Price and Prejudice? The Value of Chimeric Antigen Receptor (CAR) T-Cell Therapy.

Although chimeric antigen receptor (CAR) T-cell therapy has shown a high response rate in lymphoma patients, its cost-effectiveness is controversial due to the high price and uncertainty of the clinical evidence. In addition to the high acquisition cost of CAR T-cell therapy, procedure and facility cost increase the financial burden considering the frequency of adverse events such as cytokine release syndrome. In clinical research, relatively short follow-up periods were used compared to traditional cancer agents. In addition, head-to-head comparative effectiveness data are unavailable, which is an important factor when evaluating the cost-effectiveness of a new treatment. Additional evidence that will compensate for the uncertainty of existing clinical data is needed for full evaluation of long-term efficacy, safety, and comparative effectiveness.

Projecting Lifetime Health Outcomes and Costs Associated with the Ambient Fine Particulate Matter Exposure among Adult Women in Korea.

We sought to estimate the lifetime healthcare costs and outcomes associated with the exposure to the escalated concentration of fine particulate matter (particle size < 2.5 µm, PM2.5) among adult Korean women. We adapted a previously developed Markov model, and a hypothetical cohort composed of Korean women was exposed to either a standard (15 µg/m3) or increased (25 µg/m3) concentration of PM2.5. The time horizon of the analysis was 60 years, and the cycle length was 1 year. The outcomes were presented as direct healthcare costs and quality-adjusted life years (QALYs), and costs were discounted annually at 5%. Deterministic and probabilistic sensitivity analyses were performed. The model estimated that when the exposure concentration was increased by 10 µg/m3, the lifetime healthcare cost increased by USD 9309, which is an 11.3% increase compared to the standard concentration group. Women exposed to a higher concentration of PM2.5 were predicted to live 30.64 QALYs, compared to 32.08 QALYs for women who were exposed to the standard concentration of PM2.5. The tendency of a higher cost and shorter QALYs at increased exposure was consistent across a broad range of sensitivity analyses. The negative impact of PM2.5 was higher on cost than on QALYs and accelerated as the exposure time increased, emphasizing the importance of early intervention.

Do TRPV1 antagonists increase the risk for skin tumourigenesis? A collaborative in vitro and in vivo assessment.

A recent hypothesis suggesting that the pharmacological target TRPV1 (transient receptor potential vanilloid subfamily, member 1) may function as a tumour suppressor, which potentially impacts the development of TRPV1 antagonist therapeutics for a range of conditions. However, little is known about the long-term physiologic effects of TRPV1 blockade in the skin. In vitro and in vivo studies suggested that the potent TRPV1 competitive antagonist AMG-9810 promoted proliferation in N/TERT1 cells (telomerase-immortalised primary human keratinocytes 1) and tumour development in mouse skin that was mediated through EGFR/Akt/mTOR signalling. We attempted to reproduce the reported in vitro and in vivo findings to further explore this hypothesis to understand the underlying mechanism and the risk associated with TRPV1 antagonism in the skin. In vitro proliferation studies using multiple methods and topical application with AMG-9810 and structurally similar TRPV1 antagonists such as SB-705498 and PAC-14028 were performed. Although we confirmed expression of TRPV1 in primary human epidermal keratinocytes (HEKn) and spontaneously immortalised human keratinocytes (HaCaT), we were unable to demonstrate cell proliferation in either cell type or any clear evidence of increased expression of proteins in the EGFR/Akt/mTOR signalling pathway with these molecules. We were also unable to demonstrate skin tumour promotion or underlying molecular mechanisms involved in the EGFR/Akt/mTOR signalling pathway in a single-dose and two-stage carcinogenesis mouse study treated with TRPV1 antagonists. In conclusion, our data suggest that inhibiting the pharmacological function of TRPV1 in skin by specific antagonists has not been considered to be indicative of skin tumour development.