BackgroundPoor access to care and physician shortage are major barriers to hypertension control in sub-Saharan Africa. Implementation of evidence-based systems-level strategies targeted at these barriers are lacking. We conducted a study to evaluate the comparative effectiveness of provision of health insurance coverage (HIC) alone versus a nurse-led task shifting strategy for hypertension control (TASSH) plus HIC on systolic blood pressure (SBP) reduction among patients with uncontrolled hypertension in Ghana.Methods and findingsUsing a pragmatic cluster randomized trial, 32 community health centers within Ghana’s public healthcare system were randomly assigned to either HIC alone or TASSH + HIC. A total of 757 patients with uncontrolled hypertension were recruited between November 28, 2012, and June 11, 2014, and followed up to October 7, 2016. Both intervention groups received health insurance coverage plus scheduled nurse visits, while TASSH + HIC comprised cardiovascular risk assessment, lifestyle counseling, and initiation/titration of antihypertensive medications for 12 months, delivered by trained nurses within the healthcare system. The primary outcome was change in SBP from baseline to 12 months. Secondary outcomes included lifestyle behaviors and blood pressure control at 12 months and sustainability of SBP reduction at 24 months. Of the 757 patients (389 in the HIC group and 368 in the TASSH + HIC group), 85% had 12-month data available (60% women, mean BP 155.9/89.6 mm Hg). In intention-to-treat analyses adjusted for clustering, the TASSH + HIC group had a greater SBP reduction (−20.4 mm Hg; 95% CI −25.2 to −15.6) than the HIC group (−16.8 mm Hg; 95% CI −19.2 to −15.6), with a statistically significant between-group difference of −3.6 mm Hg (95% CI −6.1 to −0.5; p = 0.021). Blood pressure control improved significantly in both groups (55.2%, 95% CI 50.0% to 60.3%, for the TASSH + HIC group versus 49.9%, 95% CI 44.9% to 54.9%, for the HIC group), with a non-significant between-group difference of 5.2% (95% CI −1.8% to 12.4%; p = 0.29). Lifestyle behaviors did not change appreciably in either group. Twenty-one adverse events were reported (9 and 12 in the TASSH + HIC and HIC groups, respectively). The main study limitation is the lack of cost-effectiveness analysis to determine the additional costs and benefits, if any, of the TASSH + HIC group.ConclusionsProvision of health insurance coverage plus a nurse-led task shifting strategy was associated with a greater reduction in SBP than provision of health insurance coverage alone, among patients with uncontrolled hypertension in Ghana. Future scale-up of these systems-level strategies for hypertension control in sub-Saharan Africa requires a cost–benefit analysis.Trial registrationClinicalTrials.gov NCT01802372

Background: Immune cells have essential auxiliary functions and influence clinical outcomes in cancer, with high immune infiltration being associated with improved clinical outcomes and better response to treatment in breast cancer (BC). However, studies to date have not fully considered the tumor-infiltrating immune cell (TIIC) landscape in tumors. This study investigated potential biomarkers based on TIICs to improve prognosis and treatment effect in BC. Results: We enrolled 5112 patients for analysis and used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT), a new computational algorithm, to quantify 22 TIICs in primary BC. From the results of univariate Cox regression, 12 immune cells were determined to be significantly related to the overall survival (OS) of BC patients. Furthermore, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to construct an immune prognostic model based on six potential biomarkers. By dividing patients into low- and high-risk groups, a significant distinction in OS was found in the training cohort, with 20-year survival rates of 42.6% and 26.3%, respectively. Applying a similar protocol to validation and test cohorts, we found that OS was significantly shorter in the high-risk group than in the low-risk group, regardless of the molecular subtype of BC. Using the immune score model to predict the effect of BC patients to chemotherapy, the survival advantage for the low-risk group was evident among those who received chemotherapy, regardless of the chemotherapy regimen. In evaluating the predictive value of the nomogram, a decision curve showed better predictive accuracy than the standard tumor-node-metastasis (TNM) staging system. Conclusion: The immune cell infiltration-based immune score model can be effectively and efficiently used to predict the prognosis of BC patients as well as the effect of chemotherapy.

