Pancreatic cancer cells hijack tumor suppressive microRNA-26a to promote radioresistance and potentiate tumor repopulation.

Pancreatic cancer is one of the most lethal cancers with significant radioresistance and tumor repopulation after radiotherapy. As a type of short non-coding RNA that regulate various biological and pathological processes, miRNAs might play vital role in radioresistance. We found by miRNA sequencing that microRNA-26a (miR-26a) was upregulated in pancreatic cancer cells after radiation, and returned to normal state after a certain time. miR-26a was defined as a tumor suppressive miRNA by conventional tumor biology experiments. However, transient upregulation of miR-26a after radiation significantly promoted radioresistance, while stable overexpression inhibited radioresistance, highlighting the importance of molecular dynamic changes after treatment. Mechanically, transient upregulation of miR-26a promoted cell cycle arrest and DNA damage repair to promote radioresistance. Further experiments confirmed HMGA2 as the direct functional target, which is an oncogene but enhances radiosensitivity. Moreover, PTGS2 was also the target of miR-26a, which might potentiate tumor repopulation via delaying the synthesis of PGE2. Overall, this study revealed that transient upregulation of miR-26a after radiation promoted radioresistance and potentiated tumor repopulation, highlighting the importance of dynamic changes of molecules upon radiotherapy.

Smoking-Attributable Health Care Expenditures for US Adults With Chronic Lower Respiratory Disease.

Importance: Cigarette smoking is a primary risk factor for chronic lower respiratory disease (CLRD) and is associated with worse symptoms among people with CLRD. It is important to evaluate the economic outcomes of smoking in this population. Objective: To estimate smoking prevalence and cigarette smoking-attributable health care expenditures (SAHEs) for adults with CLRD in the US. Design, Setting, and Participants: This cross-sectional study used data from the 2014-2018 and 2020 National Health Interview Surveys (NHIS) and the 2020 Medical Expenditure Panel Survey. The final study population, stratified by age 35 to 64 years and 65 years or older, was extracted from the 2014-2018 NHIS data. The data analysis was performed between February 1 and March 31, 2024. Exposures: Cigarette smoking, as classified into 4 categories: current smokers, former smokers who quit less than 15 years ago, former smokers who quit 15 or more years ago, and never smokers. Main Outcomes and Measures: Smoking-attributable health care expenditures were assessed using a prevalence-based annual cost approach. Econometric models for the association between cigarette smoking and health care utilization were estimated for 4 types of health care services: inpatient care, emergency department visits, physician visits, and home health visits. Results: In the 2014-2018 NHIS study sample of 13 017 adults, 7400 (weighted 62.4%) were aged 35 to 64 years, 5617 (weighted 37.6%) were 65 years or older, and 8239 (weighted 61.9%) were female. In 2020, among 11 211 222 adults aged 35 to 64 with CLRD, 3 508 504 (31.3%) were current smokers and 3 496 790 (31.2%) were former smokers. Total SAHEs in 2020 for this age group were $13.6 billion, averaging $2752 per current smoker and $1083 per former smoker. In 2020, 7 561 909 adults aged 65 years or older had CLRD, with 1 451 033 (19.2%) being current smokers and 4 104 904 (54.3%) being former smokers. Total SAHEs in 2020 for the older age group were $5.3 billion, averaging $1704 per current smoker and $682 per former smoker. In sum, SAHEs for adults with CLRD aged 35 years or older amounted to $18.9 billion in 2020. Conclusions and Relevance: In this cross-sectional study of adults with CLRD, cigarette smoking was associated with a substantial health care burden. The higher per-person SAHEs for current smokers compared with former smokers suggest potential cost savings of developing targeted smoking cessation interventions for this population.

Navigating an unpredictable environment: the moderating role of perceived environmental unpredictability in the effectiveness of ecological resource scarcity information on pro-environmental behavior.

