First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis.

Background: The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. Methods: A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Conclusions: Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.

The impact of land resource mismatch and land marketization on pollution emissions of industrial enterprises in China.

Local governments' strategy of increasing the land supply by selling industrial land at low prices causes industrial land in China to be priced substantially below the market value. Whether under planned or market allocation, urban land is an important part of China's market-oriented economic reform. However, direct empirical research on the impact of industrial land transfer on environmental pollution is still lacking. Based on matched data, this study investigates the impact of land resource mismatch and land marketization on the pollution emissions of Chinese enterprises. Pollution emissions refer to the emission intensity of industrial enterprises' major pollutants, such as industrial water, industrial waste gas and sulfur dioxide, and it is calculated by the comprehensive index method. The impact of land resource mismatch and land marketization on the pollution emissions of Chinese enterprises is investigated using a panel fixed effect model, subsample regression, the instrumental variable method and a mediating effect model. The benchmark analysis shows that land resource mismatch increases pollution emissions. The influence mechanism analysis shows that land resource mismatch may increase the pollution emissions of enterprises by causing overinvestment and low productivity. In addition, the expanded analysis shows that China's land marketization can reduce the intensity of and have a long-term impact on the pollution emissions of enterprises. This paper provides a theoretical and scientific basis for correcting the mismatch of land resources and promoting the reform of land marketization in China.

Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis.

BACKGROUND: Ovarian cancer (OC) is the seventh most common malignancy worldwide and the most lethal gynaecological malignancy. We aimed to explore global geographical patterns and temporal trends from 1973 to 2015 for 41 countries in OC incidence and especially to analyse the birth cohort effect to gain further insight into the underlying causal factors of OC and identify countries with increasing risk of OC. METHODS: OC data were drawn from the Cancer Incidence in Five Continents databases and online databases published by governments. The joinpoint regression model was applied to detect changes in OC trends. The age-period-cohort model was applied to explore age and birth cohort effects. RESULTS: The age-standardized rate of OC incidence ranged from 3.0 to 11.4 per 100,000 women worldwide in 2012. The highest age-standardized rate was observed in Central and Eastern Europe, with 11.4 per 100,000 women in 2012. For the most recent 10-year period, the increasing trends were mainly observed in Central and South America, Asia and Central and Eastern Europe. The largest significant increase was observed in Brazil, with an average annual percentage change of 4.4%. For recent birth cohorts, cohort-specific increases in risk were pronounced in Estonia, Finland, Iceland, Lithuania, the United Kingdom, Germany, the Netherlands, Italy, Malta, Slovenia, Bulgaria, Russia, Australia, New Zealand, Brazil, Costa Rica, Ecuador, India, Japan, the Philippines and Thailand. CONCLUSIONS: Disparities in the incidence and risk of OC persist worldwide. The increased risk of birth cohort in OC incidence was observed for most countries in Asia, Central and Eastern Europe, and Central and South America. The reason for the increasing OC risk for recent birth cohorts in these countries should be investigated with further epidemiology studies.

The cost-effectiveness of alternative vision screening models among preschool children in rural China.

PURPOSE: To explore the accuracy and cost-effectiveness of three vision screening models among preschool children in rural China. METHODS: Vision screening was carried out among children aged 4-5 years in 65 preschools in two counties in Northwest China, using Crowded Single Lea Symbols to test visual acuity. Children were assigned randomly by school to one of three screening models: screening by teachers (15 schools, 1835 children), local optometrists (30 schools, 1718 children) or volunteers (20 schools, 2183 children). Children identifying ≥2 symbols incorrectly in either eye failed screening. Accuracy of screening was compared with screenings executed by experienced optometrists among 141 children selected randomly from the three screening models. Direct and indirect costs for each model were assessed. Costs to detect a true case failed screening were estimated. RESULTS: The sensitivity for three models ranged from 76.9% to 87.5%, specificity from 84.9% to 86.7% and standardized positive predictive value from 83.7% to 85.7%. None differed significantly between models. The costs per case detected were $37.53, $59.14 and $52.19 for the teachers, local optometrists and volunteers. In producing the cost estimates for teacher screening and local optometrist screening models, we used a salary payment that was identical for both models (with the salary being equal to that of the optometrist). The teacher screening model was the most cost-effective. CONCLUSION: Accuracy of screening by teachers, local optometrists and volunteers was the same in this setting, but the use of teachers was most cost-effective, reducing the cost per case detected by almost 40%.

Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach.

BACKGROUND: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. RESULTS: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. CONCLUSIONS: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time.

Risk assessment model for invasive breast cancer in Hong Kong women.

No risk assessment tool is available for identifying high risk population of breast cancer (BCa) in Hong Kong. A case-control study including 918 BCa cases and 923 controls was used to develop the risk assessment model among Hong Kong Chinese women.Each participant received an in-depth interview to obtain their lifestyle and environmental risk factors. Least absolute shrinkage and selection operator (LASSO) selection model was used to select the optimal risk factors (LASSO-model). A risk score system was constructed to evaluate the cumulative effects of selected factors. Bootstrap simulation was used to test the internal validation of the model. Model performance was evaluated by receiver-operator characteristic curves and the area under the curve (AUC).Age, number of parity, number of BCa cases in 1st-degree relatives, exposure to light at night, and sleep quality were the common risk factors for all women. Alcohol drinking was included for premenopausal women; body mass index, age at menarche, age at 1st give birth, breast feeding, using of oral contraceptive, hormone replacement treatment, and history of benign breast diseases were included for postmenopausal women. The AUCs were 0.640 (95% CI, 0.598-0.681) and 0.655 (95% CI, 0.621-0.653) for pre- and postmenopausal women, respectively. Further subgroup evaluation revealed that the model performance was better for women aged 50 to 70 years or ER-positive.This BCa risk assessment tool in Hong Kong Chinese women based on LASSO selection is promising, which shows a slightly higher discriminative accuracy than those developed in other populations.

A comparison between the pectoralis major myocutaneous flap and the free anterolateral thigh perforator flap for reconstruction in head and neck cancer patients: assessment of the quality of life.

Our study investigated the quality of life (QoL) of Chinese patients after immediate reconstruction surgery on individuals with head and neck cancer. In addition, we compared the differences between pectoralis major myocutaneous flap (PMMF) and anterolateral thigh free flap (ALTFF). The University of Washington Quality of Life questionnaire, version 4, was used to assess the QoL. Assessments were performed at least 24 months postoperatively. A total of 110 patients' records were obtained. Among them, 86 patients completed a QoL questionnaire (78.2%). No significant differences could be found in age, primary site, T stage, N stage, and postoperative radiotherapy between PMMF and ALTFF groups. However, there were significant differences between both groups in sex, operation time, and complication. A matched analysis was performed to compare the differences in QoL between patients with head and neck cancers reconstructed with PMMF or ALTFF. Patients reconstructed with ALTFF had better shoulder but worse speech functions. There was a significant effect on the QoL of head and neck cancer patients who had undergone either PMMF or ALTFF reconstruction. The result of this study provide useful information for physicians and patients during their discussion of treatment modalities for head and neck cancers.

Free fibula flap: assessment of quality of life of patients with head and neck cancer who have had defects reconstructed.

This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers.