Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors.

A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8+ tumor infiltrating lymphocytes (TILs) respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8+ TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8+ TILs, which also correlated with progressive T cell dysfunction. Cd36-/- T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8+ TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8+ T cell dysfunction and serves as a therapeutic avenue for immunotherapies.

A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer.

BACKGROUND: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. METHODS: RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3-5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. RESULTS: A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. CONCLUSIONS: CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results' uncertainty, further trials comparing these novel treatments are warranted. TRIAL REGISTRATION: Registration number: PROSPERO (CRD42022377431).

Vegetation growth responses to climate change: A cross-scale analysis of biological memory and time lags using tree ring and satellite data.

Vegetation growth is affected by past growth rates and climate variability. However, the impacts of vegetation growth carryover (VGC; biotic) and lagged climatic effects (LCE; abiotic) on tree stem radial growth may be decoupled from photosynthetic capacity, as higher photosynthesis does not always translate into greater growth. To assess the interaction of tree-species level VGC and LCE with ecosystem-scale photosynthetic processes, we utilized tree-ring width (TRW) data for three tree species: Castanopsis eyrei (CE), Castanea henryi (CH, Chinese chinquapin), and Liquidambar formosana (LF, Chinese sweet gum), along with satellite-based data on canopy greenness (EVI, enhanced vegetation index), leaf area index (LAI), and gross primary productivity (GPP). We used vector autoregressive models, impulse response functions, and forecast error variance decomposition to analyze the duration, intensity, and drivers of VGC and of LCE response to precipitation, temperature, and sunshine duration. The results showed that at the tree-species level, VGC in TRW was strongest in the first year, with an average 77% reduction in response intensity by the fourth year. VGC and LCE exhibited species-specific patterns; compared to CE and CH (diffuse-porous species), LF (ring-porous species) exhibited stronger VGC but weaker LCE. For photosynthetic capacity at the ecosystem scale (EVI, LAI, and GPP), VGC and LCE occurred within 96 days. Our study demonstrates that VGC effects play a dominant role in vegetation function and productivity, and that vegetation responses to previous growth states are decoupled from climatic variability. Additionally, we discovered the possibility for tree-ring growth to be decoupled from canopy condition. Investigating VGC and LCE of multiple indicators of vegetation growth at multiple scales has the potential to improve the accuracy of terrestrial global change models.

Impacts of systemic treatments on health-related quality of life for patients with metastatic colorectal cancer: a systematic review and network meta-analysis.

OBJECTIVE: There is limited evidence of comparative results among different treatments regarding impacts of Health-Related Quality of Life (HRQoL) for patients with metastatic colorectal cancer (mCRC). We aimed to compare efficacy of systemic treatments on HRQoL among patients with mCRC. METHODS: We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase 2 or 3 trials that evaluated at least two therapeutic regimens were included. Primary outcomes were short-term and long-term mean changes in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) scores. Secondary outcome was mean change in EQ-5D health utility scores. Mean differences (MDs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on whether patients received systemic treatments before. We conducted various sensitivity analyses, including differentiating between chemotherapy types, and analyzed patient cohorts with non-specified gene expression levels as well as those with target KRAS expression statuses. The current systematic review protocol was registered on PROSPERO (CRD42023453315 and CRD42023420498). RESULTS: Immunotherapy and targeted therapy significantly improved HRQoL over chemotherapy, with MDs of 9.27 (95% CI: 3.96 to 14.6) and 4.04 (95% CI: 0.11 to 7.94), respectively. Monotherapy significantly outperformed both combination therapy (MD 5.71, 95%CI 0.78 to 10.63) and no active treatment (MD 3.7, 95%CI 1.41 to 6.01) regarding GHS/QoL in the short-term. Combining targeted therapy with chemotherapy did not improve HRQoL. Focusing on HRQoL, cetuximab excelled when gene expression baselines were unspecified. Subgroup and sensitivity analyses upheld these robust findings, unaffected by model or patient baseline characteristics. Evidence from clinical trials without specific gene level data suggested that monotherapies, especially targeted therapies such as cetuximab, demonstrated superiority in HRQoL. For KRAS wild-type patients, no significant HRQoL differences emerged between chemotherapy, targeted therapy, or their combination.. CONCLUSIONS: Targeted therapies and immunotherapy demonstrate superior HRQoL benefits, monotherapy such as cetuximab is associated with significant improvements as compared to combination therapy. However, tailoring these results to individual gene expression profiles requires more evidence.

Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). METHODS: The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed. RESULTS: A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs. CONCLUSIONS: Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.

Economic evaluation of NALIRIFOX vs. nab-paclitaxel and gemcitabine regimens for first-line treatment of metastatic pancreatic ductal adenocarcinoma from U.S. perspective.

BACKGROUND: The cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers. METHODS: A partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model's robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold. RESULTS: In the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction). CONCLUSIONS: NALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Is it time for China to prioritize pan-genotypic regimens for treating patients with hepatitis C?

INTRODUCTION: The treatment of hepatitis C has entered the pan-genotypic era, but the effectiveness is not good for the genotype 3b patients who have a large proportion in China. The guidelines for hepatitis C recommend the use of gene-specific regimens when the regional 3b prevalence rate greater than 5%. This study is to explore rationality of this proportion and the cost-effectiveness to implement pan-genotypic regimens in China. METHODS: A decision Markov model was developed from the health system perspective to evaluate the effectiveness and cost-effectiveness between pan-genotypic and gene-specific treatment regimens for hepatitis C patients. Additionally, we set a regional genotype 3b patient proportion of 0-100% to explore at which proportion it is necessary to perform genotype identification and typing therapy on patients. Model parameters were derived from published literature and public databases. Effectiveness was measured by cured patient numbers, newly diagnosed cases of decompensated cirrhosis, hepatocellular carcinoma, need for liver transplantation, and quality-adjusted life years (QALYs). Cost-effectiveness outcomes included costs and the incremental cost-effectiveness ratio (ICER). The 1-3 times 2022 Chinese per capita gross domestic product was used as the willingness-to-pay threshold. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. RESULTS: Compared with gene-specific regimens, pan-genotypic regimens resulted in an additional 0.13 QALYs and an incremental cost of $165, the ICER was $1,268/QALY. From the view of efficacy, the pan-genotypic regimens cured 5,868 more people per 100,000 patients than gene-specific regimens, avoiding 86.5% of DC cases, 64.6% of HCC cases, and 78.2% of liver transplant needs. Identifying 3b patients before treatment was definitely cost-effectiveness when their prevalence was 12% or higher. The results remained robust in sensitivity analyses. CONCLUSIONS: In China, the prioritized recommendation of pan-genotypic therapeutics proves to be both cost-effective and efficacious. But, in regions where the prevalence of genotype 3b exceeds 12%, it is necessary to identify them to provision of more suitable therapies.

QALY-type preference and willingness-to-pay among end-of-life patients with cancer treatments: a pilot study using discrete choice experiment.

PURPOSE: Quality-adjusted life-year (QALY) is a dominant measurement of health gain in economic evaluations for pricing drugs. However, end-of-life (EoL) patients' preference for QALY gains in life expectancy (LE) and quality of life (QoL) during different disease stages remains unknown and is seldom involved in decision-making. This study aims to measure preferences and willingness-to-pay (WTP) towards different types of QALY gain among EoL cancer patients. METHODS: We attributed QALY gain to four types, gain in LE and QoL, respectively, and during both progression-free survival (PFS) and post-progression survival (PPS). A discrete choice experiment including five attributes (the four QALY attributes and one cost attribute) with three levels each was developed and conducted with 85 Chinese advanced non-small cell lung cancer patients in 2022. All levels were set with QALY gain/cost synthesised from research on anti-lung cancer drugs recently listed by Chinese National Healthcare Security Administration. Each respondent answered six choice tasks in a face-to-face interview. The data were analysed using mixed logit models. RESULTS: Patients valued LE-related QALY gain in PFS most, with a relative importance of 81.8% and a WTP of $43,160 [95% CI 26,751 ~ 59,569] per QALY gain. Respondents consistently preferred LE-related to QoL-related QALY gain regardless of disease stage. Patients with higher income or lower education levels tended to pay more for QoL-related QALY gain. CONCLUSION: Our findings suggest a prioritised resource allocation to EoL-prolonging health technologies. Given the small sample size and large individual heterogeneity, a full-scale study is needed to provide more robust results.

Effect of phenylephrine rescue injection on hypotension after spinal anaesthesia for caesarean delivery when guided by both heart rate and SBP during an early warning window: A randomised controlled trial.

BACKGROUND: Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension. OBJECTIVE: To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability. SETTING: A teaching hospital. DESIGN: A randomised controlled trial. PATIENTS: One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study. INTERVENTIONS: All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion. MAIN OUTCOME MEASURES: The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events. RESULTS: The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P  = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ±â€Š9.49 vs. 86.7 ±â€Š11.16 mmHg, P   =  0.004). There was no significant difference in the incidence of hypertension between groups. CONCLUSION: After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension. TRIAL REGISTRATION: Chictr.org.cn; Identifier: ChiCTR 2100041812.

Breaking the poverty trap in an ecologically fragile region through ecological engineering: A close-up look at long-term changes in ecosystem services.

Ecological vulnerability and poverty are interrelated and must be addressed together. The resolution of this issue will help us to meet the challenges during the process of implementing concrete actions for realizing the 2030 UN sustainable development goals (SDGs). Ecological restoration projects (ERPs) can enhance ecosystem services (ESs) while providing policy support for improving people's livelihoods. However, processes and mechanisms of ERPs on the ecological environment and socioeconomic development in poverty-stricken and ecologically fragile areas have rarely been studied. To address these issues, we conducted a comparative analysis on the changes of land use and land cover (LULC), ecosystem services (ESs), and socioeconomic development in Bijie City, a karst rocky desertification area in southwest China, before and after the implementation of ERPs in 2000, as well as the complex relationship between these factors. ERPs have affected LULCs, ESs, socioeconomics, and poverty reduction significantly since 2000. Specifically, the total ecosystem service value (ESV) in the study area has increased by more than 3 times in the past 30 years, with the ESV of tourism services and carbon storage increasing the most, from CNY 0.001 and 337.07 billion in 1990 to CNY 11.07 and 108.97 billion in 2019, respectively. The correlation between ESs is mainly synergistic, while the tradeoff between carbon storage and water yield is in a fluctuating upward trend. LULC conversion of cropland to green, and cropland to water, wetland and shrubs has positive effects on carbon storage and water yield, respectively. During study period, GDP, urbanization increased by over 70 times, 5 times, respectively, whereas poverty population, poverty incidence, and employment rate of various sectors (i.e., agriculture, forest, animal, and fishery, or AFAF) decreased by 96.4%, 97.7%, and 18.24%, respectively. Our findings emphasized that ERPs can effectively help poor and ecologically fragile areas to get out of the poverty trap and achieve the "win-win" goals of ecological and socio-economic sustainable development. These results have profound environmental management references to China and other developing countries around the world in realizing ecological restoration, poverty reduction, and the SDGs.

Estimating the cost-effectiveness threshold of advanced non-small cell lung cancer in China using mean opportunity cost and contingent valuation method.

OBJECTIVES: Monetizing health has sparked controversy and has implications for pricing strategies of emerging health technologies. Medical insurance payers typically set up thresholds for quality-adjusted life years (QALY) gains based on health productivity and budget affordability, but they rarely consider patient willingness-to-pay (WTP). Our study aims to compare Chinese payer threshold and patient WTP toward QALY gain of advanced non-small cell lung cancer (NSCLC) and to inform a potential inclusion of patient WTP under more complex decision-making scenarios. METHODS: A regression model was constructed with cost as the independent variable and QALY as the dependent variable, where the regression coefficients reflect mean opportunity cost, and by transforming these coefficients, the payer threshold can be obtained. Patient WTP was elicited through a contingent valuation method survey. The robustness of the findings was examined through sensitivity analyses of model parameters and patient heterogeneity. RESULTS: The payer mean threshold in the base-case was estimated at 150,962 yuan (1.86 times per capita GDP, 95% CI 144,041-159,204). The two scenarios analysis generated by different utility inputs yielded thresholds of 112,324 yuan (1.39 times per capita GDP) and 111,824 yuan (1.38 times per capita GDP), respectively. The survey included 85 patients, with a mean WTP of 148,443 yuan (1.83 times per capita GDP, 95% CI 120,994-175,893) and median value was 106,667 yuan (1.32 times the GDP per capita). Due to the substantial degree of dispersion, the median was more representative. The payer threshold was found to have a high probability (98.5%) of falling within the range of 1-2 times per capita GDP, while the robustness of patient WTP was relatively weak. CONCLUSIONS: In China, a country with a copayment system, payer threshold was higher than patient WTP, indicating that medical insurance holds significant decision-making authority, thus temporarily negating the need to consider patient WTP.

Preventing Spinal Hypotension During Cesarean Birth With Two Initial Boluses of Norepinephrine in Chinese Parturients: A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: Norepinephrine is effective in preventing spinal hypotension during cesarean birth; however, an optimal regimen has not been determined. We hypothesized that an initial bolus of norepinephrine improves efficacy of spinal hypotension prophylaxis beyond continuous norepinephrine alone. METHODS: In this double-blind, controlled study, 120 patients scheduled for cesarean birth under spinal anesthesia were randomly allocated to receive a norepinephrine bolus at 0.05 or 0.10 µg/kg, followed by norepinephrine infusion at a rate of 0.05 µg·kg -1 ·min -1 . The primary outcome was the frequency of spinal hypotension during cesarean birth. The doses of the rescue drug (phenylephrine), frequency of nausea or vomiting, duration of hypotension, frequency of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were also compared. RESULTS: One-hundred-fifteen patients were included in the analysis. Compared with the 0.05 µg/kg group, the frequency of spinal hypotension was lower in the 0.10 µg/kg group (20.7% vs 45.6%; odds ratio [OR], 0.31; 95% confidence interval (CI), 0.14-0.71; P = .004). Fewer rescue doses of phenylephrine (0 [0,0] vs 0 [0,80]; 95% CI for the difference, 0 (0-0); P = .006) were required, and the frequency of nausea or vomiting was lower (5.2% vs 17.5%; OR, 0.26; 95% CI, 0.07-0.99; P = .04) in the 0.10 µg/kg group. The duration of hypotension was shorter in the 0.10 µg/kg group than that in the 0.05 µg/kg group (0 [0,0] vs 0 [0,2]; 95% CI for the difference, 0 [0-0]; P = .006). The incidence of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were comparable between the 2 groups. CONCLUSIONS: With a fixed-rate norepinephrine infusion of 0.05 µg·kg -1 ·min -1 , the 0.10 µg/kg initial bolus was more effective in reducing the incidence of spinal hypotension compared with the 0.05 µg/kg initial bolus.

Cost-effectiveness and potential budget impact of non-pharmacological interventions for early management in prehypertensive people: an economic evaluation for China.

BACKGROUND: Non-pharmacological interventions (NPIs) could be considered in the early management of prehypertensive population. This study aimed to evaluate the potential cost-effectiveness of NPIs and the budget impact of implementing NPIs on prehypertensive population in China and provide evidence of chronic disease management innovation for decision-makers. METHODS: Five NPIs including usual care, lifestyle, strengthen exercise, relaxation, and diet therapy were selected based on the practice of hypertension management in China. A nine-state Markov model was constructed to evaluate the lifetime costs and health outcomes of five NPIs and a non-intervention group from the perspective of Chinese healthcare system. The effectiveness of NPIs was obtained from a published study. Parameters including transition probabilities, costs and utilities were extracted or calculated from published literature and open-access databases. Sensitivity analyses were conducted to test the uncertainty of all parameters. The impact of duration of intervention was considered in scenario analyses. A budget impact analysis (BIA) was conducted to evaluate the total cost and the medical cost saving of a hypothetical nationwide implementation of potential cost-effective NPI in prehypertensive people. Management strategies including focusing on patients with specific ages or different CVE risk levels, and different duration of implementation were taken into consideration. RESULTS: Strengthen exercise was the most cost-effective intervention with a probability of 78.1% under the given WTP threshold. Our results were sensitive to the cost of interventions, and the utility of prehypertension and hypertension. The duration of implementation had limited impact on the results. BIA results showed that the program cost was hefty and far more than the medical cost saving with the course of simulation time. Applying management strategies which focused on individual characteristics could largely reduce the program cost despite it remained higher than medical cost saving. CONCLUSIONS: Strengthen exercise was a potential NPI that can be considered in priority for early management in prehypertensive population. Although early management can acquire medical cost saving, the related program cost can be quite hefty. Precise strategies which may help reduce the cost of early management should be taken into consideration in program design.

Point-of-care detection of sevoflurane anesthetics in exhaled breath using a miniature TOFMS for diagnosis of postoperative agitation symptoms in children.