BACKGROUND: The global issue of ecological resource scarcity, worsened by climate change, necessitates effective methods to promote resource conservation. One commonly used approach is presenting ecological resource scarcity information. However, the effectiveness of this method remains uncertain, particularly in an unpredictable world. This research aims to examine the role of perceived environmental unpredictability in moderating the impact of ecological resource scarcity information on pro-environmental behavior (PEB). METHODS: We conducted three studies to test our hypothesis on moderation. Study 1 (N = 256) measured perceived general environmental unpredictability, perceived resource scarcity and daily PEB frequencies in a cross-sectional survey. Study 2 (N = 107) took it a step further by manipulating resource scarcity. Importantly, to increase ecological validity, Study 3 (N = 135) manipulated the information on both ecological resource scarcity and nature-related environmental unpredictability, and measured real water and paper consumption using a newly developed washing-hands paradigm. RESULTS: In Study 1, we discovered that perceived resource scarcity positively predicted PEB, but only when individuals perceive the environment as less unpredictable (interaction effect: 95% CI = [-0.09, -0.01], ΔR2 = 0.018). Furthermore, by manipulating scarcity information, Study 2 revealed that only for individuals with lower levels of environmental unpredictability presenting ecological resource scarcity information could decrease forest resource consumption intention (interaction effect: 95%CI = [-0.025, -0.031], ΔR2 = .04). Moreover, Study 3 found that the negative effect of water resource scarcity information on actual water and (interaction effect: 95%CI = [3.037, 22.097], ηp2 = .050) paper saving behaviors (interaction effect: 95%CI = [0.021, 0.275], ηp2 = .040), as well as hypothetical forest resource consumption (interaction effect: 95%CI = [-0.053, 0.849], ηp2 = .023) emerged only for people who receiving weaker environmental unpredictability information. CONCLUSION: Across three studies, we provide evidence to support the moderation hypothesis that environmental unpredictability weakens the positive effect of ecological resource scarcity information on PEB, offering important theoretical and practical implications on the optimal use of resource scarcity to enhance PEB.

Association between tobacco product use and respiratory health and asthma-related interference with activities among U.S. Adolescents.

Tobacco use adversely affects long-term respiratory health. We examined the relationship between sole and dual tobacco product use and both respiratory health and respiratory-related quality of life during adolescence in the U.S. Using adolescent data (baseline age 12-17) from Waves 4.5 (data collected from December 2017-December 2018) and 5 (data collected from December 2018-November 2019) of the Population Assessment of Tobacco and Health Study, we examined the associations between combustible (i.e., cigarette or cigar), vaped, and dual (i.e., both cigar/cigarette and e-cigarette) tobacco/nicotine use at baseline and two respiratory symptoms (all adolescents, n = 11,748) and new asthma diagnosis (adolescents with no baseline diagnosis, n = 9,422) at follow-up. Among adolescents with asthma (Wave 5, n = 2,421), we estimated the association between current tobacco use and the extent to which asthma interfered with daily activities. At follow-up, 12.3 % of adolescents reported past 12-month wheezing/whistling, 17.4 % reported past 12-month dry cough, and 1.9 % reported newly diagnosed asthma. Baseline current cigarette/cigar smoking was associated with subsequent wheezing/whistling and baseline report of another tobacco product use pattern was associated with subsequent asthma diagnosis. Among adolescents with asthma, 5.7 % reported it interfering with activities some of the time and 3.1 % reported interference most/all of the time in the past 30 days. Past 30-day sole cigarette/cigar smoking and dual use was positively associated with asthma-related interference with activities compared to never tobacco use and sole e-cigarette use. Combustible and dual tobacco use pose direct risk to respiratory health and indirect risk to quality of life through respiratory health.

Lenvatinib plus pembrolizumab in the patients with advanced previously treated endometrial cancer: A cost-effectiveness analysis in the United States and in China.

PURPOSE: To investigate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) compared to chemotherapy as a second-line treatment for advanced endometrial cancer (EC) from the United States and Chinese payers' perspective. METHODS: In this economic evaluation, a partitioned survival model was constructed from the perspective of the United States and Chinese payers. The survival data were derived from the clinical trial (309-KEYNOTE-775), while costs and utility values were sourced from databases and published literature. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were estimated. The robustness of the model was evaluated through sensitivity analyses, and price adjustment scenario analyses was also performed. RESULTS: Base-case analysis indicated that LP wouldn't be cost-effective in the United States at the WTP threshold of $200 000, with improved effectiveness of 0.75 QALYs and an additional cost of $398596.81 (ICER $531392.20). While LP was cost-effective in China, with improved effectiveness of 0.75 QALYs and an increased overall cost of $62270.44 (ICER $83016.29). Sensitivity analyses revealed that the above results were stable. The scenario analyses results indicated that LP was cost-effective in the United States when the prices of lenvatinib and pembrolizumab were simultaneously reduced by 61.95% ($26.5361/mg for lenvatinib and $19.1532/mg for pembrolizumab). CONCLUSION: LP isn't cost-effective in the patients with advanced previously treated endometrial cancer in the United States, whereas it is cost-effective in China. The evidence-based pricing strategy provided by this study could benefit decision-makers in making optimal decisions and clinicians in general clinical practice. More evidence about budget impact and affordability for patients is needed.

Factors Associated with Smoking Cessation and the Receipt of Cessation Services in a Public, Safety-Net Primary Care System.

BACKGROUND: Prevalence of smoking is high among patients receiving care in safety-net settings, and there is a need to better understand patient factors associated with smoking cessation and receipt of cessation services. OBJECTIVE: To identify patient factors associated with smoking cessation attempts and receipt of cessation counseling and pharmacotherapy in a large safety-net health system. DESIGN: We conducted a retrospective cohort analysis using EHR data in a safety-net system in San Francisco, CA. PARTICIPANTS: We included 7384 adult current smokers who had at least three unique primary care encounters with documented smoking status between August 2019 and April 2022. MAIN MEASURES: We assessed four outcomes using multivariate generalized estimating equation models: (1) any cessation attempt, indicating a transition in smoking status from "current smoker" to "former smoker"; (2) sustained cessation, defined as transition in smoking status from current smoker to former smokers for two or more consecutive visits; (3) receipt of smoking cessation counseling from healthcare providers; and (4) receipt of pharmacotherapy. KEY RESULTS: Of 7384 current adult smokers, 17.6% had made any cessation attempt, and of those 66.5% had sustained cessation. Most patients (81.1%) received counseling and 41.8% received pharmacotherapy. Factors associated with lower odds of any cessation attempt included being aged 45-64, non-Hispanic black, and experiencing homelessness. The factor associated with lower odds of sustained cessation was being male. Factors associated with lower odds of receiving counseling were being insured by Medicaid or being uninsured. Factors associated with lower odds of receiving pharmacotherapy included speaking languages other than English, being male, and identifying as racial and ethnic minorities. CONCLUSIONS: Health system interventions could close the gap in access to smoking cessation services for unhoused and racial/ethnic minority patients in safety-net settings, thereby increasing cessation among these populations.

A bifunctional anti-PCSK9 scFv/Exendin-4 fusion protein exhibits enhanced lipid-lowering effects via targeting multiple signaling pathways in HFD-fed mice.

Fusion protein which encompasses more than one functional component, has become one of the most important representatives of macromolecular drugs for disease treatment since that monotherapy itself might not be effective enough to eradicate the disease. In this study, we sought to construct a bifunctional antibody fusion protein by fusing anti-PCSK9 scFv with Exendin-4 for simultaneously lowering both LDL-C and TG. Firstly, three Ex4-anti-PCSK9 scFv fusion proteins were constructed by genetically connecting the C-terminal of Exendin-4 to the N-terminal of anti-PCSK9 scFv through various flexible linker peptides (G4S)n (n = 2, 3, 4). After soluble expression in E. coli, the most potent Ex4-(G4S)4-anti-PCSK9 scFv fusion protein was selected based on in vitro activity assays. Then, we investigated the in vivo therapeutic effects of Ex4-(G4S)4-anti-PCSK9 scFv on the serum lipid profile and bodyweight changes as well as underlying molecular mechanism in HFD-fed C57BL/6 mice. The data showed that Ex4-(G4S)4-anti-PCSK9 scFv exhibits enhanced effects of lowering both LDL-C and TG in serum, reducing food intake and body weight via blocking PCSK9/LDLR, activating AMPK/SREBP-1 pathways, and up-regulating sirt6. Conclusively, Ex4-(G4S)4-anti-PCSK9 has the potential to serve as a promising therapeutic agent for effectively treating dyslipidemia with high levels of both LDL-C and TG.

Cost-effectiveness analysis of an orphan drug tebentafusp in patients with metastatic uveal melanoma and a call for value-based pricing.

The normative regimens recommendations for treating metastatic uveal melanoma (mUM) are absent in the US. Recently, a phase III randomized clinical trial revealed that tebentafusp yielded a conspicuously longer overall survival than the control group. Based on the prominent efficacy, this study aimed to assess whether tebentafusp is cost-effective compared to the control group in patients with untreated mUM. A three-state partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) from the perspective of US payers. Scenario analyses and sensitivity analyses were conducted to explore the conclusion uncertainty. Compared with control group, tebentafusp therapy yielded an additional 0.47 QALYs (1.19 vs. 0.72 QALYs) and an incremental cost of $444 280 ($633 822 vs. $189 542). The resultant ICER of $953 230/QALY far outweighed the willingness-to-pay threshold of $200 000/QALY. The ICER was always more than $750 000/QALY in all the univariable and probabilistic sensitivity analyses. Scenario analyses indicated that reducing the unit price of tebentafusp to $33.768/µg was associated with a favorable result of tebentafusp being cost-effective. For treatment-naive patients with mUM, the cost of tebentafusp therapy was not worth the improvement in survival benefits at the current price compared to the investigator's choice of therapy. The cost-effectiveness of tebentafusp could be promoted using value-based pricing.

An anoikis-related gene signature predicts prognosis and reveals immune infiltration in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a global health burden with poor prognosis. Anoikis, a novel programmed cell death, has a close interaction with metastasis and progression of cancer. In this study, we aimed to construct a novel bioinformatics model for evaluating the prognosis of HCC based on anoikis-related gene signatures as well as exploring the potential mechanisms. Materials and methods: We downloaded the RNA expression profiles and clinical data of liver hepatocellular carcinoma from TCGA database, ICGC database and GEO database. DEG analysis was performed using TCGA and verified in the GEO database. The anoikis-related risk score was developed via univariate Cox regression, LASSO Cox regression and multivariate Cox regression, which was then used to categorize patients into high- and low-risk groups. Then GO and KEGG enrichment analyses were performed to investigate the function between the two groups. CIBERSORT was used for determining the fractions of 22 immune cell types, while the ssGSEA analyses was used to estimate the differential immune cell infiltrations and related pathways. The "pRRophetic" R package was applied to predict the sensitivity of administering chemotherapeutic and targeted drugs. Results: A total of 49 anoikis-related DEGs in HCC were detected and 3 genes (EZH2, KIF18A and NQO1) were selected out to build a prognostic model. Furthermore, GO and KEGG functional enrichment analyses indicated that the difference in overall survival between risk groups was closely related to cell cycle pathway. Notably, further analyses found the frequency of tumor mutations, immune infiltration level and expression of immune checkpoints were significantly different between the two risk groups, and the results of the immunotherapy cohort showed that patients in the high-risk group have a better immune response. Additionally, the high-risk group was found to have higher sensitivity to 5-fluorouracil, doxorubicin and gemcitabine. Conclusion: The novel signature of 3 anoikis-related genes (EZH2, KIF18A and NQO1) can predict the prognosis of patients with HCC, and provide a revealing insight into personalized treatments in HCC.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

STUDY QUESTION: Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? SUMMARY ANSWER: It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. WHAT IS KNOWN ALREADY: Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. STUDY DESIGN, SIZE, DURATION: Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). LIMITATIONS, REASONS FOR CAUTION: The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. WIDER IMPLICATIONS OF THE FINDINGS: When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The correlation between the costs and clinical benefits of PD-1/PD-L1 inhibitors in malignant tumors: An evaluation based on ASCO and ESMO frameworks.

Background: Life expectancy for patients with malignant tumors has been significantly improved since the presence of the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors in 2014, but they impose heavy financial burdens for patients, the healthcare system and the nations. The objective of this study was to determine the survival benefits, toxicities, and monetary of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors and quantify their values. Methods: Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors for malignant tumors were identified and clinical benefits were quantified by American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The drug price in Micromedex REDBOOK was used to estimate monthly incremental drug costs (IDCs) and the correlation between clinical benefits and incremental drug costs of experimental and control groups in each randomized controlled trial, and the agreement between two frameworks were calculated. Results: Up to December 2022, 52 randomized controlled trials were included in the quantitative synthesis. All the randomized controlled trials were evaluated by American society of clinical oncology value framework, and 26 (50%) met the American society of clinical oncology value framework "clinical meaningful value." 49 of 52 randomized controlled trials were graded by European society for medical oncology magnitude of clinical benefit scale, and 30 (61.2%) randomized controlled trials achieved European Society for Medical Oncology criteria of meaningful value. p-values of Spearman correlation analyses between monthly incremental drug costs and American society of clinical oncology value framework/European society for medical oncology magnitude of clinical benefit scale scores were 0.9695 and 0.3013, respectively. In addition, agreement between two framework thresholds was fair (κ = 0.417, p = 0.00354). Conclusion: This study suggests that there might be no correlation between the cost and clinical benefit of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors in malignancy, and the same results were observed in subgroups stratified by drug or indication. The results should be a wake-up call for oncologists, pharmaceutical enterprises and policymakers, and meanwhile advocate the refining of American Society of Clinical Oncology and European Society for Medical Oncology frameworks.

Racial and sociodemographic predictors of COVID-19 compared with influenza, appendicitis, and all-cause hospitalization: retrospective cohort analysis.

OBJECTIVE: To determine whether inequities in COVID-19 infection and hospitalization differ from those for common medical conditions: influenza, appendicitis, and all-cause hospitalization. DESIGN: Retrospective study based on electronic health records of three healthcare systems in San Francisco (university, public, and community) examining (1) racial/ethnic distribution in cases and hospitalization among patients with diagnosed COVID-19 (March-August 2020) and patients with diagnosed influenza, diagnosed appendicitis, or all-cause hospitalization (August 2017-March 2020), and (2) sociodemographic predictors of hospitalization among those with diagnosed COVID-19 and influenza. RESULTS: Patients 18 years or older with diagnosed COVID-19 (N = 3934), diagnosed influenza (N = 5932), diagnosed appendicitis (N = 1235), or all-cause hospitalization (N = 62,707) were included in the study. The age-adjusted racial/ethnic distribution of patients with diagnosed COVID-19 differed from that of patients with diagnosed influenza or appendicitis for all healthcare systems, as did hospitalization from these conditions compared to any cause. For example, in the public healthcare system, 68% of patients with diagnosed COVID-19 were Latine, compared with 43% of patients with diagnosed influenza, and 48% of patients with diagnosed appendicitis (p < 0.05). In multivariable logistic regressions, COVID-19 hospitalizations were associated with male sex, Asian and Pacific Islander race/ethnicity, Spanish language, and public insurance in the university healthcare system, and Latine race/ethnicity and obesity in the community healthcare system. Influenza hospitalizations were associated with Asian and Pacific Islander and other race/ethnicity in the university healthcare system, obesity in the community healthcare system, and Chinese language and public insurance in both the university and community healthcare systems. CONCLUSIONS: Racial/ethnic and sociodemographic inequities in diagnosed COVID-19 and hospitalization differed from those for diagnosed influenza and other medical conditions, with consistently higher odds among Latine and Spanish-speaking patients. This work highlights the need for disease-specific public health efforts in at-risk communities in addition to structural upstream interventions.

Association between e-cigarette use and food insecurity among low-income adults.

INTRODUCTION: Previous research quantifying the relationship between tobacco use and food insecurity has focused on cigarette smoking. E-cigarette use has become popular in recent years. Drawing on large, population-based survey data, this study augments the previous research, considering the association of e-cigarette use with food insecurity among low-income adults. METHODS: We analysed data from the California Health Interview Survey in 2014-2019. The study sample consisted of 25 948 respondents aged 18-64 who lived in low-income (<200% of the Federal Poverty Level) households. Multivariable logistic regression models were estimated to examine the associations of e-cigarette use as well as dual use of e-cigarettes and cigarettes with food insecurity. RESULTS: Of California low-income adults, 6.4% identified as current e-cigarette users (3.0% dual users of e-cigarettes and cigarettes, and 3.4% sole e-cigarette users) and 43.0% reported food insecurity. After controlling for confounding factors, food insecurity was significantly more likely to be reported among current e-cigarette users (adjusted OR (AOR)=1.67; 95% CI 1.25 to 2.23) compared with never e-cigarette users, and among dual users (AOR=2.21; 95% CI 1.63 to 3.00), current sole e-cigarette users (AOR=1.66; 95% CI 1.15 to 2.40), and current sole cigarette smokers (AOR=1.46; 95% CI 1.22 to 1.76) compared with never tobacco users. The odds of food insecurity among dual users were significantly greater than sole cigarette smokers but not statistically different from sole e-cigarette users. CONCLUSIONS: Using e-cigarette is an associated risk factor for food insecurity among low-income adults. Dual use of e-cigarettes and cigarettes has a significantly greater risk of food insecurity compared with smoking cigarettes alone.

Avelumab Maintenance Treatment After First-line Chemotherapy in Advanced Urothelial Carcinoma-A Cost-Effectiveness Analysis.

BACKGROUND: Recently, a clinical trial (NCT02603432) showed that avelumab maintenance treatment, post first-line chemotherapy, can significantly prolong the overall survival of patients with advanced urothelial carcinoma (UC), however, the treatment was very expensive. This study aimed to determine the cost-effectiveness of avelumab maintenance therapy in advanced or metastatic UC from the US taxpayer perspective. METHODS: Based on the data of the JAVELIN Bladder 100 clinical trial (NCT02603432), a Markov multi-state model was constructed to investigate the costs and clinical outcomes of avelumab maintenance after platinum-based chemotherapy versus best supportive care (BSC) for advanced or metastatic UC. Parameters of the model came from the 2020 Average Sales Price Drug Pricing Files and published literature. The main outputs were costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Robustness was tested by deterministic and probabilistic sensitivity analyses. The analysis was stratified to include both the overall population and a subset of programmed death-ligand 1 (PD-L1)-positive patients. RESULTS: Avelumab maintenance therapy was estimated to generate an additional 0.26 QALYs (1.46 vs. 1.20 QALYs) and costs $183,271 ($278,323 vs. $95,052) more compared to BSC alone in the overall population, yielding an ICER of $699,065/QALY. For the PD-L1-positive population, avelumab produced a 0.42 increase in QALYs (1.74 vs. 1.32 QALYs) and raised costs to $223,238 ($320,355 vs. $97,117), resulting in an ICER of $521,850/QALY for this population. Both ICERs were above the willingness-to-pay (WTP) threshold of $200,000/QALY. Sensitivity analyses manifested that the model was robust. CONCLUSION: From the perspective of the US taxpayer, avelumab maintenance therapy is considered cost-ineffective for patients with advanced or metastatic UC at a WTP threshold of $200,000/QALY in the overall population as well as in PD-L1-positive population.

Anticancer Benefit of Metformin in Patients With Early-Stage Pancreatic Cancer: A Retrospective Cohort Study.

Background: Epidemiologic studies have produced conflicting results on the effects of metformin on pancreatic cancer. This study aimed to observe and analyze whether metformin use is associated with better prognosis in pancreatic cancer. Materials and Methods: In this retrospective cohort study, all baseline data were retrieved from The Chinese Medicine Information Retrieval System (https://dc.wzhospital.cn/vpn/index.html) of The First Affiliated Hospital of Wenzhou Medical University. Survival data were collected by follow-up visits and medical records. Overall survival was the primary endpoint, while progression-free survival and disease-free survival were secondary endpoints. Progression or recurrence was assessed with radiologic images. Results: Seventy-six metformin users and 92 metformin nonusers diagnosed with pancreatic cancer from 2012 to 2020 in this hospital were enrolled. The adjusted hazard ratio for overall survival for metformin users was 0.50 (95% confidence interval = 0.33-0.76), where median overall survival was 16.0 months for metformin users versus 11.5 months for metformin nonusers. The protective effect was also found by analyzing progression-free survival (adjusted hazard ratio = 0.39, 95% confidence interval = 0.18-0.86) and disease-free survival (adjusted hazard ratio = 0.30, 95% confidence interval = 0.14-0.68). In the subgroup analysis, metformin use had a statistically significant association with prolongation of survival in stage I to II pancreatic cancer patients (hazard ratio = 0.47, 95% confidence interval = 0.25-0.91), but not for advanced tumor stage (hazard ratio for IV stage = 0.62, 95% confidence interval = 0.33-1.19), after adjustment for other risk factors. Conclusion: Metformin use is related to favorable survival outcomes of pancreatic cancer, especially in early tumor stage.

The Predictive Value of PD-L1 Expression Level in Evaluating the Cost-Effectiveness of Atezolizumab/Pembrolizumab.

