Assessing patterns of use of cardio-protective polypill component medicines in Australian women

BACKGROUND: A low-cost 'polypill' could theoretically be one way of improving medication affordability and compliance for secondary prevention of cardiovascular and cerebrovascular disease. The polypill has also been proposed as a primary prevention strategy. Yet many of the issues surrounding the polypill are still being debated and the underlying assumptions have not been proven. In this paper, we step back from the complexities of the debate and report upon the utilization of polypill component medicines in two population cohorts of Australian women who were aged 56-61 years and 81-86 years in 2007. OBJECTIVES: The aims of this study were firstly, to describe the association between the women's characteristics (health, illness, behavioural, demographic, socioeconomic) and their use of statins and antihypertensive medicines for the treatment of heart disease, and secondly, to discuss possible health and economic benefits for women with these characteristics that may be expected to result from the introduction of a cardio-protective polypill. METHODS: Survey records from the Australian Longitudinal Study on Women's Health (ALSWH) were linked to 2007 Pharmaceutical Benefits Scheme (PBS) claims for 7,116 mid-aged women and 4,526 older-aged women. Associations between women's characteristics (self-reported in ALSWH surveys) and their use of statins and antihypertensive medicines (measured through PBS claims in 2007) were analysed using Chi-square and multivariate regression techniques. RESULTS: Between 2002 and 2007, the use of statins in combination with antihypertensives by mid- and older-aged Australian women increased. A moderate yet increasing proportion of mid-aged women were taking statins without antihypertensives, and a high proportion of older-aged women were using antihypertensives without statins. A high proportion of women who were prescribed both statins and antihypertensives were in lower socioeconomic groups and reported difficulty managing on their incomes. CONCLUSION: These results suggest that a polypill may provide an easy-to-take, cheaper alternative for Australian women already taking multiple cardiovascular disease medications, with particular benefits for older women and women in lower socioeconomic groups. Future research is needed to quantify the potential social and economic benefits of the polypill

Expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in neuroblastoma: correlation with clinical features, cellular localization, and cerulenin-mediated apoptosis regulation

PURPOSE: Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein that has recently been implicated in human cancer. In the present study, we analyzed for the first time PRAF2 mRNA expression in a large set of human tumors. The high expression in neuroblastic tumors prompted us to analyze PRAF2 expression correlations with genetic and clinical features of these tumors. In addition, we determined the localization of PRAF2 protein in neuroblastoma cells and studied its regulation in apoptosis. EXPERIMENTAL DESIGN: Affymetrix microarray analysis was done with a set of 41 different tumor types (1,426 samples) in the public domain, a set of three different neuroblastic tumor types (110 samples), and a panel of 25 neuroblastoma cell lines. The subcellular localization of endogenous PRAF2 in neuroblastoma cells was identified by immunofluorescence microscopy and apoptosis detected by Annexin V staining and poly(ADP-ribose) polymerase cleavage. RESULTS: PRAF2 mRNA was detected in 970 of 1,426 samples in the public data set. All 110 neuroblastic tumors expressed PRAF2 at higher levels than any other tumor examined. Importantly, PRAF2 expression levels significantly correlated with the following clinical features: patient age at diagnosis (P = 6.19 x 10(-5)), survival (P = 1.32 x 10(-3)), International Neuroblastoma Staging System stage (P = 2.86 x 10(-4)), and MYCN amplification (P = 3.74 x 10(-3)). PRAF2 localized in bright cytoplasmic punctae and protein levels increased in neuroblastoma cells that underwent cerulenin-induced apoptosis. CONCLUSIONS: Elevated PRAF2 expression levels correlated with unfavorable genetic and clinical features, suggesting PRAF2 as a candidate prognostic marker of neuroblastom

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention