Risk assessment of imported malaria in China: a machine learning perspective.

BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.

Assessment of a Novel, Adjustable Task Trainer for Cardiac Surgical Skills.

INTRODUCTION: A recent needs assessment in Canadian cardiac surgery programs identified the desire for a coronary artery bypass (CABG) and aortic valve replacement (AVR) simulation model for home practice. We aimed to develop and assess a portable, adjustable task trainer for cardiac surgical skills with high functional task alignment. METHODS: Intraoperative measurements were taken from patients undergoing elective CABG and AVR (N = 30). Measurements were taken in 3 axes and used to create a chest cavity that resembles the mediastinal constraints of a patient undergoing CABG and AVR. The task trainer is adjustable on the following 3 levels: (1) size of the incision, (2) depth of the chest, and (3) relative position of coronary artery or aortic valve model within the chest. Three groups (novices, intermediates, and experts) of cardiac surgery members evaluated the task trainer for functional task alignment and construct validity. RESULTS: The CABG and AVR model had high functional task alignment. There was a high satisfaction for both models and all participants would recommend the AVR and CABG model as an educational tool. Performance time significantly differed between the groups for both models (CABG: P = 0.032 and AVR: P = 0.001), as well as number of errors (CABG: P = 0.04 and AVR: P = 0.043). CONCLUSIONS: Using real patient data, we were able to develop an adjustable task trainer for training principles of CABG and AVR. Our pilot study provides preliminary sources of evidence for validity and future study will look to assess transferability of skill to the operating room.

Surgical tooltip motion metrics assessment using virtual marker: an objective approach to skill assessment for minimally invasive surgery.

PURPOSE: Surgical skill assessment has primarily been performed using checklists or rating scales, which are prone to bias and subjectivity. To tackle this shortcoming, assessment of surgical tool motion can be implemented to objectively classify skill levels. Due to the challenges involved in motion tracking of surgical tooltips in minimally invasive surgeries, formerly used assessment approaches may not be feasible for real-world skill assessment. We proposed an assessment approach based on the virtual marker on surgical tooltips to derive the tooltip's 3D position and introduced a novel metric for surgical skill assessment. METHODS: We obtained the 3D tooltip position based on markers placed on the tool handle. Then, we derived tooltip motion metrics to identify the metrics differentiating the skill levels for objective surgical skill assessment. We proposed a new tooltip motion metric, i.e., motion inconsistency, that can assess the skill level, and also can evaluate the stage of skill learning. In this study, peg transfer, dual transfer, and rubber band translocation tasks were included, and nine novices, five surgical residents and five attending general surgeons participated. RESULTS: Our analyses showed that tooltip path length (p [Formula: see text] 0.007) and path length along the instrument axis (p [Formula: see text] 0.014) differed across the three skill levels in all the tasks and decreased by skill level. Tooltip motion inconsistency showed significant differences among the three skill levels in the dual transfer (p [Formula: see text] 0.025) and the rubber band translocation tasks (p [Formula: see text] 0.021). Lastly, bimanual dexterity differed across the three skill levels in all the tasks (p [Formula: see text] 0.012) and increased by skill level. CONCLUSION: Depth perception ability (indicated by shorter tooltip path lengths along the instrument axis), bimanual dexterity, tooltip motion consistency, and economical tooltip movements (shorter tooltip path lengths) are related to surgical skill. Our findings can contribute to objective surgical skill assessment, reducing subjectivity, bias, and associated costs.

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States.

Background: Axicabtagene ciloleucel (Axi-cel) is the first Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) product approved in China for treating adult patients with relapsed or refractory large B-cell lymphoma after receiving second-line or above systemic therapy. However, it cannot be widely used in clinical practice due to its high price. Objectives: To evaluate the economic value of Axi-cel fully in countries at different stages of economic development, this article, from the perspective of the medical and health system in China and the United States, evaluated the cost-effectiveness of Axi-cel in the second-line treatment of diffuse large B-cell lymphoma (DLBCL). Design: Cost effectiveness analysis of Axi-cel in the treatment of relapsed or refractory large B-cell lymphoma (LBCL). Methods: Based on the clinical trial data of ZUMA-7, a short-term decision tree and a long-term semi-Markov partitioned survival model were constructed to evaluate the cost-effectiveness of the two strategies. This model was cycled for 40 years in 1-month cycles. In this article, only direct medical costs were considered. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the base-case results. Results: In the baseline cost-effectiveness analysis, Axi-cel was associated with more quality-adjusted life year (QALY; 2.72 versus 1.46) and greater costs overall ($180,501.55 versus $123,221.34) than standard second-line chemotherapy in China. Moreover, the incremental cost-effectiveness ratio (ICER) of the Axi-cel group was $45,726.66/QALY, which was greater than the threshold of $37,654.5. To achieve cost-effectiveness, the price of Axi-cel must be reduced appropriately. In the United States, Axi-cel was associated with more QALYs (2.63 versus 1.74) and greater costs overall ($415,915.16 versus $289,564.34). The ICER for the Axi-cel was $142,326.94/QALY, below the set threshold of $150,000. Conclusion: Axi-cel is not a cost-effective option as second-line therapy for treating DLBCL in China. However, In the United States, Axi-cel has shown a cost-effectiveness advantage as a second-line treatment for DLBCL.

Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis.

Toxoplasma gondii, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against T. gondii infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from T. gondii, was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice via intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce T. gondii-specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after T. gondii challenge (P< 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively (P< 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against T. gondii infection.

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma: a cost-effectiveness analysis.

Background: The CheckMate-649 trial compared nivolumab plus chemotherapy (NC) with chemotherapy alone as first-line treatment for advanced gastric cancer (GC), gastroesophageal junction cancer (GEJC), and esophageal adenocarcinoma (EAC) and showed significant benefits to progression-free survival and overall survival. This study evaluated the lifetime cost-effectiveness of NC versus chemotherapy alone in patients with GC/GEJC/EAC from the perspective of the US payers. Methods: A 10-year partitioned survival model was constructed to evaluate the cost-effectiveness of NC and chemotherapy alone and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years. Health states and transition probabilities were modeled from the survival data from the CheckMate-649 clinical trial (NCT02872116). Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: On comparing the chemotherapy, we found that NC incurred substantial health costs, resulting in ICERs of $240,635.39/QALY, $434,182.32/QALY, and $386,715.63/QALY for the model of patients with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ⩾5, PD-L1 CPS ⩾1, and all-treated patients, respectively. All ICERs were significantly higher than the willingness-to-pay threshold value of $150,000/QALY. The main influencing factors were the cost of nivolumab, the utility value of the progression-free disease, and the discount rate. Conclusion: Compared with chemotherapy alone, NC may not be a cost-effective option for treating advanced GC, GEJC, and EAC in the United States.

Automated Quantification of Pneumonia Infected Volume in Lung CT Images: A Comparison with Subjective Assessment of Radiologists.

OBJECTIVE: To help improve radiologists' efficacy of disease diagnosis in reading computed tomography (CT) images, this study aims to investigate the feasibility of applying a modified deep learning (DL) method as a new strategy to automatically segment disease-infected regions and predict disease severity. METHODS: We employed a public dataset acquired from 20 COVID-19 patients, which includes manually annotated lung and infections masks, to train a new ensembled DL model that combines five customized residual attention U-Net models to segment disease infected regions followed by a Feature Pyramid Network model to predict disease severity stage. To test the potential clinical utility of the new DL model, we conducted an observer comparison study. First, we collected another set of CT images acquired from 80 COVID-19 patients and process images using the new DL model. Second, we asked two chest radiologists to read images of each CT scan and report the estimated percentage of the disease-infected lung volume and disease severity level. Third, we also asked radiologists to rate acceptance of DL model-generated segmentation results using a 5-scale rating method. RESULTS: Data analysis results show that agreement of disease severity classification between the DL model and radiologists is >90% in 45 testing cases. Furthermore, >73% of cases received a high rating score (≥4) from two radiologists. CONCLUSION: This study demonstrates the feasibility of developing a new DL model to automatically segment disease-infected regions and quantitatively predict disease severity, which may help avoid tedious effort and inter-reader variability in subjective assessment of disease severity in future clinical practice.

Motion Smoothness-Based Assessment of Surgical Expertise: The Importance of Selecting Proper Metrics.

