Evidence review of what works for health systems strengthening, where and when?

Comprehensive reviews of health system strengthening (HSS) interventions are rare, partly because of lack of clarity on definitions of the term but also the potentially huge scale of the evidence. We reflect on the process of undertaking such an evidence review recently, drawing out suggestions on definitions of HSS and approaches to assessment, as well as summarising some key conclusions from the current evidence base. The key elements of a clear definition include, in our view, consideration of scope (with effects cutting across building blocks in practice, even if not in intervention design, and also tackling more than one disease), scale (having national reach and cutting across levels of the system), sustainability (effects being sustained over time and addressing systemic blockages), and effects (impacting on health outcomes, equity, financial risk protection, and responsiveness). We also argue that agreeing a framework for design and evaluation of HSS is urgent. Most HSS interventions have theories of change relating to specific system blocks, but more work is needed on capturing their spillover effects and their contribution to meeting overarching health system process goals. We make some initial suggestions about such goals, to reflect the features that characterise a “strong health system.” We highlight that current findings on “what works” are just indicative, given the limitations and biases in what has been studied and how, and argue that there is need to rethink evaluation methods for HSS beyond finite interventions and narrow outcomes. Clearer concepts, frameworks, and methods can support more coherent HSS investment

Human Immunodeficiency Virus Envelope Protein Gp120 Induces Proliferation but Not Apoptosis in Osteoblasts at Physiologic Concentrations

Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05), which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism