Patient versus physician preferences for lipid-lowering drug therapy: A discrete choice experiment.

BACKGROUND: The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors offered dyslipidemia patients an alternative to statins for lipid-lowering treatment. Understanding patient and physician preferences for lipid-lowering drugs may promote shared decision-making and improve treatment outcomes. METHODS: This study utilized an online discrete choice experiment (DCE) to assess the relative importance (RI) of six attributes related to lipid-lowering drugs, including frequency of administration, mode of administration, reduction of low-density lipoprotein cholesterol (LDL-C) level, risk of myopathy, risk of liver damage, and out-of-pocket monthly cost. Respondents were recruited from dyslipidemia patients and cardiovascular physicians in China. A mixed logit model and latent class analysis were employed to estimate the preference coefficient, marginal willingness to pay (mWTP), and RI of attributes. Ethical approval has been obtained for this study. RESULTS: A total of 708 patients and 507 physicians participated in the survey. Patients prioritized the 'risk of liver damage' (RI = 23.6%) with 'mode of administration' (RI = 19.2%) and 'frequency of administration' (RI = 18.8%) following closely. Contrarily, physicians prioritized the 'reduction of LDL-C level' (RI = 33.5%), followed by 'risk of liver damage' (RI = 26.0%) and 'risk of myopathy' (RI = 16.1%). Patients placed a higher value on 'frequency of administration' (p < .001) and 'mode of administration' (p < .001) compared to physicians, while physicians valued 'reduction of LDL-C level' (p < .001) and 'risk of myopathy' (p = .012) more than patients. Physicians exhibited higher mWTP than patients for all attributes except frequency and mode of administration. The LCA revealed three distinct patient classes: focus on oral administration, focus on hepatic safety and frequency and focus on hepatic safety and cost. Likewise, three physician classes were identified: frequency-insensitive, efficacy-focused and safety-focused. CONCLUSIONS: The preferences for lipid-lowering drug therapy differed between patients and physicians in China. Physicians should take into account patients' preferences and provide personalized treatment when they formulate lipid-lowering treatment plans. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in the questionnaire design process. They engaged in a focus group discussion to determine attributes and levels and also participated in a pilot survey to assess the comprehensibility of the questionnaires. Additionally, patients were involved in the DCE survey to express their preferences. The findings of patient preference for lipid-lowering drug therapy will promote shared decision-making and optimize the treatment regimen.

Availability, price, and affordability of anti-hepatitis B virus drugs: a cross-sectional study in China.

BACKGROUND: The global prevalence of hepatitis B virus (HBV) has presented a persistent challenge for public health prevention and treatment. However, studies that assess the public's access to anti-HBV drugs are absent. AIM: To examine the availability, pricing, and affordability of anti-HBV drugs in Jiangsu province, China and provide recommendations for improvement. METHOD: An enhanced methodology developed by the World Health Organization (WHO) and Health Action International was applied in a cross-sectional study that included 1026 healthcare facilities distributed in 13 prefectural-level cities in Jiangsu province. RESULTS: Since almost all drugs had an availability of less than 30%, the accessibility of anti-HBV drugs was notably low. Primary healthcare facilities had the lowest availability, reporting 1.4% for Original Brands (OBs) and 1.7% for lowest-priced generics (LPGs). Furthermore, the northern Jiangsu region recorded the lowest availability at 0.7%. LPGs demonstrated higher availability than OBs, with median availability probabilities of 2.6% and 1.4%, respectively. The drugs listed on the WHO Essential Medicines List exhibited higher availability than those on other lists. The median price ratios for OBs, LPGs, and volume-based purchasing drugs were 0.83, 0.50, and 0.27, respectively, less than 1.5 times the international reference price. Despite favorable pricing, affordability rate was 23% for urban residents and 0% for rural residents, which was discouraging. CONCLUSION: Low availability and affordability of anti-HBV drugs were observed. Policy recommendations should emphasize the improvement of LPG availability by incentivizing priority prescribing. Healthcare subsidies should be provided more effectively and equitably.

