Healthcare providers’ accreditation is one of the standard means of assuring quality services. This paper examines the pattern of National Health Insurance Scheme accreditation results among private healthcare providers in Ghana.A cross-sectional quantitative analysis of administrative data from seven National Health Insurance Scheme healthcare provider accreditation surveys over the 2009–2012 period. Data on private healthcare providers that applied for formal accreditation between the study period were retrieved from the NHIS accreditation database using a checklist. Proportions were used to examine pattern of private healthcare provider accreditation results by region, type of care provider, and grade.Overall, 1600 healthcare providers applied for accreditation over the study years, of which 1252 (78%) passed and were accredited. Majority of healthcare providers that passed the healthcare facility assessment were in Ashanti, Greater Accra, and Western regions, and were significantly higher than those in the other regions. Among the healthcare providers that passed the assessment, pharmacies (22%) and clinics (18%) constituted the largest groups, and were significantly higher than the other types of healthcare providers. Similarly, among those that passed, majority (62%) obtained grade C and D, representing a score of 50–59% and 60–69%, respectively, and were significantly higher than those that obtained the top three grades of A+ (90–100%), A (80–89%) and B (70–79%).Majority of healthcare providers accredited to provide services to the insured are concentrated in three regions of the country, and are mainly pharmacies and clinics. Moreover, substantial proportion of the healthcare providers obtain average scores of the healthcare facility assessment, an indication that these care providers fall below the National Health Insurance Scheme applicable-predetermined standards.The online version of this article (doi:10.1186/s13690-017-0205-9) contains supplementary material, which is available to authorized users. Over the last decade, there has been an increased interest in development of accreditation programmes or tools for assessing healthcare providers and ensuring quality of care delivery in the health sector. This is being pioneered by international bodies involved in quality of care assessments to address quality of care challenges associated with increasing population and advancement in healthcare –3. OtherIn Ghana, healthcare facility accreditation is a legal requirement for all care providers and the National Health Insurance Authority (NHIA) in collaboration with the Health Facility Regulatory Agency (HEFRA) undertakes this exercise –9. HEFRASince implementation of the NHIS policy in 2004, considerable achievements have been made in the area of providing financial access to healthcare for majority of Ghanaians –16; howeThe first part of this section describes the process of the NHIA healthcare provider accreditation and performance score. The later part focuses on design of the study, the study population, and data collection techniques used.The healthcare provider accreditation process begins with an application from interested healthcare providers ; Score 1 if less than half are met (but not zero); Score 0 if no criterion is met; and Score “N/A” if the standard is not applicable . On averThis was a cross sectional quantitative study using administrative data from seven NHIS accreditation surveys covering the period, July 2009 to July 2012.All private healthcare providers that applied for NHIS accreditation between July 2009 and July 2012 were used for the study. They included pharmacies, chemical shops, maternity homes, laboratories, scan centres, clinics, primary hospitals and secondary hospitals. Other healthcare provider information were location , ownership, level of care, accreditation scores and accreditation status.The NHIA accreditation and performance score data were extracted from the NHIA accreditation database using data extraction checklist. The completeness of the data was assessed and healthcare providers whose data were incomplete were contacted through telephone or by visit to obtain missing information.A descriptive analysis was employed to examine pattern of success (or pass) and failure among private healthcare providers (PHCPs), pattern of reaccreditation among PHCPs with provisional accreditation, and pattern of upgrade among PHCPs. The analysis was conducted by region and by type of healthcare provider for all the seven batches of accreditation surveys using Microsoft Excel (2010 version). Successful accreditation per batch was estimated as proportion of accredited (passed) healthcare provider per accreditation batch; failure per batch was calculated as proportion of failed healthcare provider per accreditation batch; successful reaccreditation per batch was determined as proportion of accredited healthcare provider with provisional accreditation per batch; and successful upgrade per batch was estimated as proportion of successful upgrade per upgrade application. Confidence intervals were also estimated for proportion of healthcare providers that passed the accreditation assessments, using Stata immediate command “cii N X, level (95)”; where cii is immediate confidence interval, N is sample size or number of observations, and X is number of successes .A total of 1600 applications were received for accreditation between July 2009 and July 2012, of which clinics constituted 356 (22.3%), pharmacies, 328 (20.5%) and chemical shops, 266 (16.6)  applications were submitted over the study period for reaccreditation , reapplication , upgrade to next level of care, and downgrade  applications passed while 348 (22%) failed. Accreditation performance score by region showed that Ashanti region had the highest number of healthcare providers that passed, 304 , followed by Greater Accra region, 275  and Western region, 165  , followed by clinic 230 , and chemical shop, 225   healthcare providers obtained the top three grades  while 1349 (84%) obtained the lowest four grades   compound. Therefore, the high proportion of pharmacies and clinics could help address the challenge of geographical access to healthcare services, as well as geographical equity in access to healthcare in deprived communities.Assessment of applications by administrative region reveals significant differences in the proportion of healthcare providers that passed. In all, Ashanti region submitted the highest number of applications and also had the highest proportion of healthcare providers that passed the accreditation assessment. This was followed by the Greater Accra and Western regions. The proportion of healthcare providers in these three regions that passed the healthcare facility assessment were significantly higher than those from the other seven regions. Whilst proportion of healthcare providers in Ashanti and Greater Accra region that passed the healthcare facility assessment show no significant difference, there were significant difference between Ashanti and Western region. These results are expected due to the proportionally large number of private healthcare providers in these three regions in the country. The significance of these results is that it would facilitate easy access to healthcare provider services for the substantial number of the insured residing in these three regions. Similarly, the relatively large number of accredited healthcare providers in the Brong-Ahafo region could help address the challenge of geographical access to healthcare in the remote communities. However, the small number of healthcare providers in the three deprived regions of the country  that passed the healthcare facility assessment could pose a barrier to access to health services for the insured in these regions.Results of the study also show significant differences in the proportion of healthcare providers that passed the healthcare facility assessment by type of provider. Majority of the pharmacies, clinics and chemical shops passed the assessment; however, there were no significant differences between them. On the contrary, proportion of pharmacies that passed the assessment were significant higher than that of the other types of healthcare providers . Interestingly, the clinics also recorded the highest number of failed applications, which means that most of them fall below the NHIS applicable pre-determined standards for accreditation.Findings of the study also show that among the healthcare providers that passed the healthcare facility assessment and were accordingly accredited, about two-thirds had average score of 50% to 69% (grade C and D), and were significantly higher than those that obtained a score of 70% to 100% . Only a limited number of healthcare providers (about one-sixth) obtained the top three scores of the accreditation assessment. The plausible reason is that majority of the healthcare providers’ facilities are below the pre-determined standards. This finding supports a study by Alhassan et al. , where lThe large number of healthcare providers in the score bracket of 50–69% also raises the question of “is it the case of accreditation fraud, where healthcare providers borrow or rent equipment and other resources for the purpose of satisfying the inspection team to get the desired level of accreditation and return them after the inspection? Or is it the case where healthcare providers that do not meet the pre-established standards for accreditation tend to “buy” the inspecting team, as found in other study , 20. OneThere were gaps in the data obtained especially information on reapplication. Thus, deductions had to be made on which applications were for reaccreditation  and which ones were reapplications from healthcare providers that did not meet requirements of previous healthcare facility assessment exercises, making it a potential source of error. Secondly, the study used a 5-year old data; hence, generalisation of the findings needs to take this into account.The study reveals significant differences in accreditation scores between regions and between healthcare providers. Healthcare providers in the Ashanti, Greater Accra and Western regions recorded significantly higher assessment scores than those in the other seven regions of the country. Accreditation by type of healthcare provider also shows that pharmacies, clinics, and chemical shops obtained significantly higher scores than the other types of healthcare providers; however, they are no significant differences in pass scores between them. The study also reveals that majority of the healthcare providers that apply for accreditation obtain average assessment scores, and are significantly higher than those that obtain the top three scores. This suggests a need for regulatory authorities to enforce standards to ensure provision of quality care and better health outcomes for the population. Further study would also be necessary to assess accredited healthcare providers’ level of adherence (or compliance) to treatment protocols governing their accreditation status.


