Health insurance and subjective well-being: evidence from integrating medical insurance across urban and rural areas in China.

Health insurance coverage and the risk protection it provides may improve enrollees' subjective well-being (SWB), as demonstrated, e.g. by Oregon Medicaid's randomized expansion significantly improving enrollees' mental health and happiness. Yet little evidence from low- and middle-income countries documents the link between insurance coverage and SWB. We analyse individual-level data on a large natural experiment in China: the integration of the rural and urban resident health insurance programmes. This reform, expanded nationally since 2016, is recognized as a vital step towards attaining the goal of providing affordable and equitable basic healthcare in China, because integration raises the level of healthcare coverage for rural residents to that enjoyed by their urban counterparts. This study is the first to investigate the impact of urban-rural health insurance integration on the SWB of the Chinese population. Analysing 2011-18 data from the China Health and Retirement Longitudinal Study in a difference-in-difference framework with variation in the treatment timing, we find that the integration policy significantly improved the life satisfaction of rural residents, especially among low-income and elderly individuals. The positive impact of the integration on SWB appears to stem from the improvement of rural residents' mental health (decrease in depressive symptoms) and associated increases in some health behaviours, as well as a mild increase in outpatient care utilization and financial risk protection. There was no discernible impact of the integration on SWB among urban residents, suggesting that the reform reduced inequality in healthcare access and health outcomes for poorer rural residents without negative spillovers on their urban counterparts.

Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database.

OBJECTIVE: Bupropion, a monocyclic antidepressant, aids in smoking cessation, treats major depression, and prevents severe depression in seasonal affective disorder patients. Yet, its adverse reactions remain insufficiently studied. METHODS: All data from the raw data packages for 78 quarters from the 1st quarter of 2004 to the 2nd quarter of 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database and imported into the SAS9.4 software for data cleaning and analysis. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods were used to analyze drug adverse events and assess their compliance with various screening criteria. RESULTS: The results showed a total of 36,862 reports related to Bupropion use, identifying 364 positive reaction terms (PT) covering 23 System Organ Classes (SOCs). In addition to known side effects, some new potential adverse reactions were found, such as Stool analysis abnormal, Oculocephalogyric reflex absent, Suspected suicide, and so on. At the same time, reactions like Encephalopathy neonatal, Hyponatraemic coma, and Electrocardiogram QRS complex prolonged were prominently ranked. Notably, occurrences such as Urine amphetamine positive and Amphetamines positive were relatively high, suggesting extra caution for these potential adverse reactions during clinical use of Bupropion. CONCLUSION: These findings highlight the potential health risks of long-term Bupropion use, especially concerning efficacy, positive drug tests, and suicidal tendencies. Therefore, it is recommended to monitor and assess patients using Bupropion more stringently to use this therapeutically potential drug more safely and effectively.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China.

BACKGROUND: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). RESULTS: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. CONCLUSION: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.

Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database.

OBJECTIVE: This study aims to analysis adverse drug events (ADE) related to Brexpiprazole from the third quarter of 2015 to the first quarter of 2023 from FAERS database. METHODS: The ADE data related to Brexpiprazole from 2015 Q3 to 2023 Q1 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis. RESULTS: Among the 8559 ADE reports with Brexpiprazole as the primary suspected drug, 178 preferred terms (PT) of adverse reactions spanning 27 different system organ classes (SOC) were identified. Specifically, Metabolism and nutrition disorders and Reproductive system and breast disorders were unique adverse reactions to Brexpiprazole, with the latter not mentioned in the official drug label. Moreover, uncommon but significantly strong ADE signals, such as Egocentrism, Pharmacophobia, and Compulsions were observed. Notably, Tardive dyskinesia (n = 317, ROR 103.87, PRR 102.21, IC 6.21, EBGM 96.17) and Extrapyramidal disorder (n = 104, ROR 31.17, PRR 31.00, IC 4.57, EBGM 30.44) exhibited relatively high occurrence rates and signal strengths. Additionally, Lactation disorder (n = 6, ROR 48.09, PRR 48.07, IC 2.63, EBGM 46.71) and Breast discharge (n = 10, ROR 23.18, PRR 23.17, IC 2.94, EBGM 22.86) were observed, both presenting strong ADE signals. CONCLUSION: Brexpiprazole poses risks of various adverse reactions while providing therapeutic effects. In clinical applications, practitioners should closely monitor occurrences of Psychiatric disorders, Metabolism and nutrition disorders, Reproductive system and breast disorders, and other events.

Preclinical safety assessment of an oncolytic herpes simplex virus type 2 expressed PD-L1/CD3 bispecific antibody.

Oncolytic virotherapy is an emerging and safe therapeutic approach based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. We constructed a new type of oncolytic herpes simplex virus armed with Bispecific Antibody (BsAb) molecules targeting PD-L1/CD3 (oHSV2-PD-L1/CD3-BsAb) to treat human malignancies. We demonstrated the anti-tumor efficacy of oHSV2-PD-L1/CD3-BsAb. To move forward with clinical trials of oHSV2-PD-L1/CD3-BsAb, we conducted a comprehensive preclinical safety evaluation, including hemolysis test, anaphylaxis test, repeated dose toxicity test in cynomolgus monkeys, biodistribution in cynomolgus monkeys and tissue cross-reactivity of PD-L1/CD3-BsAb with human and cynomolgus monkey tissues in vitro. Our preclinical safety evaluation indicated that oHSV2-PD-L1/CD3-BsAb is safe and suitable for clinical trials. After undergoing a thorough evaluation by the United States Food and Drug Administration (FDA), oHSV2-PD-L1/CD3-BsAb has successfully obtained approval to initiate Phase I clinical trials in the United States (FDA IND: 28717).

Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI.

Evaluation of myelin content is crucial for attention-deficit/hyperactivity disorder (ADHD). To estimate myelin content in ADHD based on synthetic MRI-based method and compare it with established diffusion tensor imaging (DTI) method. Fifth-nine ADHD and fifty typically developing (TD) children were recruited. Global and regional myelin content (myelin volume fraction [MVF] and myelin volume [MYV]) were assessed using SyMRI and compared with DTI metrics (fractional anisotropy and mean/radial/axial diffusivity). The relationship between significant MRI parameters and clinical variables were assessed in ADHD. No between-group differences of whole-brain myelin content were found. Compared to TDs, ADHD showed higher mean MVF in bilateral internal capsule, external capsule, corona radiata, and corpus callosum, as well as in left tapetum, left superior fronto-occipital fascicular, and right cingulum (all PFDR-corrected < 0.05). Increased MYV were found in similar regions. Abnormalities of DTI metrics were mainly in bilateral corticospinal tract. Besides, MVF in right retro lenticular part of internal capsule was negatively correlated with cancellation test scores (r = - 0.41, P = 0.002), and MYV in right posterior limb of internal capsule (r = 0.377, P = 0.040) and left superior corona radiata (r = 0.375, P = 0.041) were positively correlated with cancellation test scores in ADHD. Increased myelin content underscored the important pathway of frontostriatal tract, posterior thalamic radiation, and corpus callosum underlying ADHD, which reinforced the insights into myelin quantification and its potential role in pathophysiological mechanism and disease diagnosis. Prospectively registered trials number: ChiCTR2100048109; date: 2021-07.

Equality of public health service and family doctor contract service utilisation among migrants in China.

China initiated the equalisation of an essential public health service programme in 2009 with the goal of developing a more equitable and effective public health system for all people. This study employs data from the China Migrants Dynamic Survey to examine regional-level and household-level income-related inequalities in public health service utilisation and its determinants. Wagstaff concentration indices indicate that essential public health services and family doctor contract services are concentrated among less developed prefectures and poorer households. Decomposition analysis based on recentered influence function regression shows that education contributes to pro-poor inequality in health records and health education utilisation. China's policies of essential public health services and family doctor contract services reduce income-related inequalities in health service utilisation, which has important implications for developing countries striving to achieve universal health service coverage and equal health outcomes.

A real-world cost-effectiveness study of vancomycin versus linezolid for the treatment of late-onset neonatal sepsis in the NICU in China.

BACKGROUND AND OBJECTIVE: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. METHODS: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. RESULTS: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. CONCLUSIONS: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.

The air we breathe: An In-depth analysis of PM2.5 pollution in 1312 cities from 2000 to 2020.

In recent decades, the phenomenon of rapid urbanization in various parts of the world has led to a significant increase in PM2.5 concentration, which has emerged as a growing social concern. In order to achieve the objective of sustainable development, the United Nations Global Sustainable Development Goals (SDGs) have established the goal of creating inclusive, safe, resilient, and sustainable cities and human habitats (SDG 11). Goal 11.6 aims to decrease the negative environmental impact per capita in cities, with an emphasis on urban air quality and waste management. However, the global distribution of PM2.5 pollution varies due to disparities in urbanization development in different regions. The purpose of this paper is to explore the global spatial distribution and temporal variation of PM2.5 in cities with populations greater than 300,000 from 2000 to 2020, to gain insight into the issue. The findings indicate that PM2.5 concentrations are expected to continue increasing as urbanization progresses, but the rate of evolution of PM2.5 concentration varies depending on the continent, country, and city. From 2000 to 2020, PM2.5 concentration increased significantly in Asia and Africa, with the majority of the increased concentrations located in Asian countries and some African countries. On the other hand, most European and American countries had lower PM2.5 concentrations. The results of this study have the potential to inform urbanization policy formulation by providing knowledge about the spatial distribution of PM2.5 pollution during global urbanization. Addressing the issue of PM2.5 pollution is critical in achieving SDG 11.6 and promoting sustainable and coordinated development in cities worldwide.

Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Cost-sharing reduction and health service utilisation, health-related lifestyles, and obesity: evidence from the Australian health concession card policy.

BACKGROUND: The Australian Health Concession Card (HCC) policy aims to improve access to affordable health services and medicines by providing reduced patient cost-sharing. This study explored the association between HCC holding and health service utilisation, as well as health-related lifestyles and obesity in Australian adults. METHODS: The Australian National Health Survey data were used to derive three sets of study outcomes. Multivariable generalised linear regression models were used to estimate the association between concessional status and study outcomes after controlling for socio-demographic factors. RESULTS: HCC holders, compared to their non-concessional counterparts, had more visits to GPs (1.01, 95% CI: 0.74-1.30), specialists (0.23, 95% CI: 0.02-0.44), outpatient clinics (0.19, 95% CI: 0.06-0.31), and had more hospital admissions (0.04, 95% CI: -0.05-0.91). There was no significant difference in visits to doctors and health professionals about mental health problems among HCC holders and their counterparts. Moreover, less HCC holders consumed alcohol on ≥3days a week (OR: 0.75, 95% CI: 0.59-0.93) and had less of an alcohol risk that exceeded the 2001 alcohol guidelines (0.83, 95% CI: 0.69-0.99). CONCLUSIONS: This study revealed evidence that reduced patientcost-sharing provided by HCC policy was positively correlated with more health service utilisation after adjusting for socio-demographic characteristics. Strategies to prioritise resources are necessary.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy as the first-line treatment for advanced esophageal cancer.

OBJECTIVE: The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. METHODS: A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. RESULTS: The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. CONCLUSIONS: Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

Cost-Effectiveness Analysis of Sintilimab Combined with Chemotherapy Versus Chemotherapy Alone as the First-Line Treatment for Advanced Esophageal Cancer.

Background: Esophageal cancer has a poor prognosis and currently ranks sixth in global cancer mortality rates. The ORIENT-15 trial showed sintilimab plus chemotherapy significantly improved survival when compared to chemotherapy alone. This study aimed to evaluate the cost-effectiveness of sintilimab, a programmed death-ligand 1 (PD-L1) inhibitor, plus chemotherapy in treating patients with esophageal cancer compared with chemotherapy alone. Methods: A Markov model with a 10-year horizon was developed based on the perspective of the Chinese healthcare payers. We conducted a cost-effectiveness analysis for sintilimab combined with chemotherapy based on a questionnaire. Patients were grouped into the sintilimab group based on a positive score of 10 or more (combined positive score (CPS) ≥ 10 groups), and those with any other PD-L1 expression were randomized into patient groups. We estimated the cost and the effectiveness of sintilimab on the quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) was computed. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness results. Results: In the base-case analysis, compared with chemotherapy alone, the ICER of sintilimab plus chemotherapy for all patients was $21024.05 per QALY, and in the CPS≥10 group, it was $20974.23 per QALY. This was lower than $37653 per QALY. One-way sensitivity analysis demonstrated that ICERs were most sensitive to the price of sintilimab. Conclusion: The study demonstrated that sintilimab plus chemotherapy for advanced esophageal cancer as its first-line treatment would be more cost-effective than chemotherapy alone in Chinese patients.

Cell-free DNA hypermethylated genes may have a limited role in cancer screening but a potential role in risk assessment of head and neck cancer.

Cell-free DNA (cfDNA) hypermethylation in blood-based liquid biopsy is an attractive, minimally invasive biomarker for head and neck cancer (HNC) diagnosis and risk assessment. Yet, there is a lack of adequate description and discussion on this issue. A total of 10 eligible case-control studies containing 26 different hypermethylated genes in cfDNA were retrieved. There were 2026 HNC patients and 3149 healthy individuals for determining various hypermethylated genes in cfDNA. The pooled diagnostic parameter of sensitivity, specificity, and diagnostic accuracy value (95% confidence interval) was 33.2% (31.2-35.3%), 93.3% (92.3-94.1%), and 69.8% (68.5-71.0%), respectively. Odds ratios analysis revealed that SHOX2, SEPT, HIC1, CDKN2A, and CALML5 were significantly associated with increased risk of HNC development. Collectively, cfDNA hypermethylation biomarkers had a high specificity but accompanied by a low sensitivity for HNC detection, which might have a limited role in cancer screening but a potential role in risk assessment of HNC.

A Signature Based on Costimulatory Molecules for the Assessment of Prognosis and Immune Characteristics in Patients With Stomach Adenocarcinoma.

Although costimulatory molecules have been shown to boost antitumor immune responses, their significance in stomach adenocarcinoma (STAD) remains unknown. The purpose of this study was to examine the gene expression patterns of costimulatory molecule genes in patients with STAD and develop a predictive signature to aid in therapy selection and outcome prediction. We used 60 costimulatory family genes from prior research to conduct the first complete costimulatory molecular analysis in patients with STAD. In the two study groups, consensus clustering analysis based on these 60 genes indicated unique distribution patterns and prognostic differences. Using the least absolute shrinkage and selection operator and Cox regression analysis, we identified nine costimulatory molecular gene pairs (CMGPs) with prognostic value. With these nine CMGPs, we were able to develop a costimulatory molecule-related prognostic signature that performed well in an external dataset. For the patients with STAD, the signature was proven to be a risk factor independent of the clinical characteristics, indicating that this signature may be employed in conjunction with clinical considerations. A further connection between the signature and immunotherapy response was discovered. The patients with high mutation rates, an abundance of infiltrating immune cells, and an immunosuppressive milieu were classified as high-risk patients. It is possible that these high-risk patients have a better prognosis for immunotherapy since they have higher cytolytic activity scores and immunophenoscores of CTLA4 and PD-L1/PD-L2 blockers. Therefore, our signature may help clinicians in assessing patient prognosis and developing treatment plans.

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma.

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM. Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results. Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter. Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

[Rapid screening and confirmation of 86 illegally added chemicals in fishery drugs by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry].

