Targeted genomic education and training of professionals have been identified as core components of strategies and implementation plans for the use of genomics in health care systems. Education needs to be effective and support the sustained and appropriate use of genomics in health care. Evaluation of education programs to identify effectiveness is challenging. Furthermore, those responsible for development and delivery are not necessarily trained in education and/or evaluation. Program logic models have been used to support the development and evaluation of education programs by articulating a logical explanation as to how a program intends to produce the desired outcomes. These are highly relevant to genomic education programs, but do not appear to have been widely used to date. To assist those developing and evaluating genomic education programs, and as a first step towards enabling identification of effective genomic education approaches, we developed a consensus program logic model for genomic education. We drew on existing literature and a co-design process with 24 international genomic education and evaluation experts to develop the model. The general applicability of the model to the development of programs was tested by program convenors across four diverse settings. Conveners reported on the utility and relevance of the logic model across development, delivery and evaluation. As a whole, their feedback suggests that the model is flexible and adaptive across university award programs, competency development and continuing professional development activities. We discuss this program logic model as a potential best practice mechanism for developing genomic education, and to support development of an evaluation framework and consistent standards to evaluate and report genomic education program outcomes and impacts. Genomic medicine is rapidly being incorporated into routine healthcare  and, dueWe undertook a review of genomic education produced in Australia in 2016–17  and founProgram funders and stakeholders require evidence that education interventions have successfully met tangible outcomes . If the Despite a need, there is little clarity on what defines quality genomic education interventions or successful strategies, and in which contexts . Nor areHere we describe the consultative process of engaging education and evaluation experts in developing and testing a program logic model for genomic education. We also illustrate the logic model’s utility and flexibility across a variety of settings and contexts through narrative cases.The scope of “education” considered for this program logic is education for any professional, with or without specialized genetic training, regarding the application of genomic medicine. This spans clinical and laboratory professionals and, depending on the local context, clinicians may be primary, secondary or tertiary healthcare providers. For example, they may be family physicians/general practitioners who refer patients to genetic services or hospital-based medical specialists/physicians who refer patients or directly order genomic tests. Here we use the term ‘genetic specialists’ to denote people with specialized genetic training  and ‘medical specialists’—including primary care physicians (PCPs)—as medically qualified individuals specialized in a sub-discipline other than genetics, who may refer or order genomic tests.A Working Group  developed a draft program logic model from June through to December 2017. This was based on theories of program logic, evaluation, and adult learning principles and drew on the collective knowledge and experience in developing and applying program logic models to genetic education interventions and research.The draft program logic was reviewed and refined in a 2-day co-design workshop involving 24 Australian and international genetic education and evaluation experts (see Acknowledgements) held in February 2018. All attendees were experienced in developing genetic or genomic education interventions, program evaluation and/or implementation science. The workshop included didactic, self-directed, and group activities to: develop a shared understanding of program logic structure and language; discuss the application of program logic and the associated evaluation framework to genetic and genomic education interventions; and review and refine the draft model. The workshop also considered the process for testing the logic model.To test the connections between the key elements of the logic model, clarify the intended outcomes and test feasibility, we applied a clarificative evaluation approach using authentic case studies . A samplThe logic model developed and refined by the working group and workshop participants captures four key components of the program cycle—planning, development, delivery, and outcomes—with goals, stakeholder engagement, and evaluation spanning all stages Figure 2planning stage of the education intervention involves situation and opportunity analyses. A situation analysis considers numerous factors such as: stakeholders and partners, who may have mandates and competing priorities; project parameters ; whether information exists, or can be gathered, around educational needs of target learners; and the target genomic workforce and level of genomic literacy. For example, depending on the context of the education provider , if there is no current evidence on the genomic education needs of the target learner, the provider could conduct a needs assessment—if time and resources permit. At the minimum, this could involve assessing relevant stakeholder views on areas of genomic education that would better guide practice. An opportunity analysis may encompass potential partners , resources that can be repurposed or a literature review of, for example, competencies. The outputs of planning include a clearly-defined approach to stakeholder management , goals, target groups, learning objectives, and a draft outline of the education intervention. Project management aspects overlap with components at all stages of the model. For example, at the end of the planning stage, it would be expected that education providers have all approvals and required resources in place. An evaluation plan should also be in place at this early stage—to foster transparency with stakeholders, identify questions, methods, and study design—before implementation and ensure sufficient resources for process and outcome evaluation are in place.As the logic diagram depicts, the development stage of the program logic model include evidence/theory-informed curriculum, content, and/or assessment design and development. There is growing evidence that education interventions that are based on clear theoretical foundations are more effective and have a greater impact on health professional educational outcomes than those without . The long-term outcomes could include those related to the appropriate and timely use of genomic medicine, which then relates back to the overarching goal, which is improved patient outcomes. When constructing a program logic model to describe an education intervention, an education provider may use a series of “if … then…” statements (if learners complete this genomic education intervention and attain new skills (immediate outcome) then they become genomic-competent and practice accordingly (intermediate outcome), which then facilitates the appropriate use of genomic medicine (long-term outcome), which then improves patient care .The fourth stage depicts the atements . For exaEvaluation spans both the process of developing an education intervention and evaluating delivery (processes) and its impact—here defined as immediate, intermediate, and long-term outcomes.Four workshop participants  tested the program logic model in local contexts. These included different countries  and different types of education intervention: workshops for pediatricians, a competency framework to support discussions around informed consent for genomic testing, online modules for medical specialists, and a university course. The four contexts involved varied outcomes, stakeholders and partners, and different organizations and resources. Chirag is a medical geneticist with many years’ experience developing and delivering genomic education to health professionals. He has no formal education qualification, is not supported by a university or education organization and offers occasional genomic education interventions in addition to his usual clinical workload. Chirag recently obtained funding to lead a research program exploring the use of whole genome sequencing (WGS) as a first-line investigation for pediatric patients across several tertiary specialties. For this research program to become clinically embedded and successful in the long term, hospital-based pediatricians will need to know how to order and interpret WGS tests.Chirag used the program logic model to plan and develop face-to-face workshops to increase genomic literacy among hospital-based pediatricians in his region Figure 3Chirag found the program logic model prompted him to include all the necessary considerations when planning genomic education for non-genetic health professionals.“It was great to have a formal document to use as a reference to consider all aspects of providing genomics education to non-genetics professionals. Many of the factors in the planning stage may not routinely be considered when planning smaller educational events , but clearly are essential in ensuring effectiveness and achievement of goals and outcomes for larger group educational activities like workshops. It allowed to me to ensure I had the correct resources and that I assessed the needs and current level of knowledge of my target audience, prior to designing the specific cases for the workshops.”Michelle has a postgraduate qualification in genetic counseling, a PhD in genetic education, and several years’ international experience in genetic and genomic education. Michelle works for a national genomic education organization tasked with upskilling health professionals in genomic medicine. Previous work undertaken by Michelle’s organization identified a need for competencies to support education and training of health professionals who will undertake the consent conversation for genomic testing with patients or their family members.Michelle used the logic model to assist stakeholder identification and to develop a stakeholder management plan for developing, disseminating and evaluating the competencies.We established a Working Group to oversee the development of the competencies, and I used the key points outlined in the program logic to structure the Working Group discussions. I also use these points as a checklist to structure the progress reports I submit to our Assurance Board.”““outline the set of knowledge, skills and behaviors for ‘doing the job’ rather than what someone would achieve if they undertook a training session in this area”.The initial stakeholder engagement activity included consultation with health service providers and laboratories, medical and nursing colleges and societies, and, at a separate event, consumer representative groups. All stakeholders agreed to the need for a set of competencies. The stakeholders wanted to Stakeholder consultation was also undertaken to develop a comprehensive mixed-methods evaluation plan that encompasses process and impact evaluation to both inform the refinement of the competence framework and answer the question: are health professionals who have genomic testing consent conversations competent in all areas of the competency framework? Michelle found the logic model helped stakeholders appreciate the importance of considering evaluation early in the planning and development phase.Importantly, having the key points structured in a format that aligns to the resource development cycle means that key aspects such as defining the evaluation plan are considered throughout the development of the resource and not as an afterthought.”