Treating age-related multimorbidity:the drug discovery challenge

Patients with multimorbidities have shorter life expectancy and their clinical management is more complex and expensive for healthcare systems currently focused on treating single diseases. Given that age is the major risk factor for multimorbidity, the challenge of treating these patients will only increase in coming years. Here, we review the case for targeting the core processes that drive the ageing phenotype as a novel pharmaceutical approach to multimorbidity. There is growing evidence that targeting ageing mechanisms can reduce or delay age-related diseases in animal models, and the first reports of clinical trials are now appearing. Although these trials currently focus on repurposed drugs, we propose several novel targets that would more specifically target ageing processes and thereby reduce multimorbidity and polypharmacy in future generations

Tests of analytical hadronisation models using event shape moments in {\epem} annihilation

Predictions of analytical models for hadronisation, namely the dispersive model, the shape function and the single dressed gluon approximation, are compared with moments of hadronic event shape distributions measured in \epem annihilation at centre-of-mass energies between 14 and 209 GeV. In contrast to Monte Carlo models for hadronisation, analytical models require to adjust only two universal parameters, the strong coupling and a second quantity parametrising nonperturbative corrections. The extracted values of as are consistent with the world average and competitive with previous measurements. The variance of event shape distributions is compared with predictions given by some of these models. Limitations of the models, probably due to unknown higher order corrections, are demonstrated and discussed.Comment: Ref.s [19,36] added and footnote 1 adjuste

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700