Objective: Recently, the significant improvement of atezolizumab and pembrolizumab over chemotherapy for treatment-naïve stage IV non-small cell lung cancer (NSCLC) has been demonstrated, but the cost-effectiveness of these regimens remains unknown. Methods: A Markov model was adapted from the US healthcare perspective to assess the cost-effectiveness of atezolizumab, pembrolizumab, and chemotherapy in treatment-naïve NSCLC. Pseudo-individual patient data were generated from digitized Kaplan-Meier curves. Direct medical costs and utility values were sourced from the database and literature. Quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs) were computed. Sensitivity analyses and budgetary impact analyses were calculated. Results: In any and high programmed cell death 1-ligand 1 (PD-L1) expression populations, with chemotherapy, atezolizumab provided ICERs of $234,990 and $130,804 per QALY, while pembrolizumab yielded ICERs of $424,797 and $140,873 per QALY. The ICER of atezolizumab vs. pembrolizumab was $56,635 and $115,511.82 in any and high PD-L1 expression population, respectively. The critical drivers of ICERs included the cost of atezolizumab and pembrolizumab. The accumulated incremental budgetary impact of atezolizumab vs. chemotherapy increased to approximately $39.1 million in high PD-L1 expression patients over 5 years. Conclusions: In the high PD-L1 expression population, both atezolizumab and pembrolizumab were cost-effective for stage IV NSCLC compared to chemotherapy, which is contrary to that in any PD-L1 expression population. Atezolizumab shows a higher acceptability in both populations. Treating with immune checkpoint inhibitors (ICIs) has a substantial budgetary impact on the medical burden. The PD-L1 expression level has the potential to be a predictor for the economics of ICIs.

Differences in the detection rates of depression and anxiety among middle school students in different time periods / 中国学校卫生

Objective@#To investigates the prevalence of depression and anxiety among middle school students at different times, and to provide a reference for mental health promotion among adolescents.@*Methods@#A total of 1 505 middle school students, selected from Chongqing in 2021 by using multi stage stratified random sampling method, were surveyed by using the Center for Epidemiologic Studies Depression Scale(CSE-D) and Zung Self Rating Anxiety Scale (SAS).@*Results@#At the beginning of the semester, 434(27.6%) and 601 students( 38.2 %) reported depressive and anxiety symptoms,respectively. While at the end of the semester showed that 463 cases (30.8%) were prone to depression, and 653 cases ( 43.4 %) reported depressive and anxiety symptoms,respectively. The detection rate of depressive symptoms at the end of the semester was significantly higher than that at the beginning of semester. (43.4%, 38.2 %, χ 2=8.55, P <0.05). Depressive of female students at the end of the semester( 52.8 %) was higher than that at the beginning of the semester(46.3%)( χ 2=6.19, P <0.05) The detection rate of anxiety symptoms in senior high school students at the end of the semester(44.9%) was significantly higher than that of at the beginning of the semester(28.6%) ( χ 2= 43.33 , P <0.01). No significant difference in anxiety symptoms boys and junior high school students between the beginning and the end of the semester ( χ 2=2.34, 0.71, P >0.05).@*Conclusion@#Substantial changes are observed in anxiety symptoms among female middle school students and depressive and anxiety symptoms among high school students in different periods of a semester. When investigating depression and anxiety of middle school students, time effect should be considered.

Cost-effectiveness of adding daratumumab or bortezomib to lenalidomide plus dexamethasone for newly diagnosed multiple myeloma.

