Markov diagram of health states and the possible transitions among them during each 1-month cycle.

<p>Markov diagram of health states and the possible transitions among them during each 1-month cycle.</p

The cost-effectiveness acceptability curves for the three first-line strategies for GBM in the overall cohort and the 8 subgroups.

<p>The vertical axes represent the probabilities of cost effectiveness. The horizontal axes represent the willingness-to-pay thresholds to gain 1 additional quality-adjusted life-year (QALY). The bold vertical dashed and solid lines represent the thresholds for China and Shanghai City, respectively.</p

A tornado diagram of one-way uncertainty analyses in the overall cohort.

<p>The graph shows the effects of the variables on net health benefit (in QALYs, with WTP = 11,034) between the RT and TMZ strategies. The width of the bars represents the range of the results when the variables are changed, as shown in Tables 1, 2, 3. The vertical dotted line represents the base-case results. The vertical line represents the base-case value for the net health benefit with WTP = 11,034. PFS: progression-free survival; OS: overall survival; HR: hazard ratio.</p

Analysis of the cost effectiveness of the first-line strategies for GBM in the overall cohort and the 8 subgroups.

<p>The x-axis represents the undiscounted 5-year quality-adjusted life-years (QALYs) for each strategy, and the y-axis represents the total undiscounted 5-year costs (in US dollars). The oblique line connects the RT strategy and the most cost-effective strategies; strategies above the straight lines were dominated or extended dominated.</p

Base Case Results for the Alternative Strategies for Cost, QALY Gained and ICER.

<p>Base Case Results for the Alternative Strategies for Cost, QALY Gained and ICER.</p

Trial Data and Model Estimated Values.

<p>NA: not applicable.</p

The probabilistic results of the incremental cost-utility differences for GBM in the overall cohort and the 8 subgroups.

<p>The TMZ strategy was compared to: (A) the RT strategy and (B) the NT strategy for a cohort of 1,000 GBM patients. The y-axis represents the incremental costs. The x-axis represents the incremental QALYs gained. Each ellipse represents the 95% confidence interval ellipse of the probabilistic results. The proportion of the ellipses found below the ICER threshold (the oblique lines) reflects the simulations in which the cost per additional QALY gained with the TMZ strategy was below the ICER threshold.</p

Tumor-Targeted Accumulation of Ligand-Installed Polymeric Micelles Influenced by Surface PEGylation Crowdedness

With respect to the intriguing biocompatibility and the stealthy functions of poly­(ethylene glycol) (PEG), PEGylated nanoparticulates have been intensively engineered for utilities as drug delivery vehicles. To advocate the targeted drug transportation, targeting ligands were strategically installed onto the surface of PEGylated nanoparticulates. The previous <i>in vitro</i> investigations revealed that the ligand-specified cell endocytosis of nanoparticulates was pronounced for the nanoparticulates with adequately high PEG crowdedness. The present study aims to explore insight into the impact of PEGylation degree on <i>in vivo</i> tumor-targeted accumulation activities of cRGD-installed nanoparticulates. The subsequent investigations verified the importance of the PEGylation crowdedness in pursuit of prolonged retention in the blood circulation post intravenous administration. Unprecedentedly, the PEGylation crowdedness was also identified as a crucial important parameter to pursue the tumor-targeted accumulation. A plausible reason is the elevated PEGylation crowdedness eliciting the restricted involvement in nonspecific protein adsorption of nanoparticulates in the biological milieu and consequently pronouncing the ligand-receptor-mediated binding for the nanoparticulates. Noteworthy was the distinctive performance of the class of the proposed systems once utilized for transportation of the mRNA payload to the tumors. The protein expression in the targeted tumors appeared to follow a clear PEGylation crowdedness dependence manner, where merely 2-fold PEGylation crowdedness led to remarkably 10-fold augmentation in protein expression in tumors. Hence, the results provided important information and implications for design of active-targeting PEGylated nanomaterials to fulfill the targeting strategies in systemic applications