The smooth movement of hand/surgical instruments is considered an indicator of skilled, coordinated surgical performance. Jerky surgical instrument movements or hand tremors can cause unwanted damages to the surgical site. Different methods have been used in previous studies for assessing motion smoothness, causing conflicting results regarding the comparison among surgical skill levels. We recruited four attending surgeons, five surgical residents, and nine novices. The participants conducted three simulated laparoscopic tasks, including peg transfer, bimanual peg transfer, and rubber band translocation. Tooltip motion smoothness was computed using the mean tooltip motion jerk, logarithmic dimensionless tooltip motion jerk, and 95% tooltip motion frequency (originally proposed in this study) to evaluate their capability of surgical skill level differentiation. The results revealed that logarithmic dimensionless motion jerk and 95% motion frequency were capable of distinguishing skill levels, indicated by smoother tooltip movements observed in high compared to low skill levels. Contrarily, mean motion jerk was not able to distinguish the skill levels. Additionally, 95% motion frequency was less affected by the measurement noise since it did not require the calculation of motion jerk, and 95% motion frequency and logarithmic dimensionless motion jerk yielded a better motion smoothness assessment outcome in distinguishing skill levels than mean motion jerk.

Cost-effectiveness analysis of elacestrant versus standard endocrine therapy for second-/third-line treatment of patients with HR+/HER2- advanced or metastatic breast cancer: a US payer perspective.

Background: This study evaluated the cost-effectiveness of elacestrant (ELA) and standard-of-care (SOC) as second-/third-line treatment for pretreated estrogen receptor (ER)- positive/human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (A/MBC) in the US. Methods: The 3 health states partitioned survival model (PSM) was conducted from the perspective of the US third-party payers. The time horizon for the model lasted 10 years. Effectiveness and safety data were derived from the EMERALD trial (NCT03778931). Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from published studies. One-way sensitivity analysis as well as probabilistic sensitivity analysis were performed to observe model stability. Result: ELA led to an incremental cost-effectiveness ratio (ICER) of $8,672,360/quality-adjusted life year (QALY) gained compared with SOC in the overall population and $2,900,560/QALY gained compared with fulvestrant (FUL) in the ESR1(estrogen receptor 1) mutation subgroup. The two ICERs of ELA were significantly higher than the willingness-to-pay (WTP) threshold values of $150,000/QALY. Conclusions: ELA was not cost-effective for the second-/third-line treatment of patients with ER+/HER2-A/MBC compared with SOC in the US.

Assessment of the Effect of Cold Atmospheric Plasma (CAP) on the Hairtail (Trichiurus lepturus) Quality under Cold Storage Conditions.

Cold Atmospheric Plasma (CAP) is a novel non-thermal preservation method that extends the shelf-life of food. Therefore, this study investigated the effect of CAP on the quality parameters of hairtail (Trichiurus lepturus) during cold storage conditions (at 4 °C and RH range 45−55%). For that reason, different quality parameters including the total bacteria count (TBC), total volatile basic nitrogen (TVB-N), pH, thiobarbituric acid reacting substances value (TBARS), color, texture, and sensory evaluation have been measured. The hairtail was exposed to CAP at 50 kV voltage for 2, 3, 4, and 5 min. The results showed that the samples treated with CAP at 50 kV for 5 min had significantly lower (p < 0.05) TBC (7.04 ± 0.26 log CFU/g) compared with the control sample (8.69 ± 0.06 log CFU/g). Similar results were found concerning TVB-N, which strongly decreased in the treated samples (16.63 ± 0.03 mg N/100 g) in comparison with the control sample (22.79 ± 0.03 mg N/100 g). In addition, the CAP-treated samples had lower (p < 0.05) changes in color than those of the control group. With reference to the sensory evaluation, the shelf-life of CAP-treated samples (at 50 kV for 5 min) was longer than the untreated samples by about 6 days. These results led us to the conclusion that CAP can effectively delay spoilage and deterioration, slow the rise in pH, and maintain the sensory attributes of hairtail during cold storage conditions.

First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone for advanced esophageal cancer: a cost-effectiveness analysis.

Background: This study evaluated the cost-effectiveness of nivolumab plus chemotherapy (NC) or ipilimumab versus chemotherapy as a first-line treatment for advanced esophageal squamous cell carcinoma (ESCC) in the United States and China. Methods: A partitioned survival model was constructed from the perspective of the US third-party payers and Chinese healthcare system. Health states and transition probabilities were modeled based on the survival data from the CheckMate-648 clinical trial (NCT03143153). The time horizon for the model was 10 years. Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: In the United States, nivolumab plus ipilimumab (NI) led to an incremental cost-effectiveness ratio (ICER) of $155,159.82/quality-adjusted life year (QALY) and $104,297.07/QALY gained in the overall population and in patients with tumor cell programmed death-ligand 1 (PD-L1) expression of ⩾1% (subgroup), respectively. The ICER for the subgroup was between the willingness-to-pay (WTP) threshold values of $100,000/QALY and $150,000/QALY, and the other case was higher than $150,000/QALY. NC led to an ICER of $518,062.85/QALY and $193,169.49/QALY gained in the overall population and the subgroup, respectively. Both ICERs were significantly higher than the WTP threshold of $150,000/QALY. In China, the ICERs for patients treated with the addition of nivolumab were >$90,000/QALY in all cases, significantly exceeding the WTP threshold of $37,654/QALY. Conclusions: NI is more cost-effective than NC or chemotherapy alone for treating advanced ESCC with PD-L1 expression ⩾1% in the United States. Chemotherapy alone is the only cost-effective option in China.

Cost-effectiveness analysis of nivolumab plus ipilimumab versus chemotherapy as the first-line treatment for unresectable malignant pleural mesothelioma.

Introduction: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab (NI) versus pemetrexed plus cisplatin/carboplatin (C) as the first-line treatment for unresectable malignant pleural mesothelioma (MPM) from the perspective of US payers. Methods: A 10-year partitioned survival model was constructed using survival and safety data from the CheckMate 743 clinical trial. The output metrics of the model included the patient's lifetime quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Only direct medical costs were considered. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: Among all randomized patients, group NI had an ICER of $475,677/QALY relative to group C. Among patients with epithelioid histology, group NI had an ICER of $760,955/QALY. Among patients with non-epithelioid histology, group NI had an ICER of $418,348/QALY. The ICERs of all three populations exceeded the willingness-to-pay threshold ($150,000). The results of one-way sensitivity analysis revealed that the cost of nivolumab had a great influence on the results. The results of probabilistic sensitivity analysis demonstrated that the possibility of NI being more economical in all randomized patients and in patients with non-epidemiology histology was 0. In patients with epithelioid histology, the probability that NI had an economic advantage was 0.6%. Conclusions: From the perspective of US payers, in patients with unresectable MPM, NI has no economic advantage over C.

Cost-effectiveness of olaparib, a PARP inhibitor, for patients with metastatic castration-resistant prostate cancer in China and United States.

Background: Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes metastatic castration-resistant prostate cancer (mCRPC). Olaparib has longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. In the present study, 2 Markov models were established to analyze the cost utility of olaparib in treating mCRPC from the perspectives of health services in China and the United States. Methods: Markov models were established to simulate the progress of mCRPC in China and the United States. The state transition probabilities and clinical data were extracted from the PROfound trial. The cost data were estimated from local pricing, the relevant literature and expert consultancy. The health outcomes are expressed by quality-adjusted life years (QALYs). All costs and incremental cost-effectiveness ratios (ICERs) are presented in US dollars. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty of the models. Results: Based on the Chinese Markov model, the base case ICER for olaparib versus the control group was ¥392,727.87, with incremental costs of ¥93,673.23 and an incremental QALY of 0.23, indicating that it was not cost effective from the aspect of the Chinese healthcare system. However, as shown by the American Markov model, olaparib was dominant versus the control group, with a cost saving of $69,675.20 and a gain of 0.23 QALYs. One-way deterministic sensitivity analysis and probabilistic sensitivity analyses showed that the modeling results were not significantly affected by the model parameters. Conclusions: Olaparib treatment in patients with mCRPC is not cost effective in China, but it is cost saving in the United States.

Cost-effectiveness of empagliflozin as a treatment for heart failure with reduced ejection fraction: an analysis from the Chinese healthcare perspective.

