The Medical Library Association (MLA) appointed a Diversity and Inclusion Task Force (DITF) in 2017. Sandra G. Franklin, AHIP, FMLA, chaired the task force and guided initiatives. From 2017 to 2020, the task force completed a review of MLA defining documents—including the mission, vision, values, and code of ethics—resulting in language updates to these documents. As MLA transitioned through the communities process, the DITF contributed to the transition. Other recommended essential changes to MLA profiles to promote awareness included updating pronouns to promote gender inclusivity and suggestions for the Annual Meeting Innovation Task Force. DITF members actively brought diversity and inclusion programming and engagement to MLA members at annual meetings. The task force held a fish bowl conversation, an open forum, and a Diversity Dialogues roundtable discussion; provided interactive discussion boards; and designed an MLA diversity button. Beyond MLA annual meetings, the task force hosted two critical librarianship meetings and a Twitter chat to engage MLA members with diversity and inclusion topics. Task force members promoted diversity and inclusion beyond their task force appointments with presentations at chapter meetings and other non-DITF MLA annual meeting programming. A notable task force accomplishment included completing a survey of MLA members to gather baseline demographic characteristics, including never before collected data about disability, socioeconomics, and caregiver status. This report provides an overview of DITF activities from 2017 to 2020. Teresa L. Knott, AHIP, 2016/17 Medical Library Association (MLA) president, announced the Board of Director's decision to make diversity and inclusion a strategic goal of the association in December 2016  issues, protect yourself.”“Welcome the discomfort and stress…it means that's exactly where I need to be so I can grow. I lean into it, but I also like when my mind is blown by new concepts & things I used to believe are found to be false (like my biases).”“If you think you're feeling discomfort at educating yourself about #DEI, consider how difficult life is for the marginalized populations and their struggles.”“Too often ‘resilience' or ‘grit' is code for ‘we know the system is broken and biased but it's your job to just power through it as-is.'”“Finding a sense of community outside the library for these conversations, for example, institutional support such as cultural resource centers, student services professionals, and wellness offices.”Training on intervention strategies with various levels of power involved, for example when micro (or macro) aggressions are made, how to stop them and educate someoneHow to engage library personnel who are not supportive of DEI effortsMore content on disability and accessibilityAn official certificate  that keeps track of continual learning regarding DEILGBTQIA+ allyship through action, language, or recommended readingsRecruiting and retaining librarian people of color (POC)https://twitter.com/hashtag/MLADiversity?src=hashtag_click.As is often the case with social media, the hashtag has now grown into its own and is used to discuss DEI issues of relevance to medical librarianship well beyond just the “official” use by the DITF and MLA staff. A history of the hashtag can be viewed at In addition to a proposed motion to create a new DEI Committee within the MLA structure and updates to language in MLA documents, the DITF met their objective to “build activities and programs that create and sustain diverse, inclusive, and welcoming practices” through organized activities that involve MLA membership .DITF members were ardent advocates of DEI and embodied this in their unofficial activities beyond task force membership. A few examples are notable. Bartley led and organized book clubs for MLA members that kept the conversation about diversity and inclusion at the forefront from 2018 to 2020. Pionke took the initiative and created a low stress activity during MLA '19. He brought crayons and sheets of paper and sat in a table area outside of the exhibits hall. Folx joined Pionke to restfully color and engage in conversation. Almader-Douglas designed and presented a poster at the 2018 annual regional meeting of the Medical Library Group of Southern California and Arizona (MLGSCA). Almader-Douglas's poster provided an overview of the formation of the DITF and how efforts of diversity and inclusion fit in the MLA strategic plan, along with the goals and objectives of the task force. Almander-Douglas also provided an overview of task force activities up to that point. Beyond these milestones, Almader-Douglas shared the #MLADiversity hashtag developed by task force members and encouraged MLGSCA members to provide feedback about diversity and inclusion. Finally, Almander-Douglas shared potential next steps that the task force might pursue. These few examples demonstrate the commitment that task force members had toward the topic of DEI.Other related MLA '18 and MLA '19 programmingCE related to diversity themes was offered at MLA annual meetings in 2018 and 2019. These efforts focused on implicit bias training and microaggressions .At MLA '18, the African American Medical Librarians Alliance (AAMLA) SIG sponsored the special content session, “Transforming Libraries Using Implicit Bias Training,” presented by Kimberly L. Reynolds, assistant professor of clinical pediatrics, University of Miami Miller School of Medicine and Pediatric Hospitalist, Holtz Children's Hospital at Jackson Memorial Medical Center. The event was organized and moderated by Jones and Bartley.The ninety-minute interactive session provided an overview of implicit bias, the impact it has in libraries and in health care, and how it stands in the way of diversity and inclusion. An implicit bias is when individuals have attitudes toward people or associate stereotypes with them without their conscious knowledge. Accordingly, the main goals of the session were to help attendees:increase their awareness of implicit bias and the role it plays in the work settinglearn how implicit bias can hinder or enhance the overall effectiveness of librariesgain an understanding of how implicit biases impact hiring decisionsgain practical strategies to help attendees uncover and work through their own biasesContinued interest in the topic and feedback received after this initial session led to the development of future programs and sessions, including:“Microaggressions and More: Continuing the Conversation on Implicit Bias” immersion session at MLA '19“Implicit Bias Training for Information Professionals” CE course at MLA '19, which was also presented at the Upstate New York and Ontario Chapter (UNYOC) Annual Chapter Meeting in October 2019 and at the University of Miami Libraries in March 2020MLA Reads Virtual Book Discussion Group 2018–2020A continuing education webinar was proposed by Christine Willis, AHIP, on the topic of accessibility and disability in libraries, “Serving Patrons with Disabilities in Your Library or Clinic,” and was held April 17, 2020.The “Microaggressions and More: Continuing the Conversation on Implicit Bias” immersion session was held at MLA '19. It was organized by Andy Hickner and the Social Justice Section in collaboration with several MLA communities and members:MLA sections and SIGs involved: AAMLA SIG, Health Disparities, Latinx SIG, Leadership and Management Section, LGBTQIA+ Health Sciences Librarians SIG, and Social Justice SectionMLA members and DITF members involved in organizing this event: Almader-Douglas, James Eddy Anderson, Bartley, Patricia Devine, Tara Douglas-Williams, AHIP, Hickner, Shannon D. Jones, AHIP, Brenda M. Linares, AHIP, Robert T. Mackes, AHIP, Hannah Rutledge, AHIP, Gregg A. Stevens, AHIP, Susan E. Swogger, and Megan ThreatsThe panel discussion was moderated by Linares, and the panelists were: Jones, Almader-Douglas, Rutledge, Anderson, and ThreatsAs part of an ongoing series of MLA programs exploring the topic of implicit bias, the session continued the conversation started with the MLA '18 special content session, “Transforming Libraries Using Implicit Bias Training.” The highly interactive session focused on the concept of microaggressions, defining the term, providing concrete examples of microaggressions in day-to-day professional lives, recognizing when individuals themselves may intentionally or unintentionally exhibit these behaviors, and sharing techniques for responding to them. Microaggressions researcher Threats discussed implicit bias in relation to providing health information services to diverse populations, sharing evidence on how microaggressions and implicit biases impact patients with marginalized identities. The panelists shared their personal and professional experiences with implicit bias and microaggressions. Audience participation during the session included questions for the panelists and the opportunity for audience members to share their own perspectives.JMLA article about critical librarianship that provided a good overview [At MLA '19, DITF members discussed offering a series of free webinars to introduce critical librarianship to health sciences librarians, as Jill Barr-Walker and Claire Sharifi had recently published a overview . Task foThe MLA Reads Virtual Book Discussion Group evolved from the special content session, “Transforming Libraries Using Implicit Bias Training,” which had been presented at MLA '18. Session participants expressed the need for safe spaces to learn, discuss, and process the implications of biases on their work as information professionals and in their personal lives. The virtual book discussion group provided a mechanism for thoughtful discussion on challenging issues and topics in a safe, welcoming, and inclusive environment.Blindspot: Hidden Biases of Good People, as a platform for safe and thought-provoking interactions for discussion. Funding for print books and MLA CE credits for participants was sourced from the National Network of Libraries of Medicine (NNLM) Southeastern Atlantic Region (SEA). Six sessions were held, beginning in December 2018 with a welcome session, followed by four ninety-minute virtual sessions, and culminating with an on-site session at MLA '19. Group facilitators were identified to host eight groups, with an additional facilitator for make-up sessions. They were Jones, Bartley, Melissa De Santis, AHIP, Charlene Finley, Ryan Harris, AHIP, Kathryn Houk, AHIP, Don P. Jason III, Annabelle V. Nuñez, Virginia (Ginny) Pannabecker, AHIP, and Dede Rios, AHIP.Jones and Bartley, the original organizers of the 2018 special content session, planned and facilitated the first virtual book discussion group for approximately fifty librarians on the topic of implicit bias, using Mahzarin R. Banaji and Anthony G. Greenwald's book, The Person You Mean to Be: How Good People Fight Bias by Dolly Chugh. De Santis was able to secure funding from the Midcontinental Region (MCR) of NNLM and sponsorship from the MLA Midcontinental Chapter (MCMLA). De Santis led the organization of the discussion group, along with Jones. The virtual discussion group completed activities in February 2020, with 152 participants and 29 facilitators assigned to 18 scheduled groups, and 2 make-up groups were available for those who could not meet with their assigned groups.The second book discussion took place over four sessions from November 2019 through February 2020. Continuing the conversation on implicit bias, the book chosen for the discussion was Implementing Excellence in Diversity, Equity, and Inclusion: A Handbook for Academic Libraries, to be published by the Association of College & Research Libraries. Authors are some of the original book discussion facilitators: Jones, Bartley, De Santis, Harris, Jason, and Rios.A book chapter with the same title is currently being finalized for publishing in the book, MLAConnect and as an article in the Journal of the Medical Library Association [To meet the MLA goal of gathering membership details and feedback about DEI-related demographics and issues in MLA, the DITF conducted a survey. The purpose was to capture a wide range of demographic information and to understand how the membership feels about DEI in the organization. The survey ran for two weeks in October 2019, using SurveyMonkey as the instrument. The survey's results have been distributed as a preprint in ociation , 7.A newly formed DEI Committee has been appointed as of June 1, 2020. The committee will continue to work on the unmet goals from the MLA Strategic Plan related to DEI over the next year. Accordingly, the DITF's five goals were to:build activities and programs that create and sustain diverse, inclusive, and welcoming cultures and practices;ensure that members, volunteers, and staff have a high level of awareness of issues related to diversity and inclusion;ensure that what we do as an organization, and how we do it, reflects the essential values of diversity and inclusion;attract a diverse community of members that reflects the diversity of the profession and those we serve; andapply the best practices of professional associations with regard to diversity and inclusion.As demonstrated by the 2019 membership survey results, gaps remain regarding member satisfaction with MLA and the DEI environment . Althoug


Malaria remains a significant public health issue in Indonesia. Most of the endemic areas are in the eastern parts of Indonesia, but there are a few remaining foci of persistent endemic malaria in Java, particularly in Menoreh Hills, a region bordering three districts of two provinces on this island. Despite a commitment to build a partnership to eliminate cross-border malaria, there is a lack of understanding of how this partnership might be translated into an implementable strategic plan. The study aims to provide evidence of how a participatory approach was used to strengthen the cross-border collaboration and stakeholders’ capacity to develop a joint strategic, operational, and costing plan for cross-border malaria elimination.A participatory action research was conducted from January to August 2017, involving participants from the village, district, provincial, and national levels. This study was conducted in seven phases, including document review, focus group discussions (FGDs), planning and costing workshops, and a dissemination meeting. A total of 44 participants from primary health centres (PHC) and 27 representatives of affected villages in three districts, 16 participants from the district and provincial malaria programmes and planning bureaus, and 11 participants from the national level were involved in the processes. Data on priority issues, costing, programme coverage, and administration were collected. Thematic coding and feedback were used for analysis.Problems identified by stakeholders included low community awareness and participation in malaria prevention, high mobility across three districts, lack of financial and human resources, lack of inter-district coordination, and poor implementation of migration surveillance. Cross-border strategies identified to address malaria were improving cross-border migration surveillance, strengthening the network, governance, and advocacy of malaria control implementation across borders, and developing the malaria information system. A working group composed of the three districts’ representatives authorized to decide on cross-border issues will be created.The participatory approach was applicable in cross-border malaria planning for within-country settings and useful in enhancing stakeholders’ capacities as implementers. While done in a participatory way, the joint plan crafted was a non-binding agreement; stakeholders should advocate to ensure adequate funds are poured into mobilizing the programme. Plasmodium species have been reported in Indonesia, including the new emerging Plasmodium knowlesi  . As a reAlthough there has been a commitment from all three districts to build partnerships to eliminate malaria in the region, there is a lack of understanding of how this partnership might be translated into an implementable action plan. There is also confusion about each district authority’s role and responsibilities, not only during routine programme implementation but also during outbreak response , especiaThe first step in harmonizing cross-border malaria control in the area would be to create a joint strategic, operational, and costing plan to which all parties ascribe and promise to implement. The World Health Organization ‘Open Skåne 2030’  regionalThis study aims to provide evidence of how a participatory approach can be used to strengthen the cross-border partnership. Particularly, to show how to improve stakeholders’ capacity to develop a joint strategic, operational, and costing plan geared towards eliminating malaria in an area whose boundaries are administratively governed by three districts and two provinces in Indonesia.The study was conducted in three districts in the Menoreh Hills Region: Kulon Progo District in Yogyakarta Province, as well as Purworejo and Magelang Districts in Central Java Province, Indonesia, in 2017. Routine DHO surveillance data suggested that 14 sub-districts located in the adjacent areas were affected by malaria. These subdistricts with 1.1 million people were served by 18 PHCs  .As part of the decentralization in the health sector, disease control programmes are managed at the DHO through a network of PHCs and one or more district hospitals depending on the population’s size . Inter-dThis study used a mixed-methods study combining secondary data collection and PAR methods involving four sets of participants from different health system levels . These participants were key stakeholders who play essential roles in malaria control programmes: the national and subnational malaria control programmes , health service providers , other government bodies  and representatives of the local communities . The government stakeholders were identified from the organogram and discussion within the research team. One co-author was the disease control programme manager at Kulon Progo DHO (TBR), who liaised the research team with the government stakeholders in other districts. Each DHO sent invitation letters to heads of PHCs in endemic subdistricts to participate in the group discussions, who subsequently sent invitation letters to leaders of endemic villages in their catchment areas.Data were collected through iterative processes that involved stakeholders from different levels and sectors. During all phases, typed-written notes documented the meetings; group worksheets were collected and summarized into the main worksheet. The list of priority problems identified in Phase 2 were categorized into broadly pre-determined themes, i.e., health services or programmatic, community, and geographical factors using a simple Word processor. The list of strategies and activities identified in Phase 3 was also categorized into broad strategies according to the national malaria control strategies plan using a simple Word processor.The Softcopies of the voice recordings of the FGDs with stakeholders in Phase 7 were transcribed verbatim using InqScribe Software and then translated to English. AF and TRS independently read the transcripts line by line to identify important themes and quotations. Coding and theme discrepancies were discussed within the group to solve possible disagreements. The findings categorized by themes in each phase were presented during subsequent workshops or consultations for clarification or exploration of additional possible issues. These processes ensured the saturation of the collected data.Descriptive and summary statistics were done to process the quantitative data for the costing activities in Phase 5.This study was conducted in seven phases: (1) scientific literature and administrative data review, 2) group discussion using nominal group techniques (NGT) with malaria managers and head of PHCs to identify priority problems in malaria control, (3) joint consultation with DHO staff to prioritize problems and formulate intervention, (4) costing workshop for the strategic and operational plan involving representatives from villages, PHCs and DHO, (5) joint consultation with national and provincial stakeholders about the operational plan including the results of the costing study, (6) finalization of the joint strategic and operational plan with costing study, and (7) dissemination to stakeholders and FGDs to explore the adoption of the strategic plan document. Table  group diBefore primary data collection, two key malaria control stakeholders from each health office (three DHOs and two PHOs) were recruited as facilitators. They were intensively trained to systematically facilitate each step of the joint strategic and operational planning and costing for malaria elimination. During the consultations (Phase 2–5), these trained facilitators performed group discussions and brainstorming sessions with guidance from study investigators.In Phase 2, six group discussions to explore priority problems in three districts were conducted with 40 participants from PHCs with high malaria endemicity. Group discussions were conducted separately with head and malaria programmers of PHCs. The NGT was used to elicit priority issues in malaria control. NGT is an effective method to ensure relatively equal participation, is a time-saving technique, and can produce many ideas while avoiding unnecessary conflict. The NGT has four steps in which (1) everyone in the group generates and writes down their ideas; (2) group members take turns to record each idea on a board concisely; (3) each recorded idea is discussed to obtain clarification; then, (4) each individual votes privately on the priority of the ideas. A group decision is made based on the ratings. Notes were taken during the discussions . Audio-rIn Phase 3, a two-day consultation meeting was conducted involving malaria programmers and communicable disease control managers from the three districts and two provinces. A total of 13 people participated in the meeting. During the workshop, the study investigators presented the priority problems identified during the group discussions in Phase 2 and its strategies. Participants discussed and formulated the following components of the action plan: priority problems at district and cross-border level, vision, mission and objectives, targets and indicators, strategies and activities, a monitoring and evaluation framework, and governance.Costing exercises were conducted in Phase 4, involving 44 malaria staff from PHCs and 27 village representatives. Pre-structured worksheets were used to guide the planning and budgeting exercise. The worksheets consisted of categories of technical strategies taken from the national malaria strategic plan. They also consisted of budget categories that were used in disease control programme planning. In addition, administrative data (from present and previous years), price quotations from suppliers, guidelines, and policy documents were also collected to approximate the monetary value of the joint plan’s identified needs for collaborative malaria control activities. The village representatives were consulted about exploring the possibility of organizing and funding community-based activities through the existing "dana desa". Dana Desa is a government funding scheme that was disbursed to the village level for various community-based development projects.In