Spatial spillover effect of environmental factors on the tuberculosis occurrence among the elderly: a surveillance analysis for nearly a dozen years in eastern China.

BACKGROUND: In many areas of China, over 30% of tuberculosis cases occur among the elderly. We aimed to investigate the spatial distribution and environmental factors that predicted the occurence of tuberculosis in this group. METHODS: Data were collected on notified pulmonary tuberculosis (PTB) cases aged ≥ 65 years in Zhejiang Province from 2010 to 2021. We performed spatial autocorrelation and spatial-temporal scan statistics to determine the clusters of epidemics. Spatial Durbin Model (SDM) analysis was used to identify significant environmental factors and their spatial spillover effects. RESULTS: 77,405 cases of PTB among the elderly were notified, showing a decreasing trend in the notification rate. Spatial-temporal analysis showed clustering of epidemics in the western area of Zhejiang Province. The results of the SDM indicated that a one-unit increase in PM2.5 led to a 0.396% increase in the local notification rate. The annual mean temperature and precipitation had direct effects and spatial spillover effects on the rate, while complexity of the shape of the greenspace (SHAPE_AM) and SO2 had negative spatial spillover effects. CONCLUSION: Targeted interventions among the elderly in Western Zhejiang may be more efficient than broad, province-wide interventions. Low annual mean temperature and high annual mean precipitation in local and neighboring areas tend to have higher PTB onset among the elderly.

Evaluating the impact of PD-1 inhibitor treatment on key health outcomes for cancer patients in China.

BACKGROUND: There is a lack of studies examining the influence of programmed cell death protein 1 (PD-1) inhibitors on the health outcomes of cancer patients in China. AIM: This study aimed to evaluate prospective health outcomes associated with introducing PD-1 inhibitor treatment in China over five years. METHOD: We constructed a partitioned survival model to assess disparities in health outcomes over a 5-year time frame between two scenarios: one involving the availability of PD-1 inhibitor class with standard of care and the other involving standard of care alone. The impact on various health outcomes were assessed, including life years (LYs) gained, quality-adjusted life years (QALYs) gained, progression-free survival (PFS) years gained, the reduction in the number of grade 3-5 adverse events (AEs), and the improvement in objective remission rates (ORR). A sensitivity analysis was conducted to assess the robustness and reliability of the model. RESULTS: From 2023 to 2027, the incorporation of PD-1 inhibitor class treatments was anticipated to yield substantial improvements in health outcomes, with an estimated increase of 1,336,332 LYs (+ 24.7%), 1,065,359 QALYs (+ 30.3%), and 1,177,564 PFS years (+ 57.4%) compared to standard of care alone. Simultaneously, the number of grade 3-5 AEs decreased by 334,976 (- 13.0%), and the ORR saw a 19.1% increase (+ 105.6%) relative to standard of care treatment alone. CONCLUSION: This study provides a analysis of the potential beneficial effects on health outcomes in the Chinese population after introducing PD-1 inhibitor class treatment. The findings suggest the PD-1 inhibitor class will significantly improve patient survival.

Polyketides/nonribosomal peptides from Streptococcus mutans and their ecological roles in dental biofilm.

Streptococcus mutans is the major etiological agent of dental caries in humans. S. mutans overgrowth within dental biofilms can trigger biofilm dysbiosis, ultimately leading to the initiation or progression of dental caries. Polyketides and nonribosomal peptides (PKs/NRPs) are secondary metabolites with complex structures encoded by a cluster of biosynthetic genes. Although not essential for microbial growth, PKs/NRPs play important roles in physiological regulation. Three main classes of hybrid PKs/NRPs in S. mutans have been identified, including mutanobactin, mutanocyclin, and mutanofactin, encoded by the mub, muc, and muf gene clusters, respectively. These three hybrid PKs/NRPs play important roles in environmental adaptation, biofilm formation, and interspecies competition of S. mutans. In this review, we provide an overview of the major hybrid PKs/NRPs of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin and address their ecological roles in dental biofilms. We place specific emphasis on important questions that are yet to be answered to provide novel insights into the cariogenic mechanism of S. mutans and facilitate improved management of dental caries. We highlight that S. mutans PKs/NRPs may be potential novel targets for the prevention and treatment of S. mutans-induced dental caries. The development of genomics, metabolomics, and mass spectrometry, together with the integration of various databases and bioinformatics tools, will allow the identification and synthesis of other secondary metabolites. Elucidating their physicochemical properties and their ecological roles in oral biofilms is crucial in the identification of novel targets for the ecological management of dental caries.