Background: The effect of empagliflozin on the cardiovascular outcome is consistent in heart failure with reduced ejection fraction (HFrEF) patients regardless of the presence or absence of diabetes. More evidence is needed regarding the cost-effectiveness of empagliflozin in HFrEF patients. This study sought to evaluate the economic outcomes of adding empagliflozin to the standard treatment for HFrEF patients from the perspective of the Chinese healthcare system, and thus to provide information for decision makers. Methods: Based on the EMPEROR-Reduced clinical trial and other published literature data, the direct medical costs and quality-adjusted life years (QALYs) of patients with HFrEF over a 15-year study period were simulated by a Markov model, and the incremental cost-effectiveness ratio (ICER) was calculated. The price of empagliflozin referred to the data released by Menet, the hospitalization expenses and utility values were derived from published studies in China. A one-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the model. Results: The results of the cost-effectiveness analysis showed that the cost of the combination arm was $5,220.98, with a utility of 4.86 QALYs, and the cost of the standard arm was $4,873.96, with a utility of 4.68 QALYs, which equated to an ICER of $1,893.59 per QALY gained. The subgroup analysis showed that patients with HFrEF and diabetes in empagliflozin group had a higher QALY (4.62 vs. 4.35) and a lower cost ($5,213.28 vs. $5,958.60) than standard group. The corresponding ICER for non-diabetic patients was $2,568.15 per QALY. Deterministic sensitivity analysis showed robust results. At the willingness-to-pay threshold of 3 times gross domestic product (GDP) per capita ($31,510.57), almost all of the scattered points in three scenarios were below the threshold line. Conclusions: At a willingness-to-pay threshold of $31,510.57, adding empagliflozin to standard treatment is a very cost-effective option for HFrEF patients with or without diabetes in China.

Cost-effectiveness of osimertinib versus placebo in resected EGFR-mutated non-small cell lung cancer in China.

PURPOSE: We aim to assess whether osimertinib postoperative adjuvant therapy, compared with placebo, is cost-effective in China. METHODS: We set up the Markov model that contains three health states over a 20-year period. Data were collected from the ADAURA trial that included transition probabilities and safety data. Through the analysis of literature and local charges, we explore both the cost and utility values. Sensitivity analyses were employed using TreeAge Pro software to access model stability. FINDINGS: Patients in the osimertinib group had 1.46 more Quality-adjusted Life Years (8.45 QALYs vs 6.99 QALYs) than the placebo group at an incremental cost of $14098.51($39962.99 vs $25864.48). Compared with the placebo group, the treatment strategy with osimertinib postoperative adjuvant therapy had an incremental cost-effectiveness ratio of $9661.97/QALY. The probability of the osimertinib-assisted therapy strategy being cost-effective will reach 100% if the threshold of willingness to pay is above $15,000/QALY. IMPLICATIONS: From the perspective of the Chinese Healthcare System, the treatment strategy with osimertinib postoperative adjuvant therapy is more cost-effective than the placebo strategy.

Cost-effectiveness analysis of axicabtagene ciloleucel vs. salvage chemotherapy for relapsed or refractory adult diffuse large B-cell lymphoma in China.

PURPOSE: Axicabtagene ciloleucel (Axi-Cel, 2 × 106 CAR-T cells/kg, single intravenous injection) is a chimeric antigen receptor cell immunotherapy that exhibits favorable clinical efficacy and safety in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). However, this treatment is expensive in China. This study aimed to evaluate the cost-effectiveness of Axi-Cel versus salvage chemotherapy for the treatment of R/R DLBCL from the perspective of the Chinese healthcare system. METHODS: A decision analysis model containing a short-term decision tree and long-term semi-Markov partitioned survival model was developed. The time horizon was 40 years and the period from 10 to 40 years was included in sensitivity analysis. The model was developed based on data from the ZUMA-1 and SCHOLAR-1 trials. Life years, quality-adjusted life years (QALYs), overall costs, and the incremental cost-effectiveness ratio (ICER) were estimated at a willingness to pay (WTP) threshold of US $31,320 per QALY, which is three times the gross domestic product per capita. RESULTS: The base case analysis revealed that treatment with Axi-Cel is associated with an increased overall cost of US $175,380 and improved effectiveness of 3.43 LYs and 2.61 QALYs compared to salvage chemotherapy, leading to an ICER of US $51,190 per LY and US $67,250 per QALY. The developed model is sensitive to the discount rate, utility of progression-free survival (PFS), and cost of Axi-Cel. The ICER of Axi-Cel was greater than the WTP threshold in the sensitivity and scenario analyses. To achieve cost-effectiveness, the price of Axi-Cel must be reduced by 59.19% to US $71,000. CONCLUSION: At its current price, Axi-Cel is not likely to be a cost-effective option compared to salvage chemotherapy for adult patients with R/R DLBCL.

Systematic review and cost-effectiveness of pharmacokinetically guided sunitinib individualized treatment for patients with metastatic renal cell carcinoma.