“Bronwyn has postgraduate qualifications in science communication and education, with many years’ experience planning, developing, delivering, and evaluating genetic education interventions. She works for a medical research institute, which has a genomics-focused education and outreach team that aims to improve Australasian health professionals’ understanding of, interest in, and use of genomics to facilitate its broader integration into healthcare. A previous needs assessment and opportunity analysis revealed a lack of short, accessible genomic education resources developed for Australasian medical specialists.Planning for the educational intervention was already underway when Bronwyn participated in the program logic development workshop. Contributing to the development of the broader logic gave Bronwyn an opportunity to reflect on her own project, highlighting processes that she may have done differently or at a different stage Figure 4In response to stakeholder input, the course was deliberately designed in a modular fashion.A key decision at the development stage was to have an open learning pathway so the modules could be completed as whole, or learners could select sections most relevant to them.”“However, learning analytics evaluation data reveal very few learners complete all modules. This has impacted the planned long-term evaluation of the modules, as recruitment information for the post-survey and 6-month follow-up interview was only included in the completion page of the modules, resulting in insufficient individuals being aware of the study.Bronwyn reflected that the logic model is useful even for experienced educators:As project planning was well underway by the time the program logic model was developed, it informed my input into the [international program logic model development] workshop. The aspects that extend across the model—stakeholder engagement and documentation/evaluation—are particularly valuable as reminders to review and assess the whole project at each stage. For example, a requirement to evaluate or document at both the planning and development stages may have meant we invested in a competency review at an earlier stage and/or broadened our stakeholder list.”“Alison is a clinician educator with an undergraduate education qualification and postgraduate genetic counseling and research qualifications. She is the Program Director for a new Master of Genetic Counseling course in Australia and used the program logic model to help monitor and manage a cyclical co-design process when developing, delivering and evaluating the course . Alison’Alison used co-design principles throughout the course development process, supported by the program logic model. The program was three months into the 15-month planning and development phase when Alison attended the program logic development workshop. Alison found the logic model aligned well with the co-design process and informed the ongoing development and delivery of curricula.The inclusion of frequent check points and evaluation activities is of particular importance/relevance to ensure the program is meeting the needs of the learners, and of the practicing genetic counselors who interact with them while on clinical placement.”“The program logic provided Alison with a framework for an in-depth evaluation that goes beyond her university’s usual feedback processes. In addition to university-mandated student feedback surveys, students also provided evaluative feedback and staff completed a brief reflective survey for each subject, with the evaluations and feedback discussed at an ‘end of semester’ staff retreat. Survey data and feedback from class representatives further informed the co-design approach, with students providing ongoing feedback and suggestions to ensure the program is responsive to the experiences and insight of this core group of stakeholders.Alison found the logic most helpful in illustrating the cyclical nature of planning, development, delivery and evaluation of the university award course, providing opportunities for ongoing improvement.We use the program logic in a cyclic manner, to ensure we continue to reflect on the needs and goals of all the stakeholders involved, as we seek to deliver a robust and emergent genetic counselor education program.”““I’ve found the program logic incredibly helpful, not just to guide development of the competencies but also for the project management aspect, including reporting into our Delivery Board.” While we acknowledge our logic model may be used as a project management tool, this was not the primary aim and the component was therefore removed from the Development stage.Testing the model in local contexts revealed some tensions and areas for refinement. Three participants felt that ‘Project management’ components span all stages of the model, not just during the Development stage, as was shown in the draft version , a summary of the main education and evaluation theories, common learning designs and related assessments, expert review templates, and evaluation study designs. As Bronwyn noted, via iterative workshop activities to achieve consensus, then clarificative evaluation in local contexts to test the stages and activities within the program logic model against our aim . These included education developers and providers from independent and government-funded organizations  as well as research institutes  and universities . While some members may have had past industry experience, none were able to provide current industry perspectives. The model may therefore be further strengthened by testing in industry and other contexts. Similarly, while deficits in the draft model were identified and addressed by expert consensus during development and testing, we expect that this will be the start of an iterative process as others use the model; we therefore encourage those who use the model to contact us to provide feedback.Program funders typically require evidence of achieving genomic education intervention aims and objectives however, it consistently proves difficult to gather robust evaluation data for genetic education interventions, with even simple utilization statistics sometimes difficult to ascertain . The proOur proposed suite of tools to develop, evaluate and report genomic education interventions will enable education providers and researchers to begin to establish an evidence base of effective genomic education and evaluation practice. We are currently using the model to develop, deliver and evaluate continuing genomic education interventions from the ground up. Over time, we expect that other education providers will provide feedback on use of our program logic model in many different contexts. This relies on effective dissemination of iterations of the tool: effectively promoting and sharing tools and resources is a challenge generally. Reviews of genetic and genomic education interventions .CG and SM, are co-editors of the special issue where this manuscript is featured; AN and MM are affiliated with CG and SM. CG and SM were not involved in the editorial or peer-review process. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Evidence-informed health intervention planning that incorporates theoretical and empirical evidence and engages key stakeholders and community members or patients in the planning process results in interventions that are more effective. Nevertheless, exactly how and when to use evidence, theory, and community-based participation during planning represents a challenge. In this Perspective, we describe Intervention Mapping (IM), a framework for theory- and evidence-based health promotion program planning that addresses this challenge by providing a systematic and stepwise approach to planning interventions. IM has been used to develop health promotion interventions and implementation strategies in community and clinical settings globally, with over 1000 published articles employing the framework. In this Perspective, we also highlight recent and innovative applications of IM described in the articles of the Frontiers in Public Health Special Topic on IM. We conclude by discussing new directions in the application of IM including novel methods for identifying determinants of behavior and environmental conditions, the application of IM for planning implementation strategies, and IM for adaptation of evidence-based programs in new settings. Frontiers in Public Health Special Topic on Intervention Mapping publication  and as such guides the development of multi-level interventions.IM provides guidelines and tools to ensure health promotion program is based on empirical evidence and sound theories. IM is also used for the planning and development of implementation strategies for program adoption, implementation, and maintenance . FollowiThe IM intervention development process has six steps: (1) Establish a detailed understanding of the health problem, the population at risk, the behavioral and environmental causes, and the determinants of these behavioral and environmental conditions; and, assess available resources; 2) Describe the behavioral and environmental outcomes, create objectives for changes in the determinants of behavior and environmental causes, and specify the targets of the intervention program; (3) Identify theory- and evidence-based behavior change methods that influence the determinants and translate these to practical applications that fit the intervention context; (4) Combine the intervention components into a coherent program that uses delivery channels that fit the context; (5) Develop implementation strategies to facilitate adoption, implementation, and maintenance of the program; and (6) Plan both process and outcome evaluation to assess program implementation, and efficacy or effectiveness  for the at-risk group and for those responsible for making changes in the environment. The planning group sets performance objectives breaking down each behavior and environmental condition into subcomponents by answering certain questions: “What does the person need to do to accomplish the behavior?” and “What does the environmental agent need to do to create the environmental change?” They then identify determinants of health-promoting behaviors and environmental conditions by asking: “Why would someone do this behavior?” and “Why would someone make this environmental change?”To make decisions about salient determinants that should be targeted with the intervention, IM guides planners through four core processes : (1) invIM provides guidance on how to use theory to inform the development process. Planning groups can identify appropriate theories by (1) searching the literature on the health topic, (2) matching ideas from the brainstorming process to theoretical constructs, and (3) applying frequently used theories . The theIn Step 3, the planning group discusses initial ideas for the program and selects theory- and evidence-based behavior change methods based on the determinants that they need to change . A numbeThere has been growing interest in systematic descriptions of health promotion interventions, their theoretical methods, and the determinants these methods are expected to change. Abraham and Michie , for exaIn Step 4, the various applications selected in Step 3 are organized and produced . The proEffective health education and promotion programs can lose their impact if they are not used before desired health impacts are achieved –34. IM pProgram implementers are the people who are responsible for the delivery of the program and can include organizational leaders responsible for program adoption and maintenance as well as those responsible for actual delivery of program materials and activities to participants. For example, nurses will present programs to patients, and teachers will deliver health education programs to students. Others in the organization or setting, even though they are not program implementers, may be responsible for making decisions about whether or not the program is adopted and for identifying individuals who will deliver the program. For example, school principals may not deliver health education curriculum; however, their support for program adoption and maintenance is critical.IM Step 5 can be used not only to plan implementation the first time a program is developed and used but also can be used to develop plans for scale up and spread of existing evidence-based interventions. Program planning groups can address program implementers' personal determinants, like knowledge and outcome expectations for the program and self-efficacy for enacting program activities at the individual level with methods, such as persuasive communication, tailoring, and modeling. However, implementation almost always involves organizational change, which means program planning groups also have to apply methods at environmental levels. Organizational theory and implementation science frameworks can be used to understand the determinants and contextual factors that influence implementation and to guide the selection of methods that will support program implementation , 39.Implementation Mapping.Effect and process evaluation will verify if the objectives chosen in Steps 2 and 5, respectively, have been reached, and need to be carefully planned. Previous IM steps help inform the evaluation plan since behaviors, environments, their sub-components, and determinants are clearly spelled out  describeSpecial-topic authors provide examples of the application of IM across settings and topics . There aPot et al.  present Rodriguez et al.  and SerrSerra et al.  applied Fassier et al.  describeten Hoor et al.  used IM Vissenberg et al.  used IM Mesters et al.  used IM Although IM provides guidance to identify needs and develop interventions, additional research and approaches are needed to more accurately address the questions posed by each of the steps including the identification of determinants and the selection of methods. Crutzen et al.  describeAdditional research is needed to build the evidence base for the effectiveness of certain methods to address determinants. Peters et al.  highlighhealth promotion interweaving. Building from theoretical perspectives rooted in social-ecological models, improvement science, and systems thinking, this paper advances an indigenous health intervention development approach that takes into account the environmental context, to designing interventions. While IM is specifically structured for the community and stakeholder involvement, an important contribution of this paper is its description of theory- and practice-based interweaving concepts , environmental print (information environment), appropriable organization , and shared use agreements (built environment). Springer and colleagues' exploration of health promotion interweaving as a health planning approach promotes greater intentionality for designing health promotion strategies, practices, programs, and policies (IM addresses the growing body of evidence on the influence of the environmental context on health and health behavior  by provconcepts , 50 in rpolicies , 49, 50.Using IM to plan implementation strategies has recently gained attention , 51 partBased on the recognition that evidence-based sexual health education programs are underutilized by school districts, Peskin et al.  used IM The use of IM as a tool in implementation science for the development of implementation strategies is growing –57. UsinIM helps health promoters to develop well-thought-out theory- and evidence-based programs through the identification of key changeable determinants of risk behaviors, the choice of appropriate intervention methods and applications, and the development of implementation strategies to ensure use and dissemination. Although the IM process is described through its sequential steps, IM is intended to be iterative, and, indeed, most of the studies presented above describe the IM planning process this way. Throughout the process, planners gain new knowledge about the population, determinants, environment, and/or effective and appropriate methods that sometimes requires cycling through earlier steps to expand or refine the program.The IM protocol assists program-planning groups to optimize the chances of program effectiveness, and IM has been utilized widely across multiple health domains, populations, and settings all over the world. The use of IM can make health education and health promotion programs stronger, more effective, and more widely disseminated to improve the impact of public health programs.MF, RR, CM, and GK contributed to the manuscript conceptualization, discussion of new directions and the conclusions. GK and MF contributed to the description of studies in the special topics issue.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


M ≥ 7.5 earthquakes with epicenters within 300 km of the mine during the monitoring period and increased after these earthquakes. This is a valuable finding which would give us a clue to understand pre- and post-seismic rockmass behaviors and contribute for progress in earthquake prediction in future.The amount of water drainage from Kushiro Coal Mine in Hokkaido, Japan decreased on the day of all  M7.0), a drop of groundwater level and temperature, at 30 km away from the Izu earthquake epicenter was reported1. Orihara et al.2 had reported that the water level and temperature at Goyo Hot Spa which is located 250 km from the epicenter of the Tohoku 2011 earthquake (M9.0), was dropped by 30 m and 2 °C respectively, 3 months before the earthquake and the water level was increased after the earthquake. The amount of water drainage from Kushiro Coal Mine in Hokkaido, Japan was monitored between January 1, 1993 to April 30, 2015 and it decreased on the day of all M ≥ 7.5 earthquakes with epicenters within 300 km from the mine and increased thereafter. This phenomenon is reported here because such phenomena may be important for understanding the changes in rock mass conditions before and after large earthquakes and might give clues to earthquake prediction together with the above case studies.A number of reports have suggested the pre-seismic changes of groundwater level, but only a few recorded data of pre-seismic groundwater drops were published in peer-reviewed journals. For example, a month and a half before 1978 Izu-Oshima-Kinkai earthqauake . Kushiro Coal Mine took over the operations of Taiheiyo Coal Mine on January 31, 2002. Therefore, data recorded by Taiheiyo Coal Mine are also presented. The water flowing into Taiheiyo Coal Mine was not seawater, but was fossil water from holes drilled in Cretaceous rock for water drainage and groundwater from the land4. The water flowing into Kushiro Coal Mine is only groundwater from the land.Kushiro Coal Mine is located on the coast of the Pacific Ocean, where the mining of Paleogene bituminous coal occurs under the ocean bottom  +9 hours) on the next day from the No. 2 pump pit  earthquakes, occurred during the monitoring period within 300 km from the coal mine and were catalogued in a database by the Japan Meteorological Agency . However, the change in daily coordinates for #4–#7 were shown in Fig. . HoweverThe displacements for #5 earthquake were clear and that in longitude shows an opposite motion, which might be related to the pre-seismic decrease in drainage, just before #5 Fig. .Figure 5For earthquake #7, even the largest permanent displacement in longitude was unclear Fig. . DisplacThe plots of epicentral or hypocentral distance versus magnitude Fig.  imply thet al.2 postulated that the mechanism of the change in the water level and temperature at Goyo Hot Spa due to the Tohoku 2011 was a decrease in pore pressure due to dilatancy and the formation of new water paths as a result of slow slippage before the main shock. The cause of the change in the drainage amount from Kushiro Coal Mine cannot be clarified at this stage because the 1-day time resolution of the drainage data as well as the GPS solutions are not small enough and also more data including geological, geo-hydrological, geochemical etc. are needed. However, it is estimated that a decrease in groundwater pressure due to dilatancy before the earthquakes and an opening of discontinuities due to stress relief after the earthquakes would have played a significant role as a part of the mechanisms for the changes in the drainage.Orihara 1 and three months before Tohoku 2011earthquake2. It would be very difficult to predict when earthquakes will occur from those observations. On the other hand, the decreases in drainage at Kushiro Coal Mine began on the day of the each earthquake and it would rather be easier for immediate predictions of large earthquake occurrences.The decrease in groundwater levels were observed a month and a half before Izu-Oshima-Kinkai earthquakeThere are many deep mines in the world and it is expected that they can work as much larger sensors for pre-seismic changes of rockmass conditions by recording the amount of drainage etc. without spending huge costs than newly drilling small diameter drill holes from the ground. The authors fully recognize that the pre-seismic decrease itself cannot be used to predict earthquake at this stage and hope that data accumulation from observations at a shorter sampling time at deeper mines will contribute to clarify the drainage pattern at large earthquakes and to develop earthquake prediction methods in future.Qave1 and Qave2 for the period 14 of days prior and succeeding a day are defined (Fig. Q1 is defined asQp is the drainage amount on the day. The post-seismic drainage increase ΔQ2 is defined asQ1 and ΔQ2 were calculated for the each and every day in the monitoring period except for the first and last 14 days (Fig. Q1 and ΔQ2 were calculated. The days which satisfied that they exceeded certain threshold values were selected as the days which showed the decrease and increase pattern. Setting the threshold values as the average value minus the standard deviation and the average value plus three times the standard deviation for ΔQ1 and ΔQ2, respectively, it was found that only the days for #1 (Fig. Firstly, the average values ned Fig. . Then thays Fig. , and the #1 Fig.  and #2 ( #1 Fig.  satisfie


