Barriers and facilitators to implementation of VA home-based primary care on American Indian reservations: a qualitative multi-case study
Implementation Science volume 12, Article number: 109 (2017)
Veterans Health Affairs (VA) home-based primary care (HBPC) is an evidence-based interdisciplinary approach to non-institutional long-term care that was developed in urban settings to provide longitudinal care for vulnerable older patients. Under the authority of a Memorandum of Understanding between VA and Indian Health Service (IHS) to improve access to healthcare, 14 VA medical centers (VAMC) independently initiated plans to expand HBPC programs to rural American Indian reservations and 12 VAMC successfully implemented programs. The purpose of this study is to describe barriers and facilitators to implementation in rural Native communities with the aim of informing planners and policy-makers for future program expansions.
A qualitative comparative case study approach was used, treating each of the 14 VAMC as a case. Using the Consolidated Framework for Implementation Research (CFIR) to inform an open-ended interview guide, telephone interviews (n = 37) were conducted with HBPC staff and clinicians and local/regional managers, who participated or oversaw implementation. The interviews were transcribed, coded, and then analyzed using CFIR domains and constructs to describe and compare experiences and to identify facilitators, barriers, and adaptations that emerged in common across VAMC and HBPC programs.
There was considerable variation in local contexts across VAMC. Nevertheless, implementation was typically facilitated by key individuals who were able to build trust and faith in VA healthcare among American Indian communities. Policy promoted clinical collaboration but collaborations generally occurred on an ad hoc basis between VA and IHS clinicians to optimize patient resources. All programs required some adaptations to address barriers in rural areas, such as distances, caseloads, or delays in hiring additional clinicians. VA funding opportunities facilitated expansion and sustainment of these programs.
Since program expansion is a responsibility of the HBPC program director, there is little sharing of lessons learned across VA facilities. Opportunities for shared learning would benefit federal healthcare organizations to expand other medical services to additional American Indian communities and other rural and underserved communities, as well as to coordinate with other healthcare organizations. The CFIR structure was an effective analytic tool to compare programs addressing multiple inner and outer settings.
Little is known about dissemination of home-based primary care (HBPC) to rural communities and, in particular, rural American Indian reservations. HBPC is a non-institutional long-term care program that provides ongoing comprehensive, interdisciplinary primary care to patients in their homes when healthcare can no longer be optimally provided in a clinic setting. By this definition, the Agency for Health Research and Quality  found only 19 studies that report on the outcomes of these programs: one in Canada, two in Denmark, and 16 in the USA, with 50% of US programs delivered by Veterans Health Affairs (VA) [2,3,4,5,6,7,8,9]. Recently, 14 VA medical centers (VAMC) began expansion of the evidence-based HBPC program to reach new populations of American Indian veterans living in rural reservation communities, which are served by the Indian Health Service (IHS) or Tribal Health Programs (THP) . Each VAMC independently developed strategies and models to implement their rural HBPC programs and we treat each as a case study for comparative analysis. Two HBPC programs were unable to establish programs in these communities, while 12 succeeded, leading to our study question: what are the barriers and facilitators for implementation of a new clinical program on rural American Indian reservations. Secondarily, we aim to describe how two healthcare organizations work together to optimize healthcare resources as a result of implementing the new program. Our goal is to inform planners and policymakers about factors that may facilitate or hinder successful programs in underserved communities.
VA and IHS are US federal healthcare programs that have different eligibility requirements. VA medical care is an entitlement for veterans who meet basic or enhanced eligibility requirements that consider length of military service, period of service in war or declared conflict, income, and service-connected disability or illness . Veterans are assigned to “priority groups,” which are based on factors such as the extent of service-connected injuries or illnesses and on personal income; the priority group determines if VA services are delivered at no cost or if the veterans must assume a co-pay fee to cover costs. IHS, an agency within the US Department of Health and Human Services, provides health services for 567 federally recognized sovereign Tribes . IHS is not an entitlement program and eligibility is determined by Tribal membership, residence, and location of services . Tribes may accept direct care from IHS or may administer IHS funding within their own tribal health programs (THP). Some American Indian and Native Alaska veterans are eligible for both VA and IHS/THP and co-managed care or dual use allows patients to “mix and match” services across healthcare organizations [14, 15]. American Indian veterans may travel off-reservation to a VAMC or VA community community-based outpatient clinic to receive healthcare. Any VA presence in a reservation community must be authorized by the sovereign Tribe, including clinical programs, outreach activities to describe veteran benefits, and no-cost “health fairs” to screen community members for chronic diseases and provide health education.
