BackgroundLow-income and middle-income countries (LMICs) have difficulties achieving universal financial protection, which is primordial for universal health coverage. A promising avenue to provide universal financial protection for the informal sector and the rural populace is community-based health insurance (CBHI). We systematically assessed and synthesised factors associated with CBHI enrolment in LMICs.MethodsWe searched PubMed, Scopus, ERIC, PsychInfo, Africa-Wide Information, Academic Search Premier, Business Source Premier, WHOLIS, CINAHL, Cochrane Library, conference proceedings, and reference lists for eligible studies available by 31 October 2013; regardless of publication status. We included both quantitative and qualitative studies in the review.ResultsBoth quantitative and qualitative studies demonstrated low levels of income and lack of financial resources as major factors affecting enrolment. Also, poor healthcare quality (including stock-outs of drugs and medical supplies, poor healthcare worker attitudes, and long waiting times) was found to be associated with low CBHI coverage. Trust in both the CBHI scheme and healthcare providers were also found to affect enrolment. Educational attainment (less educated are willing to pay less than highly educated), sex (men are willing to pay more than women), age (younger are willing to pay more than older individuals), and household size (larger households are willing to pay more than households with fewer members) also influenced CBHI enrolment.ConclusionIn LMICs, while CBHI schemes may be helpful in the short term to address the issue of improving the rural population and informal workers’ access to health services, they still face challenges. Lack of funds, poor quality of care, and lack of trust are major reasons for low CBHI coverage in LMICs. If CBHI schemes are to serve as a means to providing access to health services, at least in the short term, then attention should be paid to the issues that militate against their success.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-1179-3) contains supplementary material, which is available to authorized users.

Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway.

Melatonin protects the heart against myocardial ischemia/reperfusion injury via the activation of the survivor activating factor enhancement (SAFE) pathway which involves tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Toll-like receptor 4 (TLR4) plays a crucial role in myocardial ischemia/reperfusion injury and activates TNFα. In this study, we investigated whether melatonin may target TLR4 to activate the SAFE pathway. Isolated hearts from rats or mice were subjected to ischemia/reperfusion injury. Melatonin (75 ng/L) and/or TAK242 (a specific inhibitor of TLR4 signaling, 500 nm) were administered to the rat hearts before the induction of ischemia. Pre-ischemic myocardial STAT3 was evaluated by Western blotting. Lipopolysaccharide (LPS, a stimulator of TLR4) was administered to wild type, TNFα receptor 2 knockout or cardiomyocyte-specific STAT3-deficient mice (2.8 mg/kg, i.p) 45 min before the heart isolation. Myocardial infarct size was measured as an endpoint. Compared to the control, administration of melatonin reduced myocardial infarct size (34.7 ± 2.8% versus 62.6 ± 2.7%, P < 0.01). This protective effect was abolished in the presence of TAK242 (49.2 ± 6.5%). Melatonin administered alone increased the pre-ischemic activation of mitochondrial STAT3, and this effect was attenuated with TAK242. Furthermore, stimulation of TLR4 with LPS pretreatment to mice reduced myocardial infarct size of the hearts isolated from wild-type animals but failed to protect the hearts isolated from TNFα receptor 2-knockout mice or cardiomyocyte-specific STAT3-deficient mice (P < 0.001). Taken together, these data suggest that cardioprotection induced by melatonin is mediated by TLR4 to activate the SAFE pathway.