BackgroundCountries in sub-Saharan Africa (SSA) are experiencing an epidemic of cardiovascular disease (CVD) propelled by rapidly increasing rates of hypertension. Barriers to hypertension control in SSA include poor access to care and high out-of-pocket costs. Although SSA bears 24% of the global disease burden, it has only 3% of the global health workforce. Given such limited resources, cost-effective strategies, such as task shifting, are needed to mitigate the rising CVD epidemic in SSA. Ghana, a country in SSA with an established community health worker program integrated within a national health insurance scheme provides an ideal platform to evaluate implementation of the World Health Organization (WHO) task-shifting strategy. This study will evaluate the comparative effectiveness of the implementation of the WHO Package targeted at CV risk assessment versus provision of health insurance coverage, on blood pressure (BP) reduction.MethodsUsing a cluster randomized design, 32 community health centers (CHCs) and district hospitals in Ghana will be randomized to either the intervention group (16 CHCs) or the control group (16 CHCs). A total of 640 patients with uncomplicated hypertension (BP 140–179/90–99 mm Hg and absence of target organ damage) will be enrolled in this study (20 patients per CHC). The intervention consists of WHO Package of CV risk assessment, patient education, initiation and titration of antihypertensive medications, behavioral counseling on lifestyle behaviors, and medication adherence every three months for 12 months. The primary outcome is the mean change in systolic BP from baseline to 12 months. The secondary outcomes are rates of BP control at 12 months; levels of physical activity, percent change in weight, and dietary intake of fruits and vegetables at 12 months; and sustainability of intervention effects at 24 months. All outcomes will be assessed at baseline, six months and 12 months. Trained community health nurses will deliver the intervention as part of Ghana’s community-based health planning and services (CHPS) program.DiscussionFindings from this study will provide policy makers and other stakeholders needed information to recommend scalable and cost-effective policy with respect to comprehensive CV risk reduction and hypertension control in resource-poor settings.Trial registrationNCT01802372.

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BackgroundNurses in Ghana play a vital role in the delivery of primary health care at both the household and community level. However, there is lack of information on task shifting the management and control of hypertension to community health nurses in low- and middle-income countries including Ghana. The purpose of this study was to assess nurses’ knowledge and practice of hypertension management and control pre- and post-training utilizing task-shifting strategies for hypertension control in Ghana (TASSH).MethodsA pre- and post- test survey was administered to 64 community health nurses (CHNs) and enrolled nurses (ENs) employed in community health centers and district hospitals before and after the TASSH training, followed by semi-structured qualitative interviews that assessed nurses’ satisfaction with the training, resultant changes in practice and barriers and facilitators to optimal hypertension management.ResultsA total of 64 CHNs and ENs participated in the TASSH training. The findings of the pre- and post-training assessments showed a marked improvement in nurses’ knowledge and practice related to hypertension detection and treatment. At pre-assessment 26.9% of the nurses scored 80% or more on the hypertension knowledge test, whereas this improved significantly to 95.7% post-training. Improvement of interpersonal skills and patient education were also mentioned by the nurses as positive outcomes of participation in the intervention.ConclusionsFindings suggest that if all nurses receive even brief training in the management and control of hypertension, major public health benefits are likely to be achieved in low-income countries like Ghana. However, more research is needed to ascertain implementation fidelity and sustainability of interventions such as TASSH that highlight the potential role of nurses in mitigating barriers to optimal hypertension control in Ghana.Trial registrationTrial registration for parent TASSH study: NCT01802372. Registered February 27, 2013.

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Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient ( Chst14 −/− ) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14 −/− mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14 −/− mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14 −/− mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

BackgroundThe purpose of this study was to explore stakeholders' perception of an on-going evidence-based task-shifting strategy for hypertension (TASSH) in 32 community health centers and district hospitals in Ghana.MethodsUsing focus group discussions and in-depth interviews, qualitative data were obtained from 81 key stakeholders including patients, nurses, and site directors of participating community health centers involved in the TASSH trial. Qualitative data were analyzed using open and axial coding techniques.ResultsAnalysis of the qualitative data revealed three themes that illustrate stakeholders' perceptions of the ongoing task-shifting strategy for blood pressure control in Ghana and they include: 1) awareness and understanding of the TASSH program; 2) reasons for participation and non-participation in TASSH; and 3) the benefit and drawbacks to the TASSH program.ConclusionThe findings support evidence that successful implementation of any task-shifting strategy must focus not only on individual patient characteristics, but also consider the role contextual factors such as organizational and leadership factors play. The findings also demonstrate the importance of understanding stakeholder's perceptions of evidence-based task-shifting interventions for hypertension control as it may ultimately influence the sustainable uptake of these interventions into "real world" settings.