Feasibility of biomass-based flexible and transparent AuNPs-acetylcellulose membrane for multifarious surface-enhanced Raman spectroscopy detection.

BACKGROUND: Lignocellulosic biomass-based derivatives coupled with surface-enhanced Raman spectroscopy (SERS) technology have emerged as an appealing and indispensable tool in food safety and environmental monitoring for rapidly detecting trace contaminants like pesticide residues. The membrane material, serving as a substrate, ensures both sampling flexibility and test accuracy by directing the diffusion-adsorption process of the molecules. However, the existing membrane substrates, critical for the practical application of SERS, suffer from issues such as costly, intricate fabrication procedures, or restricted detection capabilities. RESULTS: Herein, we present a flexible, transparent, and biodegradable cellulose acetate membrane with gold nanoparticles (AuNPs) uniformly embedded, fabricated using a simple scraping method. This membrane achieved a limit of detection (LOD) of thiram pesticide in water at 10-8 g mL-1. The unique optical transparency of the substrates allowed for in-situ detection on surfaces, with an LOD of thiram reaching 30 ng cm-2. SIGNIFICANCE: Furthermore, SERS substrates made from corn stover-derived cellulose acetate enable the detection of various contaminants, highlighting their cost-effectiveness and eco-friendliness because of the abundance and low environmental impact of the raw materials.

Rapid and sensitive detection of methicillin-resistant Staphylococcus aureus through the RPA-PfAgo system.

Introduction: Both the incidence and mortality rates associated with methicillin-resistant Staphylococcus aureus (MRSA) have progressively increased worldwide. A nucleic acid testing system was developed in response, enabling swift and precise detection of Staphylococcus aureus (S. aureus) and its MRSA infection status. This facilitates improved prevention and control of MRSA infections. Methods: In this work, we introduce a novel assay platform developed by integrating Pyrococcus furiosus Argonaute (PfAgo) with recombinase polymerase amplification (RPA), which was designed for the simultaneous detection of the nuc and mecA genes in MRSA. Results: This innovative approach enables visual MRSA detection within 55 mins, boasting a detection limit of 102 copies/µL. Characterized by its high specificity, the platform accurately identifies MRSA infections without cross-reactivity to other clinical pathogens, highlighting its unique capability for S. aureus infection diagnostics amidst bacterial diversity. Validation of this method was performed on 40 clinical isolates, demonstrating a 95.0% accuracy rate in comparison to the established Vitek2-COMPACT system. Discussion: The RPA-PfAgo platform has emerged as a superior diagnostic tool, offering enhanced sensitivity, specificity, and identification efficacy for MRSA detection. Our findings underscore the potential of this platform to significantly improve the diagnosis and management of MRSA infection.

Cost­effectiveness analysis of tislelizumab plus chemotherapy in Chinese patients with advanced or metastatic oesophageal squamous cell carcinoma.

The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice.

First-line serplulimab plus chemotherapy versus chemotherapy in PD-L1-positive esophageal squamous-cell carcinoma: a cost-effectiveness analysis.

Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS < 10 (scenario 2), and patients with PD-L1 CPS ≥ 10 (scenario 3) populations, the ICERs were $69,025/QALY, $82,533/QALY, and $75,436/QALY for serplulimab-CF. Nevertheless, the probability of serplulimab-CF becoming cost-effective based on scenarios 1, 2, and 3 is only 2.71%, 0.94%, and 2.84%, respectively, at a WTP threshold of $38,258/QALY. When serplulimab costs < $4.84/mg, serplulimab-CF may be cost-effective at the WTP threshold of $38,258/QALY; otherwise, CF was preferred. Similar results were obtained from sensitivity analyses, suggesting the robustness of these findings. There was no cost-effectiveness in general regions of China for serplulimab-CF in PD-L1-positive ESCC compared to CF, although it is probably considered cost-effective in affluent regions. Serplulimab-CF may achieve favorable cost-effectiveness by lowering the price of serplulimab.

