Continuity of Care is Associated with Higher Appointment Adherence Among HIV Patients in Low Clinician-to-Patient Ratio Facilities in Western Kenya.

We sought to determine the relationship between continuity of care and adherence to clinic appointments among patients receiving HIV care in high vs. low clinician-to-patient (C:P) ratios facilities in western Kenya. This retrospective analysis included 12,751 patients receiving HIV care from the Academic Model Providing Access to Healthcare (AMPATH) program, between February 2016-2019. We used logistic regression analysis with generalized estimating equations to estimate the relationship between continuity of care (two consecutive visits with the same provider) and adherence to clinic appointments (within 7 days of a scheduled appointment) over time. Adjusting for covariates, patients in low C:P ratio facilities who had continuity of care, were more likely to be adherent to their appointments compared to those without continuity (adjusted odds ratio = 1.50; 95% confidence interval, 1.33-1.69). Continuity in HIV care may be a factor in clinical adherence among patients in low C:P ratio facilities and should therefore be promoted.

Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated Vasculitis.

BACKGROUND: Myeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease. METHODS: MPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN. RESULTS: Anti-CD20 mAb treatment increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell-mediated and humoral anti-MPO autoimmunity and GN. Disabling of Tregs negated the therapeutic benefit of anti-CD20 treatment. The mechanism of enhancement of Treg activity could be attributed to anti-CD20 mAb effects on inducing B cell apoptosis. Administering anti-CD20 mAb-induced apoptotic splenocytes to mice developing anti-MPO GN was as effective as anti-CD20 mAb treatment in inducing Tregs and attenuating both anti-MPO autoimmunity and GN. A nonredundant role for splenic macrophages in mediating the anti-CD20 mAb-induced immunomodulation was demonstrated by showing that administration of anti-CD20 mAb ex vivo-induced apoptotic splenocytes to unmanipulated mice attenuated autoimmunity and GN, whereas deletion of splenic marginal zone macrophages prevented anti-CD20 mAb-induced immunomodulation and treatment efficacy. Six days after administering anti-CD20 mAb to mice with murine anti-MPO GN, cell-mediated anti-MPO responses and GN were attenuated, and Tregs were enhanced, but ANCA levels were unchanged, suggesting humoral autoimmunity was redundant at this time point. CONCLUSIONS: Collectively, these data suggest that, as well as reducing humoral autoimmunity, anti-CD20 mAb more rapidly induces protective anti-MPO Treg-mediated immunomodulation by splenic processing of anti-CD20-induced apoptotic B cells.

Methemoglobinemia in Patient with G6PD Deficiency and SARS-CoV-2 Infection.

We report a case of intravascular hemolysis and methemoglobinemia, precipitated by severe acute respiratory syndrome coronavirus 2 infection, in a patient with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Clinicians should be aware of this complication of coronavirus disease as a cause of error in pulse oximetry and a potential risk for drug-induced hemolysis.

Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis.

Anti-myeloperoxidase nephritogenic autoimmunity induces severe glomerulonephritis. To assess the therapeutic potential of monoclonal antibodies targeting T helper (Th) subset differentiation determining cytokines, we studied a murine model of anti-myeloperoxidase glomerulonephritis. The temporal participation of T helper subsets was determined by quantitating gene expression of CD4+ T-cells isolated from nephritic kidneys and cytokine production by lymphocytes from nodes draining myeloperoxidase immunization sites. Th17 cytokines (IL-17A and IL-6) rose rapidly but declined as autoimmunity matured when Th1 cytokines (IL-12 and TNF) predominated. Therefore, T helper subset participation in anti-myeloperoxidase autoimmunity is biphasic, with Th17 early and Th1 late. To confirm the functional relevance of this biphasic pattern, we compared systemic anti-myeloperoxidase autoimmunity in wild type, Th17 deficient and Th1 deficient mice. Early, Th1 deficient mice developed similar autoimmunity and glomerulonephritis to wild type mice. However, Th17 deficient mice had significantly reduced anti-myeloperoxidase autoimmunity. In late autoimmunity, Th1 deficient mice developed reduced autoimmunity and were protected from anti-myeloperoxidase glomerulonephritis. The therapeutic potential of these findings were demonstrated by neutralizing monoclonal antibodies. Targeting IL-23p19 attenuated early Th17 dominated anti-myeloperoxidase autoimmunity and glomerulonephritis but not late phase disease. Targeting IL-12p35 attenuated late phase Th1 dominated anti-myeloperoxidase autoimmunity and glomerulonephritis but not early autoimmunity or glomerulonephritis. Targeting both T helper subsets with an anti-IL-12p40 monoclonal antibody was effective during both early and late phases of anti-myeloperoxidase glomerulonephritis. Thus, definition of dominant T helper differentiating subsets in anti-myeloperoxidase glomerulonephritis by renal CD4+ T-cell cytokine gene expression allows effective proper phase monoclonal antibody treatment of anti-myeloperoxidase glomerulonephritis.

Pathogenic Role for γδ T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis.

Myeloperoxidase (MPO) anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis results from autoimmunity to MPO. IL-17A plays a critical role in generating this form of autoimmune injury but its cell of origin is uncertain. We addressed the hypothesis that IL-17A-producing γδ T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN). We studied MPO-ANCA GN in wild type, αß, or γδ T cell-deficient (C57BL/6, ßTCR-/- , and δTCR-/- respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact αß T cells but was unaffected by γδ T cell deletion. Following MPO immunization, activated γδ T cells migrate to draining lymph nodes. Studies in δTCR-/- and transfer of γδ T cells to δTCR-/- mice show that γδ T cells facilitate the generation of anti-MPO autoimmunity and GN. δTCR-/- mice that received IL-17A-/- γδ T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on γδ T cell IL-17A production. Finally, transfer of anti-MPO CD4+ T cell clones to naive δTCR-/- and wild type mice with planted glomerular MPO shows that γδ T cells are also necessary for recruitment of anti-MPO αß CD4+ effector T cells. This study demonstrates that IL-17A produced by γδ T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific αß T cells.

C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis.

The prospects for complement-targeted therapy in ANCA-associated vasculitis have been enhanced by a recent clinical trial in which C5a receptor 1 (C5aR1) inhibition safely replaced glucocorticoids in induction treatment. C5aR1 primes neutrophils for activation by anti-neutrophil cytoplasmic antibody (ANCA) and is therefore required in models of glomerulonephritis induced by anti-myeloperoxidase antibody. Although humoral and cellular autoimmunity play essential roles in ANCA-associated vasculitis, a role for C5aR1 in these responses has not been described. Here, we use murine models to dissect the role of C5aR1 in the generation of anti-myeloperoxidase autoimmunity and the effector responses resulting in renal injury. The genetic absence or pharmacological inhibition of C5aR1 results in reduced autoimmunity to myeloperoxidase with an attenuated Th1 response, increased Foxp3+ regulatory T cells and reduction in generation of myeloperoxidase-ANCA. These changes are mediated by C5aR1 on dendritic cells, which promotes activation, and thus myeloperoxidase autoimmunity and glomerulonephritis. We also use renal intravital microscopy to determine the effect of C5aR1 inhibition on ANCA induced neutrophil dysfunction. We found that myeloperoxidase-ANCA induce neutrophil retention and reactive oxygen species burst within glomerular capillaries. These pathological behaviors are abrogated by C5aR1 inhibition. Thus, C5aR1 inhibition ameliorates both autoimmunity and intra-renal neutrophil activation in ANCA-associated vasculitis.

Leveraging the power of partnerships: spreading the vision for a population health care delivery model in western Kenya.