Collaboration between VA and IHS is supported by VA strategic plans , interagency agreements, and national policy  that calls for meaningful consultation and collaboration by federal agencies with Tribes. In 2010, VA and IHS executed a Memorandum of Understanding with the specific goal “to improve the delivery of care through active sharing of care processes, programs and/or services with benefit to those served by both IHS and VA.” The Memorandum of Understanding lists HBPC expansion as an example of a shared beneficial program and that expansion continues to be cited in annual progress reports to Congress .
HBPC was developed and evaluated in randomized control trials in the 1990s [19,20,21] and continues to be cost-effective [3, 4] by reducing unnecessary utilization of hospitals or emergency departments without shifting costs to Medicare [5, 22, 23]. The program has been established at over 140 of the 168 VAMC. A VA HBPC Handbook provides detailed guidance for operations under a HBPC program director and clinical supervision by a medical director. HBPC is a complex intervention using a team-based interdisciplinary approach to deliver primary care services with at least 7–10 home and telehealth visits per year. Interdisciplinary team case conferences are conducted weekly and each patient’s management plan is reviewed at least every 90 days. Originally developed for urban VAMC, caseloads average 20–30 for a registered nurse and a maximum of 34 patients for a nurse practitioner. The program is supported financially by the Veterans Equitable Resource Allocation budgeting formula that accounts for its intensive workload in allocating funds to VAMC.
As the largest integrated and open access healthcare system in the USA, VA has long been concerned about the inequities in its healthcare system. Older veterans are more likely than non-veterans to have functional limitations that are associated with increased risk of poor health outcomes [24, 25], more likely to live in rural areas, and less likely to have age-related healthcare needs adequately met [26,27,28,29,30,31]; these inequities are particularly great for American Indian veterans [32,33,34,35,36]. To address the gap in access to non-institutional long-term care, the VA Office of Rural Health provided seed funding to expand urban HBPC programs to American Indian reservations and to other rural areas . Fourteen VAMC, which were located in eight geographically dispersed regions, expressed interest in expansion and all were funded for 2 years of start-up costs with the expectation that VAMC would later sustain the program through its annual funding allocations.
HBPC expansion programs serve as a natural laboratory to understand the interacting and multi-level factors that impede and facilitate implementation. We used a qualitative observational design to retrospectively document expansion and implementation of HBPC on American Indian reservations through key respondent interviews, which were conducted after the programs were fully implemented. Each HBPC program was considered as a case study for comparative analyses [37, 38] to determine if similar issues arose in multiple contexts.
The adage, “if you’ve seen one VAMC, you’ve seen one VAMC” implies the difficulty of studying non-static implementation across multiple settings and requires an efficient analytic structure to identify and describe factors that may influence successful implementation of an intervention in different community settings. The Consolidated Framework for Implementation Research (CFIR) [39, 40] uses a comprehensive multi-level determinant framework to systematically identify barriers and facilitators in five inter-related domains: Intervention characteristics, Outer setting, Inner setting, Characteristics of individuals, and Process. These domains are further defined by 39 pragmatic constructs that reflect theories and hypotheses in organizational and implementation research. CFIR has advantages over frameworks that focus on clinical evidence, guidelines, or innovative program characteristics and, for this study, an additional advantage to CFIR is the flexibility to address complex interactions within the internal VA settings, as well as with external settings of Tribes, IHS/THP, and Native communities. CFIR domains informed the main topical areas of our semi-structured, open-interview guide and prompts were used, as needed, to explore CFIR constructs.
The study sample was structured to represent each of the 14 facilities, as well as levels of responsibility for planning and/or implementing HBPC expansion. Key respondents were selected from lists of knowledgeable persons that were requested of each Chief of Staff. The lists included HBPC administrative and clinical staff (e.g., program director, program coordinator, medical director, primary care provider, social worker), and management leadership with oversight of the HBPC program at the facility (e.g., Chief of Staff, Geriatrics/Extended Care line manager) or regional level (e.g., rural health coordinator, minority Veteran coordinator). Participation was voluntary and Chiefs of Staff were not informed about the identities of volunteer respondents. The final sample of 37 respondents included 20 HBPC clinicians and 17 managers.
Data were collected in 1:1 telephone interviews, which were recorded with respondents’ permissions, transcribed, coded by members of the study team (JK, SC, DL), and entered into Atlas-ti™ software . Coding was an iterative process. Two coders (SC, DL) initially coded narrative text, to identify and classify descriptions within the 39 CFIR constructs. Discordant coding was identified and consensus strategies were used to manage disagreements and refine code definitions as needed to be relevant to this study; if consensus was not achieved, the PI (JK) resolved the issue and provided additional training. As coding definitions were further refined, all three coders then re-coded texts using the operational definitions shown in Table 1. The study was approved by the Institutional Review Board at the VA Greater Los Angeles Healthcare System.
Each of the VAMC in this study had well-established, mature urban HBPC programs, which continued under the direction of their respective medical directors as they adapted to delivering care at a distance from the VAMC. Few formal relationships with IHS/THP facilities were in place prior to the HBPC expansion, to the best of the knowledge of the study respondents. As indicated in Table 2, local contexts for target populations varied, by size (ranging from <5000 to >100,000 active users), distance (ranging from <50 miles to >200 miles, one-way between health centers and possibly farther to patients’ homes) and on-reservation healthcare system (IHS or THP).
There were consistent similarities in challenges to be overcome, barriers that could not be addressed at the program level and facilitators across programs as shown in Table 3.
While all CFIR domains were relevant, only 12 of the possible 39 CFIR constructs emerged from the rich text of these interviews. Table 4 represents the implementation experience from the VA perspective in selected quotations. Within each domain, local contexts may be essential to explain variation across cases and we note relevant differences by domain in summary descriptions of cross-case barriers and facilitators below.
Expansion activities added complexity to the management of established HBPC programs. For most programs, a major bottleneck to implementing the intervention occurred when programs needed to recruit and hire additional nurse practitioners as primary care providers. Delays in hiring processes also contributed to postponing initiation of some rural HBPC programs. Efforts to reduce the typical difficulty in recruiting and retaining primary care providers to rural areas by adding recruitment financial incentives to attract candidates were not always successful.
Other challenges for management and service delivery were related to the rural setting. Driving long distances to see patients in their homes was commonly referred to as “windshield time.” Travel could be challenging in inclement weather and with poor road conditions. The isolation of some reservation communities and difficulty in locating patients contributed to travel times, which might involve several hours per patient. Some programs reduced caseloads to account for the impact of travel time on scheduling and providing home care. In remote areas, faulty or poor connectivity hampered communications by cell phones or internet, leading to delays in communicating with patients and HBPC team members, as well as to accessing patient electronic health records.
Another layer of complexity was adopting a new process for referring potential HBPC patients for admission screening. Unlike HBPC programs at the VAMC where patients are referred by their VA primary care providers, these expansion programs often engaged in outreach activities to identify potential patients many of whom were not yet enrolled for the VA medical benefit. This was not a normal part of HBPC activities. A common solution was participation by a VA benefits officer, along with HBPC staff, at Tribal health fairs or social gatherings to explain VA medical, financial, and burial benefits and to expedite enrollment. HBPC staff also promoted their programs directly to Tribal community members at health fairs, community meetings (e.g., Veterans of Foreign Wars), and events (e.g., pow wows).
Respondents attributed grant funding from the VA Office of Rural Health as the sole rationale for VAMC to initiate rural expansion programs; some added that the decision was based on the expectation of future financial sustainment through the annual funding allocations. The proportion of Native and non-Native veterans varied across programs from an estimated 20 to 50%, with an average daily census of 1-25 veterans. Because American Indian populations are relatively small, program sustainment also depended on expanding HBPC to non-Indian rural-dwelling veterans to justify and recoup costs in subsequent years’ funding allocation. Another concern about sustainment was balancing staffing and program growth. Programs that assigned existing personnel to rural HBPC as collateral duties might need to limit capacity if there were no additional future personnel hires.
