Background: The latest published CASPIAN trial demonstrated that adding durvalumab to etoposide and platinum (EP) improved survival dramatically for patients with extensive-stage small cell lung cancer (ES-SCLC). Considering the high cost of durvalumab, this study evaluated the cost-effectiveness of durvalumab plus EP (DEP) in the first-line setting for treatment-naïve patients with ES-SCLC from the U.S. payer perspective. Materials and Methods: We developed a three-state Markov model to simulate the disease course and source consumption of ES-SCLC over a lifetime horizon. Pseudo-individual patient-level data were generated from digitized Kaplan-Meier curves. Direct medical costs, including drug and administration costs, disease management and adverse events treatment fees, best supportive care and terminal care costs were obtained from sources including the Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, and relevant literature. Health state utility values were derived from published literature. Main outcomes considered were total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). All costs were adjusted for inflation to reflect 2019 U.S. dollars. The willingness-to-pay threshold was set as $150,000/QALY. One-way and probabilistic sensitivity analyses were used to explore the uncertainty of model assumptions. Results: Compared with EP, DEP was projected to increase life expectancy by 0.86 LYs (1.73 vs. 0.87) and 0.44 QALYs (0.93 vs. 0.49). The incremental treatment cost was $95,907, and the corresponding ICER was $216,953/QALY. The result was most sensitive to the variation of durvalumab acquisition cost. Probabilistic sensitivity analysis revealed that the probability of DEP over EP regimen to be cost-effective was 9.4% at a willingness-to-pay threshold of $150,000/QALY. In the case of reducing the price of durvalumab by 30.7%, DEP was more cost-effective than EP. Conclusion: From the perspective of the U.S. payer, adding durvalumab to EP is estimated to be not cost-effective compared with EP alone for patients with untreated ES-SCLC. Implications for Practice: The information provided by this analysis serves as a reference for decision makers. Lowering the price of durvalumab would be a potential measure to improve the economics of durvalumab plus etoposide and platinum (DEP), and the inclusion of durvalumab in the Medicare pharmacopeia could make DEP more economically available. These results may also guide physicians and patients to choose the most economically feasible treatment.
17 April 2020 in IEEE Transactions on Biomedical Circuits and Systems
The irreversible electroporation with microsecond electric pulses is a new ablation technique adopted in the tumor therapy worldwide. On the other hand, the nsPEF (nanosecond pulsed electric field) has been proved to provide a means to induce immunogenic cell death and elicits antitumor immunity, which is under intensive in-vitro and in-vivo studies and in clinical trials. Normally, one needs two different types of electric pulse generators for producing the pulses in the ranges of nanosecond and microsecond, respectively. In order to realize these two types of tumor treatments in complementary and optimize electrical pulse parameters, we have developed a compact high-voltage pulse generator with a wide pulse width tuning range, based on a capacitor discharging configuration digitally controlled by a silicon carbide MOSFET switching array through a pair of optic-coupler drivers. The developed digital pulse generator is capable of adjusting: pulse width over 100ns-100μs, voltage over 0-2kV and repetition rate up to 1.2 kHz. The pulse generator is designed in simulation, implemented and verified in the in vitro and in vivo experiments. The pulse generator is shown to deliver a complementary treatment on Murine melanoma B16 cell lines, i.e. triggering the cell early apoptosis under the 300ns pulse stimulation while a complete killing under the 100ns pulses. The pulse generator is further demonstrated to induce antitumor immunity in a preliminary in vivo study on the mice model.
The unique biological effects stimulated by short pulsed electric field have many applications in tumor treatment, such as irreversible electroporation, electrochemotherapy, gene transfection and immune therapy. These biological effects require high voltage pulses with different pulse width in the range from nanoseconds to hundreds of microseconds. To fulfill this requirement, a compact high voltage pulse generator has been designed based on a switchable capacitor array and a SiC MOSFET switching array. The proposed pulse generator has one output channel with an adjustable pulse width from 100 ns to 100 µs, an amplitude range from 0 kV to 2 kV, a repetition rate less than 1.2 kHz and a voltage drop less than 5%. The mechanism of the stacked switches circuit was investigated, in connection with a switchable capacitor array. The introduction of a switchable capacitor array extends the pulse width from nanosecond scale and microsecond scale compared with other similar design methods. The pulse generator has been designed in simulation and implemented in experiment. The developed pulse generator provides a convenient and economical tool for the further studies of the unique biological effects stimulated by different pulsed electric fields for tumor treatment.
In this work, the terahertz (THz) absorption spectra of a typical protein BSA (Bovine Serum Albumin) in aqueous solution were measured under different pH conditions. The temporal changes in the absorption spectra were analyzed using the two-dimensional correlation spectroscopy (2DCOS). By comparing the cross peaks corresponding to the different pH values, it can be obtained that the conformation is related to the pH condition. The results provide a new approach to analyze the conformation change process of protein.
In this work, a typical two-dimensional (2D) material MoS 2 has been measured by terahertz time-domain spectroscopy (THz-TDS), and its temperature dependent properties in the temperature range fom 120 K to 500 K have been studied. The transmittance and sheet conductivitiy of monolayer MoS 2 have been obtained at different temperatures. This study is useful for the understanding of 2D materials in the THz frequency regions.
Objective: The participation of general practice (GP) residents in COVID-19 prevention and control tasks touched workload participation in public health and disease prevention and control and was also a rare, valuable training experience for the residents and research material for medical education. This experience contributed to the understanding of three key points: First, was the content of the COVID-19 prevention task suited to them, or did it overload them in the present? Second, their competence in the COVID-19 prevention task reflected whether the early medical school training was sufficient or not. Third, what can be drawn from this study to promote public health training in the future? This study aimed to explore these issues by conducting a real epidemic situated training (REST) program.Methods: A situated cognition study was designed that included situational context design, legitimate peripheral participation, and the construction of a community of practice. The Task Cognitive Load Scale (NASA-TLX Scale) and self-developed questionnaires were adopted to conduct a questionnaire survey of resident doctors in a GP training program from West China Hospital of Sichuan University, and 183 questionnaires were collected. SPSS 23.0 statistical software was used for the statistical analysis of data.Results: The NASA scale showed that the intensity of field epidemic prevention and control (training) was tolerable. In particular, there was statistical difference in the cognitive load intensity of training before and after the epidemic occurred at different time points (P < 0.05). This shows that they were early trained and well-prepared before sudden outbreak of the COVID-19. Before the outbreak of the epidemic, the public health knowledge and training received came from undergraduate education (83.16%), early residents program training (69.47%), online self-study (49.16%), and continuing education (20.53%).Conclusion: Former medical school education and training at the regulatory training stage have a good effect and enable residents to master the skills required for epidemic prevention and control and to physically and mentally prepare for the task. After this stage, epidemic prevention and control training in real situations will make important contributions to the self-assessment and performance improvement of public health training.