13 research outputs found
Development of ?-Noradrenergic and Dopaminergic Receptor Systems Depends on Maturation of Their Presynaptic Nerve Terminals in the Rat Brain
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Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity.
Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity
Brain regional distributions of monoamine oxidase activities in postnatal development in normal and chronically manganese-treated rats
Neurochemical changes in rats chronically treated with a high concentration of manganese chloride
Complexes with S-Donor Ligands. 6. Synthesis of the First Family of (Trithiocarbonato)gold Complexes. Crystal Structure of [(PPh 3
What is driving HTA decision-making? Evidence from cancer drug reimbursement decisions from 6 European countries
Background
Decisions on the reimbursement of the same cancer drugs are different across European countries, but empirical work on the reasons behind these differences has been scarce. The main objective of this paper is to make a methodological contribution to existing research, specifically by outlining the systematic process of analysis to address such questions and determining the factors that might lead to different drug reimbursement decisions, and to explore its application in the field of oncology.
Methods
Reimbursement decisions on cancer drugs in six European countries (Belgium, England, Poland, Portugal, Scotland, and Sweden) between 2006 and 2014 were included in the study. A taxonomy was developed, comprising two groups of variables (system-level and product-specific) and an econometric model was specified (multilevel mixed-effects ordered probit).
Results
Only one in six evaluations in the sample reach the same reimbursement recommendation. Most health system variables were not determinants of a higher or lower probability of a positive reimbursement recommendation. However, the probability of reimbursement was higher when a drug was considered cost-effective by NICE/SMC and when there was a financial Managed Entry Agreement. This work also demonstrated a possible econometric approach for analysing differences in reimbursement decisions and contributes a structured approach for collecting and preparing data for such analyses.
Conclusions
Drug reimbursement decisions can be analysed in detail along a set of factors that are related to each decision. This information is essential, not only for understanding why a particular drug is accepted in one country and not in another but also when trying to implement a new HTA system or reform an existing one. This analysis provides policy makers and stakeholders with a model that enables a better understanding of the factors that drive HTA decisions and is adaptable to answer similar questions. Moreover, the data collection limitations encountered and described in this work shed light on the need for greater accessibility and transparency in HTA systems and regarding HTA outcomes.This research was funded under the European 7th Framework Programme with Advance-HTA (no305,983). The results presented reflect the author’s views. The EC is not liable for any use of the information communicated