The Institute of Medicine recommended the advance of innovation and entrepreneurship training programs within the Clinical & Translational Science Award (CTSA) program; however, there remains a gap in adoption by CTSA institutes. The University of Michigan’s Michigan Institute for Clinical & Health Research and Fast Forward Medical Innovation (FFMI) partnered to develop a pilot program designed to teach CTSA hubs how to implement innovation and entrepreneurship programs at their home institutions.fastPACE).The program provided a 2-day onsite training experience combined with observation of an ongoing course focused on providing biomedical innovation, commercialization and entrepreneurial training to a medical academician audience (FFMI fastPACE course or modified existing programs. Two reported greater collaboration with their technology transfer offices.All 9 participating CTSA institutes reported a greater connection to biomedical research commercialization resources. Six launched their own version of the FFMI fastPACE course and training program may be suitable for CTSA hubs looking to enhance innovation and entrepreneurship within their institutions and across their innovation ecosystems.The FFMI  The Clinical & Translational Science Award (CTSA) program was established by the National Institutes of Health (NIH) in 2006 to realize a new vision for translational and clinical science . The UniAcademic researchers engaged with the CTSAs have ideas at all stages of development, many of which hold the key to critical breakthroughs in the prevention, diagnosis, and treatment of disease in the form of novel therapeutics, devices, diagnostics, and software/mobile app solutions. However, there is a long, resource intensive route to a viable commercial pathway that leads to a product. Compounding that challenge, the commercialization of research discoveries is often a secondary pursuit for academicians who are time-constrained with clinical care, education, and research responsibilities. In addition, they have competing priorities such as a tenure and promotion goals that often emphasize traditional academic behaviors over other activities.The NIH has since partnered with The National Science Foundation (NSF) to develop an I-Corps™ program specifically focused on biomedical innovation, leveraging the model of the long-standing and successful program originally designed to improve the impact of recipients of NSF Small Business Innovation Research or Small Business Technology Transfer grants . HoweverInnovation Navigator to provide translational funding and mentorship tailored to academic researchers and clinician-scientists, (2) Business Development to connect academic researchers with industry partners, and (3) Innovation, Commercialization, and Entrepreneurship Education with programs tailored to the busy medical academician , house officer, graduate student, postdoctoral student, and medical student [fastPACE  course, a 4-week experiential learning course customized for the busy medical academician and focused specifically on teaching the foundational concepts for biomedical technology commercialization  [fastPACE course was co-developed with the U-M College of Engineering’s Center for Entrepreneurship, a long-standing NSF I-Corp™ node, to incorporate the core principles and successfully complement the NSF I-Corps™ program [In 2012, the U-M Medical School launched a research strategic plan and included development of an innovation and entrepreneurship program: Fast Forward Medical Innovation (FFMI) . FFMI’s  student . In resp Course) . The fas program .fastPACE course specifically targets early stage projects and academicians exploring an exit agnostic route to commercialization in an accelerated timeframe (4 wk). The course does not have eligibility mandates nor team formation requirements and supports enrolled academicians without a strong network of entrepreneurial contacts by connecting them with trained postdocs, medical students, and graduate students interested in a career in biomedical commercialization; as a result, potential barriers keeping the single academician from participating are eliminated. fastPACE to serve as a precursor program to NSF/NIH I-Corps™. Indeed, this potential has been demonstrated by the successful matriculation of three project teams from fastPACE cohorts 1–3 into the NSF I-Corps™ program.The fastPACE course extends to the cultivation of an innovation ecosystem that can support the successful execution of such a customized biomedical innovation education program. Key partners for fastPACE implementation include the U-M Office of Technology Transfer, core units supporting the research enterprise , diverse schools and colleges , and regional economic development agencies. Members from each group promote and advocate for the course, assist in the recruitment of project teams, and serve as course instructors. The course also serves as a means for recognizing potential gaps in the innovation ecosystem and as a foundation on which to build impactful, collaborative programming to enhance the mission of a CTSA.Since fall of 2014, the course has successfully completed 6 cohorts, graduated over 250 clinicians, researchers, and students from across the country, and helped 125 project teams navigate the early stages of commercialization by receiving more than $8 million in downstream funding and development partnerships. Outcome metrics from cohorts 1–3 have demonstrated initial success, as 3 project teams have formed startups since completing the course and one has licensed the technology to an existing company. As project teams from cohorts 4–6 (completed as recently as 2017) continue to mature, it is likely that a comparable or greater number of projects will achieve similar outcomes. Importantly, in addition to outcome metrics, the value of the fastPACE course has had on the acceleration of biomedical research commercialization, as well as its complementarity to NSF/NIH I-Corps™, FFMI and MICHR partnered to execute on the National Center for Advancing Translational Science and CTSA vision to disseminate resources and methodologies that foster innovation in translational science across the CTSA network. In March 2017, FFMI and MICHR launched a pilot fastPACE Train-the-Trainer (TtT) program designed to teach CTSA leads and other institutional collaborators how to implement the fastPACE course at their home institutions. The program attracted participation from nine CTSA institutions and 16 representatives, providing each with the training, materials, and support to launch their own fastPACE program within 6–12 months. Critical success factors, such as key partners and collaboration strategies, were introduced and workshopped to ensure broad campus-wide support and the culture change required for the success of fastPACE. To highlight the approach for disseminating biomedical commercialization education throughout the CTSA network, we fully describe the design, implementation, and outcomes from the pilot fastPACE TtT program.In recognition of the impact that the fastPACE course is tailored to the specific needs and constraints of busy academic researchers and clinicians exploring the commercial potential of biomedical and life science research projects. The course helps learners of all levels develop a basic vocabulary for commercialization and entrepreneurship, and enhances their understanding of key concepts most critical for the commercialization of life science technologies. The desired outcome is to de-risk current and future technologies by preparing academicians for successful commercialization through university exits of all types including entrepreneurship in the form of starting a new company, a license to an existing company or a research agreement with an industry partner.The fastPACE course.Over 4 weeks, the course covers innovation and entrepreneurship concepts while addressing unique biomedical commercialization risks, such as Food and Drug Administration (FDA) regulations, reimbursement strategies, and intellectual property considerations. By using a track-specific structure, where project teams are streamed into 1 of 3 product verticals , each track receives customized education for its unique vertical. For example, the FDA regulatory considerations for a healthcare software/mobile app solution versus a new drug therapy have very different levels of risk, timelines for approvals, and required resources. fastPACE TtT program provided a 2-day onsite training experience (at U-M) combined with observation of a fastPACE cohort that was launching simultaneously. The 2-day training was divided into 3 parts: (1) a fastPACE course training workshop, (2) a MICHR overview and discussion for future CTSA collaboration, and (3) observation of the fastPACE course Kickoff Event. Following the 2-day training, program participants observed the remaining weekly progression (4 wk) of the fastPACE course via weekly webinars. At the conclusion of the entire program (2-d training and observation), participants were expected to have a broader knowledge of biomedical commercialization education and resources, as well as the materials and strategies to implement the fastPACE course at their home institution. fastPACE TtT program.The fastPACE course training (day 1) workshop was intended to provide specific details on the design and implementation of the course at U-M. The 4-hour training session addressed key strategies for designing a biomedical commercialization education program at any institution, including collaboration between key campus partners , the value of expanded promotion and tenure guidelines to include innovation and entrepreneurship metrics, and the value in leveraging student groups across the university to support faculty researchers and clinicians.The Following an introduction by FFMI and MICHR leadership, participants discussed the unmet need for commercialization education at each institution. In a roundtable format, participants shared examples of existing innovation and entrepreneurship programs, as well as any gaps in programming on their campus. Remarkably, none of the existing programs described by the participating institutions specifically targeted biomedical researchers or clinicians, nor did they facilitate collaboration between faculty and students. Participants also shared challenges such as the difficulty of modifying existing programs to meet the specific needs of their CTSA, and navigating the institutional support required to start a new program. Presentations and facilitated discussion by FFMI staff addressed each of these concerns, as well as program planning strategies. For instance, strategies and processes were presented for selecting and targeting an audience of biomedical researchers, clinicians, graduate students, and medical students during a match-making and team formation process. Potential key partners and materials used for support were presented, including innovation and entrepreneurship centers from across the university, and community resource centers with access to local biomedical industry and venture experts. Specific preprogram and postprogram planning activities were also presented in the form of a timeline of key events and dates. Critical activities identified include the assembly of an expert teaching team, the request for applications and project team onboarding, and the program budget. Metrics for tracking success and opportunities for improvement were also discussed with the group. The session concluded with a panel discussion including FFMI, MICHR, and cross-campus collaborating units at U-M, including the Tech Transfer Office (both licensing and venture creation) and the Center for Entrepreneurship at the College of Engineering (NSF I-Corps™ node), to highlight strategies for successful teamwork and to summarize positive outcomes achieved.The 2-hour MICHR/CTSA collaboration session (morning of day 2) was designed to highlight the successful integration and collaboration between MICHR and FFMI, including a portfolio of programs as part of the optional CTSA renewal module for innovation (online Supplementary Appendix) submitted by MICHR in 2016. These included examples of projects utilizing FFMI innovation and entrepreneurship resources and/or MICHR programs as they leveraged various follow-on funding and additional programs to further expedite the translation of the project. Two specific FFMI initiatives presented were Business Development, a dedicated team that focuses on industry research engagement, and the Michigan Translational Research and Commercialization for Life Sciences program, a funding and mentorship program in partnership with the state’s Michigan Economic Development Corporation. Complementary MICHR programs presented included the Michigan Investigator Assistance Program, established to provide IND/IDE consultation and support, the Research Development Core, offering pre-award support and advice for research proposals, and the Pilot Grant program that supports innovative clinical and translational research. The session concluded with a roundtable discussion on best practices for sharing and disseminating materials, training, and additional resources throughout the CTSA network, as well as the discussion of formation of a special interest group focused on commercialization of life science technologies.fastPACE cohort starting at U-M. By planning the TtT concurrently with a fastPACE cohort, participants of the TtT program were able to see the composition of each participating team, the interaction with the assembled teaching team members, and the innovation, entrepreneurship, and biomedical commercialization topics taught throughout the course.The 2-day onsite training concluded (afternoon of day 2) with the opportunity to observe the course Kickoff Event for a As observing members of the course, TtT participants were provided with the same instructional materials, syllabus, presentation slide decks, notes, and handouts as participating project teams. Specific instruction observed during the course Kickoff Event provided exercises to teach the development and articulation of a value proposition, the mapping of an innovation’s ecosystem of critical stakeholders (to identify gaps in understanding), and the skills in behavior-based interviewing techniques (for eliminating any gaps identified), also known as customer development (discovery), a popular and successfully proven process used during the NSF/NIH I-Corps™ program for launching new ventures .fastPACE course weekly progression via webinar  were invited to attend an informational webinar detailing the program agenda 1 month prior to the start. Communications were also sent to individual CTSA working groups, including the Clinical Research Training for Investigators Workgroup that hosted a 15-minute informational presentation during a scheduled conference call. Additional recruitment efforts in the form of follow-up email communication and phone conversations were critical in assembling the final roster CTSA institutions and participants.fastPACE program at their home institution. In total, 9 CTSA institutions and 16 representatives participated in the program. Each individual institution determined what units, functions, and representative(s) should participate in the training program, considering who would be best equipped to implement the fastPACE course. There was no registration fee for the participating institutions; however, each institutional representative provided their own travel and accommodations estimated at $500 each.Total direct expenses for FFMI and MICHR to provide the TtT program were approximately $4800 (indirect or administrative/overhead expenses not included). Hosting for 16 institutional guests to attend the 2-day onsite training totaled $3400. Remaining expenses were $1400 for the design, printing, and distribution of all training materials including training binders, presentations, handouts, and other materials to allow institutional representatives to implement the FFMI fastPACE course, and interest in continued collaboration. The evaluation received a 31% response rate of the 16 participants (n=5). Following the onsite training, all 5 respondents strongly agreed or agreed that the program met their expectations, it was delivered appropriately across 2 days, and it successfully broadened their knowledge of biomedical commercialization resources and education. In addition, all 5 respondents strongly agreed or agreed that the program will directly impact their institution because they plan to implement all or part of the FFMI fastPACE course.An evaluation was administered via online survey tool  immediately following the initial 2-day onsite training to evaluate the program’s effectiveness across a variety of criteria, including broadening the participants’ knowledge base of biomedical commercialization resources and education, assessing potential impact on participating institutions by implementing all or part of the FFMI fastPACE course or to modify and bolster existing innovation and entrepreneurship programs at their institution. Two of the 9 institutions have recommended that project teams from their institution enroll in a fastPACE course cohort at U-M prior to receiving funding from their own translational science programs. As a near-term and temporary approach, this will allow teams to access fastPACE training while their home institution works toward potential implementation of its own program. Two participating representatives reported resulting collaboration between the technology transfer office and CTSA at their home institution. Perhaps most importantly, representatives from all attending institutions reported a greater connection to biomedical research commercialization resources and the desire to stay connected through a potential new CTSA-based consortium focused on biomedical research, innovation, and commercialization.Phone interviews were conducted with all TtT participants 3 months postprogram to capture preliminary outcomes, in the form of implementation activities and impact from attending and observing the entire 4-week program. Six of the 9 attending institutions, including University of Arkansas Medical Sciences, Ohio State University, Northwestern University, University of Kentucky, University of Washington, and Indiana University were using shared materials and online resources made available during the TtT program to launch their own version of the FFMI fastPACE TtT program successfully disseminated a valuable biomedical commercialization education program to the group of participating CTSA institutions. This result represents a proof of principle that CTSA institutes and institutional commercialization and entrepreneurship programs can partner, both internally and externally, to address the NAM’s recommendation to the CTSA program regarding enhancing its focus on innovation and entrepreneurship in education and training programs.Based on analysis of the evaluation data and preliminary outcomes, the fastPACE TtT program successfully addressed strategies for each participating institution to identify existing biomedical commercialization resources within its own ecosystem to enhance their impact through partnerships via collaborative programs such as fastPACE. As previously mentioned, none of the participating institutions knew of existing programs that addressed the unique and specific needs of biomedical faculty and academic researchers who are time-constrained and also require tailored education on specific concepts that are most relevant to the successful commercialization of their technologies. Interestingly, some of the participating institutions were in relatively close proximity to existing I-Corps™ programs, further underscoring the opportunity for fastPACE to complement I-Corps™ in preparing teams at an earlier stage than those that would typically enroll.In addition, the fastPACE at U-M has led to benefits that further address the NAM’s critique and uncovered new opportunities for partnering with our CTSA organization (MICHR), as well as many others. For example, FFMI and MICHR have partnered to create the nation’s first Continuing Medical Education accredited series of seminars for providers in an academic medical center that focuses on core topics related to commercialization, industry partnership, and entrepreneurship. Furthermore, FFMI and MICHR are working together to enhance workforce readiness with an internship program that places postdoctoral fellows and graduate students in industry settings. Students seeking a career in industry will participate in commercialization courses, including fastPACE, as a prerequisite to obtain foundational training and placement preparedness. In addition to fastPACE, FFMI has launched other commercialization education programs within the PACE portfolio with tailored formats for multiple audiences. The fullPACE program, a 12-week multidisciplinary team-based program for medical residents, fellows, graduate students, and postdocs has graduated 2 cohorts of ~35 participants since 2015. Beginning in the fall of 2017, the fullPACE program will be offered through the U-M Rackham Graduate School as a 3-credit hour course. The firstPACE series, a 3-part series on medical needs finding, design thinking for healthcare innovations, and value proposition analysis is delivered to medical students in a novel co-curricular program, known as the Path of Excellence in innovation, entrepreneurship, and commercialization, offered in collaboration with the U-M Medical School. Finally, fittedPACE offerings are customized learning opportunities for sponsoring departments within the U-M Medical School to help achieve specific strategic objectives related to innovation. As a customized program, fittedPACE has offered everything from a 9-month experiential program for an entire department of 90 faculty to short ideation sessions for an individual product vertical  that enhance learning and generate new ideas. It is clear that the potential value of a program such as fastPACE extends well beyond the parameters of a single course or framework and can have a far greater impact across the entire innovation ecosystem in which it is implemented.The success of fastPACE course and its TtT program may be suitable for a broad range of academic medical centers, including those with CTSA programs looking to enhance opportunities for innovation and entrepreneurship within their ecosystems.In conclusion, the partnership between FFMI and MICHR presents a novel model and opportunity to deliver on the overall CTSA mission to disseminate best practices and successful methodologies that accelerate the process of translating laboratory discoveries into clinical practice. Preliminary experience with the program suggests that the


