulation in blood . All three wild carnivores showing antigenemia were foxes, yielding an occurrence of 15.8% (95% CI 3.4−39.6). The same 61 animals were again tested for microfilaremia through conventional PCR, and only two wolves  tested positive, with a prevalence in the whole sampled lupine population of 4.8% (95% CI 0.6 − 16.2). Both positive samples yielded amplicons with 542 bp, being presumptively positive for D. immitis. After bidirectional sequencing, the consensus sequences showed to be identical. Basic Local Alignment Search Tool confirmed the identity (100%) of D. immitis in both lupine samples. The following accession numbers were assigned to the sequences obtained in this work: OK632269 and OK632270. One of the sequences obtained (OK632270) spanned only 77 nucleotides (nt); hence, phylogenetic analysis was performed with the other sequence. Phylogenetic analysis based on the 460 nt partial region of the 5.8S-ITS2-28S regions showed clustering with D. immitis . Although Dirofilaria microfilaremia does not necessarily correlate to an endangerment of the infected animal's health, the individual can act as a reservoir for further infection if the intermediate mosquito host is present [Dirofilaria hosts and appeared exposed to infection similarly to sympatric unprotected dogs [In this study, none of the 42 wolf samples presented evidence for ted dogs . Until tD. immitis antigenemia . Variable occurrences have been reported, namely 6.4% in Australia [D. immitis detected by necropsy of red foxes ranged from 3.2% in northern-central locations, such as Coimbra district [D. immitis circulating antigens, with positive animals found in northern and southern areas [Interestingly, the present study shows that none of the foxes presented microfilaremia, but three were positive for ustralia , 32.3% iustralia , 1.6% inustralia , 3.7% inustralia , 25.2% iustralia  and 2% iustralia . In Portdistrict , to 11.8district . In a seD. immitis infection in wild carnivore species present in Portugal, supporting their potential epidemiological role. While in endemic areas frequent chemoprophylactic treatments of domestic dogs reduce the overall prevalence of the infection, wild canids might play a crucial role in the maintenance of infection. Understanding infection and disease prevalence in wild canids is especially important because these may act as reservoirs, increasing the risk of infection for domestic pets, including urban canids [D. immitis microfilaremia in wolves, supporting that these animals can have a role as D. immitis reservoirs.The present study provides molecular and serological evidence for n canids . Infecte


Other effect sizes reported in the literature, including effect sizes related to mental health interventions and effect sizes related to mobile health  interventions  have met requirements for convincing evidence. Jacobson and colleagues argue that features of the mHealth interventions may produce heterogeneity when meta-analyses combine across intervention types. However, several of the effect sizes we reviewed were based on relatively homogeneous portions of the literature and many of the effect sizes we reviewed showed low to moderate heterogeneity. Ideally, future meta-analyses will examine intervention features as moderators of treatment effects. While an absence of publication bias may be a stringent criterion, all but 2 of the 34 effect sizes we reviewed did not report formal tests of publication bias. Clearly, there is a need to reach consensus on how the strength of evidence for mHealth interventions can be evaluated. From our perspective, convincing evidence will ultimately come from large-scale randomized controlled trials employing rigorous comparison conditions along with meta-analyses that do not combine across control condition types, that examine theoretically important moderators, and report formal tests of publication bias. It is this kind of evidence that the public, the clinicians, and the scientific community may need to encourage adoption of mHealth interventions for mental health treatment and prevention.We appreciate Jacobson and colleagues’ thoughtful commentary on our meta-review of mobile phone-based interventions for mental health. In this response, we address 2 issues raised: requiring low to moderate heterogeneity (I We appreciate Jacobson and colleagues’ thoughtful commentary on our meta-review . They ra2<50%) and requiring no evidence of publication bias. Of note, these are not standards that we invented, but have been applied previously for evaluating mental health interventions [We start by saying we fully agree with Jacobson and colleagues’ enthusiasm about this area. We adopted nomenclature from prior methodological work on umbrella reviews  and usedventions .N > 1,000, p < 0.000001) [We agree with Jacobson and colleagues that these 2 features represent a high bar. However, we disagree that these requirements are destined to fail. There have been previous meta-reviews that have found effect sizes meeting these criteria, along with the additional recommended [.000001) . In our Jacobson and colleagues note that low to moderate heterogeneity is unlikely to occur when meta-analyses combine heterogeneous mHealth intervention types that vary in theoretically important ways . We agree in principle that heterogeneity may be related to these aspects of the interventions. Meta-analysis can be an ideal method for evaluating this empirically, as these study-level features can be tested as moderators. Unfortunately, only 1 effect size  of the 3Although it is true the primary studies included in our meta-review were heterogenous, we should clarify that the meta-analyses we reviewed often included effect sizes representing relatively homogeneous portions of the literature, such as meditation apps , standalFinally, we would like to clarify the issue of requiring an absence of publication bias. Fusar-Poli and colleagues  note 2 fUltimately, we believe that convincing evidence for mHealth interventions for mental health is out there to be found and it is incumbent upon mHealth researchers to conduct rigorous investigations to find it . Convinc


In order to meta-analyze the effect of evidence-based ministration on the efficacy, incidence of pressure ulcers and prognosis of stroke are used. Literature retrieval is carried out in Wanfang Medicine, PubMed database, biomedical literature, and other medical databases through medical data and computers, focusing on the efficacy, pressure ulcer incidence, and prognosis of stroke sufferers after applying evidence-based ministration. For the relevant medical information literature on the effect, RevMan 5.2 software is used for meta-decomposition. For stroke sufferers, the application of evidence-based ministration intervention can notoriously enhance the clinical therapy effect of stroke sufferers, reduce the incidence of clinical pressure ulcers, and enhance the prognosis and quality of life of sufferers. Stroke is an acute cerebrovascular ailment with high mortality, morbidity, and disability. The number of stroke sufferers in China is as high as 5–6 million, which is the leading cause of disability in adults and the second leading cause of death in addition to cancer , 2. In aThe rest of this paper is organized as follows. During the clinical therapy of stroke sufferers, due to the need for long-term bed rest, local tissue is compressed, and nutritional deficiencies and blood supply disorders are prone to occur, resulting in the loss of normal skin function of sufferers and increasing the risk of pressure ulcers. Routine care lacks pertinence and is less effective in preventing pressure ulcers in sufferers . EvidencA ministration evidence-based management set is established to guide clinical nurses with different skills and backgrounds to engage in evidence-based ministration practice. Members of the ministration evidence-based management team can guide clinical nurses to obtain scientific evidence from ministration information and then combine the actual situation and needs of sufferers, analyze the applicability of the evidence, and formulate high-quality ministration programs. Implementation can enhance the evidence-based capacity of clinical nurses , 11. At Stroke, evidence-based ministration, efficacy, pressure ulcers, prognosis, evidence-based care, efficacy, pressure ulcers, prognosis, etc. are used as search keywords. The relevant studies on the effect of evidence-based ministration on stroke sufferers are searched by computer. The general content of the literature is understood through abstracts, and the studies that meet the conditions of stroke, evidence-based ministration, efficacy, pressure ulcers, and prognosis are strictly screened. The examination must be approved by the relevant institutions, the kits are obtained from normal channels, and the operating steps during the examination are without mistakes. At the same time, the studies with duplication of content, inconsistent examination methods, and imprecise operations are excluded from the literature.Inclusion criteria are as follows. (1) The sufferers in the study meet the diagnostic criteria for stroke. (2) The intervention measures are to receive evidence-based care and routine care during the therapy of stroke sufferers. (3) The rate of loss to follow-up during the follow-up process is less than 20% and the examination must be approved by relevant institutions. (4) The period of literature is within the range of nearly 20 years. (5) The original clinical data are complete. (6) There is no error in the operation steps during the study. (7) Except for the application of evidence-based sufferers in each set, the contents of other therapy are the same except for the disparity between ministration and usual care.Exclusion criteria are as follows. (1) Sufferers who do not conform to the diagnostic criteria of clinical CT and pathology and who are diagnosed with stroke after examination. (2) Sufferers who have received evidence-based ministration intervention before the study. (3) Animal experiments. (4) Contrary to the examination subject not relevant. (5) The article is a review, meta-analysis, case report, and conference abstract. (6) Sufferers with severe hematological ailments. (7) The dropout rate due to withdrawal or interruption of follow-up during the follow-up process is greater than 20%. (8) No evidence-based ministration intervention is applied during the study.Outcome indicators are curative effect, pressure ulcer, and prognosis.The quality of the literature is evaluated using the modified Jadad rating scale, which has a total score of 7, with 1–3 as low quality and 4–7 as high quality. For cohort studies, the Chinese version of the modified NOS scale is used to evaluate the quality of the literature. The scale has a total score of 10, with <5 as low quality and ≥5 as high quality.P < 0.1 and I2≥50%, which is statistically extensive, the source of this property is analyzed by subset or sensitivity. When the heterogeneity among the studies satisfies P < 0.1 and I2<50%, the heterogeneity is not statistically extensive, and the meta-decomposition is carried out with a fixed-effects model. When the source of heterogeneity is unclear, a random-effects model is used in the decomposition, and descriptive decomposition is used to analyze obvious clinical and methodological heterogeneity.The examination data are entered into RevMan5.2 statistical software for decomposition. Enumeration data are expressed by risk ratio (RR) and weighted mean disparity (WMD) or standard mean disparity (SMD). All effect sizes are expressed with 95% confidence interval (CI). Heterogeneity between the results of each study is tested by Chi2. When the heterogeneity among the studies satisfies After the Chinese and English databases are searched according to the search strategy, a total of 565 documents are collected, and the documents are screened according to the established inclusion and exclusion criteria. Finally, 8 documents are included, including 3 English documents and 5 Chinese documents. The 8 final included studies are randomized contrasted studies with multi-center characteristics, and all of them give detailed descriptions of the randomization method, and the method is correct –23.  FigP < 0.00001). A total of 5 studies are included for the clinical efficacy of stroke sufferers –26. The P=0.81, indicating that there is no heterogeneity among the included studies. The incidence of pressure ulcers in the ministration set is notoriously lower than that in the routine ministration set, and the disparity is statistically extensive after the combined studies , P < 0.00001), which can be considered as an effective therapy for stroke sufferers. A total of 6 studies are included for the incidence of clinical pressure ulcers in sufferers with stroke. The results of the heterogeneity test show that I2 = 0%, P=<0.00001, indicating that there is no heterogeneity among the included literature. Therefore, a fixed-effects model is used to analyze the evidence-based ministration set. The total effective rate of the sufferer's therapy is notoriously higher than that of the routine care set, and the disparity is statistically extensive after the combined studies , P=0.0001). It can be considered that the application of the therapy system for stroke sufferers is effective. A total of 5 studies are included for the clinical prognosis of stroke sufferers. The results of the heterogeneity test show that I2 = 99% and Sensitivity decomposition is performed on the 8 included studies. For stroke sufferers, evidence-based ministration intervention can notoriously enhance the clinical therapy effect of stroke sufferers, reduce the risk of pressure ulcers, and enhance the clinical quality of sufferers' prognosis, which is worthy of clinical application. At present, the effect of evidence-based ministration on stroke intervention is still at a stage of great controversy. Relevant studies on the mechanism of action and complication prevention have achieved great results, laying an examination sample basis for meta-decomposition. The quantitative decomposition of the effect of evidence-based ministration on stroke intervention can make the results more scientific and reliable.


Improving eHealth literacy (eHL) is one of the biggest challenges currently facing the global healthcare community. Indeed the use of digital services has the potential to engage patients in care as well as improve the effectiveness of chronic disease self-management, it remains highly dependent on a patient’s specific skills and experiences in the health care systems. Although eHealth literacy has gained momentum in the past decade, it remains an underresearched area, particularly eHealth literacy measurement. The aim of the review is to identify patient-reported outcome measures (PROMs) of eHealth literacy for adult populations and to summarize the evidence on their psychometric properties.We will conduct a systematic literature review of the tools used to measure eHealth literacy for adult population. The search strategy aims to find published studies. A three-step search strategy will be used in this review. Published studies will be searched in CINAHL, PubMed, PsycINFO, and Web of Science from inception until end. Grey literature will be searched to find theses. Database search strategies will be formulated and tested with the assistance of an expert Health Sciences Librarian. The selection of studies will be done by two independent reviewers. Disagreements will be resolved through consensus, and a third reviewer will solve discrepancies. Furthermore, two reviewers will independently evaluate the methodological rigor of the instruments development and testing and assign a grade using the standardized Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. Disagreements will be discussed with a third reviewer, expert in psychometrics.Extracted data will be aggregated and analyzed to produce a set of synthesized findings that will be used to develop evidence-informed recommendations in regard of eHL instruments. We will present a synthesis of all instruments, their psychometric properties, and make recommendations for eHL instrument selection in practice. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and a PRISMA flow diagram.This systematic review will summarize the evidence on the psychometric properties of PROMs instruments used to measure eHL and will help clinicians, managers, and policy-makers to select an appropriate instrument.PROSPERO CRD42021232765 The generalization of eHealth  to numerous activities in the health system is leading to changes in individual and collective health uses and practices. Improving eHealth literacy (eHL), which is a type of health literacy, continues to be a challenge worldwide , 2.A growing number of articles in the literature point out the potential benefits of eHealth interventions to improve health behaviors , clinicaFor patients, it is becoming critical to have access and skills to understand information through electronic services including health portals or electronic patient record. eHealth referred to “the organization and delivery of health services and information using the Internet and related technologies” . As a reeHL is a multidimensional concept with varying definitions , 16. ThiSeveral sources of difficulty in measuring eHL can be identified: (1) there is confusion over the term “eHealth literacy” behind the measure . (2) WhaThe challenge is to measure eHL as a set of cognitive skills necessary for the effective “use” of eHealth interventions. The literature describes eHL as a metaliteracy that comprises six different subtypes of literacies focusing on the use of online information . The relA self-reported measure of a patient’s eHL needs to be based on sound theoretical and empirical evidence and those instruments should be representative of patients’ experience of eHL in daily life . To date, there is only one self-report measure used in more than one study: the eHealth Literacy Scale (eHEALS) . This meThe