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

AIMS: The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. METHODS: A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. RESULTS: The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CONCLUSIONS: CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.

How the National Health Insurance Coverage policy changed the use of lenvatinib for adult patients with advanced hepatocellular carcinoma: a retrospective cohort analysis with real world big data.

BACKGROUND: To establish a long-term mechanism to control the cost burden of drugs, the Chinese government organized seven rounds of price negotiations for the national reimbursement drug list (NRDL) from 2016 to the end of 2022. The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the use of lenvatinib as the first-line treatment for advanced hepatocellular carcinoma (HCC) within a specific medical insurance region from the micro perspective of individual patient characteristics. METHODS: The data of HCC patients that received lenvatinib from September 2019 to August 2022 was retrieved from the Medical and Health Big Data Center and longitudinally analyzed. Contingency table chi-square statistics and binary logistic regression analysis were used to compare the differences in the categorical variables. Interrupted time-series (ITS) regression analysis was performed to evaluate the changes in the utilization of lenvatinib over 36 months. Multiple linear regression was used to analyze the impact of receiving lenvatinib on the total hospitalization expenses of hospitalized patients with advanced HCC. RESULTS: A total of 12,659 patients with advanced HCC were included in this study. The usage rate of lenvatinib increased from 6.19% to 15.28% over 36 months (P < 0.001). By controlling the other factors, consistent with this, the probability of patients with advanced HCC receiving lenvatinib increased by 2.72-fold after the implementation of the NHIC policy (OR = 2.720, 95% CI:2.396-3.088, P < 0.001). Older, residency in rural areas, lack of fixed income, treatment at hospitals below the tertiary level, and coverage by urban-rural residents' basic medical insurance (URRBMI) were the factors affecting the use of lenvatinib among patients with advanced HCC (P < 0.05). After the implementation of the NHIC policy, the total hospitalization expenses increased (Beta=-0.040, P < 0.001). However, compared to patients who received lenvatinib, the total hospitalization expenses were higher for those who did not receive the drug (US$5022.07 ± US$5488.70 vs. US$3701.63 ± US$4330.70, Beta = 0.062, P < 0.001). CONCLUSIONS: The NHIC policy has significantly increased the utilization of lenvatinib. In addition, we speculate that establishing multi-level medical insurance systems for economically disadvantaged patients would be beneficial in improving the effectiveness of the NHIC policy in the real world.

Fine Structure of the Mouthparts of Three Tomicus Beetles Co-Infecting Pinus yunnanensis in Southwestern China with Some Functional Comments.

Tomicus yunnanensis, T. brevipilosus, and T. minor are the most economically significant pests of Pinus yunnanensis in Southwestern China. Chemical and physical factors play critical roles in diverse biological activities. Here, we describe the fine structure of the adult mouthparts of these three Tomicus species using scanning and transmission electron microscopy. We identified three types of mandibular shapes, which determine their biomechanical properties, their ability to process food, and their preferred foraging locations on tree trunks. Eleven types of sensilla were discernible, including sensilla basiconica (Sb.1-2), sensilla twig basiconica (Stb.1-3), sensilla coeloconica (Sco), sensilla chaetica (Sch.1-2), sensilla trichoidea (Str.1-2), and sensilla digitiformia (Sdi). Each basiconic sensillum occurs on the palpal tips and is innervated by 2-6 dendrites. Sb.1 are gustatory receptors, Sb.2 are olfactory receptors, and the three other sensilla have dual taste and mechanical functions. Sco, Sch, and Str are mechanoreceptors. Sdi are mechanical vibration receptions, given that they are innervated by one dendrite with numerous dendritic branches into the nonporous cuticle. No significant differences among the sexes or species were identified; however, intraspecific variability in the number of Stb.3 and Sdi sensilla was evident. These results will aid future studies of Tomicus beetle behaviors.

