Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: Is it feasible?

BACKGROUND: The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool. METHODS: The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes. RESULTS: The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01). CONCLUSIONS: Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals

Estimated number of prevalent cases of metastatic bone disease in the US adult population

Shuling Li1, Yi Peng1, Eric D Weinhandl1, Anne H Blaes2, Karynsa Cetin3, Victoria M Chia3, Scott Stryker3, Joseph J Pinzone4, John F Acquavella3, Thomas J Arneson11Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, MN, USA; 2Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA; 3Center for Observational Research, 4Global Development, Amgen, Thousand Oaks, CA, USABackground: The prevalence of metastatic bone disease in the US population is not well understood. We sought to estimate the current number of US adults with metastatic bone disease using two large administrative data sets.Methods: Prevalence was estimated from a commercially insured cohort (ages 18–64 years, MarketScan database) and from a fee-for-service Medicare cohort (ages ≥65 years, Medicare 5% database) with coverage on December 31, 2008, representing approximately two-thirds of the US population in each age group. We searched for claims-based evidence of metastatic bone disease from January 1, 2004, using a combination of relevant diagnosis and treatment codes. The number of cases in the US adult population was extrapolated from age- and sex-specific prevalence estimated in these cohorts. Results are presented for all cancers combined and separately for primary breast, prostate, and lung cancer.Results: In the commercially insured cohort (mean age = 42.3 years [SD = 13.1]), we identified 9505 patients (0.052%) with metastatic bone disease. Breast cancer was the most common primary tumor type (n = 4041). In the Medicare cohort (mean age = 75.6 years [SD = 7.8]), we identified 6427 (0.495%) patients with metastatic bone disease. Breast (n = 1798) and prostate (n = 1862) cancers were the most common primary tumor types. We estimate that 279,679 (95% confidence interval: 274,579–284,780) US adults alive on December 31, 2008, had evidence of metastatic bone disease in the previous 5 years. Breast, prostate, and lung cancers accounted for 68% of these cases.Conclusion: Our findings suggest that approximately 280,000 US adults were living with metastatic bone disease on December 31, 2008. This likely underestimates the true frequency; not all cases of metastatic bone disease are diagnosed, and some diagnosed cases might lack documentation in claims data.Keywords: bone neoplasms, epidemiology, metastasis, prevalenc

Equal pay as a precondition of justice?

Equality is typically presumed to be an end of justice, however, in this chapter, we argue that it is better understood as a condition of justice. Our argument draws on the Just World Fallacy, the phenomenon of people mistakenly believing fortuitous patterns of reward or harm to be reflective of justice. This phenomenon can undermine relationships of equality even where differences in reward or harm are ostensibly deserved. If everyone received equal pay, then the propensity for people to defer to the more successful or derogate the less successful would be diminished, and thus there would be greater scope for people to enter into the sorts of relationships of equal respect and regard that just communities require