Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

Quantitative assessment of aerosol contamination generated during tooth grinding with a speed-increasing handpiece.

OBJECTIVES: Tooth grinding produces a significant amount of aerosol particles. The aim of this study was to quantitatively assess particle contamination produced from tooth grinding with a speed-increasing handpiece across a real-world clinical setting. METHODS: All molar crowns were pretreated into cylinders with a uniform size. A novel computer-assisted numerical control system was used to parametrically study the bur speed: from 20,000 (20 K) to 200 K rpm at 20 K rpm intervals. 5-minute tooth grinding was performed in triplicate at each speed setting. Three online real-time particle counters (ORPC; TR-8301, TongrenCo.) were placed at 3 positions (0.5, 1, and 1.5 m) to evaluate particle production. All experimental instruments were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Scheirer-Ray-Hare and Kruskal-Wallis/ Dunn-Bonferroni tests, p < 0.05). RESULTS: The concentration level of aerosol particles production during the grinding experiment was elevated above the control group for all conditions, and increased with bur speed at any location (the maximum peak, reaching 5.59 × 107 particles/m3, at 200 K and 1 m), with differences between conditions. The effect of speed on the increment of particles across different channels compared to the control group was statistically significant among locations (p < 0.001). CONCLUSIONS: Statistically significant particle contamination was produced using a speed-increasing handpiece, but the contamination level for each experimental condition was reduced to baseline within 30 min, and most particles with a diameter greater than 1üm produced at low speeds (80 K or lower) tended to settle within 1 m. CLINICAL RELEVANCE: Our study suggested that the use of a speed-increasing handpiece below 80 K and 30 min of fallow time may lead to an adequate reduction in the health effects of particle contamination.

Challenges with the discovery of RNA-based therapeutics for flaviviruses.

INTRODUCTION: Flaviviruses are emerging or reemerging pathogens that have caused several outbreaks throughout the world and pose serious threats on human health and economic development. RNA-based therapeutics are developing rapidly, and hold promise in the fight against flaviviruses. However, to develop efficient and safe therapeutics for flaviviruses, many challenges remain unsolved. AREAS COVERED: In this review, the authors briefly introduced the biology of flaviviruses and the current advances in RNA-based therapeutics for them. Furthermore, the authors list the challenges and possible solutions in this area. Finally, the authors give their opinion on the development and future of RNA-based therapeutics for flaviviruses. EXPERT OPINION: With the rapid development of structural biology, the crystal structures of flavivirus proteins may lay the foundation for future rational drug design. Studies regarding the interactions between the flavivirus and the host will also be invaluable to inhibitor design. Researchers should maintain the current momentum to bring about safe and effective anti-flavivirus drugs to licensure through joint efforts of academia, government, and industry.

Out-of-pocket medical expenditure and associated factors of advanced colorectal cancer in China: a multi-center cross-sectional study.

Background: Colorectal cancer (CRC) causes a substantial disease burden in China. Information on the medical expenditure of CRC patients is critical for decision-makers to allocate medical resources reasonably, however, relevant data is limited in China, especially advanced CRC. The aim of this survey was to quantify the out-of-pocket medical expenditure of advanced CRC and explore associated factors. Methods: A nation-wide, multi-center, cross-sectional survey was conducted from March 2020 to March 2021. Nineteen hospitals in seven geographical regions were selected by multi-stage stratified sampling. For each eligible CRC patient with stage III or IV disease in the selected hospitals, the socio-demographics, clinical information, and range of out-of-pocket medical expenditure data were collected based on patients' self-reporting or medical records. Multivariable logistic analysis was used to explore associated factors of medical expenditure. All statistical analyses were conducted using SAS 9.4. Results: The mean age of the 4,428 advanced CRC patients included was 59.5±11.6 years, 59.6% were male, and 80.1% of patients were in stage III or IV at the time of diagnosis. Besides, 57.2% of patients had an annual household income of less than 50,000 Chinese Yuan (CNY), 40.9% of patients had an out-of-pocket medical expenditure of 50,000-99,999 CNY. As for the affordability of medical expenditure, 33.2% could afford 50,000-99,999 CNY. Multivariate analysis showed that patients who were in the southern [odds ratio (OR): 1.63, 95% confidence interval (CI): 1.31-2.03] and southwestern (OR: 1.55, 95% CI: 1.25-1.93), were in stage III at the time of diagnosis (OR: 1.33, 95% CI: 1.13-1.57), visited three or more hospitals (OR: 1.26, 95% CI: 1.04-1.52), had sought cross-regional health care (OR: 1.60, 95% CI: 1.40-1.83), used genetic testing (OR: 1.26, 95% CI: 1.10-1.45) and targeted drugs (OR: 2.12, 95% CI: 1.79-2.51) had higher out-of-pocket medical expenditure. Conclusions: Patients with advanced CRC had a high out-of-pocket medical expenditure. It is necessary to strengthen the prevention and control of CRC to reduce the disease burden; also, it is critical to deepen the reform of the medical system, increase proportion of medical insurance reimbursement, and remove barriers to cross-regional health care.

Matrix precipitation: a general strategy to eliminate matrix interference for pharmaceutical toxic impurities analysis.

Matrix interference, which can lead to false positive/negative results, contamination of injector or separation column, incompatibility between sample solution and the selected analytical instrument, and response inhibition or even quenching, is commonly suffered for the analysis of trace level toxic impurities in drug substance. In this study, a simple matrix precipitation strategy is proposed to eliminate or minimize the above stated matrix interference problems. Generally, a sample of active pharmaceutical ingredients (APIs) is dissolved in an appropriate solvent to achieve the desired high concentration and then an anti-solvent is added to precipitate the matrix substance. As a result, the target analyte is extracted into the mixed solution with very less residual of APIs. This strategy has the characteristics of simple manipulation, high recovery and excellent anti-interference capability. It was found that the precipitation ratio (R, representing the ability to remove matrix substance) and the proportion of solvent (the one used to dissolve APIs) in final solution (P, affecting R and also affecting the method sensitivity) are two important factors of the precipitation process. The correlation between R and P was investigated by performing precipitation with various APIs in different solvent/anti-solvent systems. After a detailed mathematical reasoning process, P=20% was proved to be an effective and robust condition to perform the precipitation strategy. The precipitation method with P=20% can be used as a general strategy for toxic impurity analysis in APIs. Finally, several typical examples are described in this article, where the challenging matrix interference issues have been resolved successfully.