Vibrio cholerae. However, the antibody isotypes responsible for the serum vibriocidal activity are not fully characterized. In this study, we examined 20 clinical serum samples obtained from human subjects who had been vaccinated with a killed, whole-cell cholera vaccine and a positive control, human convalescent sera with high vibriocidal activity, to determine which isotype antibody is associated with the vibriocidal activity. Antibody isotypes from pooled convalescent sera were fractionated by size-exclusion column chromatography, and the major vibriocidal activity was detected in the IgM fraction. Depletion of IgM antibodies in the convalescent sera produced a significant (P<0.05) decrease in vibriocidal activity (16-fold decrease), whereas only a small change was observed with depletion of IgG or IgA. In addition, anti-LPS IgM antibody showed the highest correlation with vibriocidal activity (Spearman correlation coefficient r = 0.846) among antibody isotypes against heat-killed V. cholerae, lipopolysaccharide (LPS), or major outer membrane protein (Omp U), while total IgG, IgA, or IgM antibody level was not correlated with vibriocidal activity in the 20 human clinical serum samples. Furthermore, human convalescent sera significantly (P<0.001) inhibited the attachment of V. cholerae to HT-29, a human intestinal epithelial cell in vitro. Interestingly, IgM-depleted convalescent sera could not effectively inhibit bacterial adherence compared with non-depleted sera (P<0.05). Finally, bacterial adhesion was significantly inhibited by sera with high vibriocidal titer compared with low-titer sera (P = 0.014). Collectively, we demonstrated that anti-V. cholerae LPS IgM is highly correlated with serum vibriocidal activity and it could be a surrogate antibody isotype representing protective antibodies against V. cholerae.Serum vibriocidal antibody assays have long been used to evaluate the immunogenicity of cholera vaccines formulated with killed whole-cell  Vibrio cholerae causes acute diarrhea by cholera toxin-mediated intestinal fluid secretion in humans. Humoral immunity rather than cellular immunity has been considered to play a role in protection against cholera because the bacteria do not invade the intestinal epithelial barrier and are unable to survive intracellularly [V. cholerae has long been focused on V. cholerae LPS for protective immunity due to its association with protection in humans [llularly . Humoraln humans . In addin humans , choleran humans , and toxn humans  have alsV. cholerae are known to play a role in protection in humans, there is no direct evidence as to which antibody isotype is the most important to provide immunity against cholera. Two isotypes, secretory IgA and serum IgG, have been shown to provide protective immunity against V. cholerae infection [V. cholerae LPS-specific serum IgG are also augmented in response to V. cholerae infection [Although specific antibodies against nfection , 6, and nfection –9. Signinfection –12.V. cholerae. It is conceivable that IgM is much superior to IgG in complement-fixing activity because its pentameric structure has higher functional avidity than monomeric IgG [Given that IgG and IgM can trigger complement-mediated bacterial lysis through the classical complement pathway , IgM coueric IgG . Single eric IgG . In addieric IgG . Furthereric IgG , and higeric IgG .in vitro test that measures the ability of antibodies mediated by complements to kill virulent V. cholerae. Vibriocidal antibody levels increase by aging and have been shown to be inversely associated with susceptibility to cholera in endemic area [V. cholerae O1 [V. cholerae. In general, although there is no known threshold of vibriocidal titer for protection from the disease, a 4-fold increase or higher in vibriocidal titer after the vaccination has been widely accepted as an effective immunization [The vibriocidal assay is an mic area , 18. Morlerae O1 . Therefonization . For accV. cholerae O1 El Tor Inaba (strain T19479) was kindly provided by Prof. Jan Holmgren  and was used as the target bacteria for the vibriocidal assay. Brain Heart Infusion (BHI) media and Guinea pig complements were purchased from Difco  and Rockland , respectively. Protein G-agarose (PGA) and rabbit anti-human IgM (μ-chain specific) or IgA (α-chain specific) in rabbit IgG fraction were purchased from Sigma-Aldrich Co. .V. cholerae O1 Inaba, O1 Ogawa, and O139, was given with two doses at two week interval (days 0 and 14) through clinical trials [Convalescent sera with high vibriocidal antibody titers of ≥ 8,000 were pooled from cholera patients in India and used to deplete target isotype of antibody. Bivalent oral cholera vaccine , formulated with l trials –22. BlooOne milligram of PGA was initially mixed with 100 μg of IgG fraction of rabbit anti-human IgM (μ-chain specific) or IgA (α-chain specific) at room temperature for 1 h. Convalescent sera were then mixed with anti-human IgM- or IgA-bound PGA and followed by precipitation of the antibody-agarose complex to deplete serum IgM or IgA. PGA was used to deplete IgG in the convalescent sera. The supernatants were then incubated again with fresh PGA, anti-IgM-, or anti-IgA-bound-PGA; this clearance procedure was repeated 7 consecutive times.V. cholerae O1 Inaba (strain T19479) using LPS extraction kit  according to the manufacturer’s instruction as previously described [ompU gene was amplified from V. cholerae O1 Inaba (strain T19479) by PCR and recombinant OmpU was expressed in the E. coli BL21 (DE3), and purified as previously described [LPS was purified from escribed . The ompescribed .V. cholerae-specific serum antibodies, plates were coated with V. cholerae LPS (2.5 μg/ml), heat-killed V. cholerae (HKVC) (108 CFU/ml), or recombinant OmpU  at 4°C overnight. Titers of total antibody and V. cholerae-specific antibody were calculated with Softmax Pro version 4.8 (Molecular Device). Antibody titers below 40 were considered as 20 for statistical analysis as described previously [To quantify total antibody isotypes in serum samples, a 96-well plate  was coated with anti-human κ and λ light chain antibodies  overnight at 4°C and blocked with BSA. Serially diluted sera and human IgM, IgG, or IgA (1 μg/ml)  were added. After incubation at 37°C for 2 h, serum antibody isotypes were detected with alkaline phosphatase-conjugated anti-human IgM, IgG, or IgA (Jackson Immunoresearch) and developed with 4-nitrophenyl phosphate . Optical density was read at 405 nm using a microplate reader . To measure eviously .V. cholerae O1 (strain T19479) were cultured in 20 ml of BHI media for 2–3 h at 37°C until they reached mid-log phase. Bacteria were collected by centrifugation, washed with saline, and diluted with saline containing 10% guinea pig complements to adjust to 1×106 cells/ml. An equal volume of diluted bacteria was added to the 96-well plate containing serially-diluted serum samples, and the plates were incubated at 37°C for 1 h. Next, 150 μl of fresh BHI broth was added, and plates were incubated for an additional 4 h. Bacterial growth was measured at OD600 using a microtiter-plate reader . The definition of vibriocidal antibody titer was the reciprocal of the highest serum-dilution fold completely inhibiting bacterial growth.The vibriocidal assay was performed as previously described . Briefly, serum samples were diluted with 0.85% saline from 1 in 2.5 to 1 in 1,280 or more as necessary. Each well of a 96-well plate  was filled with 25 μl of sample. Fresh colonies of To see which isotype was most closely correlated with vibriocidal activity, convalescent sera were separated by size exclusion chromatography using Superdex 200 10/300GL  as previously described . A 200 μ5 cells per well at 37°C in an incubator with 5% CO2 for 1 week until the cells reached confluence, were used for adhesion assay as previously described [V. cholerae was grown at 37°C overnight in LB broth and washed three times with PBS. Then, the bacteria (1 x 106 CFU/ml) were incubated with serially-diluted sera or specific isotype-depleted sera for 1 h at 4°C and added to a 24-well plate containing HT-29 cells. After 1 h incubation with gentle shaking, HT-29 cells were washed with PBS to remove unbound bacteria and lysed cells using 0.2% Triton X-100 for 10 min. The lysed cells were diluted and plated on LB agar plate to determine the number of adherent bacteria.HT-29 cells, cultured in a 24-multi-well plate at 2 x 10r), and P values were obtained using GraphPad Prism 5 software . Statistical differences between two groups were determined by two-tailed Student’s t-tests.To compare vibriocidal antibody titers and the levels of LPS-specific antibody isotypes, the results of each serum sample obtained by two assays were plotted against each other. The relationship between the two values was examined by Spearman correlation coefficient  in the final step, respectively, during the IgM removal procedure despite about 16-fold decrease in the vibriocidal titers , LPS, or recombinant outer-membrane protein U (rOmpU), which is the most abundant outer-membrane protein of V. cholreae, to see whether there was a correlation between V. cholerae-specific antibody isotype and vibriocidal titer. As shown in r) between IgM and vibriocidal titer was 0.846 (P < 0.001) against V. cholerae LPS, 0.741 (P < 0.001) against HKVC, and 0.320 (P = 0.169) against OmpU. In contrast, serum vibriocidal titer was shown to be more weakly correlated with V. cholerae-specific IgA or IgG; r = 0.439 (P = 0.053) for anti-LPS IgG, r = 0.473 (P = 0.035) for anti-LPS IgA, r = 0.458 (P = 0.043) for anti-HKVC IgG, r = 0.416 (P = 0.068) for anti-HKVC IgA, r = -0.306 (P = 0.189) for anti-OmpU IgG, and r = 0.083 (P = 0.728) for anti-OmpU IgA. These results imply that serum anti-LPS IgM is most highly correlated with vibriocidal antibody.Next, we quantified antibody isotypes against heat-killed V. cholerae colonizes to the intestinal epithelial layer to cause disease [V. cholerae sera in the inhibition of bacterial adherence, bacteria pre-incubated with various dilutions of human convalescent sera and washed were applied to HT-29 human intestinal epithelial cells. As shown in V. cholerae to HT-29 cells, but all diluted convalescent sera significantly inhibited bacterial adhesion compared with the control group (P < 0.001). Next, to see which isotype(s) of antibodies is(are) important for inhibition of bacterial adherence, V. cholerae was mixed with each isotype-depleted convalescent serum for 1 h at 4°C and applied to HT-29 cells (V. cholerae was pre-treated with IgM-depleted sera (P < 0.05) and IgA-depleted sera (P = 0.107), respectively. These data indicate that human anti-V. cholerae antibodies play a pivotal role in prevention of the bacterial colonization in the human epithelial layer. Our results suggest that IgM is the isotype responsible for inhibition of bacterial adherence, with IgA playing a less important role.Since  disease , interfe29 cells . Non-depV. cholerae to differentiated HT-29 cells was significantly (P < 0.05) inhibited by pre-treatment with high-titer sera compared with pre-treatment with low-titer sera (P< 0.001) higher at 729 (range from 417 to 1163) than that for the low-titer group at 199 (range from 56 to 433)  . ConsideV. cholerae LPS-specific IgM was highly correlated with its bactericidal activity in the clinical specimen. The correlation was further demonstrated by showing that the fractions responsible for vibriocidal activity were IgM rather than IgG or IgA, and that depletion of IgM showed significant decrease in vibriocidal titer, which was not shown with either IgG or IgA depletion. In addition, sera with high vibriocidal titer and anti-V. cholerae LPS IgM level substantially inhibited the attachment of V. cholerae to intestinal epithelial cells, while sera with low vibriocidal titer or IgM-depleted sera did not. All these data indicate that serum anti-V. cholerae LPS IgM is responsible for vibriocidal activity and inhibition of bacterial adhesion to intestinal mucosa.Serum vibriocidal antibody titer has been widely used to evaluate protective immunity to cholera in populations suffering from infection or in those administered cholera vaccines , 29. PreV. cholerae LPS IgM is responsible for vibriocidal activity in serum, which was also found in other studies on V. cholerae as well as other bacterial infectious diseases [Escherichia coli in patients with liver cirrhosis was also associated with diminished IgM [Haemophilus influenzae Type b conjugate vaccine showed bactericidal activity and protective immunity in an infant rat model [V. cholerae LPS-specific IgG1, IgG3, and IgM are important for vibriocidal activity and agglutination antibody [V. cholerae or the vaccination. On the other hand, IgG1 and IgG3 are also associated with vibriocidal antibody as well as IgM in the secondary exposure [Our results suggest that anti-diseases , 31, 32.shed IgM . In anotat model , 