In-Situ Growth of ZnO Whiskers on Ti2ZnC MAX Phases.

ZnO whiskers have many applications, such as in medical and photocatalysis fields. In this study, an unconventional preparation approach is reported, realizing the in-situ growth of ZnO whiskers on Ti2ZnC. The weak bonding between the layer of Ti6C-octahedron and the Zn-atom layers leads to the easy extraction of Zn atoms from Ti2ZnC lattice points, resulting in the formation of ZnO whiskers on the Ti2ZnC surface. This is the first time that ZnO whiskers have been found to grow in-situ on Ti2ZnC substrate. Further, this phenomenon is amplified when the size of the Ti2ZnC grains is mechanically reduced by ball-milling, which bodes a promising route to prepare ZnO in-situ on a large scale. Additionally, this finding can also help us better understand the stability of Ti2ZnC and the whiskering mechanism of MAX phases.

Economic evaluation of the screening for Alzheimer's disease in China.

Background: We evaluated the cost-effectiveness of the screening in mainland China for Alzheimer's disease (AD) patients aged over 60. Methods: Individuals in mainland China, received an initial screening by questionnaire on mental state, and those with scores deemed suspicious for AD were referred to diagnostic tests. A 9-state Markov model was developed to simulate the disease progression of a cohort of 100,000 subjects aging from 60 to 80. In addition, several scenarios were analyzed to assess the robustness under different screening frequency, starting age, the duration of drug effects, and the health status of subjects. Results: The ICER of AD screening was 26413.77 USD per QALY [quality-adjusted life-year (QALY)] compared with no screening. The number of deaths and severe AD cases who did not receive treatment averted by screening accounted for 0.076 and 0.006% of the total population, respectively, and the net monetary benefit was 128.29 USD per capita. Under the thresholds of one and three times the gross domestic product per capita, the probability of screening being cost-effective was approximately 18 and 77%, respectively. The ICER decreased to 18132.96USD per QALY when the drug effect was prolonged, and increased when the frequency of screening was increased, the starting age was postponed, and patients suffering from comorbidities were more. However, the number of severe AD cases and deaths declined when the screening frequency increased. Conclusion: Screening for AD in individuals over 60 can reduce the numbers of severe AD cases and deaths and may be cost-effective, depending on factors such as screening frequency, starting age of screening, and duration of drug effects. Additionally, mild cognitive impairment (MCI) is an important stage at which the burden of progression to AD may be reduced and the cost-effectiveness of screening may be improved.

Identifying optimal PD-1/PD-L1 inhibitors in first-line treatment of patients with advanced squamous non-small cell lung cancer in China: Updated systematic review and network meta-analysis.

Objective: After Gemstone-302 was published in Lancet in January 2022, seven PD-(L)1 inhibitors launched or about to be launched in China, but there are no head-to-head RCTs reporting the comparative efficacy for squamous non-small cell lung cancer (sq-NSCLC). Therefore, we aimed to indirectly compare the efficacy of these treatments to provide evidence for clinical decision and Chinese national reimbursement drug listing. Methods: We collected phase III clinical trials targeted on stage IIIB-IV patients for first-line immunotherapy of sq-NSCLC by systematically searching databases. Relative effects of competing treatments were assessed by Bayesian network meta-analysis and non-parametric restricted mean survival time (RMST) model. Hazard ratio (HR), severe adverse events (SAEs, grade 3-5), progression-free survival (PFS) and overall survival (OS) years were the outcomes. Subgroup analysis was done according to PD-(L)1 expression, smoking, gender, Eastern Cooperative Oncology Group performance status, age and disease stage. Sensitivity analysis using the range of parameters distribution as well as different comparison methods was performed to test the robustness of the results. Results: A total of 7 clinical trials with 2,640 patients were included. For OS, the efficiency (HR, 95%CI) ranks from high to low were sugemalimab (0.48, 0.32-0.73), camrelizumab (0.55, 0.40-0.76), sintilimab (0.56, 0.35-0.90), pembrolizumab (0.71, 0.58-0.87) and atezolizumab (0.88, 0.73-1.05). For PFS, the efficiency ranks from high to low were sugemalimab (0.33, 0.24-0.45), camrelizumab (0.37, 0.30-0.46), tislelizumab (0.53, 0.36-0.79), sintilimab (0.54, 0.42-0.69), toripalimab (0.56, 0.38-0.83), pembrolizumab (0.57, 0.47-0.70) and atezolizumab (0.71, 0.59-0.85). Proportional hazard models and non-proportional hazard models showed consistent efficiency ranks. When extrapolated to long-term survival benefit, under non-proportional hazard ratio, sugemalimab achieved the highest PFS benefit (lifeyears, LYs) in 2 years (1.323), with camrelizumab (1.320), sintilimab (1.243), tislelizumab (1.189), pembrolizumab (0.990) and atezolizumab (0.947) ranking in order; Camrelizumab achieved the highest OS benefit (LYs) in 10 years (2.723), with atezolizumab (2.445) and pembrolizumab (2.397) ranking in order. RMST model showed similar results. In terms of safety, PD-(L)1 inhibitors increased the incidence of SAEs when combined with chemotherapy, sugemalimab and camrelizumab was the safest drugs. Conclusion: Sugemalimab is superior both in HR and long-term survival benefit for Chinese patients with advanced sq-NSCLC.

Cost-effectiveness analysis of camrelizumab plus chemotherapy as first-line treatment for advanced squamous NSCLC in China.