Background: Vertically oriented global health initiatives (GHIs) addressing the HIV/AIDS epidemic, including the President’s Emergency Plan for AIDS Relief (PEPFAR), have successfully contributed to reducing HIV/AIDS related morbidity and mortality. However, there is still debate about whether these disease-specific programs have improved or harmed health systems overall, especially with respect to non-HIV health needs.Methods: As part of a larger evaluation of PEPFAR’s effects on the health system between 2005-2011, we collected qualitative and quantitative data through semi-structured interviews with District Health Officers (DHOs) from all 112 districts in Uganda. We asked DHOs to share their perceptions about the ways in which HIV programs (largely PEPFAR in the Ugandan context) had helped and harmed the health system. We then identified key themes among their responses using qualitative content analysis.Results: Ugandan DHOs said PEPFAR had generally helped the health system by improving training, integrating HIV and non-HIV care, and directly providing resources. To a lesser extent, DHOs said PEPFAR caused the health system to focus too narrowly on HIV/AIDS, increased workload for already overburdened staff, and encouraged doctors to leave public sector jobs for higher-paid positions with HIV/AIDS programs.Conclusion: Health system leaders in Uganda at the district level were appreciative of resources aimed at HIV they could often apply for broader purposes. As HIV infection becomes a chronic disease requiring strong health systems to manage sustained patient care over time, Uganda’s weak health systems will require broad infrastructure improvements inconsistent with narrow vertical health programming. Did PEPFAR provide much needed funding, energy, and support to health systems in countries where it operated, either by “spilling-over” resources from its predominantly vertical HIV/AIDS programs, or by directly investing in health system strengthening beginning in 2008, as some have hypothesized?8 Conversely, did PEPFAR undermine health systems, even if unintentionally, by recruiting health workers away from primary care duties, distracting health decision-makers, establishing parallel service delivery and reporting structures, and prioritizing HIV/AIDS over potentially more pressing challenges, as others have suggested?12More than 10 years now since its inception, there is general consensus the US President’s Emergency Plan for AIDS Relief (PEPFAR) has been successful at its main goal – to reduce the morbidity and mortality from HIV/AIDS in targeted low-income countries.13 increased vaccination rates, antenatal care coverage, malaria diagnoses, and treatment of sexually transmitted diseases.16 There is evidence, however, health service providers have shifted focus from primary care duties, leading some to challenge the reports of positive PEPFAR spillover.17 While some studies have demonstrated PEPFAR was associated with effective task-shifting, improved in-service training, and higher job satisfaction,18 other studies have noted an internal brain-drain of doctors from the public sector to HIV programs run by non-governmental organizations (NGOs), work interruption for training, and overburdening of a health workforce already spread thin.19Studies attempting to investigate PEPFAR’s influence on health systems offer mixed evidence for productive and counterproductive effects. Some researchers have observed positive effects on primary care,20 focused on the experiences of patients21 and policy-makers,9 or assessed the marginalization of civil society organizations.22 Many studies have avoided distinguishing between PEPFAR, the Global Fund, and the World Bank’s Multi-Country HIV/AIDS Program, and have instead examined the net effects of global health initiatives (GHIs) generally.23 Those studies which have assessed a single initiative have tended to focus on the Global Fund.39 This is an important distinction because there are valid reasons to believe the varied policies and approaches of each GHI may have interacted with health systems in distinct ways.40Despite this burgeoning body of literature analyzing the interactions between PEPFAR and health systems, few researchers have asked public sector health managers in low-income countries what they think about how PEPFAR influenced the health system. This is a noteworthy shortcoming because their views could valuably inform PEPFAR policy. Studies which have included analyses of stakeholder experiences have relied on a small number of interviews in a limited geographical area,41 of whom fewer than 50 000 were receiving life-saving ART  processes.45 The majority of programmatic funding flowed to implementing partners, mostly US-based NGOs, with little direct financial support allocated to Ugandan government health budgets. These programs slowed HIV incidence and significantly expanded access to ART. By 2010, more than 200 000 HIV-positive Ugandans were receiving treatment  perceptions of how PEPFAR affected health system strength in Uganda 2005-2011. We hypothesized Ugandan DHOs would perceive PEPFAR strengthened the health system overall, particularly in the areas of health workforce trainings, increased access to medical supplies and equipment, and improved financing for the health sector. We also hypothesized DHOs would perceive PEPFAR implementation prompted the movement of health workers out of the public sector and focused attention on HIV programming at the expense of primary healthcare delivery. Therefore, DHOs would have mixed views of PEPFAR’s influence on the health system.40 and outpacing both Ugandan government health allocations and contributions from other GHIs each year 2005-2010 , DHOs are responsible for managing the delivery of public sector health services for both HIV and non-HIV care. Moreover, given the Ugandan context of a shift towards decentralized health authority and decision-making, DHO roles are increasingly important.This mixed-methods analysis of Ugandan DHOs’ perceptions about the positive and negative effects of PEPFAR is part of a larger evaluation of the influences PEPFAR had on the Ugandan health system between 2005-2011. For this paper, we collected quantitative and qualitative data through semi-structured interviews with leaders at each Ugandan district health office. After obtaining written consent to participate, we first asked each DHO to categorize whether PEPFAR’s influence on seven separate health system components (fully described below) had been positive, negative, or neutral. We then prompted DHOs to provide comments on each component. We had 30 to 60 minutes of the DHOs’ time to complete the questionnaire. During analysis, we used the categorical responses to complement the positive and negative comments each DHO offered and determine how much emphasis to place on each comment. We established the relative salience of positive and negative comments concerning each health system component based upon: (1) the number of DHOs making similar remarks and (2) the relative proportion of DHOs who categorized PEPFAR’s effects on that health system component as positive, negative, or neutral.The project was funded with a PEPFAR Public Health Evaluation award to the University of Washington (UW) from the US Centers for Disease Control (CDC) in late 2010. Prior to issuing the award, the health systems team in the Health Economics, Systems and Integration Branch, Division of Global AIDS, at CDC had outlined a proposed research protocol. The UW, in partnership with Makerere University and CDC, prepared the final research protocol, including sampling strategy and analysis plan. Makerere University, Kampala, Uganda provided in-country implementation including leadership, project management, development of the questionnaire, and data collection. The Uganda office of the CDC and the Resource Center at the Ugandan MoH also made valuable contributions to the research.Makerere University hired research assistants to collect data from the 112 district health offices. Recent university graduates, many with degrees in health and social sciences, comprised most of the team, along with some junior faculty. We conducted a one-week training in October 2011 to orient our team to the goals and the research protocol and provided a field manual outlining data collection procedures .Following the training, the research assistants were divided into six teams and assigned a geographical region. Each team consisted of three data collectors, one of whom was the designated leader. During the first week of data collection, each team visited and gathered data from nine district health offices and submitted these data to the research leadership team at Makerere University to be reviewed for thoroughness and to troubleshoot any problems. The teams then returned to the field and completed data collection from the district health offices by late December 2011.50). Consent forms promised DHOs their identities would be kept confidential in our reports.District health offices were informed of the research project in advance by a letter from the MoH authorizing participation in the research. The research assistants then contacted each district health office to schedule their visit, confirmed their appointment with a call the day prior to arrival, and carried a letter of introduction from the MoH. In addition to the interviews with DHOs, we collected quantitative data from the routine MoH health management information system (HMIS) reports , coordinate stakeholders in the health system, mobilize financial resources, and manage information systems. In this paper, we refer to these key areas of the health system as “components.” The interview guides included items that asked: (1) whether informants thought PEPFAR investment had improved, had no effect on, or decreased each component of the health system as related to the non-HIV health system; (2) to list and explain a few ways in which the PEPFAR investment had both positively and negatively affected each key component as it related to non-HIV health service delivery, regardless of whether their overall impression was of improvement, neutrality, or reduction; (3) to state whether their district had completed a number of key exercises pertaining to each health system building block in 2005/2006, 2006/2007, or 2010/2011; (4) to hypothesize two or three potential explanations why the quantitative aspects of this program analysis might find the PEPFAR investment had positive or negative effects on non-HIV health indicators; (5) to make any comments they would like to be included in the study.We used the World Health Organization’s (WHO’s) six building blocks for strong health systemsUsing the scanned copies of the structured interview guides containing the handwritten responses from each interview, we confirmed the electronic transcriptions entered into CSPro in the field were complete and accurate. In the instances where the electronic transcripts had been misentered or truncated, we corrected the electronic transcripts to reflect the notes taken during each interview verbatim.52 After initial coding, we checked intercoder agreement by randomly selecting 15 of the 112 transcripts and having a second member of the research team (TL) independently code them using the code book we had developed. We determined 15 transcripts was a sufficient sample to test intercoder agreement because all key themes and subthemes appeared more than once within the sampled transcripts, and many appeared multiple times. After the transcripts of the 15 interviews chosen had been coded by the second coder, the two coders compared how they had applied the codes and discussed the instances in which they had coded the transcripts differently. Based on the consensus the two coders reached about how and why they had applied the codes differently in each instance, the inclusion and exclusion criteria for each code were edited to minimize discrepancy between coders. We then applied the codes with the revised inclusion and exclusion criteria to the remaining 97 interview transcripts.Our coding team identified key themes and subthemes inductively through open free coding and analyzed these themes in ATLAS.ti using a content analysis approach.We interviewed DHOs (or their proxies) about how health systems and health facilities in their district were managed, including their current situation (2010/2011) and their best recall of two periods in the past  with regard to the seven health system components described in the Methods section. The goal was to assess whether, during this period of PEPFAR engagement in Uganda, there was a trend towards districts more completely performing a number of key activities to strengthen each health system building block  capacity, stakeholder coordination, and information management.Examining DHO perceptions of PEPFAR’s effects on each health system component individually, respondents in large numbers (78%-92%) reported PEPFAR’s effects as beneficial for six of the seven health system components studied: Almost all (98%) DHOs reported they had a strategic plan in 2011, and 80% of these plans included the activities of NGOs working within the district . OverallOnly about half of DHOs said private labs were monitored, but 2/3 said private clinics were supervised and 3/4 said private drug shops were monitored. These figures did not change substantially over the period of PEPFAR investment, though 81% of DHOs said HIV initiatives improved their ability to monitor and evaluate non-HIV services in their districts.53 Half (49%) of DHOs said they had applied for funds to support their operations beyond the MoH, from either an NGO or other donor, up from about a third at the start of PEPFAR programming. However, only