35. In antibody , 14. In exposure , 14. Recexposure . Thus, IV. cholerae LPS is considered as a major virulence factor, and anti-V. cholerae LPS antibody is closely associated with protective immunity against cholera [data not shown). The role of LPS was further supported by a previous result that cross-serotype challenge of V. cholerae O1 after primary exposure to either O1 Inaba or O1 Ogawa in human volunteers elicited prolonged stool excretion of vibrio compared with homologous serotype challenge [V. cholerae LPS IgM and vibriocidal antibody titer after cholera vaccination have a positive correlation with inhibition of bacterial colonization in human epithelial cells. Similar results have been reported previously, indicating that vibriocidal antibody, but neither anti-V. cholerae LPS IgG nor anti-toxin IgA, is associated with protection against V. cholerae O1 colonization and disease occurrence [V. cholerae O1 adheres to M cells in the human small intestine and is transported to Peyer’s patches for induction of immune responses [V. cholerae O1 cells were attached to M cells in immunized rats compared with unimmunized animals, suggesting that V. cholerae infection interferes with active mucosal immune responses [V. cholerae LPS IgM may play a role in the inhibition of bacterial adherence. cholera , 38. In  cholera  and chil cholera . It is challenge . In the currence , and a 1currence . Previouesponses , 42. Fewesponses . Anti-V.V. cholerae in serum may be an indirect indicator of blocked bacterial adhesion to intestinal cells. In fact, a small proportion of IgA may be directly secreted from gut-derived B cells in the blood [V. cholerae LPS-specific secretory IgA is increased in convalescent sera and intestinal fluids of cholera patients [in vitro may be useful to assess intestinal colonization of V. cholerae.Here, we found that bacterial adherence to human epithelial cells increased by depletion of IgA as well as by depletion of IgM in serum, although the effect of IgA was not statistically significant . Polymerhe blood , and up he blood . Furtherpatients , 8. In apatients . It is ipatients , 47. ThuV. cholerae. The colonization of V. cholerae to the epithelium of small intestine has been well described in several factors including TCP [V. cholerae but such effect was not observed with antiserum devoid of anti-LPS antibodies [V. cholerae OSP or LPS-specific antibodies may arrest and/or agglutinate bacteria in the mucosal area and reduce opportunity to interact with intestinal epithelium [IgM-mediated inhibition of bacterial adhesion seems to be associated with agglutination of ding TCP , GbpA [4ding TCP , outer mding TCP , and LPSding TCP . Antibodtibodies . Moreovetibodies  which isithelium , 51, 52.in vitro model for interaction between host and enteric pathogens due to the similarity of structure and their function [V. cholerae in the HT-29 cell may be useful in vitro tool to investigate the interaction with intestinal epithelium, there are some limitations to reflect in vivo phenomena of small intestine in respect to the different mucus layer. Goblet cells of small intestine secrete highly glycosylated mucin, MUC-2, and have higher viscosity and complex structure [V. cholerae colonizes differently in the regions  of small intestine [The human colon carcinoma cell line, HT-29 cells, have been widely used for function , 54. Espfunction . Althougtructure  while HTtructure . Furtherntestine .Previous study reported that oral cholera vaccination preferentially increased intestinal IgG-secreting cells rather than IgM-secreting cells in the IgA-deficient patients . TherefoV. cholerae LPS IgM is highly correlated with serum vibriocidal activity and it could be a surrogate antibody isotype representing protective antibodies against V. cholerae.In conclusion, we demonstrated that anti-


Veterans who access both the Veterans Health Administration (VA) and non-VA health care systems require effective care coordination to avoid adverse health care outcomes. These dual-use Veterans have diverse and complex needs. Gaps in transitions of care between VA and non-VA systems are common. The Advanced Care Coordination (ACC) quality improvement program aims to address these gaps by implementing a comprehensive longitudinal care coordination intervention with a focus on Veterans’ social determinants of health (SDOH) to facilitate Veterans’ transitions of care back to the Eastern Colorado Health Care System (ECHCS) for follow-up care.The ACC program is an ongoing quality improvement study that will enroll dual-use Veterans after discharge from non-VA emergency department (EDs), and will provide Veterans with social worker-led longitudinal care coordination addressing SDOH and providing linkage to resources. The ACC social worker will complete biopsychosocial assessments to identify Veteran needs, conduct regular in-person and phone visits, and connect Veterans back to their VA care teams.We will identify non-VA EDs in the Denver, Colorado metro area that will provide the most effective partnership based on location and Veteran need. Veterans will be enrolled into the ACC program when they visit one of our selected non-VA EDs without being hospitalized. We will develop a program database to allow for continuous evaluation. Continuing education and outreach including the development of a resource guide, Veteran Care Cards, and program newsletters will generate program buy-in and bridge communication. We will evaluate our program using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, supported by the Practical, Robust Implementation and Sustainability Model, Theoretical Domains Framework, and process mapping.The ACC program will improve care coordination for dual-use Veterans by implementing social-work led longitudinal care coordination addressing Veterans’ SDOH. This intervention will provide an essential service for effective care coordination. Veterans with complex health care needs increasingly utilize both the Veterans Health Administration (VA) and non-VA hospitals –3. RoughCurrently, gaps are common in systematic methods of care coordination between the VA and non-VA hospitals. As a result, some Veterans must manage their own care coordination  or rely Successful care coordination programs are imperative to assist the VA in meeting its goal of providing high-quality, timely access to care for Veterans , 25, andThis social-work led program will complete comprehensive assessments to evaluate each Veteran’s SDOH and their areas of need. Complete care coordination will include health assessments that review medical, psychosocial, behavioral health, and functional needs, regular phone contact and home and community visits as needed, and utilization of a multidisciplinary approach. This program will add value to the pre-existing care coordination system by efficiently using VA and community resources and by avoiding the duplication of health care services provided to Veterans, as duplicated services could create unnecessary confusion. Additionally, as the Eastern Colorado Health Care System (ECHCS) and non-VA hospitals are equal participants in this collaborative program, internal and external stakeholder engagement is paramount to the success of an enhanced care coordination program.The Advanced Care Coordination (ACC) program is designed to be an ongoing quality improvement (QI), social worker-driven program that provides longitudinal care coordination for up to 90 days to address SDOH for dual-use Veterans who access non-VA EDs. The objectives of the ACC program are 1) to identify gaps in the collaboration process between the ECHCS and non-VA health care systems and to decrease non-VA ED use due to SDOH, and 2) to implement a comprehensive longitudinal care coordination intervention with a focus on Veterans’ SDOH that will enhance existing care coordination within the ECHCS and improve continuity of care for Veterans. With the Mission Act in place, timely care coordination is required. This care coordination program aims to reduce adverse outcomes for dual-users by enhancing care coordination services and improving access to high quality, timely, efficient care for dual-use Veterans.The ACC program was modeled after our existing Veteran-centered, nurse-led care coordination programs, the Community Hospital Transitions Program (CHTP) and the rural Transitions Nurse Program (TNP). The CHTP was designed to provide short-term care coordination to Veterans who use both VA and non-VA health services and have been hospitalized at a non-VA facility . The TNPDrawing on insights from key informant interviews completed for the implementation of CHTP, the ACC program will address identified gaps in care coordination by implementing social worker-led longitudinal care coordination between the VA and non-VA EDs. The ACC program will initially be implemented through the ECHCS Rocky Mountain Regional VAMC (RMR VAMC) in Aurora, Colorado. We plan to expand this program to the VA Nebraska-Western Iowa Health Care System after the program has been implemented at the ECHCS. Lessons learned during the development of the CHTP will be utilized to inform a successful implementation of the ACC program.The ACC program will provide comprehensive care coordination for dual-use Veterans who access non-VA EDs within the Denver, Colorado metro area. We will identify non-VA EDs in the areas that experience a large volume of Veteran admissions based on data available through the VA Business Office. From these data, we will determine which non-VA EDs will provide the most effective partnership based on location in relation to the RMR VAMC and Veteran need. We anticipate that our enrolled sample size will be 250–300 Veterans per year. Staff from our selected non-VA EDs will be asked by the ACC social worker to call us or to fax the Veteran’s History and Physical to notify us that a Veteran has been admitted to their non-VA ED. If the Veteran was discharged home from the non-VA ED, the ACC social worker will reach out to and enroll the Veteran into the ACC program. Veterans who are hospitalized in non-VA hospitals will not be enrolled into the ACC program and will be referred to the CHTP to avoid duplication of services.Veterans who access our selected non-VA EDs will be eligible for enrollment into the ACC program if they meet the following criteria: 1) the Veteran is already receiving care through the ECHCS VA, or 2) the Veteran would like to establish care at the ECHCS VA. Veterans who are already enrolled into services in the ECHCS and are receiving ongoing case management from an ECHCS social worker will not be eligible for the ACC program as this would be a duplication of services. Additionally, Veterans who are discharged from the non-VA ED to a skilled nursing facility, long-term care facility, or assisted living facility will be excluded from the ACC program as they will receive case management at these respective facilities. Veterans with no working phone or who have been unable to reach after being called three times by the ACC social worker over a period of 2 weeks will also be excluded. Veterans who do not want to receive care through the VA will not be enrolled into the ACC program.The ACC program consists of four core components  to 4 (having significant needs), which the ACC social worker will use to guide further interventions.Based upon the Veteran’s acuity level, the ACC social worker will intervene with the goal of improving the Veteran’s health outcomes and reducing the Veteran’s total health care costs using the VA Office of Community Care (VA OCC) Care Coordination guidelines as a resource. The VA OCC guidelines state that the VA must provide seamless Veteran-centered care coordination and collaboration between the VA and non-VA providers, in order provide Veterans with quality and timely health care services. Additionally, the VA OCC website outlines how best to coordinate quality health care services for Veterans with the VA . The ACCThe ACC social worker will provide varying degrees of case management to each Veteran. Veterans with a lower acuity will be enrolled into the ACC program for 2 weeks or less. Veterans with a higher acuity level will be enrolled into the ACC program for up to 90 days post non-VA ED discharge. The 90-day limit is based on a demonstrated gap in Veteran care during transition periods in the first 90 days post non-VA ED discharge. As part of the clinical intervention, the ACC social worker will provide weekly or bi-weekly phone calls, and if deemed necessary will visit the Veteran in his/her home or in the community if the Veteran is homeless, to complete clinical interventions. These clinical interventions will address needs regarding the Veteran’s SDOH. The interventions will help link the Veteran to resources (both non-VA and VA), such as transportation, rent resources, housing resources, food assistance, financial assistance, home health care, mental health and primary care, and substance use treatment. The ACC social worker will utilize teach-back methodology and Motivational Interviewing techniques to understand and address gaps in discharge preparedness and disease care management. Finally, the ACC social worker will complete a warm hand-off of to the ECHCS PACTs once the clinical interventions have been completed. If the Veteran is still in need of case management services after 90 days of assistance through the ACC program, the ACC social worker will connect the Veteran with a PACT social worker who works closely with the Veteran’s assigned primary care physician for continued case management. Data collected from these interventions will be stored in the ACC program database.We will provide frequent outreach and continuing education to both the ECHCS and non-VA providers to elicit program feedback and ensure effective collaboration between the ACC social worker, the non-VA ED partners, the ECHCS PACTs, and Veterans admitted to non-VA EDs. Before implementing the program, we will conduct initial in-service meetings with each partner non-VA ED and related VA departments to discuss the program’s benefits and responsibilities. These meetings will promote awareness and collaboration during the program’s initial rollout. After the program’s initiation, we will provide frequent in-services to non-VA ED staff as well as ECHCS providers to facilitate information transfer with the ECHCS and to educate them on program adaptations as well as to elicit feedback for program improvement. During these in-services we will also solicit program feedback from the meeting participants to enhance collaboration and adapt the ACC program as necessary. We will design a transitions of care resource guide modeled on the resource guide employed by the CHTP , which wOur education in non-VA EDs will be supplemented by Veteran outreach, which we will accomplish by creating a Veteran Care Card that we will mail out to Veterans who participate in the ACC program. The Care Card will include relevant care coordination resources including direct secure phone and fax numbers for the ACC program, resources for the VA Billing department, and the name of the Veteran’s ECHCS Primary Care Provider. We will also send out a letter with the Care Card that further outlines care coordination resources for the Veterans and that includes their PACT social workers’ contact information. Once Veterans have completed their involvement with the ACC program we will mail them a graduation letter with pertinent information regarding resources for the Veterans, goals that were worked on during their involvement with the ACC program, goals the Veterans are continuing to work on, and pertinent provider contact information. With the essential information at hand, these Veterans will have a one-stop-resource to initiate care coordination when admitted to non-VA EDs.This project will be carried out in partnership with the VA OCC, ECHCS stakeholders, and the Veterans Integrated Service Network (VISN) 19. The ACC program is funded through the Office of Veterans Access to Care (OVAC) and the Office of Rural Health (ORH). These departments provide protected time for project personnel to participate in this QI intervention. The ACC program has been integrated into the Triple-Aim Quality Enhancement Research Initiative (QUERI) Program, which funded the CHTP. QUERI has funded these programs with the purpose of supporting QI interventions to enhance Veteran care and promoting learning healthcare systems as well as enhancing clinical practice through research. The proposed program will enhance ECHCS and non-VA partnerships by facilitating care coordination among non-VA ED utilizers.We have a multidisciplinary team consisting of experts in qualitative and quantitative research, statistics, data management, implementation science, clinical intervention specialists and consultants, public health, nursing, medicine, health economics, social work, and a national training educator. Our team has unique and diverse expertise that allows us to evaluate the implementation of a comprehensive care coordination program in the VA and its expansion to other sites.We will evaluate our intervention and implementation strategies using a multi-level approach   measuresReach will be defined by the number, proportion, and representativeness of Veterans who received full and/or partial interventions through the ACC program. We will develop and utilize the ACC program access database to gather the number, proportion, and representativeness of all the Veterans referred to the ACC program. In addition, we will utilize the ACC program database to assess the number, proportion, and representativeness of Veterans who reached out to the ACC program after receiving our Care Card and the Care Card letter. Information on basic characteristics, including reason for non-VA ED visit, co-morbidities, level of acuity , and Care Assessment Need (CAN) scores of the Veterans who were enrolled into the ACC program will also be collected in the ACC program database. The above information will also be collected through the VA’s Computerized Patient Record System (CPRS) and Corporate Data Warehouse (CDW), fee basis data, and the stakeholder engagement spreadsheet developed for our program. These data will be obtained bi-annually from our program database. We will complete weekly database checks and will review the reports section in our database to assess the data.Effectiveness will be evaluated in several ways. We will measure hospitalization and both VA and non-VA ED 90-day readmission rates for Veterans who received the ACC program intervention by reviewing our program database as well as CDW/fee basis data. This review will be conducted annually. We will obtain VA readmission data through CDW/fee basis data as well as through readmission rates in our program database. We have paid to obtain claims data from some of our partner non-VA hospitals and will use it to help measure 90-day readmission rates. Finally, we will determine the number, proportion, and representativeness of Veterans who received additional care and services due to the ACC program’s involvement.We will analyze the information above by reviewing our program database and CDW/fee basis data annually. We will develop a survey to evaluate Veteran and provider satisfaction of care coordination and will utilize Interactive Voice Response (IVR) technology to implement the survey annually. We will evaluate the quality of transitions of care using the validated Care Transition Measure , 36. In Adoption will be measured by the number, proportion, and representativeness of times that non-VA EDs notify the ACC program of a Veteran’s non-VA ED visit/discharge. We will collect information through the notification method checklist for each referral  in our program database. We will also measure the number and roles of VA providers who collaborate with and provide referrals to the ACC program throughout the duration of the intervention. We will utilize CPRS notes as well as our program database to obtain this information. The evaluation team will have regular database checks and data will be pulled bi-annually for further analyses.Implementation will be assessed by determining barriers and facilitators to implementation as well as through an economic evaluation that includes measuring costs associated with implementation and comparing them to potential cost offsets and health outcomes gained. We will track adaptations to the intervention and will complete a final assessment post-intervention completion to determine fidelity to the program delivery. The secure access database we create for the ACC program will be our primary measurement tool to track the ACC program interventions for each core component. The ACC social worker will enter data for the core components into the database in real-time. Database checks to see all or part of the core component completion will be done bi-annually. We will utilize the database to measure the acuity levels of the Veterans, the quantity of Veterans who completed all four core components, the length of time the Veterans are enrolled in the ACC program, the interventions Veterans have received from the ACC social worker, and readmission rates for Veterans who have been enrolled into the ACC program. Our health economist will complete a tool that tracks all implementation costs and will analyze it in the final assessment of the program. At the completion of the program we will execute a final analysis of implementation costs. We will complete qualitative interviews as a final assessment at the end of data collection to evaluate our implementation.We will employ conventional content analysis study design to collect and analyze qualitative data for program implementation and evaluation. We will collect qualitative and process data during our mid-line evaluation 8 months after program rollout to inform the evaluation of the implementation outcomes. We will develop and then conduct semi-structured interviews guided by the PRISM framework  and the Atlas.ti will be used to manage qualitative content. Transcripts will be organized and labeled by role and site in Atlas.ti to ensure ability to examine site-specific and role-specific information as well as overall data. We will use team-based consensus building to create a codebook and analyze for emerging themes. Analysis codes will be organized into domains and larger themes as they emerge. Key findings from all coded interviews will be summarized into one process map and process narrative. Variations in the process of transferring patients from non-VA EDs to the assigned VA primary care team will be included in the process narrative. A team of experienced qualitative analysts will conduct analyses using inductive and deductive approaches.Our qualitative analysts will create a process map to depict the ideal transitions of care process. On a monthly basis, they will collaborate with the ACC social worker to revisit the program’s process and will update the process map to reflect changes and adaptations to the ACC program. Information to inform the process map will be collected throughout the implementation of the program. Any adaptations will also be recorded in our adaptations spreadsheet. This iterative process will allow the team to analyze, revise, and adapt our program until an ideal process is reached. We will train the ACC social worker at each site to use the Lean Six Sigma approach  to map hWe will track adaptations to the program as its implementation at each site and changes that are made to make the program fit to each local context. Adaptations will be tracked by the ACC social worker on monthly basis. These adaptations will be documented through changes to process maps and in a modified Stirman spreadsheet. Additional data will be collected through semi-structured interviews that we will develop approximately 6 months after the rollout and at the end of outcome data collection. Adaptations data will be analyzed during the summative evaluation with a goal of informing implementation outcomes.Maintenance will be measured by assessing local adaptability and continued implementation of the ACC program after the funding period ends through internal and external communication. We will also determine the maintenance of the ACC program through rapid prototyping and the feasibility of intervention expansion. We will measure this through our quantity of expansion sites and their ability to implement the program.We will administer the Relational Coordination Survey, in partnership with RC Analytics , 40, to The ACC program will promote care coordination for dual-use Veterans who access non-VA EDs by utilizing a social worker to provide longitudinal care coordination and resource referrals with an emphasis on SDOH. By expanding the work done with the CHTP, the ACC program will bridge additional identified gaps in care coordination for dual-use Veterans and provide smooth transitions of care back to their VA primary care.This program may be constrained by a few limitations. The program will rely upon receiving notifications from non-VA ED staff when Veterans access their non-VA ED. It is not guaranteed that non-VA staff will incorporate this process into their workflow. However, based upon interviews with stakeholders from non-VA EDs, we expect non-VA EDs to embrace and collaborate with our program. Additionally, Veterans may be readmitted to non-VA EDs or to the VA ED while enrolled in this program, which could cause challenges for continuity of care. Limitations regarding sustainability may arise due to extra cost associated with an additional full-time equivalent (FTE) for a social worker. An economic evaluation will provide further information regarding efficiency for this program. We did not pay for claims data at each partner hospital, and will not have access to admission or utilization readmission rates data at these non-VA ED locations. This could limit the data we have access to when we are evaluating adverse outcomes through 90-day readmission rates. Finally, the ACC program will initially be implemented at two sites with the hope of expanding to more locations in the future. We will initially have a limited cohort; thus, this quality improvement program may not be generalizable to other sites or populations in the beginning phases of implementation.Despite these limitations, the ACC program has numerous strengths. The ACC program is an innovative program within the ECHCS that directly partners with non-VA EDs to facilitate efficient use of health care resources and to reduce the utilization of non-VA EDs due to SDOH issues and to provide Veterans with enhanced continuity of care. The ACC program will implement system changes through offering direct phone and fax lines for the ACC social worker to enhance non-VA providers’ ability to collaborate with and coordinate care for Veterans with ECHCS providers, ultimately improving the relationship between the ECHCS and non-VA hospitals. Additionally, through regular in-services with non-VA providers, the ACC program will enhance community care provided to Veterans by educating non-VA providers about the process of accessing various services provided through the ECHCS. If successful, this program will enhance care provided to dual-use Veterans and will increase efficient use of resources.The ACC program intervention is designed to provide support to Veterans during a vulnerable period of transition from hospital to home. The ACC program will offer case management services to Veterans during this time, linking them to appropriate resources and enhancing their stability in order to reduce potential non-VA and VA ED or hospital readmissions. The ACC program consists of a multidisciplinary team to effectively discuss complex cases, to review best ways to improve care for dual-use Veterans, and to ultimately link dual-use Veterans to comprehensive services with the intention of providing quality care tailored to each Veteran’s specific needs.The ACC program will improve care coordination for dual-use Veterans. By expanding the CHTP to incorporate longitudinal care coordination and SDOH, the ACC program will provide the necessary steps to close gaps in care coordination and to ensure quality transitions of care for Veterans who access non-VA EDs.


Experiences of sexual prejudice threaten the quality of life and psychological well-being of sexual minority youth. The aim of this paper is to provide a comprehensive overview of how we developed a theory- and evidence-based sexual prejudice reduction program suitable for the Dutch high school context, guided by the intervention mapping approach (IM). In line with IM, six steps were followed: an initial needs assessment in which empirical, theoretical, and new data were gathered to acquire a thorough understanding of the problem (step 1); the formulation of program objectives for both students and teachers (step 2); the selection of theory-based methods and applications (step 3); program development (step 4); the provision of an adoption and implementation plan (step 5); and the development of an evaluation plan (step 6). In conclusion, developing a sexual prejudice reduction program for schools is a challenging but feasible process. IM is an effective tool for the systematic (theory- and evidence-driven) development of such a program. Although acceptance of homosexuality is slowly increasing in several Western countries Smith, , prejudiWhile the Netherlands is one of the more tolerant countries regarding acceptance of homosexuality , and the personal story method . Both approaches have shown mixed results in terms of changing students’ and teachers’ attitudes and behaviors towards LGB youth  which focuses on a thorough problem analysis, resulting in a “logic model of the problem.” This includes a description of the health-related problem; quality-of-life impact; the at-risk population; and social-cognitive, behavioral, and environmental factors (and their determinants) thought to be related to the problem. Next, planners select target groups and formulate objectives for change at the behavioral level and at the social-cognitive level, based on importance and changeability (step 2). In step 3, planners select theory-based methods and strategies which are then integrated into the final program (step 4). Program adoption and implementation is described in step 5 and the program evaluation plan is produced in the last step (step 6).explain behavior and theories that can be used to understand how to change behavior  and Rutgers  published their report on the sexual health of youth in the Netherlands called “sex below 25”  quality of life and (high) prejudice experiences between subgroups, each subgroup also has to deal with unique quality of life issues and prejudice experiences , 51.1% girls). For reasons of homogeneity , we decided to focus only on negative intentions towards homosexual individuals as the outcome measure and not specifically used lesbians and bisexuals in the formulation of the questions. Relative importance analyses were then performed in order to select the most important determinants involved in sexual prejudice   were all strongly related to prejudiced responses. For a more comprehensive report on individual determinants and their relative importance in influencing sexual prejudice, see Mevissen et al. Correlates of sexual prejudice among Dutch adolescents: A relative importance approach (under review). Based on these analyses, the following most important and changeable determinants influencing sexual prejudice were selected to be targeted (in 15+ high school students enrolled in higher level secondary education) by the sexual diversity program: attitude, contact, attribution, and affect (emotions).Based on the findings of step 1, we decided to focus on the following three program goals: (1) reduction of sexual prejudice, including homophobic bullying, among high school students; (2) teachers and students creating a safe school environment; (3) increased well-being among LGB students.Together with a multidisciplinary linkage group, objectives were formulated in order to attain the program goals defined at the end of step 1. At this stage, the linkage group consisted of 22 participants: two stigma research experts, four applied psychology researchers ), one social worker, one public health worker, and 14 teachers. Together with the researchers, the social worker, and the public health worker, the PI defined desired changes for the target population at the behavioral level .respect sexual diversity and leave sexual minorities alone), while those for the bystanders are more directed towards active involvement . We expected the perpetrators to be the most strongly prejudiced against homosexuality and to be the most difficult to change. Trying to make the perpetrators befriend LGB individuals is thus not a realistic goal and the number of POs for them was therefore limited. The concept of “respect” and being respected—or being able to be yourself—is a very important issue for adolescents, and may be something more easily taken on board by perpetrators than a request to “accept sexual diversity.”As no examples of systematically developed sexual prejudice-reduction interventions were available in the literature to guide the development of the objectives, the project team decided to look again into the literature addressing school-based bullying behavior and prevention Olweus, . The worFurthermore, we developed POs for LGB individuals with the aim of increasing well-being by helping them to cope with sexual prejudice and self-stigma. We formulated three POs in relation to LGB students. The first is to mobilize  support if needed. Research has shown that LGB individuals who are supported by others suffer less from the consequences of sexual prejudice Kwon, . Other sFinally, the POs for the teachers focused on intervening  and providing support for young LGB students. The studies conducted by Olweus  and HoniAfter formulating the POs, determinants related to each PO had to be selected. The selection of determinants was based on theories of stigma, theories of health behavior, and the relative importance analyses conducted as part of our needs assessment. The selection was not only based on the importance of a specific determinant for a specific PO, but also on its changeability. For example, the determinant “social norm” was expected to have a big influence on the PO “Leave LGB peers (or those you think may be LGB) alone,” especially within a school context. However, the literature shows that changing social norms is relatively difficult . The goals and objectives were discussed and fine-tuned in collaboration with the members of the linkage group. During two focus group interviews, feedback provided by the teachers was used to finalize the matrix.After determinants for each PO had been selected, the objectives for change at the social-cognitive level could be formulated. Changes objectives (COs) were formulated by matching each determinant with its specific PO, after which the COs content were guided by the needs assessment. For example, in relation to the PO for perpetrators “Leave LGB peers (or those you think may be LGB) alone,” we selected “attitude” as one of the determinants. For this specific attitude–PO combination, we formulated the CO “perpetrators acknowledge the importance of not giving negative attention to LGB peers,” as the needs assessment showed that perpetrators of bullying behavior are difficult to change—so this CO seemed to be the most achievable option. Likewise, in relation to the PO for bystanders “Report sexual prejudice or bullying to a teacher or a confidential advisor,” we selected “skills” as one of the determinants, and the related CO was formulated as “Describe how you recognize  prejudice and bullying,” as the needs assessment showed that bullying behavior can be difficult to recognize as it often happens in a hidden way Marston, . Table 2Unfortunately, and again due to time and money restrictions, at the end of step 2, the program developers concluded that it was not possible to develop an intervention or training program specifically for the teachers in order to target the POs and COs that were formulated to change their behavior. According to the teachers, this was not too much of a problem because they already felt sufficiently able to intervene in cases of bullying and were confident that they could support LGB students.Having defined objectives for change, theoretical methods were selected from the literature. Methods were then translated into practical applications appropriate for the school-based context of the program. The selection of methods and applications was an iterative process: methods were selected from the literature and, following a brainstorming session, were translated into a potentially feasible practical application. However, the opposite process also took place: existing stigma-reduction programs were reviewed for their applicability in our sexual diversity program. If applicable, the program was related to theoretical methods. If necessary, adjustments were made such that the application was fully in line with the evidence-based theoretical method. We asked for feedback from the teachers on these methods and applications in a focus group interview.Our sexual diversity program was developed as part of a larger school-based program on sexual health called LLL+ . LLL+ wThe project team therefore selected methods and applications that would fit the context in which the sexual diversity program would be used. This meant that the final program should be flexible in use, easy to adjust to different classroom circumstances, and mainly comprised of off-line assignments. In addition, our target group included pre-university students; the program should therefore be mentally challenging enough to match the target groups’ mental capacities. Also, the program would need a comprehensive and detailed teacher manual to guide the teacher in performing the lessons. Table To target, for example, the CO “mention that homosexuality is nature and not nurture,” which relates to the determinant “knowledge,” we selected the methods “active learning,” “discussion,” and “elaboration.” All three methods are expected to change knowledge in a long-lasting way , that specific component was pilot-tested among students in the classroom by one or several of the teachers and—if necessary—the component was adjusted. Table The final program consists of five assignments divided over two teaching hours or lessons. The first lesson includes three assignments which introduces the topic of sexual diversity, provides some background information and facts, and focuses on breaking down stereotypical ideas about homosexuality by targeting the determinants knowledge, awareness, empathy, and subjective norms. The second lesson includes two assignments addressing coming out, first introduced from the perspective of the LGB-person (“how would it be?”) and, in the next assignment, from the perspective of the bystanders (“what can YOU do to make your school/class a bully-free environment?”). This lesson focuses more on attitudes, empathy, affect, self-efficacy, and skills.www.coc.nl). All materials are provided for free via the website that was developed as part of the larger school-based sexual health program  LGB students—or those students who are still uncertain of their sexual identity—with information on LGB community and support websites. The two videos included in the program were adopted from COC  program objectives, program applications, etc.) such that it would fit the teachers’ context and overcome any barriers they mentioned, and partly by including guidance via the teacher manual . Another potential constraint is that group-work or individual assignments do not always work well in each class. To deal with this barrier, the teacher manual provides multiple suggestions in relation to each assignment. In this way, the teacher can select the strategy that best fits the specific class-context, without having to skip an assignment (influencing completeness) or having to adjust an assignment (influencing fidelity).Regarding outcome belief for teachers is the importance of the student learning outcomes and whether students like the lessons  had to be taken into account. We used several strategies in order to accomplish this.From the beginning of the project, it became clear that the teachers’ main concern was related to time. The teachers in the linkage group stressed repeatedly that they have a very busy schedule, with many competing targets and too little teaching hours to include everything that they would like to. This time constraint, which was not mentioned in the literature, is probably explained by the fact that our target group is high school students who are entering their graduation years . Teachers thus experience a lot of pressure to fulfill all official learning objectives as stated by the government. It was clear for the project team that these time constraints  on the one hand, and fitting everything into a limited number of teaching hours (2 h) on the other. Having a program that needed too many teaching hours would be a serious threat for its adoption. This meant that a selection had to be made in terms of which COs to include in the final program. The decision-making process with regard to which COs to exclude was partly guided by the literature (theory and evidence) on the importance and changeability of the determinants and COs in question. Additionally, our aim was to include a logical and comprehensive selection of topics in the final program. Together, these decision-making processes resulted in, for example, leaving out COs related to social norms, as these are more difficult to change —particularly important if the teacher is short of time. Hopefully, this will guarantee that at least the most important objectives will be targeted. While we are aware that the latter suggestion is not in line with having the program implemented completely, we are also aware of the need to be pragmatic. Throughout the entire developmental process, teachers repeatedly emphasized their lack of time to us. We therefore concluded that it was better to provide guidance in terms of which exercises to prioritize in situations where their time is very limited. Finally, and probably most importantly, another strategy we used to enhance adoption and implementation was to ensure that the objectives of the program matched the learning objectives as formulated by the government. At the time of developing our sexual diversity program, the learning objectives for Biology were being updated and reformulated. One of the teachers in our linkage group was a member of the committee that contributed to the reformulation of the learning objectives concerning the topic of sexuality. The objectives formulated for LLL+ by the project team were adopted by this committee and subsequently by the government. In addition, the committee included the Long Live Love program, including the sexual diversity program described here, in the list of recommended school programs that could be implemented to fulfill the learning objectives as formulated by the government.The teachers in the linkage group said that they did not need support in teaching sexual diversity , but that it could be an issue for other teachers. We did not have funds available to develop further supporting materials for teachers  as part of the sexual diversity program. The project team therefore decided to refer teachers to an e-coaching website that was developed as part of another project  sexual prejudice, outcomes for the students  as well as outcomes for the implementers, the teachers  were identified. For the students, it was decided that the performance objectives as formulated in step 2—as well as the determinants and change objectives as described in the matrices—would be adequate evaluation measures and preferable to the use of standardized, more general measures of sexual prejudice. The project group recommended testing the effectiveness of the programs among a wider sample of Dutch high schools using a randomized controlled trial. For the process evaluation, it was decided that interviews with both teachers and students should be conducted, focusing on their assessment of the program and factors influencing completeness and fidelity of program implementation. The actual evaluation of the sexual prejudice reduction program took place as part of a pilot implementation of the entire LLL+ program. The reports on these evaluations are currently in progress.www.langlevedeliefde.nl). The aim of this sexual prejudice reduction program is to reduce negative behavior towards lesbian, gay, and bisexual (LGB) individuals, mobilize social support, and strengthen the coping skills of LGB teenagers. Research on (reduction of) sexual prejudice so far lacks a tradition in systematic intervention development  program for senior high school students aged 15+ (in Dutch Lang Leve de Liefde Bovenbouw. See Applying each of the different steps of IM provided useful insights which then guided subsequent steps. As part of the needs assessment (step 1), additional data were gathered on determinants of sexual prejudice among Dutch high school students. These data provided information on the relative importance of each of the determinants ).—findings that guided the decisions made regarding the intervention objectives in the subsequent step (step 2). Another important contribution in terms of shaping the intervention objectives in step 2 were the insights gained from reviewing the literature on bullying behavior Olweus, . Some asIn our view, the multidisciplinary linkage group was vital to the development of the program. The input from different experts not only guided theory- and evidence-based decisions, but also resulted in many creative solutions being put forward. The input from the teachers was extremely influential in terms of shaping the final intervention into a program that would be feasible for them to implement, i.e., a program flexible in use, that can be adjusted to suit different school contexts and class-dynamics, and, importantly, one that is not too time consuming. Although actual levels of adoption and implementation of the sexual prejudice reduction program have not yet been evaluated, it is likely that both the existence of official governmental policies requiring inclusion of the topic of sexual diversity in the school curriculum and the fact that teachers were involved in program development will help in enhancing program implementation  will contribute to increased health and well-being among LGB youth by providing them support and by reducing sexual prejudice among their peers. Additionally, our work may not only inspire researchers but also teachers and other people around the globe working with youth on how to develop their own prejudice reduction programs in a systematic way. Finally, this paper may guide policy makers in developing standards and guidelines for the adoption and implementation of theory- and evidence-based sexual prejudice reduction programs and interventions.