Cost-effectiveness of alternative NTRK testing strategies in cancer patients followed by histology-independent therapy with entrectinib: an analysis of three European countries.

Aim: To explore variations in the cost-effectiveness of entrectinib across different testing strategies and settings. Methods: Four testing strategies where adult cancer patients received entrectinib if they tested positive for NTRK gene fusions compared with 'no testing' and standard of care (SoC) for all patients were evaluated. Results: Immunohistochemistry for all patients followed by RNA-based next-generation sequencing after a positive result was the optimal strategy in all included countries. However, the incremental net monetary benefit compared with SoC was negative in all countries, ranging between international euros (int€) -206 and -404. In a subgroup analysis with only NTRK-positive patients, the incremental net monetary benefit was int€ 8405 in England, int€ -53,088 in Hungary and int€ 54,372 in The Netherlands. Conclusion: Using the cost-effectiveness thresholds recommended by national guidelines, none of the testing strategies were cost-effective compared with no testing. The implementation of entrectinib is unlikely to become cost-effective in Hungary, due to the large cost difference between the entrectinib and SoC arms, while there might be more potential in England and The Netherlands.

Histology-independent pharmaceuticals are a new phenomenon in cancer care. Most chemotherapies are prescribed based on the tumor's (primary) location, while histology-independent therapies are prescribed based on genetic markers in the tumor DNA. In this study, the added value of the histology-independent treatment entrectinib, which is aimed at cancer patients with so-called NTRK gene fusions, was investigated. Because these patients must be identified before they can be given entrectinib, various strategies for diagnostic testing were considered. An economic model was programmed to gain insight into the costs and health outcomes associated with the different testing strategies. The same analysis was done for three different countries (England, Hungary and The Netherlands) using local data. In all three countries, the health gains from receiving entrectinib may be large for patients with NTRK gene fusions. However, treatment with entrectinib was also much more expensive than standard-care treatment, especially in Hungary. In each of the three countries, all evaluated testing strategies were found to offer a negative net benefit to society (i.e., a net loss). This may be partially explained by the fact that NTRK gene fusions are rare, meaning that a large group of cancer patients has to receive (costly) testing while, subsequently, only a few patients enjoy the benefit of switching to a treatment that is more effective for them (i.e., entrectinib). Nonetheless, in England and Hungary, even if the most accurate test was provided for free, the net benefit to society of implementing entrectinib remained negative. Further changes, such as a reduction in the price of entrectinib, may therefore be needed.

Preliminary Findings on the Optimization of Visual Performance in Patients with Age-Related Macular Degeneration Using Biofeedback Training.

Biofeedback training has been used to improve fixation stability in subjects with central vision loss, but the psychophysiological mechanisms underlying the functional improvements resulted was not reported. The aim of this study was to investigate the effects of microperimetric biofeedback training on different visual functions and self-reported quality of vision in subjects with age-related macular degeneration. This case-control study included six subjects (72.0 ± 6.1 years of age) diagnosed with age-related macular degeneration (wet or dry) with low vision (best corrected visual acuity ranging from 0.5 to 0.1 in the study eye) and five healthy volunteers (64.2 ± 3.7 years of age). Ophthalmological and functional examinations were obtained from all subjects twice with an approximately 3-month interval. Subjects with central vision loss performed 12 sessions (10 min each) of biofeedback training between the two examinations. Functional evaluation included: microperimetry, spatial luminance contrast sensitivities, color vision thresholds, visual acuity, and reading speed. Visual performance during daily activities was also assessed using a standardized questionnaire. The ratio (2nd/1st examination) of the spatial luminance contrast sensitivity at lower spatial frequencies were much higher for the training subjects compared with the controls. In addition, self-reported quality of vision improved after the training. The significant improvement of the visual function such as spatial luminance contrast sensitivity may explain the better self-reported quality of vision. Possible structural and physiological mechanisms underlying this neuromodulation are discussed.

Correlations between colonization of onion thrips and leaf reflectance measures across six cabbage varieties.

The main purpose of this study was to reveal if the UV-A, and visible light reflection of leaves of white cabbage varieties is correlated to resistance against onion thrips. The antixenotic resistance (AR) against onion thrips and thrips damage differed between varieties Balashi, Bloktor, Riana - considered resistant - and Green Gem, Hurricane, Quisor - considered susceptible. The solar UV-A (340-400 nm) and visible (401-650 nm) light reflection of white cabbage leaves were recorded. Correlation between AR against onion thrips and reflection of leaves in UV-A and visible range of the studied white cabbage varieties were computed. According to the AR evaluation onion thrips density was always higher on susceptible than on resistant varieties. The UV-A light reflection of head forming leaves and the contrast between head and exterior leaves (H/E) was negatively correlated with onion thrips host preference at an early stage of cabbage head formation. The visible light reflection of both head forming and exterior leaves was also negatively correlated with onion thrips host preference. Susceptible varieties had greater damage ratings at harvest than resistant ones and positive correlations were observed between AR and damage. AR against onion thrips may be affected by differences in reflection of cabbage leaves at an early growth stage. It is suggested that more intensive reflection of leaves and/or higher contrast values between the reflectance intensity of head versus outer leaves made the resistant varieties less attractive to onion thrips. Our results reported here provide the first evidence of negative correlation between UV-A and visible reflection of leaves and AR of white cabbage against a dangerous insect pest, opening new perspectives for understanding the role of reflection by plant leaves in pest management.

Transcranial direct current stimulation modulates human color discrimination in a pathway-specific manner.

Previous research showed that transcranial direct current stimulation (tDCS) can modulate visual cortex excitability. However, there is no experiment on the effects of tDCS on color perception to date. The present study aimed to investigate the effects of tDCS on color discrimination tasks. Fifteen healthy subjects (mean age of 25.6 ± 4.4 years) were tested with Cambridge Color Test 2.0 (Trivector and ellipses protocols) and a Forced-choice Spatial Color Contrast Sensitivity task (vertical red-green sinusoidal grating) while receiving tDCS. Anodal, cathodal, and sham tDCS were delivered at Oz for 22 min using two square electrodes (25 cm(2) with a current of 1.5 mA) in sessions separated by 7 days. Anodal tDCS significantly increased tritan sensitivity (p < 0.01) and had no significant effect on protan, deutan, or red-green grating discrimination. The effects on the tritan discrimination returned to baseline after 15 min (p < 0.01). Cathodal tDCS reduced the sensitivity in the deutan axis and increased sensitivity in the tritan axis (p < 0.05). The lack of anodal tDCS effects in the protan, deutan, and red-green grating sensitivities could be explained by a "ceiling effect" since adults in this age range tend to have optimal color discrimination performance for these hues. The differential effects of cathodal tDCS on tritan and deutan sensitivities and the absence of the proposed ceiling effects for the tritan axes might be explained by Parvocellular (P) and Koniocellular (K) systems with regard to their functional, physiological, and anatomical differences. The results also support the existence of a systematic segregation of P and K color-coding cells in V1. Future research and possible clinical implications are discussed.