In the operation using sevoflurane as an anesthetic, some patients, especially children, will have agitation symptoms after awakening from anesthesia. The incidence of agitation is about 20%, and current detection methods cannot predict the probability of a patient with agitation. In this paper, a magnetic field enhanced photoelectron ionization (MEPEI) miniature time-of-flight mass spectrometer (TOFMS) was developed for point-of-care detection and verification of the relationship between postoperative agitation symptoms and sevoflurane concentration in exhaled breath. The MEPEI source is water vapor resistant and can directly ionize sevoflurane via capillary sampling and obtain its characteristic ion [C4H3F6O]+ (m/z 181), and the analysis time of exhaled breath is only 60 s. Three standard curves of 0.5-80 ppmv, 80-2000 ppmv and 2000-15 000 ppmv were formulated to quantitatively detect sevoflurane in different scenarios, the coefficient of determination (R2) was higher than 0.9882 and the relative standard deviation (RSD) of signal intensity was only 1.24%. The results indicated that four of the 46 child patients had agitation symptoms. Partial least squares-discriminant analysis (PLS-DA) was performed to analyze the data, and an identification and treatment strategy was established for child patients with agitation symptoms. The new miniature MEPEI-TOFMS was also successfully used to evaluate the concentration of sevoflurane in a medical environment. The real-time monitoring of sevoflurane concentration in exhalation indicates the potential of this method for low-cost and convenient point-of-care (POC) detection and diagnosis of agitation symptoms.

Treatment patterns in patients with metastatic non-small-cell lung cancer in the era of immunotherapy.

Background: Chemotherapy (CT) alone was previously standard first-line (1L) therapy for metastatic non-small-cell lung cancer (NSCLC) but alternative treatments, including immunotherapy (I-O), are now available. Patients & methods: In this retrospective study, adults with stage IV NSCLC who initiated 1L treatment between 1 August 2018 and 31 December 2019 and had ≥2 visits were identified in the Flatiron database. Patients were followed up until 30 June 2020. Baseline characteristics and treatment patterns were described by treatment group: CT, I-O + CT, I-O monotherapy and other. Results: Approximately 20% of patients received 1L CT in the 2018-2019 timeframe studied; these patients tended to have squamous histology and low (≤49%) programmed death ligand-1 expression. Conclusion: A proportion of patients with metastatic NSCLC still receive 1L CT despite the availability and widespread use of I-O therapies.

Inequality in health service utilization among migrant and local children: a cross-sectional survey of children aged 0-14 years in Shenzhen, China.

BACKGROUND: Shenzhen is characterized with the largest scale of migrant children among all the cities in China. Unequal access to health services among migrant and local children greatly affects health equity and has a profound impact on the quality of human capital. This study aimed to investigate differences in using community-based healthcare between local and migrant children and to identify the influencing factors in Futian District of Shenzhen. METHODS: Households in 12 communities in Futian District of Shenzhen were randomly sampled. Children aged 0-14 years were investigated using self-administered questionnaire - the 2018 Survey of Health Service Needs of Chinese Residents. Differences in healthcare including physical examination, feeding guidance, development guidance, disease prevention guidance, injury prevention guidance, oral health guidance, and mental health guidance, were tested between local and migrant children. Binary logistic regressions were used in identifying potential influencing factors which affected the use in the above healthcare items. RESULTS: A total of 936 participants from1512 families were sampled and 508 of them were included. Compared with local children, migrant children had less use of development guidance (OR = 0.417, 95% CI: 0.279-0.624) and oral health care guidance (OR = 0.557, 95% CI: 0.381-0.813). Children whose father received higher education level enjoyed a better use of disease prevention guidance as compared to whose father stopped at junior high school education or below (senior high vs junior high and below, OR = 1.286, 95% CI: 0.791-2.090; bachelor and above vs junior high and below, OR = 2.257, 95% CI: 1.417-3.595). Children whose fathers were blue-collar workers had less use of injury prevention guidance (OR = 0.750, 95% CI: 0.334-1.684) and mental health guidance (OR = 0.784, 95% CI: 0.295-2.080) as compared to whose father were white collar workers. CONCLUSIONS: Except feeding guidance, healthcare utilization were lower among migrant children than among local children. Generally, fathers have a stronger influence on children's use of community-based healthcare than mothers do. The potential influence of fathers in promoting children's healthcare use behaviors should be carefully considered, and fathers' attention to children's health should be increased.

Safety of intraoperative hypothermia for patients: meta-analyses of randomized controlled trials and observational studies.

BACKGROUND: Previous studies have shown that intraoperative hypothermia was associated with higher risks of clinical adverse events, but we found otherwise from recent evidences. This study aims to synthesize the existing evidence evaluating safety of intraoperative hypothermia. METHODS: Articles, reviews, ongoing trials and grey literatures were retrieved from PubMed, The Cochrane Library, Clinical Trails and CNKI (a Chinese national database) till February 2nd, 2019. Both randomized controlled trials and observational studies compared incidences of all sorts of intra- and post-operative consequences between hypothermia and normothermia were included. Researches comparing different warming systems were excluded. We also examined risks of hypothermia using lowered standards (35.5 °C and 35 °C) from a Chinese trial (ChiCTR-IPR-17011099). RESULTS: A total of 9 RCT studies and 11 observational studies were included. RCT-synthesized results showed that intraoperative hypothermia was associated with higher risks of bleeding (MD = 131.90, 95%CI: 117.42, 146.38), surgical site infection (RD = 0.14, 95%CI: 0.06, 0.21) and shivering (RD = 0.32, 95%CI: 0.06, 0.58) but with no significant differences in duration of surgery, hospital stay or mortality. Observational study-synthesized evidences showed that intraoperative hypothermia did not result in higher risks in any of these adverse events. Results didn't change even if the standard of hypothermia was lowered by 0.5-1.0 °C. CONCLUSIONS: The study indicates that the synthesized risks resulted by intra-operative hypothermia might be overestimated and the eligibility of 36 °C to define hypothermia is not sensitive enough. Given body-temperature protection has not been popularized in China, it is still critical to normalize the hypothermia prevention at this stage.

Per-Prescription Drug Expenditure by Source of Payment and Income Level in the United States, 1997 to 2015.

OBJECTIVES: To evaluate expenditures and sources of payment for prescription drugs in the United States from 1997 to 2015. METHODS: The Medical Expenditures Panel Survey (MEPS) was used for this analysis. Individuals with one or more prescription medicines were eligible for inclusion. Outcomes were the inflation-adjusted cost per prescription across all payment sources (self or family, public, private, and other sources) before and after the Medicare Part D benefit and the Affordable Care Act. RESULTS: The cost per prescription increased from $38.56 in 1997 to $73.34 in 2015. Nevertheless, consumers' out-of-pocket expenditures decreased from $18.19 to $9.61, whereas public program expenditures per prescription increased from $5.61 to $34.43 over this time. Out-of-pocket expenditures of individuals in the low-income group and near-poor group had larger declined percentages from 51.4% to 20.4% and 46.5% to 17.2% relative to individuals in higher-income groups before and after implementation of the Medicare Part D, respectively. Over 90% prescription purchases were covered by medical insurance by 2015. The per-prescription cost for medications consumed by uninsured individuals increased at a lower rate from $31.83 to $54.96 versus $40.12 to $75.58 for privately insured and $36.00 to $70.96 for publicly insured (P < .001). CONCLUSIONS: Prescription drugs expenditures have increased over the past 2 decades, but public sources now pay for a growing proportion of prescription drugs cost regardless of health insurance coverage or income level. Out-of-pocket expenditures have significantly decreased for persons with lower incomes since the implementation of Medicare Part D and the Affordable Care Act.

Nasotracheal intubation-extubation-intubation and asleep-awake-asleep anesthesia technique for deep brain stimulation.

BACKGROUND: The asleep-awake-asleep (AAA) technique and laryngeal mask airway (LMA) is a common general anesthesia technique for deep brain stimulation (DBS) surgery. However, the LMA is not always the ideal artificial airway. In this report, we presented our experiences with nasotracheal intubation-extubation-intubation (IEI) and AAA techniques in DBS surgery for Parkinson's disease (PD) patients to meet the needs of surgery and ensure patients' safety and comfort. CASE PRESENTATION: Three PD patients scheduled for DBS surgery had to receive general anesthesia for various reasons. For the first asleep stage, general anesthesia and nasotracheal intubation was completed with routine methods. During the awake stage, we pulled the nasotracheal tube back right above the epiglottis under fiberoptic bronchoscope (FOB) guidance for microelectrode recording (MER), macrostimulation testing and verbal communication. Once monitoring is completed, we induced anesthesia with rapid sequence induction and utilized the FOB to advance the nasotracheal tube into the trachea again. To minimize airway irritations during the process, we sprayed the airway with lidocaine before any manipulation. The neurophysiologists completed neuromoinitroing successfully and all three patients were satisfied with the anesthesia provided at follow-up. CONCLUSION: Nasotracheal IEI and AAA anesthetic techniques should be considered as a viable option during DBS surgery.