Reduced incidence of hypertension after heterotopic cardiac transplantation compared with orthotopic cardiac transplantation Evidence that excision of the native heart contributes to post-transplant hypertension

ObjectivesThis study was designed to test the hypothesis that heterotopic heart transplant (HHT) patients have lower blood pressure than orthotopic cardiac transplant (OCT) patients because their native heart is involved in blood pressure homeostasis.BackgroundHypertension occurs more frequently after OCT than after liver or lung transplantation, suggesting that transplantation of the heart itself contributes to post-transplant hypertension.MethodsBlood pressure and related measurements in 233 OCT and 38 HHT patients were studied retrospectively post-transplant.ResultsSystolic blood pressure (SBP) was persistently lower among HHT patients (means 121 vs. 137, 126 vs. 137, 125 vs. 139, and 128 vs. 143 mm Hg at month 3 and years 1, 3, and 5 respectively, p < 0.005). Left ventricular and aortic systolic pressures were also lower (130 vs. 143 mm Hg, p = 0.01 and 129 vs. 142 mm Hg, p = 0.01). Multivariable analysis with age, gender, body mass index, creatinine, steroids, cyclosporine, use of antihypertensive medication, donor left ventricular ejection fraction, donor weight, and type of transplant as covariables showed HHT to be independently associated with a lower SBP at each time point (beta-coefficients −16.2, −12.1, −13.3, and −14.2 mm Hg, p < 0.01). The adjusted hazard ratio for the development of systolic hypertension among HHT compared with OCT patients was 0.59 (95% confidence interval 0.39 to 0.91, p = 0.017).ConclusionsHeterotopic heart transplant patients had lower SBP than OCT patients, consistent with the hypothesis that the native heart continues to contribute to blood pressure homeostasis

Close-to-community providers of health care: increasing evidence of how to bridge community and health systems.

This article was published in Human Resources for Health [© 2016 BioMed Central Ltd.] and the definite version is available at: https://human-resources-health.biomedcentral.com/articles/10.1186/s12960-016-0132-9Publishe

Exploring perceptions of community health policy in Kenya and identifying implications for policy change

Background Global interest and investment in close-to-community health services is increasing. Kenya is currently revising its community health strategy (CHS) alongside political devolution, which will result in revisioning of responsibility for local services. This article aims to explore drivers of policy change from key informant perspectives and to study perceptions of current community health services from community and sub-county levels, including perceptions of what is and what is not working well. It highlights implications for managing policy change. Methods We conducted 40 in-depth interviews and 10 focus group discussions with a range of participants to capture plural perspectives, including those who will influence or be influenced by CHS policy change in Kenya (policymakers, sub-county health management teams, facility managers, community health extension worker (CHEW), community health workers (CHWs), clients and community members) in two purposively selected counties: Nairobi and Kitui. Qualitative data were digitally recorded, transcribed, translated and coded before framework analysis. Results There is widespread community appreciation for the existing strategy. High attrition, lack of accountability for voluntary CHWs and lack of funds to pay CHW salaries, combined with high CHEW workload were seen as main drivers for strategy change. Areas for change identified include: lack of clear supervisory structure including provision of adequate travel resources, current uneven coverage and equity of community health services, limited community knowledge about the strategy revision and demand for home-based HIV testing and counselling. Conclusion This in-depth analysis which captures multiple perspectives results in robust recommendations for strategy revision informed by the Five Wonders of Change Framework. These recommendations point towards a more people-centred health system for improved equity and effectiveness and indicate priority areas for action if success of policy change through the roll-out of the revised strategy is to be realized

How does context influence performance of community health workers in low- and middle-income countries? Evidence from the literature

Background Community health workers (CHWs) are increasingly recognized as an integral component of the health workforce needed to achieve public health goals in low- and middle-income countries (LMICs). Many factors intersect to influence CHW performance. A systematic review with a narrative analysis was conducted to identify contextual factors influencing performance of CHWs. Methods We searched six databases for quantitative, qualitative, and mixed-methods studies that included CHWs working in promotional, preventive or curative primary health care services in LMICs. We differentiated CHW performance outcome measures at two levels: CHW level and end-user level. Ninety-four studies met the inclusion criteria and were double read to extract data relevant to the context of CHW programmes. Thematic coding was conducted and evidence on five main categories of contextual factors influencing CHW performance was synthesized. Results Few studies had the influence of contextual factors on CHW performance as their primary research focus. Contextual factors related to community (most prominently), economy, environment, and health system policy and practice were found to influence CHW performance. Socio-cultural factors (including gender norms and values and disease related stigma), safety and security and education and knowledge level of the target group were community factors that influenced CHW performance. Existence of a CHW policy, human resource policy legislation related to CHWs and political commitment were found to be influencing factors within the health system policy context. Health system practice factors included health service functionality, human resources provisions, level of decision-making, costs of health services, and the governance and coordination structure. All contextual factors can interact to shape CHW performance and affect the performance of CHW interventions or programmes. Conclusions Research on CHW programmes often does not capture or explicitly discuss the context in which CHW interventions take place. This synthesis situates and discusses the influence of context on CHW and programme performance. Future health policy and systems research should better address the complexity of contextual influences on programmes. This insight can help policy makers and programme managers to develop CHW interventions that adequately address and respond to context to optimise performance

Nuclear receptors PPARβ/δ and PPARα direct distinct metabolic regulatory programs in the mouse heart

In the diabetic heart, chronic activation of the PPARα pathway drives excessive fatty acid (FA) oxidation, lipid accumulation, reduced glucose utilization, and cardiomyopathy. The related nuclear receptor, PPARβ/δ, is also highly expressed in the heart, yet its function has not been fully delineated. To address its role in myocardial metabolism, we generated transgenic mice with cardiac-specific expression of PPARβ/δ, driven by the myosin heavy chain (MHC-PPARβ/δ mice). In striking contrast to MHC-PPARα mice, MHC-PPARβ/δ mice had increased myocardial glucose utilization, did not accumulate myocardial lipid, and had normal cardiac function. Consistent with these observed metabolic phenotypes, we found that expression of genes involved in cellular FA transport were activated by PPARα but not by PPARβ/δ. Conversely, cardiac glucose transport and glycolytic genes were activated in MHC-PPARβ/δ mice, but repressed in MHC-PPARα mice. In reporter assays, we showed that PPARβ/δ and PPARα exerted differential transcriptional control of the GLUT4 promoter, which may explain the observed isotype-specific effects on glucose uptake. Furthermore, myocardial injury due to ischemia/reperfusion injury was significantly reduced in the MHC-PPARβ/δ mice compared with control or MHC-PPARα mice, consistent with an increased capacity for myocardial glucose utilization. These results demonstrate that PPARα and PPARβ/δ drive distinct cardiac metabolic regulatory programs and identify PPARβ/δ as a potential target for metabolic modulation therapy aimed at cardiac dysfunction caused by diabetes and ischemia

Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesity.

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol that results in the development of fibrotic cardiomyopathy. Cardiac lipids and candidate gene expression were analyzed at 3 days, and histology at 5 days of repetitive I/R. Total free fatty acids (FFAs) in the cardiac extracts of DIO mice were significantly elevated, reflecting primarily the dietary fatty acid (FA) composition. Compared with lean controls, cardiac FA oxidation (FAO) capacity of DIO mice was significantly higher, concurrent with increased expression of FA metabolism gene transcripts. Following 15 min of daily repetitive I/R for 3 or 5 days, DIO mice exhibited increased susceptibility to I/R and, in contrast to lean mice, developed microinfarction, which was associated with an exaggerated inflammatory response. Repetitive I/R in DIO mice was associated with more profound significant downregulation of FA metabolism gene transcripts and elevated FFAs and triglycerides. Maladaptive metabolic changes of FA metabolism contribute to enhanced myocardial injury in diet-induced obesity

Community participation and maternal health service utilization: lessons from the health extension programme in rural southern Ethiopia

Background Health extension workers (HEWs) are the implementers of the unique primary health care programme of Ethiopia. They facilitate community participation in maternal health service delivery via the health development army (HDA) and pregnant women forums (PWFs). As part of a quality improvement intervention, HEWs received training, guidance and supervision focused on facilitation of HDA meetings and PWFs. We aimed to assess the effect of the intervention on maternal health service utilization and explore the perceptions of stakeholders regarding efforts to enhance community participation in maternal health. Methods We conducted a mixed method study in Shebedino woreda (district), Sidama Zone, southern Ethiopia. The research team observed HDA meetings and PWFs (15), conducted in-depth interviews with 32 HEWs, 8 HEW supervisors and maternal health program managers, and conducted 8 focus group discussions (FGDs) with community members. The interviews and FGDs were recorded, transcribed, translated, coded in Nvivo and thematically analysed. We also collected quantitative data on HDA and PWF participation, antenatal care attendance and skilled delivery and analysed using Excel (Microsoft Inc, Seattle, WA, USA). Results The proportion of HDA leaders and pregnant women who attended the HDA and PWF meetings increased by 30.6% and 36% respectively, over 18 months of the intervention. The percentage of pregnant women identified and referred by HDA leaders increased from 42% to 85%, the antenatal care utilization increased from 73.4% to 77.6% and skilled delivery increased from 76.7% to 83.3%,) (p<0.05). From interviews with stakeholders, we found improved awareness about maternal health services and increased health seeking behaviour. However, lack of incentives and reporting formats for HDA leaders, absenteeism and limited support from kebele administrators constrained community participation in maternal health. Conclusion With focused training, guidance and regular supportive supervision, HEWs were able to stimulate and enhance community participation, resulting in better maternal health service utilization in rural communities. HEWs, volunteer HDAs, pregnant women and the wider community have a role to play in quality improvement of maternal health services

Proposed Regulation of Gene Expression by Glucose in Rodent Heart

Background: During pressure overload-induced hypertrophy, unloading-induced atrophy, and diabetes mellitus, the heart induces ‘fetal’ genes (e.g. myosin heavy chain β; mhcβ). Hypothesis: We propose that altered glucose homeostasis within the cardiomyocyte acts as a central mechanism for the regulation of gene expression in response to environmental stresses. The evidence is as follows. Methods and Results: Forced glucose uptake both ex vivo and in vivo results in mhc isoform switching. Restricting dietary glucose prevents mhc isoform switching in hearts of both GLUT1-Tg mice and rats subjected to pressure overload-induced hypertrophy. Thus, glucose availability correlates with mhc isoform switching under all conditions investigated. A potential mechanism by which glucose affects gene expression is through O-linked glycosylation of specific transcription factors. Glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the flux generating step in UDP-N-acetylglucosamine biosynthesis, the rate determining metabolite in protein glycosylation. Ascending aortic constriction increased intracellular levels of UDP-N-acetylglucosamine, and the expression of gfat2, but not gfat1, in the rat heart. Conclusions: Collectively, the results strongly suggest glucose-regulated gene expression in the heart, and the involvement of glucose metabolites in isoform switching of sarcomeric proteins characteristic for the fetal gene program