phase 5, consultation meetings with the district, provincial, and national stakeholders were organized. The meeting was attended by district and provincial malaria managers, district and provincial planning bureaus, MoH representatives, malaria experts, and other relevant stakeholders Table . They weAll the findings from Phase 2–5 were incorporated into the strategic and operational plan documents during Phase 6. Data collected from scientific literature in cross-border malaria abroad were used as complements to guide the initial draft of the strategic, operational, and costing plan. The study investigators developed the planning document through an iterative consultation process with the district and provincial health offices’ facilitators. Feedback from the DHOs and PHOs were incorporated to revise further and refine the document. All DHOs and PHOs approved the final document.Phase 7, after all districts and provinces agreed with the documented strategic and operational plan, a dissemination meeting was conducted. All relevant stakeholders who were involved in the development process were invited. The meeting was also used to obtain an endorsement from the national malaria control programme. At the end of the dissemination meeting, we organized FGDs with the meeting participants to explore the acceptance and the best way to adopt the strategic and operational plan into district and provincial policies.Priority problems identified by participants during FGDs in Phase 1 included (1) health service aspects: lack of financial and human resources, lack of inter-district coordination between PHCs and DHOs, insufficient endorsement of migration surveillance policy, and limited role of local government; (2) community aspects: low community awareness and participation in malaria prevention, and high mobility of residents between districts, and 3) geographical challenges: rugged terrains and too many breeding sites along most of rivers or streams in the area. Table  geographAdditionally, funding mechanisms and cycles were considered a potential problem for implementing the proposed strategic plan. Phase 2 to Phase 6 were conducted between April and September 2017. However, the funding planning cycle for 2018 had already been closed before the strategic plan was finished.“Although we really would like to execute this action plan as soon as possible to achieve elimination in 2021, our funding cycle for 2018 has been closed, so we have to propose these activities in the 2019 district budget.“(District manager).During Phase 3, three strategies were identified as the joint operational plan pillars: (1) strengthening early detection and rapid response systems, (2) addressing malaria focus through local mass approach and vector control, and (3) ensuring availability and access of diagnosis and management for malaria cases.Both participants from Phase 2 and 3 also identified the following strategies to address cross-border malaria: (1) intensifying population migration surveillance, (2) strengthening networking, governance, and advocacy of the implementation of malaria control across borders with relevant stakeholders, including cross-sectoral, and (3) the development of a malaria information system in Menoreh Hills area. Furthermore, malaria managers from three districts agreed to create a working group composed of representatives from the three districts authorized to address cross-border issues related to malaria. They also identified four major funding allocations required: indoor residual spraying, distribution of long-lasting insecticide-treated nets, diagnosis and treatment, and surveillance and reporting.The proposed intervention strategies, activities, and the corresponding costings were presented and consulted during the national meeting in Phase 5. The national meeting’s objective was to harmonize and refine the proposed strategies with the national malaria strategic plan, taking into account national malaria stakeholders’ inputs. Inputs gathered during the discussion include revision of district activities based on effectiveness and relevance, revision of costing based on the number of foci, and further clarifying roles of the district, province, and national stakeholders.The 5-year Malaria Elimination Action Plan in Menoreh Hills was developed. Inputs and feedback from various stakeholders covering all health system levels were used to shape the document. The action plan was approved by stakeholders from the three districts and the MoH Indonesia. This joint action plan covers detailed information on the settings’ baseline profiles, strategic issues, vision, mission, and goals for malaria elimination in the region, malaria elimination strategies, costing and budgeting, implementation and governance, and monitoring and evaluating the 5-year Malaria Elimination Action Plan. The joint action plan document will then be implemented as local-specific guidance for malaria elimination activities in the region.As part of the Malaria Elimination Action Plan, a joint task force to implement and evaluate the joint operational plan was proposed. The national malaria control programme supports this proposal via the MoH Indonesia Decree (KepMenKes RI No HK.01.07/Menkes/498/2017). The joint task force is responsible for: (1) decision making and inter-district coordination, (2) programme planning, monitoring, and evaluation, (3) establishing information systems in the region, (4) technical activities planning and implementation, and (5) data validation and synchronization. Furthermore, a technical officer will assist with three main areas: epidemiology, entomology, and community engagement. The technical officer is responsible for: (1) assisting the execution of decisions related to programme implementation made by the joint task force, (2) acting as an information clearinghouse to accommodate and ensure information is regularly shared between the three districts, (3) validating and synchronizing data for monitoring and evaluation purposes, (4) ensuring programme planning, monitoring and evaluation are periodically performed, and (5) providing technical support for the malaria elimination programme in the three districts. The technical officer is hired by and reports to the national malaria programme for the period of implementing the strategic plan.Participants mentioned that the action plan is urgently needed to achieve malaria elimination in the area by 2021. Malaria elimination has been included as a district’s development indicator and provincial mid-long term development plan. To be operationalized, the action plan needs to be anchored with the district’s and province’s mid-long term development plan to allow funding allocation. It is also important to synchronize the action plan with the district’s funding cycle, as previously mentioned by participants when discussing problems for implementing the strategic plan.In terms of costing and budget planning for the action plan, it was agreed that all levels should be involved to ensure adherence to the funding guideline.“The national budget already has their menu items for activities, but some of the activities in this action plan are not listed. So, the MoH needs to join the budget discussion because they will know what is needed. For the local budget, it is more flexible.“.Although most participants recognized the importance of the research process in informing the development of the action plan, there was a difference in the timeline between the research process and development milestones.“Academics have to undergo a long process – these might indeed be the necessary steps, but as practitioners, we wanted a quick result.“.“While developing the mid-long term development plan, we had to develop a strategic plan within one month, so this action plan will not be able to catch up.“ .Participants also agreed that involving stakeholders from other sectors is essential, and for this, establishing a legal basis for the action plan execution is very important.“There should be a regulation from the District Head or the Governor to support the action plan, and in there, the roles of each government unit of other sectors will be specified. Each should determine their target. Since this involves more than one province, there should be a joint decree from both Governors for the districts.“.Participants also agreed that tackling cross-border malaria requires joint commitment and collaboration.This study showed that the participatory approach’s applicability to tackle cross-border malaria in an in-country area whose jurisdiction is shared by three districts and two provinces within a decentralized health system. As was done by the World Health Organization in the GMS , a bottoThe issue of cross-border malaria is a critical issue that hampers the elimination of malaria globally. It has been made more difficult because of logistical and political technicalities in areas that are considered shared territories. The findings of this study suggest that difficulties of cross-border malaria control in within-country settings are similar to challenges encountered in inter-country settings. Different programme capacities, people mobility across borders, lack of joint planning and coordination, and inadequate cross-border surveillance and response were among the main themes identified –29. LikeThe study adds to the body of evidence as to how participatory action research methods can be used for health planning in vector-borne diseases. While the participatory approach has been previously used in inter-country cross-border malaria, this study demonstrated that this can also be useful in within-country settings that are seemingly disjunct because of decentralization policies. Indeed, programme managers and stakeholders’ participation have been found to stimulate local capacities and potentially spur sustainable interventions . The nexAlthough we used a participatory approach where everyone should have the same opportunity to contribute their views, participants in the FGDs and workshops had hierarchical relationships at work. This relationship could create reluctance among some participants to express their views. However, to compensate for this limitation, conversation with different participants between group discussion sessions was used to explore different opinions. There were many malaria control ideas proposed by participants from the PHCs and DHOs/PHOs staff, for example involving local artist and traditional art to mobilize the community. However, they were restricted by the strict reporting guidelines, especially on financing.Mismatch in the timeline between programme and research was one of the barriers encountered during the process. While the action plan must be produced within a short timescale, the researchers had to undergo several steps to deliver the action plan. This is a common problem in the effort of linking research and policy .This study found that the participatory approach involving key stakeholders is applicable in coordinated inter-district malaria planning. The participatory approach facilitated joint priority settings and joint programme planning, including sharing resources and budgeting, which was not feasible in the routine health system. Stakeholders found this approach to be useful, especially in enhancing their capacities as implementers. While done in a participatory way, the joint action plan crafted is a non-binding agreement; stakeholders should advocate to ensure that adequate funds are allocated so that plans can be mobilized. Studies to identify bottlenecks in implementation fidelity are suggested. Future studies should also consider the quantification of within-country, cross-border movement as additional evidence to further guide elimination strategies.