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China.

Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option.

Assessing Serplulimab's Value in Treating Advanced Esophageal Cancer in China In China, esophageal cancer patients often need chemotherapy due to late diagnosis. Serplulimab, an expensive new treatment, is not cost-effective when combined with chemotherapy for most patients. However, for specific patient groups with a PD-L1 expression CPS ⩾ 10, it is both effective and affordable. This finding helps health care leaders create better pricing strategies.

Effects of pharmacist-led interventions on glycaemic control, adherence, disease management and health-related quality of life in patients with type 2 diabetes: a protocol for a network meta-analysis.

INTRODUCTION: The increase in the number of patients with uncontrolled type 2 diabetes mellitus (T2DM) is in need of effective management interventions. However, research to date has been limited to the evaluation of the outcomes of community pharmacists alone. Therefore, the aim of the study protocol is to compare the effects of clinical pharmacist-led intervention strategies for the management of T2DM in the outpatient settings. METHOD AND ANALYSIS: The study will collect and analyse data applying standard Cochrane methodological procedures. A search for eligible studies and ongoing trials will be conducted using PubMed, Embase, Medline (via Ovid), EBSCO (via Ovid), Lippincott Williams & Wilkins (LWW) Journals (via Ovid), ProQuest Health and Medical Complete, and ClinicalTrials.gov (clinicaltrials.gov) from database inception to December 2023. Clinical and health outcomes will be measured using both glycaemic control related indicators (eg, glycated haemoglobin, fasting blood glucose, postprandial glucose) and general indicators (eg, adherence, disease management and health-related quality of life). The meta-analysis will conduct pairwise meta-analysis using random effects models and network meta-analysis (NMA) employing the Bayesian hierarchical model. The visualisation and statistical analysis will be carried out using RevMan, R Studio and ADDIS. Additionally, we will evaluate the certainty of the evidence by using Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: There will be no primary data collection from NMA participants, and there is no requirement for formal ethical review. Our aim is to present the results of this NMA in a peer-reviewed scientific journal, at conferences, and in the mainstream media. PROSPERO REGISTRATION NUMBER: CRD42022355368.

The impact of the national volume-based procurement policy on the use of policy-related drugs in Nanjing: an interrupted time-series analysis.

BACKGROUND: In September 2019, the "4 + 7" centralized procurement pilot program was expanded nationwide aiming at reducing drug prices by means of volume-based procurement and using accredited generic drugs for branded drug substitutes. Given the current uncertain effect of the policy outside pilot areas, this study was conducted to evaluate the impact of the National Volume-based Procurement policy on the use of policy-related drugs after expansion. METHOD: A single-group interrupted time series was applied using drug purchase data, covering 25 months from December 2018 to December 2020. Drugs related to the centralized procurement policy were selected as samples, including 25 first-batch policy-related drugs and 56 alternative drugs. Centralized procured drugs can be divided into bid-winning and non-winning products, where non-winning products were sorted into generic and branded drugs, and alternative products were classified according to different degrees of substitution. Purchase volume, expenditures, and daily costs were measured. RESULTS: After the implementation of the policy, a significant increase was associated with the volume of bid-winning drugs (p < 0.001) and the volume of generic and branded drugs decreased immediately. The DDDc of drugs under the same generic name significantly reduced (an instantaneous drop of bid-winning drugs by approximately 25%, 7.62 CNY for generics and 3.07 CNY for branded drugs), saving 48.2 million CNY of drug expenditures. The policy has a significant effect on the drug for the treatment of cardiovascular diseases and exerted little influence on the drug for the treatment of nervous diseases, and the substitution of generics for antitumor-branded drugs was not obvious. In addition, the procurement volume of alternative drugs appeared to be a "carry-over". CONCLUSIONS: These findings indicated that the policy demonstrated positive effects in terms of price reductions and cost savings and accelerated the substitution of generics against branded drugs. The "patent cliff" for branded drugs has gradually emerged. Besides, a short-term "spillover effect" of the volume of alternative drugs was observed, requiring special attention and vigilance.