standardized Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias checklists , 35 provThe measures of eHL need to produce consistent and reproducible results if they are to be trusted in practice (reliability). These measures are PROMs, which are defined as standardized, validated questionnaires  completed by patients . Data arCurrently, there is one systematic review  that ideThe current systematic review seeks to examine the quality of PROMs (used for patients: adults > 18 years old) and to identify the best instrument for field use. These findings could assist in informing evidence-based practice for the use of PROMs of eHL. We expect that the findings will assist researchers and clinicians in identifying and selecting the most appropriate instrument when measuring eHL.The aim of this review is to systematically identify, synthesize, and evaluate the methodological quality of all relevant studies on the development and validation of eHL PROMs for adult populations. The research question for this review is: which PROMs have been developed to assess eHL and what are their psychometric qualities?Following the methods for conducting systematic reviews outlined in the Cochrane Handbook , we deveThe search strategy will aim to find published studies describing the development and the validation of eHL self-reported instrument from their inception until July 2021. A three-step search strategy will be used in this review . An initFinally, a last search on PubMed with a filter specifically created for the search of PROMs will be done  and MeShThis review will consider all studies conducted on the development and/or validation  of measures of eHL in adults (> 18 years old). Studies relating to human health and published between 2000 and 2021 in English, French, Spanish, or Italian will be considered for inclusion. The adoption of e-health by health institutions start in the early 2000’s with the rapid emergence of technology use during that time . TherefoTitles and abstracts will be screened against the inclusion criteria for the review. Studies that meet the inclusion criteria will be retrieved in full (including full text) and their citation details imported into Covidence . The fulThis research will be done without patient involvement. As this review aims at synthesizing methodological information about existing eHL instruments, patient and public experience is not directly mobilized. However, patient and public will be involved at a later stage in this project.Data will be extracted from the selected studies using the data extraction form Table  proposedTwo researchers will independently extract the data for all included studies and agree, through consensus, about the accuracy and completeness of the data. Where consensus is difficult to achieve, a third reviewer will be used to reach agreement verification (including psychometrics) to minimize bias and potential errors in data extraction. The data extracted will include general information about the article, and specific details about the instrument as well as the psychometrics. Findings will be extracted and assigned a level of credibility Table .We will apply the COSMIN checklist to evaluate the methodological rigor and results of the instruments . The cheFollowing COSMIN guidelines, only the studies that have a “good” methodological quality in content validity will undergo data extraction analysis and synthesis. The quality of included studies will be considered in the analysis and will therefore be reflected in the findings and a grade will be given in conclusion of the systematic review . If we hThe quality of each measurement property of an instrument will be evaluated using the quality criteria proposed by Terwee et al.  who partEach measurement property will be given a rating result . There is currently no empirical method to pool together results of measurement properties; therefore, synthesis is recommended .Research findings will be synthesize using the COSMIN “Scoring quality form boxes” tool . These cAs recommended by the COSMIN Group ‘a best evidence synthesis’ will be used to synthesize all the evidence on measurement properties of different instruments. The procedure used will follow the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework . This prThree steps will be taken to obtain the overall rating for a measurement property. First, the methodological quality of a study on each measurement property will be done using the COSMIN checklist. According to COSMIN, measurement properties from inadequate quality studies may be included to contribute to ‘the best evidence synthesis’. Second, the quality of each measurement property of an instrument will be evaluated using Terwee’s quality criteria , 50. ThiFollowing COSMIN guidelines, the results from inadequate quality studies may be included when synthesizing or summarizing the results from all studies, or if the results of inadequate studies are consistent with the results of better quality .. We will systematically discuss the main issues in the testing of a subjective health measurement instrument in regard to existing systematic reviews in the eHL study domain . We will discuss operational issues related to the conduct of this systematic review of PROMs. The approach which consists of using eHealth resources has led to improvements in clinical outcomes and health service efficiency and might potentially improve access to care and reduce healthcare costs. For clinical practice, it is important to have a good instrument to appraise patients’ eHL level in order to correctly use eHealth resources and maximize benefits for the patient’s disease self-management. It is also essential to provide patients and providers with a rigorous evaluation of e-HL competencies that facilitate the use of eHealth in the relevant context.This review will present a synthesis of eHL’s PROMs, their psychometric properties, and make recommendations for selection in practice and research. This review will provide some insight regarding the challenges of using self-report instruments in assessing eHL