Domain: outer setting
Local contexts were particularly evident in the degree of networking between VA and IHS/THP. For instance, one VAMC successfully arranged for joint privileging of several VA and THP staff, while another VAMC was advised against such an arrangement by its regional legal advisors. Some programs insisted that VA be the provider of record while other programs allowed for patient choice between VA and IHS. Coordinated case management with IHS/THP also varied from fully integrated, to simple notification of recommendations, to no formal coordination. Having a previous working relationship between a VAMC and IHS/THP or Tribe did not guarantee acceptance of the previously unknown HBPC service or its requirement to deliver care in patients’ homes on reservations.
Networking between VA and IHS/THP clinicians was advantageous to programs and patients. Availability of local IHS/THP services allowed HBPC care managers to expand the range of resources to meet patients’ needs and preferences. For instance, where VA physical therapy services were not available in distant remote communities, patients might receive care locally through IHS/THP. Likewise, IHS/THP care managers were able to expand the range of resources, such as durable medical equipment, through the VA. Clinical coordination occurred on an ad hoc basis. Co-location of VA and IHS clinics facilitated relationships between providers but if HBPC moved to another site, that past advantage diminished.
Other formal and informal co-management strategies were also found in multiple cases, VA prescriptions were accepted at IHS/THP pharmacies. Availability through IHS/THP was advantageous for patients without residential mail delivery because the VA does not send medications to post office boxes. It was also advantageous for many patients because there is no co-pay requirement if medications were dispensed by IHS/THP. Several programs also developed processes to work with an IHS/THP partner to identify appropriate patients by direct phone call to a HBPC point of contact, a standardized referral form, or shared electronic health record.
Patient needs and resources
Patients’ needs are identified through a standardized HBPC screening process before admission to the program. Once admitted to the program, patients have access to comprehensive interdisciplinary primary care as well as referrals to other specialized VA services. In addition, the importance of the IHS/THP resource was a recurring theme in managing patient-centered care with resources that might be locally available from IHS/THP and at a reduced cost to the patient.
External policies and incentives
The VA-IHS Memorandum of Understanding supported collaborations but seamless and effective co-management and communication about mutual patients was stymied in most programs by the lack of a shared electronic health record. Even where joint privileging occurred, current federal policy prevents records from being interoperable; providers and staff entered patient information separately into both VA and IHS/THP records. At the patient level, seamless co-management was impacted by VA policy requiring co-pays depending on priority group, which sharply contrasted with IHS/THP policy to provide healthcare at no charge. These unexpected policy differences may have been a disincentive to patient enrollment for the VA medical benefit that might require co-pays for VA medical services and medications.
The direct incentive to initiate expansion was financial grant support. Indirect incentives included oversight from mandatory reporting requirements for HBPC and progress reports for the expansion grant; these were monitored by VAMC and regional managers as well as by the VA Offices of Rural Health and Geriatrics/Extended Care. VA provided no centralized guidance on how to conduct expansion but convened voluntary monthly telephone conferences for about a year that allowed programs to share experiences.
Domain: inner setting
HBPC is a mature program with well-defined structure and quality performance standards that allow flexibility to operate within local conditions (e.g., drive times, coverage area, patient complexity, staff turnover). The program goal remained unchanged but access for all rural-dwelling veterans was limited by staff size and round-trip distance to patients’ homes.
Networks and communication
The internal VA electronic health record and availability of Virtual Private Networks and cellphones to allow electronic health record access were assets. However, use of these technologies was often challenged by poor cell phone reception or inadequate internet connectivity in rural areas, as well as lack of networked office equipment at VA, IHS/THP, government, or non-government facilities where office space was assigned to HBPC staff.
Implementation climate: compatibility
HBPC programs regularly receive admission referrals from VA primary care clinics. One respondent recalled a colleague’s remark describing HBPC as “magic” because of the program’s success in managing complex patients. Weekly interdisciplinary team meetings to address the comprehensive needs of patients also functioned to support teamwork regardless of staff physical location or catchment areas. These regular team interactions became opportunities for peer-to-peer education. Nearly every program identified the team-based case conferences as sources of cultural competency education for working with American Indian veterans. Organizationally, HBPC is also recognized as a valuable fiscal asset to VAMCs through the VA annual funding formula.
Knowledge and beliefs
Many key clinical and administrative personnel were knowledgeable about HBPC approach and goals because they were expanding an existing clinical program. Several clinicians noted, however, that they had been unfamiliar with the requirements for VA benefits (i.e., medical, burial, and financial) when they started outreach efforts on reservations and tried to expedite enrollment for the VA medical benefits for potential HBPC users and other Native community members. Overall, HBPC staff perceived the intervention as positive, both to communities and to veterans who had previously been under-served.