With the rapid expansion of fisheries, one of the most significant limitations to the sustainable development of fisheries in China is the quality and safety of fishery products owing to the abuse of fishery drugs and the use of illegal and/or restricted chemicals in fishery drugs. A range of chemicals that are potential hazards to fishery drugs were selected for screening in this study. A comprehensive analytical method was developed, based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), for the rapid screening of 86 types of illegally added chemicals in fishery drugs. The fishery drug samples were extracted with 80% (v/v) acetonitrile aqueous solution and diluted to reduce matrix effects. The 86 target compounds were separated on an ACQUITY PREMIER HSS T3 column (100 mm×2.1 mm, 1.8 µm), with methanol and 0.1% formic acid as mobile phases, via gradient elution. The extract was directly analyzed by UPLC-Q-TOF-MS using electrospray ionization in the positive mode. The external standard method was used for quantification. In this study, the extraction reagent and purification procedure were selected to develop a simple and effective pre-treatment protocol. The effects of the chromatographic column, mobile phase, and fragmentation voltage on the separation and sensitivity of the 86 substances were evaluated to determine the optimum instrument conditions. An accurate mass database and fragment ion library were created for the rapid qualitative and quantitative analysis of the 86 illegally added chemicals in fishery drugs. The retention time, isotopic abundance and spacing, and precise mass of the principal diagnostic ion for each analyte were used for identification. The information on the fragment ions obtained from the target MS/MS profiles was compared with that from a database to ensure the accuracy of the qualitative results. The chromatographic peak area of each target analyte was used for quantification. The analytical detection was based on the retention time deviation of ±0.35 min, accurate mass deviation of ±10×10-6, and major adduct forms, including [M+H]+, [M+Na]+, and [M+NH4]+. To evaluate the matrix effects of the 86 target chemicals at varied dilution ratios, two types of antibiotics and four types of Chinese herbal medicines were selected as typical samples. Considering the instrument tolerance as well as sensitivity and accuracy of the procedure, the recommended dilution ratios for antibiotics and Chinese herbal medicines were 50 times and 10 times, respectively. Two different types of calibration curves were prepared; one was the solvent calibration curve for antibiotics and the other was the matrix calibration curve for Chinese herbal medicines. For a given concentration, the calibration curves of the 86 target chemicals were linear with correlation coefficients of at least 0.99. The recoveries ranged from 76.8% to 112.1% with relative standard deviations (RSDs) (n=3) of less than 11.7%. The limit of quantification (LOQ) ranges of the compounds in Chinese herbal medicines and antibiotics were 1-15 mg/kg and 5-75 mg/kg, respectively. To evaluate the screening detection limits (SDLs) of each compound, a mixed standard solution was added to a fishery drug sample at varied concentrations. The SDL ranges of the compounds in Chinese herbal medicines and antibiotics were 1-15 and 5-50 mg/kg, respectively. This approach resulted in SDLs that satisfy the actual screening requirements. Because of its rapid nature, simplicity, accuracy, and sensitivity, the method may be used in the high-throughput screening and identification of illegally added chemicals in many types of fishery drugs. This method was applied to a monitoring project for the quality and safety of fishery inputs in Zhejiang Province. Sixty fishery drug samples were evaluated, among which eight Chinese herbal medicine samples were found to contain unspecified ingredients and one antibiotic sample was found to be free of any active substances. Thus, an effective technical method to monitor the quality and safety of fishery drugs was developed.

Laser-induced graphene (LIG)-driven medical sensors for health monitoring and diseases diagnosis.

Laser-induced graphene (LIG) is a class of three-dimensional (3D) porous carbon nanomaterial. It can be prepared by direct laser writing on some polymer materials in the air. Because of its features of simplicity, fast production, and excellent physicochemical properties, it was widely used in medical sensing devices. This minireview gives an overview of the characteristics of LIG and LIG-driven sensors. Various methods for preparing graphene were compared and discussed. The applications of the LIG in biochemical sensors for ions, small molecules, microRNA, protein, and cell detection were highlighted. LIG-based physical physiological sensors and wearable electronics for medical applications were also included. Finally, our insights into current challenges and prospects for LIG-based medical sensing devices were presented.

Cost-effectiveness analysis of different screening strategies for colorectal cancer in Guangzhou, southern China: a Markov simulation analysis based on natural community screening results.

OBJECTIVES: To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model. METHODS: Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty. RESULTS: All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively. CONCLUSIONS: All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.