Cost-effectiveness of open pancreaticoduodenectomy with or without Heidelberg TRIANGLE operation for pancreatic cancer in China.

OBJECTIVE: Pancreatic cancer is a digestive malignancy with dismal prognosis. The advent of Heidelberg TRIANGLE dissection technique brings a turning point to improve the chance of survival. Our study aimed to evaluated the cost-effectiveness of open pancreaticoduodenectomy (OPD) versus OPD combined with TRIANGLE operation (OPD-TRIANGLE) for patients with pancreatic cancer from the perspective of healthcare system in China. METHODS: Two hundred forty-six patients with pancreatic cancer who underwent OPD or OPD-TRIANGLE from January to September 2022 were enrolled in this study. We performed a decision tree model to assess clinical and economic implications of different surgical strategies. Estimation of health utilities was based on published literature, while costs were acquired from the hospitals, clinical expert consultations, and other local charge. The incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Uncertainty of the findings was addressed via sensitivity analyses and scenario analyses. RESULTS: The results indicated that OPD-TRIANGLE group yielded additional 0.0402 QALYs at an incremental cost of US$1501.83 compared with OPD group, and the corresponding ICER was US$37,358.96 per QALY. The probabilities of OPD-TRIANGLE as the prior option were 52.8% at the WTP threshold of 60,000 US$/QALY. The main factors lined with costs incorporating total medical costs and operation-related costs. With 5-20% price reduction of OPD-TRIANGLE, the outcomes were also economically attractive. CONCLUSION: The findings of this population-based study suggested that OPD-TRIANGLE was likely to be cost-effective for patients with pancreatic cancer when compared against OPD. Further in-depth studies should be conducted to provide more comprehensive evidence.

Influencing Factors of Treatment Outcomes Among Patients with Pulmonary Tuberculosis: A Structural Equation Model Approach.

Background: Pulmonary tuberculosis (PTB) is a serious infectious disease, and the factors and pathways that influence final treatment outcomes are unclear. Here, we aimed to assess the factors that influence treatment outcomes in patients with PTB using a structural equation model. Methods: Participants completed a questionnaire covering demographics, understanding of PTB, psychological status, and history of medical treatment. Exploratory factor analysis and reliability testing were performed, and a structural equation model was constructed using the SPSS and Amos software. Results: A total of 251 participants were enrolled. Symptoms of depression were observed in 94.4% of participants, whereas 6% showed mild or greater anxiety. Through factor rotation, four common factors were extracted with a total variation of 66.15%. The structural equation model indicated that regular tuberculosis-related follow-up behaviour had a direct and positive effect on the final treatment outcome, with a path coefficient value of 0.20; the level of PTB understanding had a direct positive effect on the testing behaviour for PTB, with a path coefficient of 0.26; patients' psychological characteristics had a direct negative impact on regular testing behaviour, with a path coefficient of -0.13. The psychological characteristics and level of disease understanding of patients exerted indirect effects on the treatment outcome by affecting the way patients approached tuberculosis detection behaviour. Conclusion: Interventions aimed at improving the treatment outcomes of patients with PTB should mainly focus on financial support and improvements in psychological status in addition to a greater understanding and knowledge of PTB. Furthermore, patients should be encouraged to undergo regular PTB testing during the follow up period, as this mediates the effect of other factors on treatment outcomes and also helps in achieving favourable treatment outcomes.

The effect of diabetes mellitus on tuberculosis in eastern China: A decision-tree analysis based on a real-world study.

OBJECTIVES: The public health system faces major challenges due to the double burden of diabetes mellitus (DM) and tuberculosis (TB) in China. We aimed to investigate the prevalence and impact of diabetes on patients with TB. METHODS: Stratified cluster sampling was used to select 13 counties as study sites in the Zhejiang province. Patients who visited designated TB hospitals in these areas participated in this study between 1 January 2017 and 28 February 2019. Multiple logistic regression models were performed to investigate the association between DM and bacteriological and imaging results. A decision tree was used to predict the bacteriology and imaging results under the influence of DM. RESULTS: Of 5920 patients with newly diagnosed pulmonary tuberculosis, 643 (12.16%) had DM. Patients with pulmonary TB and DM were more likely to have pulmonary cavities (adjusted odds ratio [aOR], 2.81; 95% confidence intervals [95% CI]: 2.35-3.37) and higher rates of positive bacteriological tests (aOR, 2.32; 95% CI:1.87-2.87). Decision-tree analysis showed similar results. CONCLUSIONS: Concurrence of DM and pulmonary TB makes patients more likely to have positive bacteriological results and pulmonary cavities. Therefore, appropriate measures are necessary to promptly identify and manage patients with TB and DM.

Cost-effectiveness analysis of toripalimab plus chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer in China.

Background: Toripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required. Methods: A partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental cost-effectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model. Results: In the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel. Conclusion: At a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China.

[Latest Findings on Polyketides/Non-ribosomal Peptides That Are Secondary Metabolites of Streptococcus mutans].

Dental caries is a chronic infectious disease that occurs in the hard tissue of teeth under the influence of multiple factors, among which bacteria being a key factor. Streptococcus mutans ( S. mutans) is considered a major pathogen that causes caries. Secondary metabolites, including bacteriocins and polyketides/non-ribosomal peptides, are a class of small-molecule compounds synthesized by S. mutans. To date, polyketides/non-ribosomal peptides identified in S. mutans include mutanobactin, mutanocyclin, and mutanofactin, which are synthesized by the mub, muc, and muf biosynthetic gene clusters, respectively. These polyketides/non-ribosomal peptides play important roles in bacterial inter-species competition, oxidative stress, and biofilm formation. In this review, we provided an overview of the synthesis, function and regulation of three polyketides/non-ribosomal peptides of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin, aiming to provide new insights into the cariogenic mechanism of S. mutans and to promote the better management of dental caries.

Spatial-temporal analysis of pulmonary tuberculosis among students in the Zhejiang Province of China from 2007-2020.

Background: Pulmonary tuberculosis (PTB) is a serious chronic communicable disease that causes a significant disease burden in China; however, few studies have described its spatial epidemiological features in students. Methods: Data of all notified PTB cases from 2007 to 2020 in the student population were collected in the Zhejiang Province, China using the available TB Management Information System. Analyses including time trend, spatial autocorrelation, and spatial-temporal analysis were performed to identify temporal trends, hotspots, and clustering, respectively. Results: A total of 17,500 PTB cases were identified among students in the Zhejiang Province during the study period, accounting for 3.75% of all notified PTB cases. The health-seeking delay rate was 45.32%. There was a decreasing trend in PTB notifications throughout the period; clustering of cases was seen in the western area of Zhejiang Province. Additionally, one most likely cluster along with three secondary clusters were identified by spatial-temporal analysis. Conclusion: Although was a downward trend in PTB notifications among students during the time period, an upward trend was seen in bacteriologically confirmed cases since 2017. The risk of PTB was higher among senior high school and above than of junior high school. The western area of Zhejiang Province was the highest PTB risk settings for students, and more comprehensive interventions should be strengthened such as admission screening and routine health monitoring to improve early identification of PTB.

Potential mechanisms of Shenmai injection against POCD based on network pharmacology and molecular docking.

BACKGROUND: As the population ages, the number of patients with postoperative cognitive dysfunction increases. This study aims to investigate the mechanisms of Shenmai injection as a therapeutic strategy for postoperative cognitive dysfunction using a network pharmacology approach. METHODS: Shenmai injection and its targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Postoperative cognitive dysfunction-associated protein targets were identified using the GeneCards and DisGeNET databases. Subsequently, a protein-protein interaction network was constructed using the String database. For treating postoperative cognitive dysfunction, the core targets of Shenmai injection were identified through topological analysis, followed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed for annotation. Molecular docking was performed on the screened core targets and components. RESULTS: One hundred and eighty-two related targets of Shenmai injection in treating postoperative cognitive dysfunction were identified. Eleven active ingredients in Shenmai injection were detected to have a close connection with postoperative cognitive dysfunction-related targets. Additionally, Gene Ontology analysis revealed 10 biological processes, 10 cellular components and 10 molecular functions. The Kyoto Encyclopedia of Genes and Genomes analysis identified 20 signaling pathways. The docking results indicated five active ingredients from Shenmai injection can fit in the binding pockets of all three candidate targets. CONCLUSIONS: Thus, the present work systematically explored the anti-postoperative cognitive dysfunction mechanism of potential targets and signaling pathways of Shenmai injection. These results provide an important reference for subsequent basic research on postoperative cognitive dysfunction.

Dielectric Property and Breakdown Strength Performance of Long-Chain Branched Polypropylene for Metallized Film Capacitors.

At high temperatures, the insulation performance of polypropylene (PP) decreases, making it challenging to meet the application requirements of metallized film capacitors. In this paper, the dielectric performance of PP is improved by long-chain branching modification and adding different kinds of nucleating agents. The added nucleating agents are organic phosphate nucleating agent (NA-21), sorbitol nucleating agent (DMDBS), rare earth nucleating agent (WBG-Ⅱ) and acylamino nucleating agent (TMB-5). The results show that the long-chain branches promote heterogeneous nucleation and inhibit the motion of molecular chains, thereby enhancing the dielectric properties at high temperatures. Nucleating agents modulate the crystalline morphology of long-chain branched polypropylene (LCBPP), which leads to a decrease in the mean free path of carriers and an increase in trap energy level and trap density. Therefore, the conductivity is reduced and the breakdown strength is improved. Among the added nucleating agents, NA-21 showed a significant improvement in the electrical properties of LCBPP films. At 125 °C, compared with PP, the breakdown strength of the modified film is increased by 26.3%, and the energy density is increased by 66.1%. This method provides a reference for improving the dielectric properties of PP.

[Comparative study on the clinical features of familial clustered and sporadic vestibular migraine].

Objective:To compare and analyze the clinical features of family clustered vestibular migraine（FCVM） and sporadic vestibular migraine（SVM）. Methods:A total of 118 patients with vestibular migraine were selected and divided into FCVM group（66 cases） and SVM group（52 cases）, and the clinical features such as age, the form of symptoms, provoking and relieving factors, audiological manifestations, sequelae and complications, were compared and analyzed. Results:The onset of headache in FCVM group was earlier than that in SVM group （[23.88±11.45] years old and [28.77±11.85] years old, χ²=2.267, P=0.025） with a longer interval between headache and vertigo attack （[13.11±10.08] years old and [8.50±9.26] years old, χ²=2.554, P=0.012）.Patients with positional vertigo in the FCVM group were more than those in the SVM group （12[18.2%] and 0[0], χ²=3.171, P=0.002）. Mental anxiety（P<0.001）, neck stiffness（P=0.028）, and concentration difficulties（P=0.001） were more common in patients with FCVM at the end of the episode than in patients with SVM. Comorbid primary motion sickness combined was more common in FCVM group than in SVM group（49 cases[74.2%] and 25 cases[48.1%], χ²=2.906, P=0.004）. Conclusion:The onset of FCVM is earlier and the prognosis is often poor. Primary motion sickness can be used as a reference for the early diagnosis of FCVM.