Adverse events associated with immune checkpoint inhibitors in non-small cell lung cancer: a safety analysis of clinical trials and FDA pharmacovigilance system.

Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, the application of ICIs can also cause treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). This study was to evaluate both the irAEs and trAEs of different ICI strategies for NSCLC based on randomized clinical trials (RCTs). The study also examined real-world pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) regarding claimed ICI-associated AEs in clinical practice. Methods: Based on Pubmed, Embase, Medline, and the Cochrane CENTRAL, we retrieved RCTs comparing ICIs with chemotherapy drugs or with different ICI regimens for the treatment of NSCLC up to October 20, 2023. Bayesian network meta-analysis (NMA) was performed using odds ratios (ORs) with 95% credible intervals (95%CrI). Separately, a retrospective pharmacovigilance study was performed based on FAERS database, extracting ICI-associated AEs in NSCLC patients between the first quarter (Q1) of 2004 and Q4 of 2023. The proportional reports reporting odds ratio was calculated to analyze the disproportionality. Results: The NMA included 51 RCTs that involved a total of 26,958 patients with NSCLC. Based on the lowest risk of any trAEs, cemiplimab, tislelizumab, and durvalumab were ranked as the best. Among the agents associated with the lowest risk of grades 3-5 trAEs, tislelizumab, avelumab, and nivolumab were most likely to rank highest. As far as any or grades 3-5 irAEs are concerned, atezolizumab plus bevacizumab plus chemotherapy is considered the most safety option. However, it is associated with a high risk of grades 3-5 trAEs. As a result of FAERS pharmacovigilance data analysis, 9,420 AEs cases have been identified in 7,339 NSCLC patients treated with ICIs, and ICIs were related to statistically significant positive signal with 311 preferred terms (PTs), and comprehensively investigated and identified those AEs highly associated with ICIs. In total, 152 significant signals were associated with Nivolumab, with malignant neoplasm progression, death, and hypothyroidism being the most frequent PTs. Conclusion: These findings revealed that ICIs differed in their safety profile. ICI treatment strategies can be improved and preventive methods can be developed for NSCLC patients based on our results.

Cost-effectiveness analysis of durvalumab, tremelimumab, and etoposide-platinum in first-line treatment of extensive-stage small cell lung cancer.

BACKGROUND: Durvalumab plus etoposide-platinum (DEP) showed sustained overall survival improvements in patients with extensive-stage small-cell lung cancer (ES-SCLC) compared to etoposide-platinum (EP), but adding tremelimumab to DEP (DTEP) did not significantly improve outcomes. A third-party payer perspective is taken here to evaluate the cost-effectiveness of DTEP, DEP, and EP for ES-SCLC. METHODS: The cost-effectiveness was evaluated by partitioning survival models into 3 mutually exclusive health states. In this model, clinical characteristics and outcomes were obtained from the CASPIAN. Model robustness was evaluated through 1-way deterministic and probabilistic sensitivity analyses. Outcome measurements included costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, life-years, incremental net health benefit, and incremental net monetary benefit. The analysis was conducted with a 10-year lifetime horizon in a United States setting. RESULTS: Compared with EP, DEP, and DTEP were associated with an increment of 0.480 and 0.313 life-years, and an increment of 0.247 and 0.165 QALYs, as well as a $139,788 and $170,331 increase in cost per patient. The corresponding ICERs were $565,807/QALY and $1033,456/QALY, respectively. The incremental net health benefit and incremental net monetary benefit of DEP or DTEP were -0.685 QALYs and -$102,729, or -0.971 QALYs and -$145,608 at a willingness to pay threshold of $150,000/QALY, respectively. Compared with DTEP, DEP was dominated. DTEP and DEP were 100% unlikely to be cost-effective if the willingness to pay threshold was $150,000/QALY. DEP was cost-effective compared to EP when durvalumab was priced below $0.994/mg. Compared with EP, DEP, and DTEP were unlikely to be considered cost-effective across all subgroups. CONCLUSION: DEP and DTEP were not cost-effective options in the first-line treatment for ES-SCLC compared with EP, from the third-party payer perspective in the United States. Compared with DTEP, DEP was dominated.

