The global impact of non-communicable diseases on macro-economic productivity: a systematic review

© 2015, The Author(s). Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case–control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million US dollars (USD) for COPD to 20.9 billion USD for colon cancer. CHD costs the Australian economy 13.2 billion USD per year. People with DM, COPD and survivors of breast and especially lung cancer are at a higher risk of reduced labor market participation. Overall NCDs generate a large impact on macro-economic productivity in most WHO regions irrespective of continent and income. The absolute global impact in terms of dollars and DALYs remains an elusive challenge due to the wide heterogeneity in the included studies as well as limited information from low- and middle-income countries.WHO; Nestle´ Nutrition (Nestec Ltd.); Metagenics Inc.; and AX

The role and regulation of caspases during T cell activation and proliferation

In the present study, the effects of two caspase inhibitors, z-VAD-FMK and z-IETD-FMK, on T cell activation and proliferation were compared to the negative control, z-FA-FMK. All three compounds inhibited T cell proliferation, blast formation, CD25 expression, IL-2 signalling and nuclear translocation of the NF-kappaB subunit, p65. However, unlike z-VAD-FMK and z-IETD-FMK, z-FA-FMK inhibited IL-2 and IFN-gamma secretion and blocked cell cycle entry. Furthermore, although both z-VAD-FMK and z-IETD-FMK inhibited Fas-induced caspase activation, they had no effect on caspase-8 and -3 processing during T cell activation. In contrast, z-FA-FMK, which did not inhibit caspase processing during apoptosis, blocked caspase-8 and -3 processing in activated T cells. This suggests that peptidyl-fluoromethylketones have pleiotropic immunosuppressive properties which may not involve the processing of caspase-8 or -3. In addition, these data suggest that the processing of caspases is regulated differently during T cell activation compared to apoptosis. To further characterise the role of caspase-8 during T cell activation, an activation-induced cell death (AICD) model using caspase-8-/- Jurkat T cells was examined. In addition, the involvement of FADD, the docking protein for caspase-8, was also investigated. Caspase-8-/- Jurkat T cells were resistant to AICD induced by PMA and ionomycin, whereas FADD-/- Jurkat T cells underwent TNF-alpha-mediated necrosis. These data suggest that caspase-8 but not FADD is required for the T cell activation signalling pathway and also implicate TNF-alpha in AICD in the absence of the Fas-signalling pathway. In conclusion, the results suggest that non-specific effects of caspase inhibitors are involved in the inhibition of T cell activation and proliferation and that the regulation of caspases during T cell activation is different from that during apoptosis