Pragmatic clinical trials of mental health services are increasingly being developed to establish comparative effectiveness, influence sustainable implementation, and address real world policy decisions. However, use of time and resource intensive qualitative methods in pragmatic trials may be inconsistent with the aims of efficiency and cost minimization. This paper introduces a qualitative method known as Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE) that combines the techniques of Rapid Assessment Procedures with clinical ethnography. A case study is presented to illustrate how RAPICE can be used to efficiently understand pragmatic trial implementation processes and associated real world policy implications. A PCT cA key aspect of pragmatic trials is an emphasis on efficiency in research processes so as to minimize costs per subject randomized . In partAlthough several pragmatic clinical trials have incorporated the use of qualitative methods in their designs , such meOver the past decade, members of the investigative team have established a stakeholder partnership with the American College of Surgeons (ACS) Committee on Trauma (College) whereby the results of behavioral health pragmatic clinical trials can be translated into policy requirements and best practice guidelines for the regulation of US trauma care systems nationally . The ACSIn this paper, we introduce Rapid Assessment Procedure-Informed Clinical Ethnography (RAPICE), an approach to collection and utilization of qualitative data in pragmatic clinical trials of mental health services implementation that is informed by clinical ethnography and rapid assessment procedures. Additionally, an illustrative case study is presented that highlights how RAPICE can help understand the interplay between pragmatic trial behavioral health implementation processes and associated trauma center policy.Ethnography refers to both a process and outcome of research that produces an interpretation and description of a particular group, organization, or system, including behaviors at all levels, customs, norms, roles, and methods of interaction . It is tParticipant observation is the “process of learning through exposure to or involvement in the day-to-day routine activities of participants in the research setting” , p. 91. Clinical ethnography is defined as culturally- and clinically-informed self-reflective immersion in local worlds of suffering, healing, and wellbeing to produce data that is of clinical as well as anthropological value. This approach seeks to combine and balance the anthropological method of participant-observation with clinical evaluation of others and reflexive evaluation of self . It is aThere are numerous examples of the application of ethnographic methods in clinical settings, including mental health settings. In dissemination and implementation (D&I) research, participant observation and ethnography are commonly paired with in-depth interviews and quantitative data collection to produce a more comprehensive understanding of the ways in which a project was implemented, describe the extent of fidelity to the intervention, and identify and understand barriers and facilitators of implementation . ResearcWhile clinical ethnography seems to be an approach that is well suited to mental health services research, it is usually applied in a manner similar to classic ethnographic techniques, which are used over a long period of time, usually by a single individual. One method for efficient collecting and analyzing qualitative data in a relatively shorter period of time is a technique developed by anthropologists known as Rapid Assessment Procedures or RAP. This approach is designed to provide depth to the understanding of the event and its community context that is critical to the development and implementation of more quantitative  approaches involving the use of survey questionnaires and diagnostic instruments . DistingRapid assessment procedures have been used in evaluation studies of healthcare organization and delivery . For insRAP has also been used in conducting evaluations of program implementation . For insThe procedures that constitute the RAPICE method are outlined below. The RAPICE method is initially presented with the potential for application to a broad range of pragmatic trial contexts. This description of RAPICE methods is then followed by a specific case example of the use of RAPICE in a pragmatics trial in the acute care medical setting.In 2011, Zatzick and colleagues articulated the combination of RAP and clinical ethnographic techniques in developing and implementing a single site stepped collaborative care comparative effectiveness trial targeting PTSD and related comorbidities . The metWhen combined with quantitative methods in mixed method designs, RAPICE can be used to collect and analyze data to address important research questions that govern the principles and practice of implementation science. These include the following: (1) what factors act as barriers and facilitators to implementing a specific evidence-based policy, program or practice in a specific setting or context; (2) do these barriers and facilitators exist in other settings or contexts; (3) what are the characteristic features of the process of successful implementation; (4) what strategies are associated with successful implementation of specific policies, programs and practices; (5) how do we determine whether or not these strategies are successful; and (6) why are these strategies effective in producing successful implementation outcomes?Procedures for the collection and analysis of ethnographic data on implementation context, process, barriers, facilitators and outcomes are outlined as a series of steps in The approach to documentation of site visit and trial activities simultaneously aims to satisfy the pragmatic trial requirements for the minimization of time and resource intensive research methods that require extensive adjudication  and the Data analysis in RAPICE can incorporate different styles of analysis that vary markedly in resource and adjudication intensity. The immersion/crystallization style can be used exclusively in scenarios where pragmatic trial resources devoted to qualitative analyses are minimal. The immersion/crystallization style is used to provide interpretations of the data by both the PO and MMC, and “consists of a prolonged immersion into and experience with the text and then emerging, after concerned reflection, with an intuitive crystallization of the text” , p. 19. The more time intensive editing style utilizes a methodology of focused thematic analysis  that wouAs with thematic analysis, template analytic techniques can be introduced into better-resourced pragmatic trial designs. “Template analytic techniques all share the use of a template or analysis guide, which is applied to the text being analyzed” , p. 19. Because RAPICE is conducted in clinical settings, reporting requirements and assessment of quality should be consistent with standards that have been proposed for health services that emphasize rigor . One of Over the past decade, members of the investigative team have developed and rolled out two large-scale effectiveness-implementation hybrid pragmatic clinical trials in the acute care medical practice context, the Disseminating Organizational Screening and Brief Intervention (DO-SBIS) and the Trauma Survivors Outcomes and Support (TSOS) investigations. Both trials simultaneously aimed to impact clinical effectiveness for patient outcomes while also targeting national trauma center implementation policies. Conducted between 2007 and 2012, DO-SBIS randomized twenty US level I trauma centers to usual care control (n = 10) and intervention (n = 10) conditions (patient N = 878) , 2014. APreviously articulated procedures for the documentation of clinical trial activities were adapted for the current pragmatic trial approach , 2016. SOver the course of the DO-SBIS and TSOS investigations, study team members conducted semi-structured key informant interviews with consenting front-line providers to better understand the interplay between the rollout of study procedures and national ACS policy requirements and best practice guidelines. Interview data used in this case study derive from the end-of-study DO-SBIS provider interviews , as wellIn an effort to triangulate data derived from other RAPICE sources, results from a national trauma center survey conducted by the study team were used to augment the results of the qualitative analyses. Specifically, survey results were used to substantiate, on a national level, individual participant reports of policy dictated uptake of behavioral health screening and intervention services. The study team conducted a survey of all US Level I trauma centers between June 2006 and November of 2007 to assess alcohol screening and brief intervention practices before the widespread institution of College alcohol policy requirements . Trauma In this case study, RAPICE was used to better understand how various levels of ACS policy facilitated, constructed barriers to, or failed to address key acute care medical implementation processes associated with a pragmatic trial rollout. The RAPICE method allowed the study team to review multiple data sources including field notes and jottings, semi-structured interview data, policy summit logs and national trauma center practice surveys. The spectrum of ACS policy activity and initiatives was assessed using a RAPICE-informed review of logs derived from prior study team sponsored ACS policy summits. Pragmatic trial implementation processes were described using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework, a widely adopted set of measures of implementation outcomes . The temLimited resource allocations for mixed method assessments in the DO-SBIS and TSOS studies necessitated a pragmatic trial data analytic framework that emphasized time efficiency and minimal adjudication; the immersion/crystallization analytic approach was used to provide interpretations of the data. Due to pragmatic trial requirements for conducting analyses in a time-efficient manner, the PO often reviewed data in real time and presented monthly summaries to the MMC, rather than undertaking extensive, time intensive coding procedures.The RE-AIM framework was used to develop categories of pragmatic trial implementation processes that could be informed by the multiple data sources collected by the study team. For example, national survey data informed observations of the reach of behavioral health screening and intervention, while semi-structured interview data facilitated more granular assessments of the implementation and maintenance of high quality behavioral health screening and intervention procedures. As study team members iteratively reviewed data from these multiple sources, a series of themes emerged related to the interrelationships between ACS regulatory policy and site level implementation processes. Study team logs of policy summit proceedings identified four categories of ACS policy activity including: (1) policy requirements, (2) clinical practice best guideline recommendations, (3) description of an activity without a requirement or guideline, and (4) no mention.An example of the data collected from semi-structured interviews conducted during the site visits is provided in Three themes derived from consensus coding procedures were observed in a field jotting related to a TSOS trauma center site visit . The firIt still would be happening, unfortunately we don’t administer it to every patient, which I think from this study that we’ve done, the incidence of PTSD is so much greater than we probably expected. And so, when the surgeons or the mid-levels see a patient and they feel like perhaps PTSD is a problem for them, then they would ask for the screening to be done. And I think, going forward, it should be done on everybody.During piloting of the TSOS trial, providers were asked to reflect on the progression of ACS behavioral health policy beginning with alcohol and extending to PTSD. Consensus coding identified multiple themes in this interview segment. The first theme pertained to familiarity with the ACS guideline prior to the pragmatic trial. In this instance, the study participant was not aware of the screening protocol recommended by the guideline: “actually, the first time I heard about it was when you contacted us and started talking about PTSD, and then I did go to the orange book and look at what the college [ACS], what their recommendation was.” The second theme pertained to prior experience with PTSD screening. At this site, staff had conducted PTSD screening, albeit with a protocol that was not outlined in the ACS guideline. According to the provider, “we have been doing a screening for PTSD in our trauma follow-up clinic for many years. We had a questionnaire that the patients would score and then those that scored at a certain level, we would try to get into some type of treatment.” Finally, a third theme pertained to current practice in screening for PTSD. When asked if the PTSD screening was still being used, the provider commented on the inability to screen all patients for PTSD (Reach):As evidence of the Reach of the intervention, the two trauma center surveys attained 73% (148/204) and 78% (172/221) national level I trauma center response rates respectively. The surveys also documented that prior to the alcohol screening and brief intervention requirement 72.4% of level I trauma centers routinely screened patients for alcohol, and that after the requirement 91.9% of trauma centers screened patients for alcohol (χ(1) = 21.1, P < 0.001). Similarly, before the requirement, 40.7% of centers reported delivering evidence-informed interventions; after the requirement 64.0% of centers delivered an evidence-informed intervention (χ(1) = 17.1, P < 0.001). The second survey also asked questions about routine PTSD screening and intervention; less that 10% of sites reported routine PTSD screening and intervention when the survey was conducted .Themes derived from study team discussions were how different types of ACS regulatory policy  influenced site-specific adoption, implementation and maintenance processes. With regard to adoption, the study team observed how the alcohol policy mandate required that all trauma centers implement alcohol screening and intervention procedures; trauma centers were required to demonstrate alcohol screening and intervention procedure implementation during ACS verification site visits that occurred every three years. In contrast, clinical practice guidelines and other Resource Guide informational suggestions were only likely to be rolled out by early adopter centers. Over the course of the DO-SBIS and TSOS trials, the study team made longitudinal field observations regarding the extent to which high quality behavioral health screening and intervention procedures were being implemented in the wake of policy requirement or clinical best practice guideline recommendations. Multiple factors, including provider team compositions, trauma center administrative support, staff turnover, and other trauma center resource availability, were observed to influence the longer-term implementation and maintenance of behavioral health screening and intervention procedures. RAPICE-informed study team reviews suggested that while a regulatory mandate successfully required site adoption of alcohol screening and brief intervention, the requirement did not ensure high quality procedures would be implemented and maintained with adequate staffing and resources.This paper provides an example of the RAPICE-informed integration of implementation science and pragmatic trial approaches as applied to U.S. trauma center behavioral health policy. Over the past decade, members of the investigative team spent hundreds of hours immersed in the acute care medical trauma center clinical context as clinician-investigator participant observers. The study team collected multiple types of data over this period, including field notes and jottings during trauma center site visits and logs of national trauma center policy summit activities. Informal and semi-structured interviews were conducted with trauma center providers involved in pragmatic trial behavioral health screening and intervention procedure rollouts. The study team also conducted two national surveys of trauma center behavioral health screening and intervention uptake over this period. RAPICE allowed for an ideal mixed method for the integration of these multiple data sources and was feasibly embedded within the study team nationwide pragmatic trial rollouts.As noted earlier, qualitative methods have become a standard feature of implementation research through their use in mixed methods and hybrid effectiveness-implementation designs . HoweverIn the DO-SBIS and TSOS, four of these strategies  were embedded within the RAPICE methodology. Triangulation involved the use of multiple theories or perspectives to interpret the data (theory triangulation), use of participant observation and semi-structured interviews to study implementation process and barriers , use of more than one observer during field visits to achieve inter-subjective agreement (observer triangulation), and use of interviews, observational field jottings, and national trauma center survey materials) (data triangulation) . FurtherIn addition to the four strategies used in the TSOS study, RAPICE can easily incorporate other strategies for enhancing rigor and trustworthiness such as negative case analysis and auditing. However, as a front-line provider immersed in the clinical setting, the PO’s presentations to the MMC are vulnerable to internal data reduction and selective recall biases. Compared to traditional methods of ethnographic research and semi-structured interviews, RAPICE may be associated with less detailed field notes, fewer observations of important events or implementation processes, fewer and shorter semi-structured interviews with study participants, and less depth in coding, analysis and interpretation of qualitative data collected. These limitations, in turn, may adversely impact the utility of qualitative data in mixed methods designs to achieve the aims of convergence, complementarity, expansion, development, and sampling .On the other hand, use of RAPICE allows for more opportunities to conduct “repeated measures” of qualitative data through multiple site visits. This represents a different form of prolonged engagement in that the observations may be of shorter duration, but over a longer period of time than is the case with ethnographic methods used in other mental health services research . RAPICE Perhaps most importantly, RAPICE directly addressed pragmatic trial efficiency standards. Rather than requiring time and resource intensive in-depth qualitative research procedures, RAPICE facilitated efficient mixed method data collection and analyses that are in harmony with the pragmatic trial aim of reducing costs per subject randomized through combined input and iterative discussion from both PO and MMC team member perspectives, structuring of roles of research team members to capitalize on their expertise. RAPICE also allows an increasingly more research intensive analytic approach that can potentially incorporate immersion/crystallization, editing/thematic content, and template analysis methods in phases.The findings of the case study also highlight the importance of understanding the interplay between national behavioral health policy and implementation processes as described by frameworks such as RE-AIM. National trauma center surveys conducted over the past decade documented the enhanced reach of alcohol screening and brief intervention procedures in the wake of ACS policy requirements. Combined with longitudinal field observations, semi-structured interview data highlighted site struggles with staff turnover and the maintenance of high quality screening and intervention procedures over time. Analysis of field jotting data suggested that although alcohol screening and intervention procedures might satisfy ACS verification site visit criteria and thus require adoption by all trauma center sites, the procedures did not adhere to principles derived from the evidence-based practice literature .Another strength of the RAPICE method is the iterative generation of novel data about implementation processes. The summary matrix derived from field observations, semi-structured interview coding, national survey data and, most importantly, multidisciplinary team discussions, yields important insight into the limitations of implementation strategies that rely on policy requirements alone . While cThe RAPICE method also may reveal ways in which emerging implementation science constructs may not fully capture novel health service delivery system contextual factors. From an implementation science perspective, acute care medical trauma center inpatient settings are distinct from other primary and acute care settings in that the ACS has the ability to mandate screening and intervention procedures. Thus, the integration of behavioral health screening and intervention services at United States trauma centers is occurring in a unique regulatory “make it happen” context, in contrast to a negotiated “help it happen” implementation context in other general medical settings . The ACSThe description of effectiveness-implementation hybrid trials has not routinely included the targeting of health care policy change as a potential implementation mechanism . A revieRAPICE also provides qualitative data and analysis comparable to that utilized in mixed methods designs in implementation research. In addition to the use of qualitative data for the purpose of convergence described earlier, data collected and analyzed through RAPICE procedures can be used to complement the functions of quantitative methods or expand and explain the findings acquired through the use of quantitative methods .Finally, RAPICE offers greater transparency in the integration of investigator and study participant perspectives on the phenomena of interest. Unlike Rapid Assessment Procedures as they have been used in public health, the use of RAPICE in this case study did not involve the participation or the insight of community members, or in this case, clinicians participating in the pragmatic trial. Consistent with the aims of the pragmatic trial, input from clinicians at the field sites preceded the implementation of the TSOS. However, in assessing the process of implementation and identification of potential barriers and facilitators, the insider perspective on implementation normally provided by community stakeholders in RAP studies was provided largely by the PO and other study team members  who simultaneously occupy the dual roles of clinician-investigators and front-line trauma center providers. The outsider perspective was provided largely by the MMC. Consistent with the RAP methodology , the twoAlthough the use of RAPICE in the TSOS suggested potential in addressing important research questions related to the implementation of evidence-based mental health services in a PCT format, additional research is required to conduct a formal comparison of this methodological approach to standard qualitative methods in implementation research. Such an evaluation might compare RAPICE with more resource-intensive mixed methods on measures such as use of specific strategies to enhance rigor, timeliness, use of research in policy or practice, and cost-effectiveness. For instance, compared to more resource-intensive methods, we hypothesize that RAPICE would provide the same or similar levels of theoretical saturation  of inforWhen applied to evidence-based practice implementation in pragmatic trials, RAP-informed clinical ethnographic methods combine efficient documentation of implementation context, processes and outcomes with periodic review by an expert mixed-method consultant. The methods straddle the continuum between time intensive qualitative procedures and cursory study team review of field observations. Although we have focused here on the potential use of RAPICE in pragmatic clinical trials to examine implementation barriers, facilitators, processes and strategies within specific settings and contexts, we should note that it could be an equally useful in other forms of health research including needs assessments and efficacy and effectiveness clinical trials. Future comparative mixed method investigations could contrast themes derived from RAPICE with themes derived from more in-depth qualitative procedures. In this way, the value added to the clinical trial and implementation processes evaluations by more in-depth qualitative research procedures could be more directly assessed.In this applied example, the RAPICE approach simultaneously satisfied the pragmatic trial requisite for minimization of time intensive research methods that require extensive adjudication, and the implementation science goal of understanding and documentation of trial processes that could yield sustainable maintenance of screening and intervention procedures through ACS policy. The RAPICE approach furthers the goal of integrating pragmatic trial and implementation science methods by embedding a multidisciplinary implementation team within a health care system pragmatic trial rollout.Palinkas & Zatzick Supplementary data tables


Herewith, we review an updated progress of regenerative medical products using human embryonic stem cells (ESCs) in Japan. Two groups from Kyoto University and the National Center for Child Health and Development (NCCHD) established a novel derivation/cultivation system of ESCs for potential application in translational and clinical research. At the first stage of ESC derivation, murine feeder cells have been used in line with Japanese guidelines on public health associated with the implementation of the xenograft. To avoid exposure of ESCs to animal products in culture media, a xeno-free cultivating system has been established. Twelve ESCs  are now available under a clinically relevant platform for industrially and clinically applicable regenerative medical products. NCCHD submitted an investigative new drug application to the Pharmaceuticals and Medical Devices Agency (PMDA) for using ESC-based products in patients with hyperammonemia due to genetic defects on March 2018 under the Pharmaceutical Affairs Law . Currently, up to ten ESC-based products are being prepared for intractable and rare disorders in Japan. Once effective and efficient differentiation protocols are established to obtain a target cell, human ESCs are expected to stably supply a major portion of raw cell substrate materials used for manufacturing regenerative medical products. Kyoto University and the National Center for Child Health and Development (NCCHD) strictly complied with the Guidelines for Derivation and Distribution of Human Embryonic Stem Cells (3) and the Guidelines for Utilization of Human Embryonic Stem Cells (4) for human dignity to establish ESCs in Japan. In these two guidelines, the basic issues concerning the protection of personal information and protocols of derivation and usage of human ESCs are defined from the viewpoints of bioethics. The guidelines are now for development of novel treatments and pharmaceuticals/medical devices (6).Human ESCs have high potential to be raw material to produce a variety of cell types due to their pluripotency when compared with somatic stem cells which have limited abilities in differentiation and self-renewal (9). KhES-1, KhES-2, and KhES-3 can be maintained in culture for up to 2 years without significant alteration in differentiated capability and karyotypes (7). Meanwhile, SEES-4, SEES-5, SEES-6, and SEES-7 can also be stably cultivated under xenogeneic-free conditions (9). SEES-1, SEES-2, and SEES-3 have been established by utilizing murine feeder cells. For a quality evaluation, we thus need to follow “Derivation and Characterization of Cell Substrates Used for the Production of Biotechnological/Biological Products,” “Guidelines on Public Health Infection Issues Accompanying Xenotransplantations,” and “Guidelines on Epithelial Regenerative Therapy Using 3T3J2 Strain or 3T3NIH Strain Cells as Feeder Cells” in order to prevent contamination of feeder cells and transmission of bacteria, fungi, viruses, and prions. KthES11, KthES12, KthES13, and KthES14 cells were established by Kyoto University in a feeder-free culture system to avoid contamination of murine cell components. Suemori has been generating KhESC lines at Kyoto University and has inserted a letter “t” to a name of newly established ESC, which are called KthES-11 cells, because he intends to apply KthES cells for therapeutic purpose in a clinical setting.Twelve human ESC lines  are available as a resource of cell substrates to manufacture regenerative medical products at present for clinical usage under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act  (10). The Act on the Safety of Regenerative Medicine, in place of the Medical Practitioners Act and the Medical Care Act, provides regulations on medical professionals’ practices and clinical studies on regenerative medicine. Under the new “Act on the Safety of Regenerative Medicine,” regenerative medicine is classified into three categories depending on each therapy’s potential risk factor. The risk of regenerative medicine studies using ESCs is considered high; thus, ESC-based therapy will be placed in the high-risk medical technology category (Class I). Regardless of risk factor, all plans of using regenerative medicine must be submitted to the Ministry of Health, Labour and Welfare (MHLW). Moreover, before submitting plans to the MHLW, a certified special committee must submit their opinion on the preliminary plan created by the medical institution that intends to offer ESC-based therapy. This committee fulfills the legal accreditation criterion laid down by the MHLW. Once the committee gives its opinion, regardless of the recommendation, the medical institution may submit their preliminary plan for practicing regenerative medicine along with the committee’s opinion to the MHLW. In addition, medical institutions are obligated to conduct follow-up reports detailing the adverse effects and annual details about their regenerative medicine plan implementation, including the treatment provided, the number of patients treated, and the effectiveness of the treatment to the MHLW and the committee.A new regulatory framework to supervise regenerative medicine, i.e., the “Act on the Safety of Regenerative Medicine” and the “Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act,” was enacted in November 2015 (6). These guidelines have different standpoints and, therefore, conflict: the former guideline focuses on protection of donors’ personal information and human dignity, and the latter prioritizes safety of raw materials.We follow two regulations for different legal benefits, namely, “safety and quality”  and “ethics”  (5). Infection with cytomegalovirus, Epstein-Barr virus, or West Nile virus shall also be ruled out, if necessary, via appropriate clinical laboratory tests. In addition, the eligibility of donors should be assessed whether he or she ever received a blood transfusion or underwent a transplantation procedure. Alternatively, it is conceivable to assess infectious pathogens at intermediate products during differentiation from the viewpoint of ethical and scientific rationality.If human ESC lines are established for the purpose of clinical use, donors need to be selected appropriately. Selection criteria and eligibility of the donors are important. Infection with hepatitis B virus, hepatitis C virus, human immunodeficiency virus, adult human T-lymphotropic virus, or parvovirus B19 shall be ruled out via physician-donor interviews and clinical laboratory tests, such as serological tests and nucleic acid amplification tests. Infection controls at the right time need to be done by retesting, taking into consideration the window period; however, such retesting is not practically allowed for ESCs according to the Guidelines on the Derivation of Human Embryonic Stem Cells ESCs are considered the most undifferentiated cells similar to inner cells of blastocysts. Thus, the manufacturing process from undifferentiated ESCs to functional differentiated cells or final products is complicated and requires a long timeline, which may be challenging to perform. From the viewpoint of consistency and robustness, the most ideal foundation in the sustainable manufacture of ESC-based products is intermediate cell products/lines that have been well characterized . Prefera(20). Clinical trials using hESC-derived cells for transplantation were identified by exploring the public database  database. We also evaluated original research articles and the sponsor’s websites on the respective clinical trials and/or transplant products for additional information. For example, ESC-derived products are being tested for use to patients with age-related macular degeneration, Stargardt disease, type 1 diabetes, and spinal cord injury in the United States; age-related macular degeneration and Stargardt disease in South Korea, the United Kingdom, China, and Brazil; age-related macular degeneration in Israel; severe heart failure in France; and Parkinson’s disease in Australia. We have filed a new investigational drug application to PMDA for ESC-based regenerative medical products to patients with congenital metabolic disorders and have ESC-derived mesenchymal stromal cells, epidermal cells, intestinal organoids, and hepatocytes in the development pipeline (22).Human ESC-based products have been developed for clinical trials worldwide database . We usedNoneTakashi Igarashi is the Deputy Editor of JMA Journal and on the journal's Editorial Staff. He was not involved in the editorial evaluation or decision to accept this article for publication at all.


Autophagy is a highly conserved degradative process that conveys dysfunctional proteins, lipids, and organelles to lysosomes for degradation. The post-mitotic nature, complex and highly polarized morphology, and high degree of specialization of neurons make an efficient autophagy essential for their homeostasis and survival. Dysfunctional autophagy occurs in aging and neurodegenerative diseases, and autophagy at synaptic sites seems to play a crucial role in neurodegeneration. Moreover, a role of autophagy is emerging for neural development, synaptogenesis, and the establishment of a correct connectivity. Thus, it is not surprising that defective autophagy has been demonstrated in a spectrum of neurodevelopmental disorders, often associated with early-onset epilepsy. Here, we discuss the multiple roles of autophagy in neurons and the recent experimental evidence linking neurodevelopmental disorders with epilepsy to genes coding for autophagic/lysosomal system-related proteins and envisage possible pathophysiological mechanisms ranging from synaptic dysfunction to neuronal death. Macroautophagy (henceforth autophagy) is a highly conserved cellular process that tackles dysfunctional proteins, lipids, and organelles to lysosomes for degradation. Substrates are initially isolated by a double membrane, the phagophore, which subsequently elongates and surrounds the substrates with a membranous structure, the autophagosome  requires autophagy to maintain its homeostasis. Since the ubiquitous deletion of core autophagy genes is lethal at the embryonic or perinatal stages, several nervous system-specific knockout mouse models have been developed to explore the roles of autophagy in CNS. Removal of Atg5 and Atg7 in neuronal precursor cells (NPCs) leads to the accumulation of cytoplasmic inclusion bodies, with neurodegeneration and progressive motor deficits, further pointing to autophagy as a key quality control system in neurons over their lifespan  in a single patient with severe cortical atrophy and dysplasia, optic nerve atrophy, intellectual disability, spasticity, ataxia, muscle wasting, and seizures. The L1224R mutation leads to an accumulation of autophagy substrates in patient’s fibroblasts. In the same study, a forebrain-specific conditional Vps15 mouse model was developed revealing that loss of Vps15 resulted in severe cortical atrophy accompanied by autophagic impairment and progressive degeneration of the hippocampus and cortex  proteins  is a proton pump responsible for acidification of intracellular organelles and secretory granules that regulates several cellular processes such as protein trafficking, maturation, and degradation , responsible for ATP hydrolysis, and a transmembrane domain (v0), responsible for H+ transport. Recessive mutations in ATP6V1A, coding for the “A” subunit of the v1 sub-complex, have been first described in patients with cutis laxa, dysmorphic features, and seizures in the context of a severe condition with premature lethality (Van Damme et al., de novo heterozygous mutations in ATP6V1A in four patients with developmental delay and epilepsy with variable of severity, ranging from mild intellectual disability and epilepsy to early-onset epileptic encephalopathies accompanied by myelination defects and brain atrophy. Pathogenic mutations affect lysosomal homeostasis in patients’ cells and impair neurite development and synaptic contacts when expressed in murine neurons. The mutations associated with the severe phenotype result in loss of function and autophagy impairment (Fassio et al., The vacuole H Forgac, . Acidifi Forgac, . V-ATPasde novo deletion variant of the v-ATPase accessory protein ATP6AP2 has been found in a patient with neurodevelopmental disorder characterized by fulminant degeneration (Hirose et al., A DMXL2, a member of WD40 protein family known to regulate v-ATPase trafficking and activity (Yan et al., Dmxl2 is embryonically lethal in mice (Tata et al., Dmxl2 mice show macrocephaly and corpus callosum dysplasia, confirming the DMXL2 role in brain development (Kannan et al., In addition to ATP6AP2, v-ATPase assembly and activity relies on several parameters, including kinase activity, nutrient and stress levels, extra- and intra-cellular pH, and accessory proteins that interact with v0 and v1 components (McGuire et al., Altogether, these pieces of evidence support a primary role of autophagy dysregulation in epileptogenesis and suggest that severity of the clinical manifestations variably evolving in a neurodegenerative disorder might depend on different timing and specificity of molecular events underlying epilepsy and neurodegeneration. Defects altering early stages of neuronal development and, therefore, synaptic activity could underlie pro-epileptogenic changes in neuronal circuitries followed by progressive accumulation of autophagy substrates and consequent neuronal stress and degeneration. Our hypothesis is that the spectrum of phenotypes and clinical severities of the epileptic syndromes associated with mutations of autophagy genes primarily derive from an initial synaptic dysfunction, with structural and functional synaptic alterations that, depending on gene dosage and/or severity of the pathogenic mutations, may turn into neuronal damage with degeneration and death. Future work on disease murine models and/or patient-derived neurons needs to be performed to unravel the cellular and molecular mechanisms linking autophagy failure to brain hyperexcitability, seizures, and fulminant neurodegeneration and to evaluate the ability of autophagy inducers as novel therapeutic strategies for these intractable disorders.AFas and AFal wrote the manuscript and prepared the table and the figure. AE, DA, and RG revised the manuscript. FB coordinated the preparation of the review and revised the manuscript for submission.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.


