Projections of global health outcomes from 2005 to 2060 using the International Futures integrated forecasting model.

OBJECTIVE: To develop an integrated health forecasting model as part of the International Futures (IFs) modelling system. METHODS: The IFs model begins with the historical relationships between economic and social development and cause-specific mortality used by the Global Burden of Disease project but builds forecasts from endogenous projections of these drivers by incorporating forward linkages from health outcomes back to inputs like population and economic growth. The hybrid IFs system adds alternative structural formulations for causes not well served by regression models and accounts for changes in proximate health risk factors. Forecasts are made to 2100 but findings are reported to 2060. FINDINGS: The base model projects that deaths from communicable diseases (CDs) will decline by 50%, whereas deaths from both non-communicable diseases (NCDs) and injuries will more than double. Considerable cross-national convergence in life expectancy will occur. Climate-induced fluctuations in agricultural yield will cause little excess childhood mortality from CDs, although other climate-health pathways were not explored. An optimistic scenario will produce 39 million fewer deaths in 2060 than a pessimistic one. Our forward linkage model suggests that an optimistic scenario would result in a 20% per cent increase in gross domestic product (GDP) per capita, despite one billion additional people. Southern Asia would experience the greatest relative mortality reduction and the largest resulting benefit in per capita GDP. CONCLUSION: Long-term, integrated health forecasting helps us understand the links between health and other markers of human progress and offers powerful insight into key points of leverage for future improvements.

Pharmacokinetics and metabolism of lumiracoxib in healthy male subjects.

Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a novel, chemically distinct cyclooxygenase-2 selective inhibitor, which has been developed for the treatment of osteoarthritis, rheumatoid arthritis, and acute pain. The absorption, metabolism, disposition, and mass balance of [14C]lumiracoxib were investigated in four healthy male subjects after a single 400-mg oral dose. Serial blood and complete urine and feces were collected for 168 h postdose. Lumiracoxib was rapidly absorbed, achieving mean plasma concentrations >1 microg/ml within 1 h of dosing. Unchanged drug in plasma accounted for 81 to 91% of radioactivity up to 2.5 h postdose, suggesting a modest first-pass effect; unchanged drug was the major circulating component in plasma, accounting for approximately 43% of the AUC(0 to 24 h). The terminal half-life of lumiracoxib in plasma was 6.5 h. Major plasma metabolites were the 5-carboxy, 4'-hydroxy, and 4'-hydroxy-5-carboxy derivatives. Excretion involved both renal (54.1%) and fecal (42.7%) routes, and dose recovery was almost complete (96.8%). Lumiracoxib was extensively metabolized before excretion, with little unchanged drug in urine (3.3% of dose) or feces (2.0% of dose). The major metabolic pathways of lumiracoxib were oxidation of the 5-methyl group and hydroxylation of the dihaloaromatic ring. Glucuronic acid conjugates of lumiracoxib metabolites (and to a minor extent lumiracoxib itself) were identified, although there was no evidence of cysteine, mercapturic acid, or glutathione conjugates. In summary, orally administered lumiracoxib is rapidly absorbed and undergoes extensive metabolism before excretion via urine and feces, with no evidence of formation of potentially reactive metabolites.