Nivolumab plus ipilimumab versus the EXTREME regimen in recurrent/metastatic squamous cell carcinoma of the head and neck: a cost-effectiveness analysis.

In the CheckMate 651 study, nivolumab plus ipilimumab versus EXTREME (cisplatin/carboplatin + cetuximab + fluorouracil) regimen was compared for effectiveness. It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15 years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free survival and overall survival (OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000/QALY. The probability of nivolumab plus ipilimumab being cost-effective was > 99% in patients with combined positive score (CPS) ≥ 1, CPS 1-19, or CPS ≥ 20. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.

2D Film-Like Magnetic SERS Tag with Enhanced Capture and Detection Abilities for Immunochromatographic Diagnosis of Multiple Bacteria.

Here, a multiplex surface-enhanced Raman scattering (SERS)-immunochromatography (ICA) platform is presented using a graphene oxide (GO)-based film-like magnetic tag (GFe-DAu-D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe-DAu-D/M tag with universal bacterial capture ability is fabricated through the layer-by-layer assembly of one layer of small Fe3O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built-in nanogap on monolayer GO nanosheets followed by co-modification with 4-mercaptophenylboronic acid (MPBA) and 5,5'-dithiobis-(2-nitrobenzoic acid).The GFe-DAu-D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real-world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL-1. The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe-DAu-D/M-ICA platform for the highly sensitive monitoring of bacterial infections or contamination.

Reconstruction of unreported subgroup survival data with PD-L1-low expression in advanced/metastatic triple-negative breast cancer using innovative KMSubtraction workflow.

BACKGROUND: Among patients with advanced/metastatic triple-negative breast cancer (TNBC) with high/positive programmed death-ligand 1 (PD-L1) expression, a superior survival outcome has been demonstrated with immune checkpoint inhibitors (ICIs). However, it remains unclear whether ICIs are beneficial for patients with low PD-L1 levels. Here, we derived survival data for subgroups with low PD-L1-expressing and conducted a pooled analysis. METHODS: After a systematic search of Embase, PubMed, MEDLINE, and CENTRAL from inception until May 18, 2023, randomized controlled trials (RCTs) reporting progression-free survival (PFS), overall survival (OS), or duration of response (DOR) for metastatic TNBC treated with ICI-based regimens were included. Kaplan-Meier curves were extracted for the intention-to-treat population and high PD-L1 subgroups. KMSubtraction was used when survival curves were not provided for subgroups with low PD-L1 expression. A pooled analysis of survival data was then conducted. RESULTS: A total of 3022 patients were included in four RCTs: Impassion130, Impassion131, KEYNOTE-119, and KEYNOTE-355. Unreported low PD-L1-expressing subgroups were identified, including PD-L1 immune cell (IC)<1%, combined positive score (CPS)<1, and 1≤CPS<10. Compared with chemotherapy, ICI-chemotherapy combinations did not significantly differ in OS, PFS, or DOR in the Impassion PD-L1<1%, KEYNOTE-355 PD-L1 CPS<1, and KEYNOTE-355 1≤CPS<10 subgroups. In the KEYNOTE-119 CPS<1 subgroup, the risk of tumor progression was increased with pembrolizumab (HR, 2.23; 95% CI, 1.62 to 3.08; p<0.001), as well as in the 1≤CPS<10 subgroup (HR, 1.64; 95% CI, 1.22 to 2.20; p<0.001). A pooled analysis using a scoring system found no significant difference in OS and PFS among the subgroups with an IC of <1% between immunochemotherapy and chemotherapy. OS (HR, 1.07; 95% CI, 0.91 to 1.26), PFS (HR, 0.96; 95% CI, 0.84 to 1.10), and DOR were also not significantly different in pooled analysis of first-line trials for those with low PD-L1 expression. CONCLUSION: ICI-based regimens are not associated with a survival benefit versus chemotherapy in subgroups of advanced/metastatic TNBC that express low PD-L1 levels.

Cost-effectiveness analysis of first-line serplulimab combined with chemotherapy for extensive-stage small cell lung cancer.

Background: For patients with extensive-stage small cell lung cancer (ES-SCLC), serplulimab plus chemotherapy is beneficial as the first-line treatment. It is uncertain whether serplulimab plus chemotherapy will be more cost-effective. The aim of this study was to evaluate from the perspective of the Chinese healthcare system to assess the cost-effectiveness of serplulimab plus chemotherapy for patients with ES-SCLC. Materials and methods: This study employed a partitioned survival model. Patients in the model were selected from ASTRUM-005 for their clinical characteristics and outcomes. In order to assess the robustness of the model, we conducted deterministic one-way sensitivity analyzes as well as probabilistic sensitivity analyzes. Subgroup analyzes were also conducted. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were analyzed. Results: Based on the base-case analysis, serplulimab plus chemotherapy contributed to an increase in 0.826 life-years and 0.436 QALYs; an incremental cost of $52,331, yielded ICER of $120,149/QALY. Based on the willingness to pay (WTP) threshold of $37,669/QALY and $86,569/QALY, the INHB was -0.954 QALYs and - 0.169 QALYs and the INMB was -$35,924 and -$14,626, respectively. Based on the probabilistic sensitivity analysis results, serplulimab plus chemotherapy was unlikely to be cost-effective at a WTP threshold of $37,669/QALY and $86,569/QALY. One-way sensitivity analysis indicated that cost of serplulimab and body weight had the greatest impact on the model. Serplulimab plus chemotherapy could be cost-effective at a WTP threshold of $86,569/QALY when the cost of serplulimab was less than $5.24/mg or when the weight of the patient was less than 40.96 kg. Regardless of the WTP threshold at $37,669/QALY or $86,569. Serplulimab plus chemotherapy was not cost-effective in all subgroups. Conclusion: Serplulimab plus chemotherapy was not cost-effective, despite having a prior clinical benefical and a relative safety profile compared with chemotherapy. With the reduction in the price of serplulimab, ES-SCLC patients treated with serplulimab plus chemotherapy may be able to achieve a favorable cost-effectiveness rate.

Cost-effectiveness of trastuzumab deruxtecan for previously treated HER2-low advanced breast cancer.

OBJECTIVE: The clinical efficacy and safety profile of trastuzumab deruxtecan (T-DXd) have been demonstrated in previously treated patients with human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer (BC). It is, however, necessary to evaluate the value of T-DXd considering both its clinical efficacy and its cost, given that it is high. This study aimed to evaluate the cost-effectiveness of T-DXd versus chemotherapy in patients with previously treated HER2-low advanced BC. METHODS: We used a partitioned survival model that included three mutually exclusive health states. The patients in the model were identified based on their clinical characteristics and outcomes from the DESTINY-Breast04. Probabilistic and one-way sensitivity analyses were performed to evaluate the model's robustness. Subgroup analyses were also conducted. The measures included costs, life years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHBs), and incremental net monetary benefits (INMBs). RESULTS: The ICERs of T-DXd vs. chemotherapy were $83,892/QALY, $82,808/QALY, and $93,358/QALY in all HER2-low advanced BC patients, HER2-positive (HER2+) advanced BC patients and HER2-negative (HER2-) advanced BC patients, respectively. In one-way sensitivity analysis, the cost of T-DXd and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were also identified as key drivers. If the price of T-DXd decreased to $17.00/mg, $17.13/mg, and $14.07/mg, it would be cost-effective at a willingness to pay (WTP) threshold of $50,000/QALY in all HER2-low advanced BC patients, HER2+ advanced BC patients and HER2- advanced BC patients, respectively. At a WTP threshold of $100,000/QALY, the probability of T-DXd being cost-effective was 81.10%, 82.27%, and 73.78% compared to chemotherapy for all HER2-low advanced BC patients, HER2+ advanced BC patients and HER2- advanced BC patients, respectively. Most subgroups of patients with HER2+ disease had a cost-effectiveness probability of > 50%. CONCLUSION: From a third-party payer's perspective in the United States, the findings of the cost-effectiveness analysis revealed that, at the current price, T-DXd is a cost-effective alternative to chemotherapy for patients with prior HER2-low advanced BC, at WTP threshold of $100,000/QALY.

Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer (NSCLC); however, evidence regarding their relative efficacy and safety is lacking. This study compared the efficacy and safety of all currently available ICI treatments in patients with advanced NSCLC to identify optimal treatment regimens. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases were systematically searched for randomized controlled trials (RCTs) published up to August 8, 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR) and adverse events (AEs). RESULTS: Forty RCTs involving 22,526 patients were selected, and a total of 26 treatment regimens were identified. Treatment with anti-programmed cell death protein-1 (anti-PD-1) provided superior OS compared with anti-programmed death ligand 1 (anti-PD-L1) treatment. ICIs plus platinum-based chemotherapy (PBC) were superior to ICIs treatment alone, although the addition of PBC increased treatment toxicity. Cemiplimab ranked first for OS and lowest for any-grade AEs in advanced NSCLC patients without PD-L1 selection. Regarding grade ≥3 AEs, the toxicity of ICI monotherapy or ICI-ICI combination was consistently lower than that of the other treatments. For patients without PD-L1 selection, cemiplimab showed the best OS, pembrolizumab plus docetaxel (Pem-DXT) showed the best PFS, and atezolizumab plus bevacizumab and PBC (Atezo-Beva-PBC) showed the best ORR. Pembrolizumab plus PBC and Atezo-Beva-PBC were the most likely optimal treatments for OS and PFS in patients with PD-L1 expression <1%, respectively. In patients with PD-L1 expression ≥1%, treatment regimens containing anti-PD-1 provided superior OS benefits compared with those of anti-PD-L1 treatment, and sintilimab plus PBC (Sint-PBC) provided the best OS benefit; as for PFS, ICI plus PBC consistently showed greater PFS benefits than ICI or PBC alone. For patients with anti-PD-L1 expression of 1-49%, camrelizumab plus PBC provided the best benefit for OS and PFS among included treatment. Durvalumab-tremelimumab-PBC and Atezo-Beva-PBC respectively presented the highest OS and PFS for patients with PD-L1 expression ≥50%. Moreover, cemiplimab and Atezo-Beva-PBC yielded the best OS and PFS benefits as first-line treatments for patients with advanced NSCLC, respectively. CONCLUSIONS: Although ICI plus PBC likely resulted in superior survival outcomes compared to ICI treatment alone, it did increase toxicity. Cemiplimab presented a well-balanced efficacy and safety profile in advanced NSCLC treatment. Our findings with the current ICIs comparisons will aid future trials for cancer immunotherapy. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ , CRD42022323879.

Cost-effectiveness of camrelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer.

Objectives: A cost-effectiveness study of camrelizumab plus chemotherapy for advanced squamous non-small-cell lung cancer in China was conducted versus chemotherapy alone. Methods: Survival data were derived from CameL-Sq. Cost-effectiveness is indicated by an incremental cost-effectiveness ratio (ICER) less than the willingness-to-pay threshold. The partitioned survival model stability was assessed by sensitivity analyses. Results: With camrelizumab plus chemotherapy, quality-adjusted life years increased by 0.83, and cost increased by $21,259/patient versus chemotherapy. The ICER was $25,674/quality-adjusted life year. The probability of cost-effectiveness was >90% regardless of PD-L1 expression level. Regardless of the variation in each parameter across a wide range, the ICER never transcended the willingness to pay. Conclusion: Camrelizumab plus chemotherapy is a cost-effective first-line treatment for advanced squamous non-small cell lung cancer in China.