about half (46%) said PEPFAR improved their ability to mobilize resources in their districts, an additional one in five (22%) said it decreased their ability to do so, and a third (30%) said it had no effect. DHOs predominantly attributed this mixed effect on resource mobilization to the unavailability of grants for non-HIV related health programs as well as the perception that the windfall of HIV funding had sufficiently provided for the entire health sector  reported a negative effect on planning capacity, and 11% said PEPFAR had been detrimental both to M&E capacity and HR capacity.In comparison, very few DHOs (3%) said PEPFAR had harmed Though nearly 90% of DHOs said HIV programs had improved their district’s ability to manage medical supplies, the portion of districts reporting the completion of key activities changed modestly 2005-2011. Three-quarters (76%) of DHOs said they had received reports detailing the state of medical equipment and inventory needs in 2010/2011, up from 65% in 2005/2006. During this same period, the percentage of districts with a designated inspector for drugs dropped from 75% to 60%.Most DHOs (90%) said they used the national guidelines for supportive supervision, and their district had been doing so since before PEPFAR started. Similarly, 84% said they had a plan for developing HR capacity at the time of the interview (2011).About 42% of DHOs said their districts now had a desk officer for coordinating public/private partnerships, whereas only 22% had such a position at the start of PEPFAR. Also, 59% said they had conducted activities to determine levels of community satisfaction in 2010/2011, up from 42% in 2005/2006.The biggest changes over the PEPFAR investment period were in the area of information systems. Whereas at the start of PEPFAR, only 9% had a staff person with a degree in statistics in charge of the HMIS, by 2011, almost half (45%) said they did. Data were routinely transmitted to the Ministry’s Resource Center electronically by almost all (89%) districts, whereas only half (55%) did so in 2007/2008. Fully 90% of DHOs said HIV programs improved their management of information systems.After asking DHOs to categorize the overall effects of PEPFAR on health system components as positive, negative, or neutral, we prompted them to offer comments in response to open-ended questions about specific positive and negative influences they had experienced. Staff capacity building, integration of HIV and non-HIV services, and improved access to medical supplies and funding emerged as salient positive themes. Key negative themes included vertical HIV programming linked to HIV-specific targets and objectives, set before arriving at the district level, leaving DHOs with little flexibility to address non-HIV health priorities, increased workload, and loss of health service staff to NGOs providing HIV services. Post hoc analyses revealed no discernible differences in the perception of PEPFAR between respondents with different professional titles or duration of tenure in the district .HR capacity, specifically the skills health workers gained. Two in three respondents said trainings had increased the ability of health workers to manage both HIV and non-HIV healthcare at levels ranging from Village Health Teams to skilled service providers. In the words of one respondent, HIV programs and district health offices “built capacity of staff in different skills making them competent in-service delivery not only for HIV, but also in non-HIV service delivery.” Beyond the component of HR capacity, many DHOs said additional training improved the management of medical supplies as well, outweighing in importance even the direct provision of medical resources. Moreover, many DHOs reported trainings were helpful across all other health system components. Trainings intended to improve M&E of HIV activities also provided skills that could be applied to tuberculosis (TB) control programs. Likewise, skill sets developed to manage pharmacies and forecast stocks of HIV medications also strengthened the supply chain for other essential medicines.When we asked open-ended questions about the specific means by which PEPFAR had a positive effect on the non-HIV health system, DHOs most often named training, mentoring, and capacity building as the key themes which cut across all components studied. The greatest number of DHOs said the most important positive effect of PEPFAR was on M&E capacity and planning capacity. Integration allowed district health offices to supervise HIV services concurrently with non-HIV services using the same transportation and staff, and using forms and registers which included indicators necessary for the evaluation of both programs: “They [implementing partners] supported the district by funding the monitoring exercise of HIV programs; in turn, our staff used the opportunity to evaluate other district programs,” summarized one respondent. DHOs also reported positive effects on planning capacity, emphasizing program integration improved the ability of district health offices to plan together with various implementing partners working in the district. One DHO said, “HIV/AIDS organizations have increased multi-sectoral collaboration which has led to a more integrated planning system for the district.” In addition to the particular importance of integration for the components of M&E capacity and planning capacity, respondents also said the integration of HIV and non-HIV was important to all other components of the health system because district health offices could use medical supplies, transport, and funding for staff allowances procured through HIV programs to support non-HIV services as well.After training, the second most often named positive effect was the opportunity to integrate HIV and non-HIV program activities. Respondents reported this integration of services as most important to the components of information management, management of medical supplies, and HR capacity. However, a sizable minority of DHOs also cited positive effects of directly supplied resources on resource mobilization and M&E capacity. Comments about the material support provided to bolster information management focused primarily on the provision of computer hardware, software, and internet connectivity at health centers, hospitals, and district health offices. Respondents said these resources helped data analysis and timely report submission. DHOs also reported direct material support fortified management of medical supplies via the provision of a wider range of equipment. These supplies included microscopes and other lab equipment, refrigerators for cold chain expansion, reagents for diagnostic tests, and buffer stocks of sundry medications for the treatment of malaria, TB, and other bacterial infections.Thirdly, DHOs said the direct provision of medical supplies, transport, and staff allowances, whether through integration of HIV and non-HIV programs or direct support for non-HIV programs, was a major positive effect of PEPFAR. This additional support for non-HIV activities was particularly important to the components of resource mobilization, M&E capacity, and planning capacity. Respondents said M&E capacity and planning capacity were health system building blocks which both benefited by integration of HIV and non-HIV programming while also suffering from vertical HIV funding streams. This contradiction highlights the sometimes divergent ways DHOs perceived PEPFAR’s effects and suggests M&E capacity and planning capacity may be health system building blocks that experienced the most variable influence. A noteworthy minority of respondents commented on how few grant opportunities were available for non-HIV programming as well as the high number of monitoring reports required for HIV activities. Perhaps, though, the most counterproductive effect of PEPFAR mentioned by DHOs attributable to an overemphasis on HIV centered on how PEPFAR funding and support from NGOs changed the political and behavioral landscape in which district health offices operated. Addressing the ability of district health offices to advocate for more funding from the finance ministry, one respondent stated, the:Many DHOs reported PEPFAR’s vertical nature and narrow focus came at the expense of, or did not sufficiently address, public health priorities other than HIV. Many DHOs critiqued the verticality of HIV programs, while acknowledging beneficial spillover of resources. DHOs said the narrow focus of programming was most acutely damaging to the health system components of Wrong perception [was] created that the health department has a lot of money because of many HIV activities, which makes it difficult for central and local government to allocate [additional] resources.""To complicate the matter further, in some cases district health offices themselves changed their resource seeking activities to become more passive and defer to NGOs:The district is not writing proposals for non-HIV services funding because they are being ‘spoon-fed’ by HIV organizations, ie, they expect funds whether they [district health offices] apply or not.""resource mobilization than any other component underscores the importance of both of these challenges , even if the quantitative evaluation revealed only marginal strengthening of the health system.50During our interviews we observed DHOs were rather pessimistic about the long-standing weaknesses in health system infrastructure in Uganda including an overburdened health workforce, health facilities in disrepair, and insufficient medical equipment. Uganda’s population growth during the study period is unlikely a confounding factor. No DHO cited overall population growth as a key cause of increased stress on health workforce or facilities, and our quantitative analyses DHOs’ comments also contain a number of insights with PEPFAR policy implications. Though space does not permit listing of all implications, the three that follow are the authors’ synthesis of the largest portion of respondents. They are listed with recognition there may be ongoing efforts to address these issues in Uganda or elsewhere:Ugandan DHOs recognize many of the services currently funded by PEPFAR will not be financially sustainable for the Ugandan MoH if PEPFAR funding ended. PEPFAR funding depends on both annual US budget appropriations and periodic five-year congressional reauthorizations. Thus, PEPFAR and other key stakeholders should consider engaging with the Government of Uganda to plan an increasingly sustainable and locally-led HIV-response.PEPFAR should consider continuing, and further emphasizing, its coordination with the Ugandan MoH during the annual Country Operational Plan (COP) budget planning exercise to ensure HIV activities are consistent with national priorities and funding pipelines complement each other.58PEPFAR should consider encouraging the implementing partners through which it works to adopt policies which limit the loss of public sector healthcare workers to private HIV-focused NGOs.Funding for our research was provided through a PEPFAR Public Health Evaluation award through CDC, a US government agency with a major role in implementing PEPFAR in Uganda. UW co-authors received PEPFAR funding for multiple projects, including this one, and I-TECH, affiliated with UW, was a major implementing partner and recipient of PEPFAR funding in Uganda and elsewhere during the study period. Other limitations include the brief amount of time we spent with each DHO, which limited the depth of responses we received. The interview portions of our visits with DHOs were necessarily succinct. Indeed, our ability to have conversations with health officers in all 112 Ugandan districts, a unique strength of our research, is attributable to the efficiency of each visit. Our choice to rely on handwritten interview transcripts, rather than audio recordings, is also an inherent limitation of this approach. While we can generalize our findings to all of Uganda, observations are still limited to Uganda’s specific political, professional, and economic contexts and do not necessarily apply to the experiences of public sector health leaders with HIV initiatives