BACKGROUND: The Academic Model Providing Access to Healthcare (AMPATH) has been a model academic partnership in global health for nearly three decades, leveraging the power of a public-sector academic medical center and the tripartite academic mission - service, education, and research - to the challenges of delivering health care in a low-income setting. Drawing our mandate from the health needs of the population, we have scaled up service delivery for HIV care, and over the last decade, expanded our focus on non-communicable chronic diseases, health system strengthening, and population health more broadly. Success of such a transformative endeavor requires new partnerships, as well as a unification of vision and alignment of strategy among all partners involved. Leveraging the Power of Partnerships and Spreading the Vision for Population Health. We describe how AMPATH built on its collective experience as an academic partnership to support the public-sector health care system, with a major focus on scaling up HIV care in western Kenya, to a system poised to take responsibility for the health of an entire population. We highlight global trends and local contextual factors that led to the genesis of this new vision, and then describe the key tenets of AMPATH's population health care delivery model: comprehensive, integrated, community-centered, and financially sustainable with a path to universal health coverage. Finally, we share how AMPATH partnered with strategic planning and change management experts from the private sector to use a novel approach called a 'Learning Map®' to collaboratively develop and share a vision of population health, and achieve strategic alignment with key stakeholders at all levels of the public-sector health system in western Kenya. CONCLUSION: We describe how AMPATH has leveraged the power of partnerships to move beyond the traditional disease-specific silos in global health to a model focused on health systems strengthening and population health. Furthermore, we highlight a novel, collaborative tool to communicate our vision and achieve strategic alignment among stakeholders at all levels of the health system. We hope this paper can serve as a roadmap for other global health partners to develop and share transformative visions for improving population health globally.

Water sources and mixing in riparian wetlands revealed by tracers and geospatial analysis.

Mixing of waters within riparian zones has been identified as an important influence on runoff generation and water quality. Improved understanding of the controls on the spatial and temporal variability of water sources and how they mix in riparian zones is therefore of both fundamental and applied interest. In this study, we have combined topographic indices derived from a high-resolution Digital Elevation Model (DEM) with repeated spatially high-resolution synoptic sampling of multiple tracers to investigate such dynamics of source water mixing. We use geostatistics to estimate concentrations of three different tracers (deuterium, alkalinity, and dissolved organic carbon) across an extended riparian zone in a headwater catchment in NE Scotland, to identify spatial and temporal influences on mixing of source waters. The various biogeochemical tracers and stable isotopes helped constrain the sources of runoff and their temporal dynamics. Results show that spatial variability in all three tracers was evident in all sampling campaigns, but more pronounced in warmer dryer periods. The extent of mixing areas within the riparian area reflected strong hydroclimatic controls and showed large degrees of expansion and contraction that was not strongly related to topographic indices. The integrated approach of using multiple tracers, geospatial statistics, and topographic analysis allowed us to classify three main riparian source areas and mixing zones. This study underlines the importance of the riparian zones for mixing soil water and groundwater and introduces a novel approach how this mixing can be quantified and the effect on the downstream chemistry be assessed.

A text messaging intervention to improve heart failure self-management after hospital discharge in a largely African-American population: before-after study.

BACKGROUND: There is increasing interest in finding novel approaches to reduce health disparities in readmissions for acute decompensated heart failure (ADHF). Text messaging is a promising platform for improving chronic disease self-management in low-income populations, yet is largely unexplored in ADHF. OBJECTIVE: The purpose of this pre-post study was to assess the feasibility and acceptability of a text message-based (SMS: short message service) intervention in a largely African American population with ADHF and explore its effects on self-management. METHODS: Hospitalized patients with ADHF were enrolled in an automated text message-based heart failure program for 30 days following discharge. Messages provided self-care reminders and patient education on diet, symptom recognition, and health care navigation. Demographic and cell phone usage data were collected on enrollment, and an exit survey was administered on completion. The Self-Care of Heart Failure Index (SCHFI) was administered preintervention and postintervention and compared using sample t tests (composite) and Wilcoxon rank sum tests (individual). Clinical data were collected through chart abstraction. RESULTS: Of 51 patients approached for recruitment, 27 agreed to participate and 15 were enrolled (14 African-American, 1 White). Barriers to enrollment included not owning a personal cell phone (n=12), failing the Mini-Mental exam (n=3), needing a proxy (n=2), hard of hearing (n=1), and refusal (n=3). Another 3 participants left the study for health reasons and 3 others had technology issues. A total of 6 patients (5 African-American, 1 White) completed the postintervention surveys. The mean age was 50 years (range 23-69) and over half had Medicaid or were uninsured (60%, 9/15). The mean ejection fraction for those with systolic dysfunction was 22%, and at least two-thirds had a prior hospitalization in the past year. Participants strongly agreed that the program was easy to use (83%), reduced pills missed (66%), and decreased salt intake (66%). Maintenance (mean composite score 49 to 78, P=.003) and management (57 to 86, P=.002) improved at 4 weeks, whereas confidence did not change (57 to 75, P=.11). Of the 6 SCHFI items that showed a statistically significant improvement, 5 were specifically targeted by the texting intervention. CONCLUSIONS: Over half of ADHF patients in an urban, largely African American community were eligible and interested in participating in a text messaging program following discharge. Access to mobile phones was a significant barrier that should be addressed in future interventions. Among the participants who completed the study, we observed a high rate of satisfaction and preliminary evidence of improvements in heart failure self-management.