Other personal attributes
Most expansion programs were facilitated by clinical and coordination personnel that had gained culturally appropriate experience from being a tribal member or from previous employment with IHS/THP. Their familiarity with American Indian customs and their culturally sensitive interactions with Tribes, IHS/THP, and Native communities promoted acceptance of HBPC. Without this background, staff and clinicians were also successful in promoting HBPC if they accepted the guidance of community members, including participation in community events and meetings and visiting communities repeatedly to build trust and acceptance. These personalized relationships were beyond the scope of the typical clinical visit and were valued by both the Native community and by the HBPC personnel.
At each VAMC, planning focused on internal processes of expanding staff or catchment area. Population-based needs assessments were not conducted to estimate the potential number of American Indian HBPC-users prior to implementation. A common, but erroneous, assumption was that all of veterans in the catchment area would be eligible for the VA medical benefit. Although VA and/or IHS/THP staff identified potential HBPC users, some of these vulnerable patients were turned away after failing to meet the financial criterion for medical benefits eligibility. As a result, it may have appeared that VA was not delivering the promised care to veterans who were in need.
Clear VA champions emerged in implementation of HBPC in the roles of the program coordinators or clinicians who were able to establish relationships with American Indian communities as well as with IHS/THP. Most respondents easily identified the one individual who had the most impact for their respective programs and cited the personal attributes as a reason for that individual’s success. In some locales, kick-off activities may also have benefitted from the direct involvement of leadership at the facility, regional administration, or headquarters level to initiate introductions and promote HBPC with a Tribe or IHS/THP clinic.
Overall, program implementation took longer than anticipated and was facilitated by champions who emerged in American Indian communities. Community Veteran advocates assisted HBPC expansion by introducing the program leadership at community meetings; over time, the program became accepted and its value embraced by the community. In addition to the usual internal VAMC referral process, referrals to HBPC were made on an ad hoc basis from IHS/THP clinicians, Veterans Service Officers, Tribal Veteran Representatives, and other Tribal health and service departments. Family members began reaching out to HBPC on behalf of their loved ones. Several HBPC programs developed unique direct referral options for IHS/THP using a FAX version of the VAMC standardized referral form, electronic health record referral process, or telephone call to a VA point of contact.
HBPC improved the image of VA in most communities by promising a service and delivering on that promise. HBPC personnel’s frequent visits for patient care, for outreach and to participate in community events established personal relationships of acceptance and greater trust for the VA. Positive experiences were associated with successful formal or informal efforts to integrate clinical collaborations between VA and IHS/THP.
All interviews ended with a query about recommendations to other VAMC based on lessons learned from the implementation experiences. Common responses were about building relationships with both the Tribe and IHS/THP, recognizing their roles and inputs as stakeholders and allowing them to define their level of participation. Joint planning efforts would also be valuable to define the catchment area, estimate the potential population, and determine if there are gaps in care. Expansion of VA services was also envisioned through telehealth collaborations with IHS/THP, better clinical integration through shared medical or pharmacy records, identifying space for HBPC staff in American Indian communities or IHS/THP buildings, and executing contracts with Tribal and non-Indian home health agencies that might operate in areas too distant for HBPC to regularly visit. Finally, recommendations also included awareness of practical issues, such as adapting to the distances involved in rural areas and training HBPC staff in local cultures and about the VA medical benefit.
This study begins to fill gaps in the literature on implementing HBPC in rural areas, as well as developing clinical programs in coordination with IHS/THP. CFIR was a useful instrument to systematically organize data and identify shared issued across sites. Despite variation in local contexts, there was consistency in experiences that might inform planning to expand access for medical services for populations in remote rural communities and to coordinate services among healthcare providers. Although HBPC is a standard benefit with centrally authorized guidelines, implementation in rural areas added complexity to intervention’s existing program structures and processes. Key personnel facilitated successful expansion programs through their personal interactions to with Tribes, IHS, and community members. These individuals were not in management leadership positions but represented the HBPC program and, consequently, the VA. In the process of implementation, champions arose in both the VA and American Indian communities, underscoring the significance for this population of developing personal relationships to establish trust and acceptance of new programs . External policies promoted expansion of a well-established urban program but allowed local programs the flexibility to manage the practical aspects of coordinating care with other healthcare organizations and other government entities. Flaws in the process were noted by respondents, including the lack of a population-based needs assessment, planning in coordination with IHS/THP, as well as differing policies for medical benefits and for inter-agency communications. Those problems indicate potential conflicts between outer and inner settings in implementing programs into underserved communities.
Several challenges and barriers were identified, some that could not be overcome. Difficulty in recruiting staff and delays inherent in the VA hiring process led to postponing programs, limiting program growth, or developing new program models. The distance to the most remote areas of a reservation may continue to be an obstacle to full access for American Indian and Alaska Native veterans. With relatively small numbers of American Indian veterans admitted to HBPC, sustainability over time depends on the average daily census of rural-dwelling non-Indian patients. Finally, differing VA and IHS policies on eligibility for medical benefits and schedules of cost for services were significant external barriers. The VA medical benefit income test resulted in turning away American Indian veterans who may have met HBPC admission criteria or who opted out of using HBPC when co-payment was required.
This study has a number of limitations. Respondents were selected for knowledge of the program but may have lacked overall background knowledge about the VAMC relationships with Tribes and may not have been fully aware of federal and Tribal policies. Interviews took place after the original grant-funding period and memories may have faded. Data collection was limited to interviews and no other source of information (e.g., diaries, meeting minutes) was available.
A goal of qualitative research is to document the range of variation and identify common experiences rather than a statistical description of variation and, therefore, the results may be limited to these specific case studies. The USA is unique in that American Indian and Alaska Native communities are considered sovereign nations under the US Constitution. Although other countries do not extend right of sovereignty to Native populations (e.g., Canadian First Nations and Australian Aborigines), the study may be applicable to expanding access and coordinating healthcare in discrete ethnic communities. The scope of the study is also limited by its focus on developing a non-institutional long-term care service for populations that may be served by other providers of record. However, the need to collaborate across healthcare organizations is also a unique contribution of this study. The literature on HBPC has not previously addressed how healthcare organizations reach out beyond their own patient populations to expand access. Finally, since there is no comparative literature on implementation of HBPC in rural areas , corroboration of our findings requires further research to understand the extent to which these barriers and facilitators might apply to other rural communities.
The context for expansion of access to deliver non-institutional long-term care was the policy agreement detailed in the VA-IHS Memorandum of Understanding of 2010. Overall, HBPC expansion efforts were successful although the target populations were relatively small. Where enrollment for VA benefits was uncommon in some communities, HBPC case finding efforts were linked to identifying and enrolling veterans for medical and other benefits. The HBPC Handbook places the responsibility for all aspects of management, planning, and developing community relationships on the HBPC program director. Thus, the expansion and innovation experiences might not be widely shared through the VAMC or regional levels unless a national level effort is undertaken.
Opportunities for shared learning would benefit federal healthcare organizations to expand other medical services to remote rural areas, American Indian reservations, and other underserved communities. Planning efforts should take into account conducting a population-based needs assessment and allowing sufficient time to develop trusting relationships with Tribes, IHS/THP, and Native or other underserved communities. Bottlenecks and delays in the hiring processes should also be considered in determining if the rollout will be phased or the program implemented at full capacity. Planning efforts should also consider availability of IHS/THP resources for patients and develop opportunities for co-management to prevent unintended duplication of effort, over-prescribing of medications, and other inefficiencies. For the VA, these planning and coordination activities may become increasingly important as VAMC enter into Reimbursement Agreements for primary care services provided by IHS/THP to veterans and as VA continues to expand HBPC to other rural areas.
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This project was made possible with the generous support of VA Research and Development grants: 12-434 and 12-063.
Availability of data and materials
The authors can confirm that all relevant qualitative data are included in the article as tables or supplementary information files.
Ethics approval and consent to participate
This study was approved by the Institutional Review Board of the VA Greater Los Angeles Healthcare System as project #0013: VA-Indian Health Service Collaborations in Rural Health: HBPC.
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The authors declare that they have no competing interests.
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Kramer, B., Cote, S.D., Lee, D.I. et al. Barriers and facilitators to implementation of VA home-based primary care on American Indian reservations: a qualitative multi-case study. Implementation Sci 12, 109 (2017). https://doi.org/10.1186/s13012-017-0632-6