in other countries. In many cases, respondents had not been appointed to their job or posted in their current district for the full duration of the 2005-2011 time frame we investigated. During the study period some DHOs were appointed or promoted to pre-existing districts, and others rose to DHO positions as Uganda decentralized its public health system and split 56 districts into 112. We did not ask respondents to comment specifically on periods prior to their current placement and this analysis cannot assess how PEPFAR’s influence may have varied by district over the years. Additionally, the retrospective study design may have induced recall bias. DHOs may have been reticent to appear unappreciative of the significant financial contributions of PEPFAR by expressing criticisms and in some cases may have benefited personally from PEPFAR themselves, for example, through receiving per diem allowances to attend PEPFAR-supported trainings. Moreover, DHOs’ knowledge that our study was funded by PEPFAR may have limited expression of criticism. Therefore, our results may have under-reported negative perceptions of PEPFAR and over-reported positive perceptions. To minimize the likelihood this would happen, we informed respondents their opinions and statements would not be attributed to them personally and their names would not be used in data analyses or reports. We also conducted all interviews in private settings and trained the data collection teams to establish collegial rapport with respondents before beginning the interviews. Lastly, though PEPFAR comprised the large majority of Uganda’s budget for HIV/AIDS in during the study period, it is difficult to parse the discrete contributions of the various GHIs supporting HIV/AIDS programming in Uganda between 2005-2011. DHOs frequently mentioned PEPFAR by name in their responses, but it remains difficult to attribute specific results to the effects of a single funding stream.60 Still, the goals of PEPFAR-supported health system strengthening, and efforts to develop HRs for health, remain HIV-focused.Ugandan DHOs reported PEPFAR strengthened their health systems between 2005-2011. However, DHOs were not unanimously or uniformly positive. While the overall satisfaction rate with PEPFAR approached 80% positive ratings among DHOs, fewer than half reported an improvement in their ability to mobilize resources to strengthen the health system beyond HIV services. These challenges are neither new nor unique to the Ugandan context. As PEPFAR proceeds into its third phase, focusing on sustaining control of the HIV epidemic while gradually transferring leadership to ministries of health, increased emphasis has been placed on improved government engagement and health system strengthening.61 As HIV infection becomes a chronic disease requiring strong health systems to manage sustained patient care over time, Uganda’s weak health systems will require broad infrastructure development inconsistent with narrow vertical health programming. DHOs expressed significant concerns about what will happen to health system advances funded by HIV programs once PEPFAR ends. Ultimately, any improvements to either HIV or non-HIV health service delivery systems will depend almost entirely on the sustainability of activities undertaken with funding from PEPFAR and other donors. Nonetheless, health system leaders in Uganda at the district level were appreciative of resources aimed at HIV they could often leverage for broader purposes.DHOs also offered constructive criticisms of PEPFAR’s effects on other health system components. They tended to credit improvements in health system strength to PEPFAR’s influence, while attributing declines to pre-existing shortcomings in health system infrastructure and workforce. This tendency is consistent with DHOs’ positive perception of PEPFAR’s effects, despite modest evidence for increased health service utilization from separate quantitative analyses.This study was conducted with data provided by the MoH of the Republic of Uganda, Kampala, Uganda with support from the CDC-supported Prevention Research Center, Schools of Medicine and Public Health, University of Washington, Seattle, WA, USA. We appreciate the additional contributions to the cost of data collection by the College of Health Sciences, Makerere University, Kampala, Uganda and the Schools of Medicine and Public Health, University of Washington, Seattle, WA, USA. We appreciate the two-dozen Ugandan team members who travelled throughout the nation to collect data (often in hazardous conditions), and the many Ugandan clinic and district staff persons who carefully competed their routine data reports for us to collect. Thanks to Aida Namubiru and Evelyn Bakengesa for their administrative assistance.Research funding was provided by PEPFAR through the CDC under the terms of the Public Health Evaluation project entitled “Assessment of the Impact of PEPFAR/Global Disease Initiatives on non-HIV Health Services and Systems in Uganda” [grant number CE.08.0221]. While the CDC cleared this manuscript for publication, the findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC.Institutional review board approval was obtained from the Uganda National Council for Science and Technology, the Makerere University School of Medicine, Kampala, Uganda and the University of Washington, Seattle, WA, USA. The study protocol went through scientific and technical review and received approval at the division and center level at CDC. All parties signed a data user agreement stipulating that the Uganda MoH owns the data.Our study of the health systems effects of PEPFAR was supported with PEPFAR funding. The lead author currently works as a contract employee with the PEPFAR-Mozambique Strategic Information team.NL developed the analytical framework and completed analysis of qualitative data with contributions from AH, TL, and JP. NL and AH drafted the manuscript with contributions from SL, BS, TL, FM, NK, FL, AN, EM, SB, and JP. AH, SB, and BS developed the research protocol with contributions from SL, TL, NK, AN, and EM. SL, FM, NK, FL, and EM oversaw data collection and quality and contributed to analysis of quantitative data.1Department of Global Health, University of Washington, Seattle, WA, USA. 2Department of Health Services, University of Washington, Seattle, WA, USA. 3Faculty of Health Sciences, Makerere University, Kampala, Uganda. 4Division of Global HIV and Tuberculosis, Atlanta, GA, USA. 5Resource Center for the Uganda Ministry of Health, Uganda Ministry of Health, Nakasero, Uganda.District Health Officers (DHOs) and other public sector health managers have a unique perspective on the massive growth in the number of individuals on HIV care and treatment since 2003. As Uganda and other countries with high HIV prevalence align with the latest World Health Organization (WHO) recommendations and adopt universal HIV test and start treatment strategies, their input will be invaluable to the development of effective and sustainable policies.HIV is quickly becoming a chronic infection requiring increased health system capacity to manage an exponential rise in the number of individuals on HIV treatment. It is important to leverage HIV support for broader health system strengthening.Policy-makers should consider continuing to monitor the extent to which funding specifically targeted for HIV programs may make it more difficult for public sector health managers to mobilize resources for non-HIV programs.The global community has set a goal to eliminate AIDS by 2030, but doing so will require massively expanding HIV testing and treatment programs. President’s Emergency Plan for AIDS Relief (PEPFAR) and other global health initiatives (GHIs) directly targeting HIV have proven it is possible to scale-up HIV treatment services quickly and effectively. Yet, it remains unclear how growing HIV programs have strengthened and stressed broader health systems. The experience of Ugandan District Health Officers (DHOs) between 2005-2011 illustrates many of the opportunities and challenges public sector health managers will face as HIV programs continue to enroll more people on treatment. It is important the public be engaged in this process of expansion by supporting those on HIV treatment, demanding donors continue to fund treatment for those who cannot afford it, and advocating HIV funding be employed for broader health service delivery. As echoed by the comments of Ugandan DHOs, it will take broad-scale engagement of both HIV-negative and -positive Ugandans to ensure the substantial funding entering Uganda vertically targeted at HIV programs supports sustainable health system improvement.


Although several studies have documented retinal cell dysfunction in schizophrenia , the extent to which these abnormalities contribute to, and/or result from, other features of the condition is unclear. Thus we sought to: 1) evaluate associations between retinal signaling anomalies as measured with flash electroretinography (fERG) and previously reported changes in visual evoked potentials (VEPs), contrast sensitivity, visual acuity, and contour integration in people with schizophrenia ; 2) determine whether fERG anomalies are related to retinal structural abnormalities as indicated by optical coherence tomography (OCT); 3) examine relationships between fERG changes and psychiatric symptoms; 4) determine relationships between fERG anomalies and frequent medical comorbidities in schizophrenia that are known to affect the retina ; and 5) examine potential medication effects on these findings.We have assessed 25 patients with schizophrenia and 25 controls who are free of medical comorbidity with fERG and measures of visual function and symptom severity, and data collection is ongoing with patients and controls with diabetes and/or hypertension using these same measures. In addition, we are in the process of completing data collection with two additional groups of patients and controls, one with fERG and OCT (n=12 to date), and another with fERG and VEPs (n=13 to date). fERG data are being collected under both light- and dark-adapted conditions, using a range of flash intensities, backgrounds, and temporal frequencies. The primary fERG variables of interest are a-wave and b-wave amplitudes, which reflect photoreceptor and bipolar cell responses, respectively, and the photopic negative response (PhNR), which reflects ganglion cell activity.On photopic fERG tests, patients with schizophrenia demonstrated significantly weaker photoreceptor response when a flash was presented against an unlit background (p<.05), and during a steady-state flicker test (p<.005). On scotopic tests, the rate of response gain per unit of intensity increase was significantly weaker for patients than controls (p=.001). In both light- and dark-adapted conditions, patients demonstrated weaker signaling of bipolar cells (ps < .005). The schizophrenia group was also characterized by a weaker PhNR (p<.05). Weaker retinal cell responses were related to contrast sensitivity impairments in the schizophrenia group (ps < .05 and .001), but not to visual acuity or contour integration. Reduced responsiveness to low-intensity light was related to more severe negative symptoms, suggesting a reduced dynamic range within which environmental events  are represented. Measures of retinal cell function were not related to antipsychotic medication dose. Preliminary findings indicate that attenuated fERG signals are not associated with weaker visual cortical responses (EEG-measured VEPs), presumably due to gain control mechanisms. We will report on the extent to which fERG anomalies are related to retinal structural changes and comorbid medical conditions.Reduced signaling of photoreceptor, bipolar, and ganglion cells are characteristics of schizophrenia, and are not related to extent of antipsychotic medication use. These changes are related to reduced contrast sensitivity and increased negative symptoms, and may reflect an attenuated ability to accurately represent changes in the intensity of environmental stimuli. Data collection is ongoing for studies examining relationships between ERG indices and VEPs and medical comorbidities.


V). Members of the STX group, known collectively as paralytic shellfish toxins (PSTs), are produced among three genera of marine dinoflagellates and about a dozen genera of primarily freshwater or brackish water cyanobacteria. In contrast, toxins of the TTX group occur mainly in macrozoa, particularly among puffer fish, several species of marine invertebrates and a few terrestrial amphibians. In the case of TTX and analogs, most evidence suggests that symbiotic bacteria are the origin of the toxins, although endogenous biosynthesis independent from bacteria has not been excluded. The evolutionary origin of the biosynthetic genes for STX and analogs in dinoflagellates and cyanobacteria remains elusive. These highly potent molecules have been the subject of intensive research since the latter half of the past century; first to study the mode of action of their toxigenicity, and later as tools to characterize the role and structure of NaV channels, and finally as therapeutics. Their pharmacological activities have provided encouragement for their use as therapeutants for ion channel-related pathologies, such as pain control. The functional role in aquatic and terrestrial ecosystems for both groups of toxins is unproven, although plausible mechanisms of ion channel regulation and chemical defense are often invoked. Molecular approaches and the development of improved detection methods will yield deeper understanding of their physiological and ecological roles. This knowledge will facilitate their further biotechnological exploitation and point the way towards development of pharmaceuticals and therapeutic applications.Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and ion flux blockage capacity for voltage-gated sodium channels (Na Many living forms have developed complex neurological systems to receive and transduce vital information from the environment where they live and to elicit appropriate behavioral responses to such stimuli. Generation of neuro-electrical signals is crucial not only for sensory functions including transmission and processing of information in the neurological center (or brain), but also for muscle contraction, secretion of hormones and distributing response signals to the rest of the tissues. All these electrical signals are conducted by members of the ion channel protein superfamily, comprising more than 140 structurally related pore-forming proteins -TTX has also been validated as an alternative radio-ligand to STX in a heterologous receptor binding assay for PSTs [In recent configurations, the RBA has been designed as a competitive radioligand binding assay with a radio-labelled active molecule  applied to a rat brain membrane preparation containing a known number of available receptor sites. With this approach, competitive detection has been achieved with  or TTX) ,126,127. or TTX)  and this or TTX) . The usefor PSTs . Modificfor PSTs  or with for PSTs .3H-labelled ligand has not always been consistent. The requirement for radioisotopes and handling facilities for their use has been an impediment for many laboratories and jurisdictions, although the International Atomic Energy Agency (IAEA) continues to provide global support and encouragement for the application of this method, particularly in developing countries where analytical instrumentation and technical expertise for toxin analysis is often lacking.The radio-label approach remains the most common RBA configuration for guanidinium toxins, but the availability of Natural toxins and venoms have been used in traditional remedies since ancient times, but research on the specific potency, mode of action and secondary effects of natural bioactive molecules as pharmaceuticals has developed only within the last 60 years. The intensive research on guanidinium toxins as potential therapeutants has focused on their ion-channel blocking activity, but the scope has been limited due to their known high acute toxicity  and relaChronic pain treatment has been declared a global health priority, but the multivariate causes, such as cancer, diverse nerve injuries or nerve damage, rheumatoid arthritis, among others, creates a complexity of syndromes that is difficult to treat. Conventional pain control medications all have potentially critical secondary effects, especially when administered in high dosages and for extended periods. In particular, natural and synthetic opioids have been increasingly prescribed to manage long-term chronic pain, but this has led to higher rates of opioid use disorders and drug abuse ,134, as V 1.5 channels, the main sodium channel in the heart [The functional effects of guanidinium toxins on ion-channel blockage and desensitization have guided potential application in pain management. Given the fact that they do not cause myocardial depression or arrhythmias because they do not bind significantly to Nahe heart , allows he heart , and theSome studies in rabbits have demonstrated that the application of TTX produces local anesthesia that allowed corneal surgery in rabbits , and forCertain purified STX analogs have also been applied as therapeutants and have shown considerable success in recent medical trials. An epimeric mixture of gonyautoxins 2 and 3 (GTX 2/3) see , has beeApart from pain control, guanidinium toxins have also been explored as potential treatments of unregulated drug dependence. Studies with rats have found that microinjections of TTX into specific brain regions decreased the demand for cocaine-induced stimuli, and helped to increase knowledge regarding activity and function of drug dependence mechanisms and related brain structures . Recent Computational approaches and imaging tools are being developed and implemented as valuable techniques for research on ion channels to decipher their ultrastructure, and to understand the binding properties of guanidinium toxins to their molecular target . To someV models have been proposed to clarify the mode of action of guanidinium toxins and to interpret experimental data with molecular accuracy [V channels when compared to K+ channels, and this could partially explain why NaV channels provide access of guanidinium toxins to the selectivity-filter residues [V channel, simulations have been therefore typically performed with homology models based on crystal structures of bacterial NaV channels [The accuracy of models for computational studies is dependent upon their characteristics to yield precise free energy calculations . Severalaccuracy ,155. Theresidues . Bioinfochannels ,154, but+ channel structural models for humans, rapid advancements in molecular studies of homologs from other animal nervous systems, such as insects  and the electric eel have generated novel structural and functional insights. The structure of an NaV from a eukaryotic organism, the American cockroach Periplaneta americana, has now been fully elucidated [+ ion channel structural aspects in insects as related to insecticide resistance [Electrophorus electricus the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms have been determined, and the quantification of the mRNA transcript levels in the main electrogenerative organs served to elucidate differential functional aspects among electrocytes from different tissues [+ ion channel studies on insecticide resistance and electrogenesis for predation, defense and sensory detection, respectively, are not strictly applicable to the interpretation of structural-functional interactions of Na+ blocking toxins in mammals, they could provide templates for molecular bioinformatic modelling following application of guanidinium toxins, in particular.In spite of the lack of Naucidated , and thisistance  provides tissues . AlthougV bioinformatic models become more accurate, the information obtained with this approach will be more precise as well. Precision is currently limited [+ channel blocking activity, this approach has been applied mainly to μ-conotoxins [V channel 1.4 with TTX and µ-conotoxins to predict their optimal orientation and the interaction energy consistent with experimental results; their analysis suggested that Na+ channels are more similar to K+ channels than expected. This approach has also provided theoretical information about ligand properties and molecular interactions between STX and many of their naturally occurring analogs, and the same isoform of the NaV channel [Molecular docking tools can reveal the mechanisms involved in binding recognition in great detail, and in a way that cannot be deduced merely from electrophysiological research . This ap limited  because  limited . With renotoxins , small dnotoxins  have per channel .Stichodactyla helianthus was conducted in 1991 [V channel research was the generation of homology model simulations of the NaV channel recognition properties towards the tarantula peptide toxin psalmotoxin-1 [+ channels and open when H+ binds, unlike the NaV channels involved in recognition of guanidinium toxins, the general MD modelling approach should be applicable for these non-peptidic toxins. Recent MD simulations have been useful to better understand the human NaV1.5 channel. For example, Ahmed et al. [+ ion at the channel selectivity filter. By employing a more refined technique, called steered molecular dynamics (SMD), they were also able to identify the key residues related to this process, none of these molecular bioinformatic approaches are sufficient to describe the exquisiteness of ion channels and their interactions with ligands , but a combination of docking modelling and MD, supplemented with electrophysiological and genetic information could be an effective strategy to explain the binding variability properties and chemical diversity of Na+ channel blockers. This would contribute to a better understanding of the structure of the channel and assist in defining the molecular mechanisms for drug interactions in finer detail. Such a comprehensive strategy has yet to be applied to interaction of guanidinium toxins with NaV ion channels.Molecular dynamics (MD) is an alternative approach that evaluates different structural conformations to provide more precise information, although this approach increases computational costs and is more time consuming than molecular docking simulations. The first pioneering MD simulation with the peptide neurotoxin I (SH1) from the sea anemone  in 1991 . A laterotoxin-1 , which cd et al.  developeV ion channels have been explored for many decades and are rather well understood. Nevertheless, there remain incremental challenges to scientific knowledge and progress, from the ongoing search for new natural sources and biosynthetic mechanisms for known and novel structures to potential technological applications as research tools, e.g., in diagnostic detection systems, and as pharmacological treatments. Further development and application of advanced chromatographic techniques for toxin analyte separation and enhanced high resolution detection systems, such as mass spectrometry, supported by nuclear magnetic resonance (NMR), will yield structural elucidation of novel guanidinium toxins from cryptic natural sources. Configuration of these analytical systems for surveillance of guanidinium toxins in food safety regimes is, however, dependent on a reliable supply of putative toxins for calibration