Background: Sunitinib has a narrow therapeutic window, with considerable differences between patients. Dosing based on pharmacokinetics (PK) may help overcome some of those issues. This study aims to evaluate and compare the cost-effectiveness of PK-guided individualized treatment of sunitinib with its standard dose in patients with metastatic renal cell carcinoma (mRCC). Methods: A comprehensive literature search was performed, and relevant values were used to provide information for the decision analysis model. Utility data were derived from published studies, and costs were obtained from the perspective of payers in China and the United States. A Markov model was established to evaluate the associated costs and health outcomes for patients. The primary outputs of the model included lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were conducted to evaluate the potential uncertainties of parameters. Results: Cost-effective analysis showed that the QALY of the PK-guided group increased by 0.83 compared with that in the standard dose group. From the perspective of both countries' health systems, the cost of PK-guided dose was lower than that of standard dose. Hence, PK-guided treatment was the dominant strategy. One-way and probability sensitivity analyses confirmed the reliability of these results. Conclusion: On the basis of currently available data, PK-guided sunitinib treatment may be a safe, effective, and economical intervention for patients with mRCC.

Fixed-dose administration and pharmacokinetically guided adjustment of busulfan dose for patients undergoing hematopoietic stem cell transplantation: a meta-analysis and cost-effectiveness analysis.

This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided adjustment of Bu dose for patients who underwent hematopoietic stem cell transplantation. The efficacy and safety of both dosing strategies were compared using a systematic review and meta-analysis. A Markov model was used in estimating relevant cost and health outcomes from the perspective of the health system. The primary outcomes of interest were lifetime cost, quality adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratio (ICER) in dollar per QALY gained. Results showed that progression-free survival and overall survival in the PK-guided group were higher than that in the fixed-dose group, and the PK-guided group was associated with low non-relapse mortality and relapse rate. In contrast to safety, the incidence of acute graft-versus-host disease (GVHD) was the same in the two groups (P > 0.05). Cost-effectiveness analysis showed that the QALY of the PK-guided group (12.8135 QALYs and $582,475.07) increased by 2.0609 relative to that in the fixed-dose group (10.7526 QALYs and $562,833.20), and the ICER was $9530.72/QALY. One-way and probability sensitivity analyses confirmed the reliability of the results. In conclusion, the PK-guided approach has higher efficacy and is safer.

Improving Performance of Breast Cancer Risk Prediction by Incorporating Optical Density Image Feature Analysis: An Assessment.

RATIONALE AND OBJECTIVES: The purpose of this study is to improve accuracy of near-term breast cancer risk prediction by applying a new mammographic image conversion method combined with a two-stage artificial neural network (ANN)-based classification scheme. MATERIALS AND METHODS: The dataset included 168 negative mammography screening cases. In developing and testing our new risk model, we first converted the original grayscale value (GV)-based mammographic images into optical density (OD)-based images. For each case, our computer-aided scheme then computed two types of image features representing bilateral asymmetry and the maximum of the image features computed from GV and OD images, respectively. A two-stage classification scheme consisting of three ANNs was developed. The first stage included two ANNs trained using features computed separately from GV and OD images of 138 cases. The second stage included another ANN to fuse the prediction scores produced by two ANNs in the first stage. The risk prediction performance was tested using the rest 30 cases. RESULTS: With the two-stage classification scheme, the computed area under the receiver operating characteristic curve (AUC) was 0.816 ± 0.071, which was significantly higher than the AUC values of 0.669 ± 0.099 and 0.646 ± 0.099 achieved using two ANNs trained using GV features and OD features, respectively (P < .05). CONCLUSION: This study demonstrated that applying an OD image conversion method can acquire new complimentary information to those acquired from the original images. As a result, fusion image features computed from these two types of images yielded significantly higher performance in near-term breast cancer risk prediction.

NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China.

OBJECTIVE: The cost-effectiveness of NUDT15 genetic testing-guided initial 6-mercaptopurine (6-MP) dosing in children with acute lymphoblastic leukemia (ALL) was evaluated. METHODS: A decision tree model was used to evaluate the cost to China's medical system per quality-adjusted life-year (QALY) gained and cost per case of severe leukopenia avoided of NUDT15 genetic testing using public clinical data. RESULTS: Genetic testing-guided initial 6-MP dosing reduced overall costs by $518.61, and prevented 0.221 cases of Grade III-IV leukopenia and increased QALY by 0.00136 per patient. Results were robust in one-way analyses and probabilistic sensitivity analyses. CONCLUSION: NUDT15 genetic testing prior to the initial administration of 6-MP in pediatric ALL patients in China is less expensive than standard dosing without genetic testing.