SummaryHere we show that Mtl1, member of the cell wall integrity pathway of Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS). The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial function. This is reflected in a descent in oxygen consumption during the postdiauxic state, an increase in the uncoupled respiration and mitochondrial membrane potential and also a descent in aconitase activity. We demonstrate that all these effects are a consequence of signalling defects suppressed by TOR1 (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A (PKA) inactivation. Mtl1 also plays a role in the regulation of both Bcy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1 phosphorylation, although additional targets are not excluded. Mtl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule.

Background: Adverse drug events (ADEs) result in excess hospitalizations. Thorough admission medication histories (AMHs) may prevent ADEs; however, the resources required oftentimes outweigh what is available in large hospital settings. Previous risk prediction models embedded into the Electronic Medical Record (EMR) have been used at hospitals to aid in targeting delivery of scarce resources. Objective: To determine if an AMH scoring tool used to allocate resources can decrease 30-day hospital readmissions. Design, Setting, and Participants: Propensity-matched cohort study, Medicine/Surgery patients in large academic safety-net hospital. Intervention or Exposure: Pharmacy-conducted AMHs identified by risk model versus standard of care AMH. Main Outcomes and Measures: A total of 30-day hospital readmissions and inpatient ADE prevention. Results: The model screened 87 240 hospitalizations between June 2017 and June 2019 and 4027 patients per group were included. There were significantly less 30 day readmissions among high-risk identified patients that received a pharmacy-conducted AMH compared to controls (11% vs 15%; P = 0.004) and no significant difference in readmission rates for low-risk patients. While there was significantly higher documentation of major ADE prevention in the pharmacy-led AMH group versus control (1656 vs 12; P < 0.001), there was no difference in electronically-detected inpatient ADEs between groups. Conclusions: A risk tool embedded into the EMR can be used to identify patients whom pharmacy teams can easily target for AMHs. This study showed significant reductions in readmissions for patients identified as high-risk. However, the same benefit in readmissions was not seen in those identified at low-risk, which supports allocating resources to those that will benefit the most.

From time immemorial, the evaluation of new pharmaceutical products includes efficacy, effectiveness, and safety considerations. More recently, inter disciplinary health care researchers have developed tools and techniques for the evaluation of the economic effects of clinical care and latest medical techniques. Phamacoeconomic evaluation techniques framework includes the research methods-related to cost-minimization, cost-effectiveness, cost-benefit, costof-illness, cost-utility, cost consequences, and decision analysis, as well as quality-of-life and other humanistic assessments, are conducted in a manner similar, but vary in measurement of value of health benefits and outcomes. Moreover, the role of health economics is well-recognized for efficient and equitable health system. In developing countries, the health care system faces challenges which are slightly different from developed countries, but however health economics tools are equally applicable. A vital step to establish Health Technology Assessment (HTA) in India is by preparing pharmacoeconomics guidelines. The main reason of such strong guidelines is due to medicines which account for 20-60% of health care spending in developing and transitional countries, compared with 18% in countries of the Organization for Economic Co-operation and Development. It has been estimated up to 90% of the population in developing countries purchase medicines through out-of-pocket payments, making medicines the largest family expenditure item after food. As a result, medicines are unaffordable for large sections of the global population and are a major burden on government budgets in addition to lack of social insurance and inadequate publicly subsidized services. The maximum benefit able areas in which HTA could be applied in the Indian context include, drug pricing, development of clinical practice guidelines, prioritizing interventions, reimbursement that represent the greatest value within a limited budget.