BACKGROUND: Multiple myeloma survival rates are steadily increasing due to availability of new drug classes used in combination with corticosteroids and chemotherapy. The latest treatments are daratumumab or bortezomib in combination therapy with lenalidomide and dexamethasone (Rd). Daratumumab, a CD38-targeted, human IgG1k monoclonal antibody, and bortezomib, a proteasome inhibitor, are both approved as regimens for transplant-ineligible relapsed/refractory multiple myeloma (RRMM). There have been cost-effectiveness analyses for daratumumab and bortezomib use in RRMM, but there are limited data regarding cost-effectiveness for daratumumab or bortezomib use in newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation. OBJECTIVE: To compare the cost-effectiveness of 3 separate regimens-(1) daratumumab, lenalidomide, and dexamethasone triple therapy (DRd); (2) bortezomib and lenalidomide plus dexamethasone triple therapy (VRd); and (3) lenalidomide plus dexamethasone (Rd)-in patients with multiple myeloma ineligible for autologous stem cell transplant. METHODS: A 2-state Markov model was developed using a US health system perspective and lifetime time horizon. Transition probabilities were calculated from the latest progression-free survival data reported in two phase 3 randomized controlled trials-MAIA and SWOG S0777-and extrapolated using a Weibull distribution based on the Hoyle Henley method. National data sources were used to obtain costs in 2019 US dollars, discounted by 3%. Health state utilities from available literature were applied to each health state. Utility decrements for adverse events were individualized in each choice branch with utility decrement weighted by the percentage of patients who experienced the adverse event in the MAIA and SWOG S0777 trials. We assumed a treatment would be cost-effective at a willingness to pay (WTP) of $150,000 per progression-free quality-adjusted life-year ($/PFQALY). One-way and probabilistic sensitivity analyses were conducted. RESULTS: Rd standard therapy had the lowest overall cost at $329,867, followed by VRd at $385,434 and DRd with the highest overall total cost at $626,900. Rd was estimated to result in the least amount (1.24) of PFQALYs, followed by VRd at 1.35 PFQALYs and DRd at 1.52 PFQALYs. With a WTP threshold of $150,000 per PFQALY, VRd was not cost-effective compared with Rd standard therapy, with an incremental cost-effectiveness ratio (ICER) of $530,256 per PFQALY. DRd was not cost-effective compared with VRd (ICER = $1,396,318 per PFQALY), nor as compared with Rd standard therapy (ICER = $1060,832). One-way sensitivity analysis showed that our model was sensitive to cost of DRd, VRd, and Rd drugs. Probabilistic sensitivity analysis showed that only at a WTP threshold of $550,000 was VRd cost-effective for 40% of iterations. There were no reasonable WTP thresholds, up to $800,00, where DRd became more cost-effective than VRd. CONCLUSIONS: This study is the first analysis to directly compare the cost-effectiveness of 3 acceptable chemotherapy treatment regimens for patients with multiple myeloma ineligible for autologous stem cell transplant. Neither DRd nor VRd triple therapy were found to be cost-effective vs Rd. Further cost-effectiveness analyses that include overall survival data for daratumumab and bortezomib triple therapies are needed to demonstrate an ICER in QALYs. DISCLOSURES: No funding was received for this study. At the time of this study, Narsipur was a UCSF-Actelion Clinical Research and Medical Communications Fellow, unrelated to this study. The other authors have nothing to disclose.

Genomic Instability-Related LncRNA Signature Predicts the Prognosis and Highlights LINC01614 Is a Tumor Microenvironment-Related Oncogenic lncRNA of Papillary Thyroid Carcinoma.

BACKGROUND: Genomic instability (GI) is among the top ten characteristics of malignancy. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in GI. So far, the clinical value of GI-related lncRNAs (GIlncs) in papillary thyroid cancer (PTC) has not been clarified. METHODS: Integrative analysis of lncRNA expression and somatic mutation profiles was performed to identify GIlncs. Analysis of differentially expressed lncRNAs in the group with high- and low- cumulative number of somatic mutations revealed significant GIlncs in PTC. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify hub-GIlncs. RESULTS: A computational model based on four lncRNAs (FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1) was identified as a quantitative index using an in-silicon discovery cohort. GILS score was significantly associated with poor prognosis, as validated in the TCGA dataset and further tested in our local RNA-Seq cohort. Moreover, a combination of clinical characteristics and the composite GILS-clinical prognostic nomogram demonstrates satisfactory discrimination and calibration. Furthermore, the GILS score and FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 were also associated with driver mutations and multiple clinical-pathological variables, respectively. Moreover, RNA-Seq confirmed the expression patterns of FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 in PTC and normal thyroid tissues. Biological experiments demonstrated that downregulated or overexpressed LINC01614 affect PTC cell proliferation, migration, and invasion in vitro. Activation of the stromal and immune cell infiltration was also observed in the high LINC01614 group in the PTC microenvironment. CONCLUSION: In summary, we identified a signature for clinical outcome prediction in PTC comprising four lncRNAs associated with GI. A better understanding of the GI providing an alternative evaluation of the progression risk of PTC. Our study also demonstrated LINC01614 as a novel oncogenic lncRNA and verified its phenotype in PTC.