Occurrence and sources of microplastics on Arctic beaches: Svalbard.

Plastic pollution is recognised as a major global environmental concern, especially within marine environments. The small size of microplastics (< 5 mm) make them readily available for ingestion by organisms in all trophic levels. Here, four beach sites in Adventfjorden on the west coast of Svalbard, were sampled with the aim of investigating the occurrence and abundance of microplastics on beaches to assess potential sources of microplastic pollution. High variability in microplastic amount, type and polymers were found at all sites ranging from means of 0.7 n/g (number) at the remotest site and 2.2 n/g (number) at the site closest to Longyearbyen. Statistical analyses suggested that patterns observed were linked to direct proximity to human activities through land uses and effluent discharge. These findings point to an increased importance of localised factors on driving elevated microplastic pollution in beach sediments over oceanic controls in remote but inhabited Arctic locations and have important implications for our understanding and future assessments of microplastic pollution in such settings.

Standards of diabetes care and burden of hypoglycaemia in people with diabetes on peritoneal dialysis: Results from a real-world clinical audit.

There is limited data on the standards of diabetes care in people on peritoneal dialysis (PD). Our aim was to assess the standards of diabetes care and the burden of hypoglycaemia in people with diabetes on PD. We performed a retrospective study at three university hospitals from December 2021 to January 2022. Clinical data were extracted from electronic health records. Diabetes care of people on PD was compared against recommended standards for people with diabetes on haemodialysis (as there are no agreed standards for PD). The degree of hypoglycaemia awareness was assessed by validated questionnaires. A total of 65 adults (15 type 1, 49 type 2 and 1 monogenic-diabetes) with a mean age of 63 (range 29-88) years were evaluated. Of them, 92% had diabetes retinal screening with annual review. In contrast, in this high-risk group for foot disease, only 77% had annual foot reviews. The rates of diabetes specialist reviews were variable between hospitals at 63-94% and 10 (15%) had impaired hypoglycaemia awareness. Of the cohort, 32% had HbA1c within the acceptable range of 58-80 mmol/mol (7.5-8.5%), 21% had HbA1c below 58 mmol/mol (7.5%) and 21% (n = 14) reported at least one hypoglycaemic event per month. Our results indicate variation of care within and between different centres, and the need for improved diabetes care in people on PD. Further work is required to establish agreed standards/recommendations of diabetes care in this population. Our findings highlight the necessity of an integrated multidisciplinary approach to improve the standard of diabetes care for people on PD.

OpenMRS Analytics Engine: A FHIR Based Approach.

As the Electronic Health Record (EHR) data keeps growing in volume at an unprecedented rate, there is an increasing need for a more collaborative and scalable approach for designing and engineering clinical data pipelines. To address these two critical needs, we present a scalable analytics pipeline architecture, designed from the bottom-up to harness the power of FHIR (Fast Healthcare Interoperability Resources) for improving collaborative efforts in health data analytics and indicator reporting.

OpenMRS as an emergency EMR-How we used a global good to create an emergency EMR in a week.

BACKGROUND: As the coronavirus pandemic progressed through the United States, Indianapolis Emergency Medical Services (IEMS) identified a gap between the health system capacity and the projected need to support an overwhelmed health care system. In addressing emergencies or special cases, each medical institution in a metropolitan area typically has a siloed process for capturing emergency patient records. These approaches vary in technical capabilities and may include use of an electronic medical record system (EMR) or a hybrid paper/EMR process. Given the projected volume of patients for the COVID-19 pandemic and the proposed multi-institutional team approach needed in case of significant provider illness, IEMS sought a simple, efficient, consolidated EMR solution to support planning for the potential capacity gap. IEMS approached Regenstrief Institute (RI), an established partner with experience in supporting OpenMRS, a global good EMR platform that had been deployed in multiple settings globally. OBJECTIVE: The purpose of this project was to determine if OpenMRS, a global good, could be used to quickly stand up a system that would meet the needs for health emergency data collection and reporting. DESIGN AND IMPLEMENTATION METHODS: The team used an "all hands on deck" approach, bringing together technical and subject matter experts, and a human-centered and iterative process to ensure the system met the key needs of IEMS. The OpenMRS Reference Application was adapted to the specific need and deployed as Docker containers to servers within the Indiana Health Information Exchange. PROJECT OUTCOMES AND LESSONS LEARNED: In less than two weeks, the Regenstrief team was able to install, configure and set up a working version of OpenMRS to support the desired electronic record requirements for the IEMS disaster field clinics. Using a human-centered approach, the RI team developed, tested, and released a user-friendly, installation-ready solution complete with an end user manual and a base support plan. IEMS and RI are sharing this approach to demonstrate how a global good can quickly generate a solution for COVID-19 and other disaster responses. CONCLUSIONS: Open source global goods can rapidly be adapted to meet local needs in an emergency. OpenMRS can be adapted to meet the needs of basic emergency medical services registration, triage, and basic data collection.

Abdominal aortic aneurysm secondary to infection with Pseudomonas aeruginosa: a rare cause of mycotic aneurysm.

Infection is a cause of rapidly enlarging aortic aneurysms. Pseudomonas aeruginosa is an uncommon pathogen affecting blood vessels and has mainly been seen following invasive procedures in immunosuppressed patients. Pseudomonas aortitis has a high mortality. We describe a case of a rapidly enlarging juxta-renal aortic aneurysm in an immunocompetent patient who was treated with open surgery. In this patient, intra-operative specimens revealed infection with Pseudomonas aeruginosa. The patient received a long course of antibiotics and remains well at 8 months postsurgery.

Comparison of machine learning methods for predicting viral failure: a case study using electronic health record data.

Background: Human immunodeficiency virus (HIV) viral failure occurs when antiretroviral therapy fails to suppress and sustain a person's viral load count below 1,000 copies of viral ribonucleic acid per milliliter. For those newly diagnosed with HIV and living in a setting where healthcare resources are limited, such as a low- and middle-income country, the World Health Organization recommends viral load monitoring six months after initiation of antiretroviral treatment and yearly thereafter. Deviations from this schedule are made in cases where viral failure occurs or at the discretion of the clinician. Failure to detect viral failure in a timely fashion can lead to delayed administration of essential interventions. Clinical prediction models based on information available in the patient medical record are increasingly being developed and deployed for decision support in clinical medicine and public health. This raises the possibility that prediction models can be used to detect potential for viral failure in advance of viral measurements, particularly when those measurements occur infrequently. Objective: Our goal is to use electronic health record data from a large HIV care program in Kenya to characterize and compare the predictive accuracy of several statistical machine learning methods for predicting viral failure at the first and second measurements following initiation of antiretroviral therapy. Predictive accuracy is measured in terms of sensitivity, specificity and area under the receiver-operator characteristic curve. Methods: We trained and cross-validated 10 statistical machine learning models and algorithms on data from over 10,000 patients in the Academic Model Providing Access to Healthcare care program in western Kenya. These included parametric, non-parametric, ensemble, and Bayesian methods. The input variables included 50 items from the clinical record, hand picked in consultation with clinician experts. Predictive accuracy measures were calculated using 10-fold cross validation. Results: Viral load failure rate is about 20% in this patient cohort at both the first and second measurements. Ensemble techniques generally outperformed other methods. For predicting viral failure at the first follow up measure, specificity was over 90% for these methods, but sensitivity was typically in the 50-60% range. Predictive accuracy was greater for the second follow up measure, with sensitivities over 80%. Super Learner, gradient boosting and Bayesian additive regression trees consistently outperformed other methods. For a viral failure rate of 20%, the positive predictive value for the top-performing methods is between 75 and 85%, while the negative predictive value is over 95%. Conclusion: Evidence from this study suggests that machine learning techniques have potential to identify patients at risk for viral failure prior to their scheduled measurements. Ultimately, prognostic virologic assessment can help guide the administration of earlier targeted intervention such as enhanced drug resistance monitoring, rigorous adherence counseling, or appropriate next-line therapy switching. External validation studies should be used to confirm the results found here.

Repeat-associated plasticity in the Helicobacter pylori RD gene family.

The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Since repetitive DNA can facilitate adaptive genomic flexibility via increased recombination, insertion, and deletion, we searched the genomes of two H. pylori strains for nucleotide repeats. We discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a conserved 3' region, a variable mid-region encoding 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intrahost variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, enzyme-linked immunosorbent assay and immunoblot studies revealed no consistent seroreactivity to a recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect slipped-strand mispairing or domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host.

Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS) in western Kenya: a study protocol of a cluster randomized trial.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease (CVD), yet treatment and control rates for hypertension are very low in low- and middle-income countries (LMICs). Lack of effective referral networks between different levels of the health system is one factor that threatens the ability to achieve adequate blood pressure control and prevent CVD-related morbidity. Health information technology and peer support are two strategies that have improved care coordination and clinical outcomes for other disease entities in other settings; however, their effectiveness and cost-effectiveness in strengthening referral networks to improve blood pressure control and reduce CVD risk in low-resource settings are unknown. METHODS/DESIGN: We will use the PRECEDE-PROCEED framework to conduct transdisciplinary implementation research, focused on strengthening referral networks for hypertension in western Kenya. We will conduct a baseline needs and contextual assessment using a mixed-methods approach, in order to inform a participatory, community-based design process to fully develop a contextually and culturally appropriate intervention model that combines health information technology and peer support. Subsequently, we will conduct a two-arm cluster randomized trial comparing 1) usual care for referrals vs 2) referral networks strengthened with our intervention. The primary outcome will be one-year change in systolic blood pressure. The key secondary clinical outcome will be CVD risk reduction, and the key secondary implementation outcomes will include referral process metrics such as referral appropriateness and completion rates. We will conduct a mediation analysis to evaluate the influence of changes in referral network characteristics on intervention outcomes, a moderation analysis to evaluate the influence of baseline referral network characteristics on the effectiveness of the intervention, as well as a process evaluation using the Saunders framework. Finally, we will analyze the incremental cost-effectiveness of the intervention relative to usual care, in terms of costs per unit decrease in systolic blood pressure, per percentage change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION: This study will provide evidence for the implementation of innovative strategies for strengthening referral networks to improve hypertension control in LMICs. If effective, it has the potential to be a scalable model for health systems strengthening in other low-resource settings worldwide. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03543787 . Registered on 29 June 2018.

Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya.

BACKGROUND: Ineffective referral networks in low- and middle-income countries hinders access to evidence-based therapies by hypertensive patients, leading to high cardiovascular mortality and morbidity. The STRENGTHS (Strengthening Referral Networks for Management of Hypertension Across Health Systems) study evaluates strategies to improve referral processes utilizing the International Association of Public Participation framework to engage stakeholders. OBJECTIVES: This study sought to identify and engage key stakeholders involved in referral of patients in the Ministry of Health, western Kenya. METHODS: Key stakeholders involved in policy formulation, provision, or consumption of public health care service were mapped out and contacted by phone, letters, and emissaries to schedule meetings, explain research objectives, and obtain feedback. RESULTS: Key stakeholders identified were the Ministry of Health, the Academic Model Providing Access to Healthcare, health professionals, communities and their leadership, and patients. Engaging them resulted in permission to contact research in their areas of jurisdiction and enabled collaboration in updating care protocols with emphasis on timely and appropriate referrals. CONCLUSIONS: Early stakeholder identification and engagement using the International Association of Public Participation model eased explanation of research objectives, building consensus, and shaping the interventions to improve the referral process.

The C3aR promotes macrophage infiltration and regulates ANCA production but does not affect glomerular injury in experimental anti-myeloperoxidase glomerulonephritis.

The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity. However, it promoted macrophage recruitment to the inflamed glomerulus and inhibited the generation of MPO-ANCA whilst not influencing T cell autoimmunity. Thus, whilst the C3aR modulates some elements of disease pathogenesis, overall it is not critical in effector responses and glomerular injury caused by autoimmunity to MPO.