standards and for specific toxicity assays. The toxicity of many recently discovered guanidinium analogs remains unknown, mostly due to a lack of purified material for analytical standards and toxicity trials.The basic neurophysiology and mode of interactions of guanidinium toxins with NaResearch on marine toxins also faces new challenges, such as the expanding ban on the use of animals for toxicity testing in many global jurisdictions. Requirements for research and improved regulatory regimes will lead to further development of analytical standards and instruments, as well as new assay methods, in particular biologically based functional assays, and in silico bioinformatic tools.V channels, and the relative lack of adverse acute or chronic secondary effects, makes them valuable molecules for analgesic and anesthetic purposes.Pharmacological applications of guanidinium toxins have a promising future, as already shown by encouraging results for pain treatment and wound healing. The exquisite specificity of these toxins for certain NaV channels preceded the development of neurons, and presumably were permeable to both Na+ and Ca2+ in early metazoans [V channel homologs would help to elucidate biological functions and the evolutionary pathway of NaV channels. How Na+ selectivity could have evolved from Ca2+ (and perhaps even earlier from K+) selectivity by sequential mutations will require further explorations on ion selectivity of these respective channels [V channel function will open the door to generation of more accurate hypotheses on ligand binding interactions of toxins with these respective proteins. After bioinformatic refinements in the near future, accurate prediction of specific toxicity of known and novel guanidinium analogs will be feasible with such in silico analyses.The biggest challenge is to elucidate and understand the cellular functions of guanidinium toxins within the producing organisms, and to determine their eco-evolutionary significance. The evolution of Naetazoans . Yet thechannels . Better Given that predicted climatic changes may favor proliferation and range extension of toxigenic marine microalgal and freshwater cyanobacterial blooms through increased water temperatures and other related climate-driven properties of aquatic systems, it is of critical importance to achieve an ecological understanding of toxigenic mechanisms. Anthropogenic factors ,165, inc


The knowledge, attitudes, and practices surrounding bushmeat consumption and importation in the United States are not well described. Focus groups of West African persons living in Minnesota, USA, found that perceived risks are low and unlikely to deter consumers. Incentives for importation and consumption were multifactorial in this community. Bushmeat hunting and butchery are risk factors for zoonotic disease transmission  minimum age 18 years, 2) self-identification as West African, and 3) willingness to discuss bushmeat in a group setting. The partner organization recruited community members by using a combination of purposeful sampling and social media advertisement and facilitated 3 focus groups  in January and February 2016; a designated research team member attended each session. A standard guide for questions was used for each session . The UniSessions were audio recorded and transcribed; participants were not identified. Nonverbal cues  and other participant interactions were added to the transcript by a notetaker. We analyzed the collected data by using a modified grounded theory method with inductive analysis as previously described ; represeParticipants had resided in the United States from 6 months to 35 years; approximately half were female  Table 1.Most participants reported preference for what they described as “dried bushmeat.” “Drying” involved varying degrees of smoking, aging, and desiccation. Dried bushmeat, compared with raw or partially smoked products, was preferred for importation because its decreased odor is believed to reduce detection. Concern about zoonotic or foodborne disease dissuaded few participants from obtaining or consuming bushmeat, despite heightened awareness that wildlife could harbor Ebola virus. Among those who acknowledged this potential, most believed careful preparation and thorough cooking mitigated risk. For instance, participants cited traditional Liberian cooking techniques (extensive boiling for long durations) as a protective factor . Some participants were knowledgeable of hunting and butchering techniques, but most participants purchased dried consumer products and had not participated in the processing of carcasses. Although there were consistent gaps in knowledge of import regulations, it was commonly perceived that political, public health, or discriminatory  justifications were factors .These focus groups yielded detailed and nuanced information on the knowledge, attitudes, and practices related to bushmeat use and consumption among Liberians and Liberian Americans in a US metro area. Although this study did not directly enumerate the volume and type of bushmeat imported into the United States, our results provide a description of sociocultural factors involved on the demand side of the supply chain, a common gap in most risk assessments, and give insight into potential education and risk management strategies. We found that engaging the community in a culturally appropriate manner encouraged open dialogue, creating opportunities for education regarding import regulations and risk mitigation strategies .Additional information for study of cultural perspectives and knowledge, attitudes, and practices surrounding bushmeat importation and consumption among members of the Liberian community living in the Minneapolis–St. Paul area of Minnesota, USA.


A recent multicenter analysis in pediatric intensive care units shows, that despite of therapeutic advances, the disease burden and mortality of children with pulmonary arterial hypertension (PAH) remains significant . This caThis land marking echocardiographic approach of Beghetti uses direct and indirect echocardiographic measurements including the commonly used tricuspid regurgitant (TR) jet velocity, pulmonary regurgitation (PR) jet , D-shaping of the left ventricle (LV), the LV eccentricity index, right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler imaging (TDI) parameters. This approach is in parts in agreement with recent US and European pediatric PAH guidelines –6. To daDue to the convincing approach of Maurice Beghetti will from now follow this approach in our ICU.Currently there is an ongoing discussion on the indication/need for cardiac catheterization in children with suspected PAH . If propWe want to thank the author for addressing the need for quick, simple, and reproducible measurements in children with suspected PAH and/or RV dysfunction for the intensivist and want to highlight his article, which now provides essential tools to acquire this target . It woulAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. Osteoarthritis (OA) is the progressive loss of normal joint function and is characterized by the degeneration of articular cartilage leading to pain, stiffness, and loss of joint mobility. OA is the world's leading cause of physical disability in adults, in the UK 20% of adults aged between 50–59 and 50% aged between 80–89 have symptomatic disease in one or both knee joints  with the majority of the cell's energy requirements coming from glycolysis Lafont, . DespiteArticular cartilage defects caused by trauma or chronic injury are classified into two categories: Partial-thickness and full-thickness , and neuropeptides. These molecules unbalance the matrix degradation and repair equilibrium resulting in excessive secretion of the proteolytic enzymes and cartilage ECM breakdown  that suppress CD4+ T cell proliferation and polarize them toward T-helper cells (TH1/TH2) and anti-inflammatory T-regulatory cells (Tregs)  there are approximately 500 clinical trials currently utilizing MSCs as therapy for a diverse range of disease , in that they are a rare population occurring with a frequency of 0.01–0.001%   of the digest. The floating population of mature adipocytes can be removed and the pelleted portion of the samples can be regarded as stromal vascular fraction (SVF). SVF contains various cell types, such as endothelial cells, fibroblasts, white blood cells, macrophages and the subject of our interest, pericytes/multipotent stromal cells. These multipotent mesenchymal cells can be selected from this mixed cell population on the basis that they are strongly adherent to plastic cell culture surfaces, thus the final step for the ASC isolation is the establishment of adherent cell cultures of SVF  can be expanded in vitro than matched BM-MSCs  of the normal knee joint and their number increases over 10-fold in OA or injured joints  have been shown to display multipotency at single cell level and meet the criteria for classification as MSCs  harvested from murine skeletal muscle. MDSCs are isolated using a pre-plating technique, an enrichment technique that eliminates more adherent cell types  appear to have important advantages for regenerative medicine applications. These MSCs are relatively young given their isolation from discarded umbilical cord collected at birth, they can be harvested painlessly with no donor site morbidity, and they also co-express MSC and embryonic stem cell markers and therefore possess greater stemness properties. Wharton Jelly-derived MSCs have short population doubling time, exhibit non-lineage-restricted multipotency, are hypoimmunogenic and, most importantly, they do not form tumors in immunodeficient mice , enzymes involved in ECM production , its own partners in transcription (such as SOX5 and SOX6), as well as key signaling pathway mediators  , nuclear factor kappa B member RELA, and notch signaling mediator RBPj  . CM is supported by the New National Excellence Program of the Ministry of Human Capacities in Hungary, and the European Commission through a Marie Curie Intra-European Fellowship for Career Development grant  awarded to AM. AM is also a member of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) Consortium, a 5-year project funded by the European Commission's Innovative Medicines Initiative (IMI). APPROACH is a public-private partnership directed toward osteoarthritis biomarker development through the establishment of a heavily phenotyped and comprehensively analyzed longitudinal cohort. The research leading to these results has received partial support from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115770, resources of which are composed of financial contribution from the European Union's Seventh Framework programme (FP7/2007-2013) and EFPIA companies' in kind contribution. AM has received funding from Arthritis Research UK (grant number 21076) and financial support from the Deanship of Scientific Research (DSR), King Abdulaziz University (grant no. 1-141/1434 HiCi). He is also member of the Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, funded by Arthritis Research UK (Grant Reference Number: 20194). IK is supported by the UK Regenerative Medicine Platform.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. The reviewer VT and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.