Camrelizumab is a drug, and this drug can be used for advanced squamous non-small-cell lung cancer. Our study showed that patients with non-small-cell lung cancer treated with camrelizumab plus chemotherapy are related to an acceptable price and better clinical outcomes compared with chemotherapy in China. Benefit groups include patients under 65 years of age or over 65, male patients, patients who were current or former smokers and those with or without liver or brain metastases.

Rapid and Ultrasensitive Detection of Plasmodium spp. Parasites via the RPA-CRISPR/Cas12a Platform.

Microscopic examination of thick and thin blood smears stained with Giemsa dye is considered the primary diagnostic tool for the confirmation and management of suspected clinical malaria. However, detecting gametocytes is relatively insensitive, particularly in asymptomatic individuals with low-density Plasmodium infections. To complement existing diagnostic methods, a rapid and ultrasensitive point-of-care testing (POCT) platform for malaria detection is urgently needed and necessary. A platform based on recombinase polymerase amplification (RPA) followed by CRISPR/Cas12a (referred to as RPA-CRISPR/Cas12a) was developed and optimized for the determination of Plasmodium spp. parasites, particularly Plasmodium falciparum, using a fluorescence-based assay (FBDA), lateral flow test strips (LFTS), or naked eye observation (NEO). Then, the established platform was assessed with clinical malaria isolates. Under optimal conditions, the detection threshold was 1 copy/µL for the plasmid, and the limit of detection was 3.11-7.27 parasites/µL for dried blood spots. There was no cross-reactivity against blood-borne pathogens. For the accuracies of RPA-CRISPR/Cas12a, Plasmodium spp. and P. falciparum testing were 98.68 and 94.74%, respectively. The method was consistent with nested PCR results and superior to the qPCR results. RPA-CRISPR/Cas12a is a rapid, ultrasensitive, and reliable platform for malaria diagnosis. The platform requires no or minimal instrumentation for nucleic acid amplification reactions and can be read with the naked eye. Compared with similar diagnostic methods, this platform improves the reaction speed while reducing detection requirements. Therefore, this platform has the potential to become a true POCT for malaria parasites.

Cost-effectiveness of cemiplimab plus chemotherapy versus chemotherapy for the treatment of advanced non-small cell lung cancer.

Background: In patients with advanced non-small cell lung cancer (aNSCLC), cemiplimab plus chemotherapy prolonged overall survival (OS) and progression-free survival (PFS) significantly compared to chemotherapy alone. The cost-effectiveness of these drugs is still uncertain. The aim of this study is to assess the cost-effectiveness of cemiplimab plus chemotherapy compared with chemotherapy for the treatment of aNSCLC from the third-party payer perspective in the United States. Materials and methods: The cost-effectiveness of cemiplimab with chemotherapy versus chemotherapy for the treatment of aNSCLC was evaluated using a partitioned survival model containing three mutually incompatible health states. The clinical characteristics and outcomes used in the model were gathered from EMPOWER-Lung 3 trial. We have conducted deterministic one-way sensitivity analysis and probabilistic sensitivity analysis in order to evaluate the robustness of the model. The primary outcomes considered were the costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB). Results: Treatment of aNSCLC with cemiplimab plus chemotherapy increased efficacy by 0.237 QALYs and was associated with an increased total cost of $50,796 compared to chemotherapy alone, resulting in an ICER of $214,256/QALY gained. At a WTP threshold of $150,000/QALY, the INHB of cemiplimab plus chemotherapy was 0.203 QALYs and the INMB was $304,704 compared to chemotherapy alone. The probabilistic sensitivity analysis revealed that there was only a 0.04% chance that cemiplimab with chemotherapy would be cost-effective at a WTP threshold of $150,000/QALY. The performance of model was mainly determined by the price of cemiplimab, according to a one-way sensitivity analysis. Conclusions: From the third-party payer perspective, cemiplimab combined chemotherapy is unlikely to be a cost-effective option for the treatment of aNSCLC at the WTP threshold of $150,000/QALY in the United States.

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.

Background: The efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States. Methods: We performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Results: SG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be cost-effective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY. Conclusion: From a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The cost-effectiveness of SG can be improved if the price is substantially reduced.

Immune checkpoint inhibitors in first-line therapies of metastatic or early triple-negative breast cancer: a systematic review and network meta-analysis.

Background: The optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a result of various randomized controlled trials (RCTs). The purpose of this study was to compare the efficacy and safety of ICIs in patients with metastatic or early TNBC. Methods: RCTs comparing the efficacy and safety of ICIs in patients with TNBC were included in the studies. Based on PRISMA guidelines, we estimated pooled hazard ratios (HRs) and odds ratios (ORs) using random-effects models of Bayesian network meta-analysis. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included pathologic complete response rate (pCR), grade ≥ 3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and grade ≥ 3 irAEs. Results: The criteria for eligibility were met by a total of eight RCTs involving 4,589 patients with TNBC. When ICIs were used in patients without programmed death-ligand 1 (PD-L1) selection, there was a trend toward improved PFS, OS, and pCR, without significant differences. Pembrolizumab plus chemotherapy is superior to other treatment regimens in terms of survival for TNBC patients based on Bayesian ranking profiles. Subgroup analysis by PD-L1 positive population indicated similar results, and atezolizumab plus chemotherapy provided better survival outcomes. Among grade ≥ 3 trAEs and any grade irAEs, there was no statistically significant difference among different ICI agents. The combination of ICIs with chemotherapy was associated with a higher incidence of grade ≥ 3 irAEs. Based on rank probability, the ICI plus chemotherapy group was more likely to be associated with grade ≥ 3 trAEs, any grade irAEs, and grade ≥ 3 irAEs. Hypothyroidism and hyperthyroidism were the most frequent irAEs in patients receiving ICI. Conclusions: ICI regimens had relatively greater efficacy and safety profile. Pembrolizumab plus chemotherapy and atezolizumab plus chemotherapy seem to be superior first-line treatments for intention-to-treat and PD-L1-positive TNBC patients, respectively. It may be useful for making clinical decisions to evaluate the efficacy and safety of different ICIs based on our study. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354643.

Sugemalimab plus chemotherapy vs. chemotherapy for metastatic non-small-cell lung cancer: A cost-effectiveness analysis.

Background: Sugemalimab is a newly developed inhibitor of programmed death ligand 1 (PD-L1). As a first-line treatment for metastatic non-small-cell lung cancer (NSCLC), sugemalimab plus chemotherapy (Sugema-Chemo) has been proven effective. Still, its cost-effectiveness has not yet been determined. The objective of this study was to assess the cost-effectiveness of Sugema-Chemo from a health care perspective in China. Methods: A partitioned survival model was used. According to the GEMSTONE-302 trial, the clinical characteristics and outcomes of the patients were obtained. The outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB) and incremental net monetary benefits (INMB). The robustness of the model was further evaluated, as well as subgroup analyses. When the ICER was lower than the willingness to pay (WTP) threshold ($38,017/QALY or $86,376/QALY, defined as three times the per capita gross domestic product value of the general region and Beijing), the cost-effectiveness of Sugema-Chemo was assumed for general regions or Beijing. Results: Compared with chemotherapy alone, Sugema-Chemo resulted in an incremental gain of 0.82 QALYs, an incremental gain of 1.26 life-years, as well as an average increase cost of $72,472. The ICER was $88,744/QALY. Model outcomes were susceptible to average body weight and cost of sugemalimab. Sugema-Chemo was cost-effective at a WTP threshold of 86,376/QALY if the average body weight was <62.44 kg or if the price of sugemalimab was <$2.996/mg. As well, Sugema-Chemo was also cost-effective when the cost of sugemalimab was <$1.839/mg for a WTP threshold of $38,017/QALY. Sugema-Chemo had a probability of > 50% being considered cost-effective in most subgroups at the $86,376/QALY threshold. However, Sugema-Chemo did not achieve cost-effectiveness (0%) in any of the subgroups when WTP was set at $38,017/QALY. Conclusion: Sugema-Chemo might not be cost-effective in patients with metastatic NSCLC in China. In deciding between Sugema-Chemo and chemotherapy alone, it is essential to consider both the body weight of patients and the price of sugemalimab. A price reduction of sugemalimab under the National Healthcare Security Administration may be an effective measure to improve the cost-effectiveness of the drug.

Tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as first-line therapy for advanced non-squamous non-small cell lung cancer.

Background and objective: Tislelizumab is a programmed cell death protein-1 (PD-1) inhibitor. Tislelizumab plus chemotherapy as first-line option for advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy alone, resulted in significantly prolonged survival outcomes; however, evidence regarding its relative efficacy and cost is lacking. We aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy compared with that of chemotherapy alone, from the health care perspective in China. Methods: A partitioned survival model (PSM) was used for this study. The survival data were obtained from the RATIONALE 304 trial. Cost-effectiveness was defined as incremental cost-effectiveness ratio (ICER) less than the willingness to pay (WTP) threshold. Incremental net health benefits (INHB), incremental net monetary benefits (INMB), and subgroup analyses were also assessed. Sensitivity analyses were further established to assess the model stability. Results: Compared with chemotherapy alone, tislelizumab plus chemotherapy increased by 0.64 quality-adjusted life-years (QALYs) and 1.48 life-years, and yielded an increase of $16,631 in cost per patient. The INMB and INHB were $7,510 and 0.20 QALYs at a WTP threshold of $38,017/QALY, respectively. The ICER was $26,162/QALY. The outcomes were most sensitive to the HR of OS for tislelizumab plus chemotherapy arm. The probability of tislelizumab plus chemotherapy being considered cost-effective was 87.66% and >50% in most of the subgroups at the WTP threshold of $38,017/QALY. At the WTP threshold of $86,376/QALY, the probability achieved 99.81%. Furthermore, the probability of tislelizumab plus chemotherapy being considered cost-effective in subgroups of patients with liver metastases and PD-L1 expression ≥50% were 90.61 and 94.35%, respectively. Conclusion: Tislelizumab plus chemotherapy is likely to be cost-effective as a first-line treatment for advanced non-squamous NSCLC in China.

Comparative efficacy and safety of immune checkpoint inhibitors for unresectable advanced melanoma: A systematic review and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have entered the treatment paradigm for unresectable advanced melanoma, but there is a lack of evidence regarding its relative efficacy and safety. This study aim to compare the efficacy and safety of ICIs in patients with advanced unresectable melanoma. METHODS: Studies included randomized clinical trials (RCTs) that compared ICIs, or combination therapy of ICIs, or with chemotherapy drugs, different ICIs, or one of the ICIs at different dosing schedules. Random-effects models of Bayesian network meta-analysis were performed following the PRISMA reporting guideline. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events. PROSPERO: CRD42021229086. RESULTS: Twenty-four RCTs with 18 different treatment regimens for advanced melanoma involving 10,090 patients were included. Overall, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg treatment regimen were associated with the highest beneficial effect on OS, PFS, and DCR. Closely followed by nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, and nivolumab plus relatlimab treatment regimens. However, three regimens had less favorable safety profiles. Although ipilimumab 0.3 mg/kg was ranked as the best options with the lowest risk of grade ≥ 3 treatment or immune-related adverse events, less therapeutic benefit was performed. The pembrolizumab 10 mg/kg regimen may be the preferred treatment with relative higher efficiency and safety among the ICIs regimens reported, as well as the nivolumab 3 mg/kg regimen. Head-to-head trials showed similar results. CONCLUSIONS: This study shown the preferred treatment regimens with relatively higher efficiency and safety among the reported ICI regimens. Our results may complement the current standard of care, while its direct drug comparisons will aid future trials.