Access to specialized care is essential for people with Parkinson´s disease (PD). Given the growing number of people with PD and the lack of general practitioners and neurologists, particularly in rural areas in Germany, specialized PD staff (PDS), such as PD nurse specialists and Parkinson Assistants (PASS), will play an increasingly important role in the care of people with PD over the coming years. PDS have several tasks, such as having a role as an educator or adviser for other health professionals or an advocate for people with PD to represent and justify their needs. PD nurse specialists have been established for a long time in the Netherlands, England, the USA, and Scandinavia. In contrast, in Germany, distinct PDS models and projects have been established. However, these projects and models show substantial heterogeneity in terms of access requirements, education, theoretical and practical skills, principal workplace (inpatient vs. outpatient), and reimbursement. This review provides an overview of the existing forms and regional models for PDS in Germany. PDS reimbursement concepts must be established that will foster an implementation throughout Germany. Additionally, development of professional roles in nursing and more specialized care in Germany is needed. Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor symptoms such as tremor, rigidity, bradykinesia, and a plethora of nonmotor symptoms (NMS). The appearance and severity of motor symptoms and NMS vary throughout the disease course and contribute to different degrees of functional impairment and reduced quality of life . TherefoPeople with PD need specially structured and cooperative therapy, education, and care concepts both in the short and long run. Qualified PD-specific nonphysician staff (PDS), such as PD nurse specialists (PD nurse) and Parkinson Assistants (PASS), can play an important role. Among others, PDS can fulfill a role as an educator or adviser for other health professionals in hospitals and be an advocate for the people with PD to represent and justify their needs. Such is also relevant given the lack of general practitioners (GP) and neurologists in rural areas . ExperieThe expenditure of time needed to care for people with PD has increased enormously recently. Such is based on a higher complexity of revised clinical diagnostic criteria, new technical diagnostic methods, and individualized therapeutic care considering the growing known spectrum of PD symptoms defining different motor and nonmotor subtypes of PD . SpecialHelp to cope with PD, answer frequent and everyday questions and give advice where doctors lack the necessary time: Typical questions are for example “What do I have to pay attention to with the medication?”, “Can I go on holiday?”, or “Can I do sports?”Use assessments to identify and monitor symptoms, side effects, and family problemsAdvise on the motor and NMS and complications.Counsel relatives and monitor their burdenTeach other health and social care professionals )Inform comprehensively about therapy options, self-help groups or socio-medical aspects, such as applying for care levels or certificates for severely disabled personsHelp to improve adherence to medicationAssist in the initiation and adjustment of continuous therapies or take over most of them independentlySupport in making the PD diagnosis Make referrals to other professionals such as speech and language therapists, occupational therapists, physiotherapists or social workers and support networking between different therapeutic playersAssist in advanced care planning (ACP)Discontinued care and lack of self-management are frequently associated with improper handling of PD medication. Nonadherence to medication is a significant issue in PD. It results in frequent hospitalizations, reduced quality of life, and causes a financial burden for the health system ,24,25,26In the UK, distinct competency levels for PD nurses were defined, ranging from a registered competent nurse , experienced specialist nurse (Level 6), expert specialist nurse (Level 7) to consultant nurse (Level 8) . In contSpecialized nurses for patients with PD  have been available for over 40 years in several countries, including England, the USA, and the Scandinavian countries. PD nurses are acknowledged and valued as part of the multi-professional PD team . The worThe German Parkinson Society (DPG), the German Parkinson Association (dPV), the Competence Network Parkinson (KNP) and the Association of Parkinson Nurses and Assistants (VPNA e.V.) have developed an education curriculum representing the standard for PD nurses in Germany. The first training course started in 2007. Applicants should be qualified health and nursing professionals and have a minimum of two years of professional experience in acute neurological departments or PD hospitals . TraininThe most reported tasks of PD nurses in Germany are giving information and advice to people with PD and their next of kin in the context of medication and side effects, education and counseling to PD symptoms and specialized therapies (and education of other nursing staff) ,29. AddiAs a future goal, PD nurses can support palliative outpatient teams when caring for the patient and the relative in the last phase since PD patients often suffer from symptoms unknown to palliative care teams. They might visit the patient together with the team or could be the specialist visiting the patient while a telemedical approach discusses symptom control .At the end of 2000, the Association for Quality Development in Neurology and Psychiatry (QUANUP e.V) was founded as a joint initiative of the Professional Association of German Neurologists (BVDN) and the Professional Association of German Neurologists (BDN). QUANUP has developed a training program for nonmedical staff in neurological doctor´s practices and neurological units in hospitals to qualify them as PASS. Participants were mainly medical assistants with formerly three-year training . Since 2The PASS should be a competent contact person for patients with PD and their relatives in outpatient settings, Parkinson day clinics, and the wards in the hospitals. Through the joint, coordinated deployment of qualified physicians and qualified PASS, work processes in the practices should be made more efficient. PASS cares for people with PD and relatives through short distances and low-threshold contact offers. They provide necessary information for patients and their families and are the hub between patients, neurologists, therapists, and care institutions. Among others, PASS can also be involved in: (1) visits of neurological practice unspecialized in PD, (2) PD-specialized practices (Parkinson’s Practice) , and (3)For the certificate “Parkinson’s Practice” awarded by the German Parkinson Association , a list of criteria has been compiled . The cerFor PD care in rural areas, telemedicine supplied as outpatient video-supported therapy is a suitable option to provide many PD patients access to specific PD care. Homecare via telemedicine may improve patient satisfaction, increase participation, and adherence to therapy substantially. A low-threshold connection between patients and relatives through PASS in neurological practices is another critical issue. This, for example, can significantly reduce complications due to incorrectly taken medication. A structured approach must be developed for Germany on how televisits should be carried out by PDS. Moreover, a reimbursement of this service by the health insurance companies is required.The target group for the Parkinson care specialist includes nursing staff from wards and outpatient clinics from nursing homes and outpatient nursing and care services as well as staff from nursing support and advice centers . To becoDue to the increasing number of chronically ill people and the increasing shortage of GPs but also of hospital-based care, especially in rural areas ,35, therMoNi stands for Model of Lower Saxony (Modell Niedersachsen). It is a similar project to AGnES and VERAH in cooperation with the Ministry for Social Affairs, Women, Family, Health Care and Integration of Lower Saxony and the physician Association of Lower Saxony. MoPra means mobile practice assistant (Mobile Praxisassistentin) and meets the criteria and tasks of AGnES. MoPra is well established in Saxony-Anhalt.http://www.akademienordrhein.info/eva-entlastende-versorgungsassistentin.In cooperation with the Association of Statutory Health Insurance Physicians North Rhine-Westphalia, the North Rhine-Westphalian Academy offers in-service training to become a “relieving care assistant” (EVA–Entlastende Versorgungsassistentin). The prerequisite for participation is a qualified professional qualification as a Medical Specialist Assistant or nurse. Moreover, at least three years of professional activity in a family doctor’s practice must be proven. Depending on the professional experience, the total EVA training comprises 170–221 h of theoretical instruction and 20–50 h of practical training. In this course, approximately 30% self-study is integrated on a learning platform. The specialization qualification EVA concludes with a certificate from the Association of Statutory Health Insurance Physicians of North Rhine-Westphalia. The further training aims to give the medical assistant the skills to take over delegable services in outpatient practice. The EVA acquires the competence to take over services in the outpatient practice eligible for delegation. In this way, EVA relieves the physician of the burden of accompanying and supporting patients and their relatives in various tasks relating to the treatment process. The training includes different aspects, such as geriatric syndromes, care and support of oncology and palliative patients, pharmaceutical supply, wound care and wound management, coordination and organization of therapy and social measures, telemedical basics, communication management, medical documentation, and practical training (home visits). Details are given on the homepage of the North Rhine-Westphalian Academy: In terms of PD, the North Rhine-Westphalian Academy offers advanced training to become a “Support Care Assistant in Neurology/Psychiatry (EVA-NP).” This training includes skills required to take over delegated services in specialist neurological and psychiatric practice. EVA-NPs are familiar with many neurological and psychiatric clinical syndromes and disorders and are a qualified contact person for patients. Depending on the professional experience, the complete training for the EVA-NP comprises 197–247 h of theoretical instruction and 20 h of practical training (home visits). Various modules are offered within the theoretical instruction. A PD module (24 lessons) can be taken as part of the optional part.The tasks in every project/position are quite similar. There is an increasing effort to relieve medical doctors and to support the patients. Many healthcare services delegated to healthcare assistants are appreciated and accepted by patients . The incBecause of the high workload of PD nurses in the UK, they usually work in collaboration with community matrons as generic practitioners . CommuniToday, PDS training in Germany is very heterogeneous and differs in terms of duration, content, and target group. There are courses for health care assistants in general or neurological practices. Within these courses are differences in the specialized view on PD . Additionally, there are existing trainings for nurses. While PD nurses mainly work in specialized hospitals and outpatient clinics, the community health nursing will be operating more in an outpatient setting. In the future, it should be discussed how to integrate more specific PD knowledge in community health nursing qualification, especially for supporting long term care settings and in the community. Moreover, it is essential to develop approaches how these different qualifications could create a functional network for supporting people with PD and their next of kin . In partDue to the increasing complexity of PD therapy and the availability of specialized therapies for different stages of the disease, an optimized PD treatment requires expert and multi-professional care. However, for many PD patients in Germany, care is provided only by non-specialized neurological practices or GPs without close exchange with neurologists or specialized university outpatient clinics for movement disorders . PDS areWe also need more research on how PDS can improve patient reported outcome and aspects like management/medication adherence, quality of life, palliative care, and functional status/improving function . PDS sti