Objective: Results of CameL-sq has revealed the clinical benefits to patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). This study aims to evaluate the cost-effectiveness of camrelizumab plus chemotherapy to treat sq-NSCLC from the perspective of the Chinese healthcare system. Methods: We used a partitioned survival model with a lifetime horizon to evaluate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in treating sq-NSCLC. Baseline characteristics of patients and key clinical data were extracted from CameL-sq. Costs and utilities were collected from the open-access database and published literature. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICERs) were chosen as economic outcome indicators. We also performed a sensitivity analysis, subgroup analysis, and scenario analysis to verify the stability of the basic analysis results and explore the results under different scenarios. Results: Combination therapy added 0.47 QALYS and 0.91 life-years with an incremental cost of $6,347.81 compared with chemotherapy, which had an ICER of $13,572 per QALY. The probabilistic sensitivity analysis indicated that camrelizumab plus chemotherapy had a 37.8% probability of cost-effectiveness at a willingness-to-pay threshold (WTP) of 1 time GDP per capital. When WTP was set as 3 times GDP per capital, combination therapy had significant cost-effectiveness. Deterministic sensitivity analysis showed that cost of the best supportive care was the factor with the greatest influence. The subgroup analysis found that combination therapy was associated with cost-effectiveness in several subgroups, namely, patients with disease stage IIIB/IIIC and with PD-L1 tumor proportion score ≤ 1%. Scenario analysis showed that ICER was positively correlated with the price of camrelizumab. Conclusion: In this economic evaluation, camrelizumab plus chemotherapy was unlikely to be cost-effective compared with chemotherapy in the first line therapy of sq-NSCLC from a perspective of the Chinese healthcare system. Reducing the price of camrelizumab and tailoring treatments based on individual patient factors might improve the cost-effectiveness. Our findings may provide evidence for clinicians in making optimal decisions in general clinical practice.

Cost-effectiveness analysis of colonoscopy and fecal immunochemical testing for colorectal cancer screening in China.

Objective: This study aimed to evaluate the cost-effectiveness of the colorectal cancer screening in China, and that when the screening was implemented in a specific region. Methods: A 13-state Markov model was established to compare four screening protocols, including annual fecal immunochemical testing (FIT1), biennial fecal immunochemical testing (FIT2), electronic colonoscopy every 10 years (e-CSPY10), and electronic colonoscopy every 5 years (e-CSPY5), with no screening from the perspective of Chinese healthcare system. The model simulated the health states of a cohort of 100,000 average-risk individuals aging from 50 to 75. Additionally, scenarios including the implementation in a specific region, starting from 40, and incompletely successful treatment of cancer were also analyzed. Results: Annual and biennial FIT could save 8.13USD (US Dollar) and 44.96USD per person, and increase 0.0705QALYs (Quality-Adjusted Life Years) and 0.2341 QALYs compared with no screening, respectively. Annual FIT could decrease costs by 36.81USD per person and increase 0.1637 QALYs in comparison to biennial FIT. The results showed that both annual and biennial FIT for screening were dominant over no screening, and annual FIT was dominant over biennial FIT. The ICER (Incremental Cost-Effectiveness Ratio) for e-CSPY10 were 1183.51USD/QALY and 536.66USD/QALY compared with FIT1 and FIT2. The ICER for e-CSPY5 were 1158.16USD/QALY and 770.85USD/QALY compared with FIT1 and FIT2. And the ICER for e-CSPY5 relative to e-CSPY10 was 358.71USD/QALY. All the ICER values were lower than the economic threshold of 2021 Chinese GDP (Gross Domestic Product) per capita in 2021(12554.42USD). Conclusions: It is worthwhile to popularize CRC screening in mainland China, as FIT always saving costs and colonoscopy is cost-effective. Regions with high income can take electronic colonoscopy every 10 years, or even every 5 years into consideration when determining the specific strategies.

Value of Perampanel as Adjunctive Treatment for Partial-Onset Seizures in Epilepsy: Cost-Effectiveness and Budget Impact Analysis.

Introduction: China has ~6 million patients with active epilepsy every year, around 60% of whom suffer from partial-onset seizures. Perampanel (PER) is a novel anti-epileptic drug for partial-onset seizures. PER has been included in the latest Chinese National Reimbursement Drug List (NRDL) in 2020. However, there is still a lack of evaluation evidence on the value of PER in China. Methods: This study selected a health system perspective. A Markov model was established to simulate the lifelong transition of different response levels and calculate the number of seizures in Chinese patients. Based on the utility value and mortality risk, the life years and quality-adjusted life years (QALYs) of patients using PER vs. lacosamide (LCM) were estimated. Efficacy data were derived from clinical trials and the literature. Cost data (in US dollars) included drug costs and medical service costs. A lifetime horizon was adopted. Health outcomes and costs were discounted at an annual discount rate of 5%. Deterministic sensitivity analysis, probability sensitivity analysis, and scenario analysis were performed. The impact of the inclusion of PER in the NRDL on the medical insurance budget over 3 years (2021-2023) was also estimated. Results: Cost-effectiveness analysis indicates that 8 mg/day of PER increases QALYs by 0.054 and saves costs by $2,390 compared with 400 mg/day of LCM. 4 mg/day of PER increases QALYs by 0.010 and saves costs by $860 compared with 200 mg/day of LCM. Deterministic sensitivity analysis reveals that utility value and the extreme discount rate are the factors with the greatest impact on the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis and scenario analysis show that the results are robust. Budget impact analysis indicates that after inclusion of PER in the NRDL, the incremental budget would be $1.28, $2.83, and $4.56 million from 2021 to 2023, respectively, but covering more eligible epileptic patients in the same time (1,918, 4,287, and 8,983, respectively). Conclusion: PER (8 or 4 mg/day) is of relatively high value as an add-on therapeutic regimen for partial-onset seizures in China because of its dominate advantage of cost-effectiveness over LCM and acceptable budget impact.