Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand–foot syndrome and a combination of grade 1–2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Bichromatic electromagnetically induced transparency in cold rubidium atoms

In a three-level atomic system coupled by two equal-amplitude laser fields with a frequency separation 2$\delta$, a weak probe field exhibits a multiple-peaked absorption spectrum with a constant peak separation $\delta$. The corresponding probe dispersion exhibits steep normal dispersion near the minimum absorption between the multiple absorption peaks, which leads to simultaneous slow group velocities for probe photons at multiple frequencies separated by $\delta$. We report an experimental study in such a bichromatically coupled three-level $\Lambda$ system in cold $^{87}$Rb atoms. The multiple-peaked probe absorption spectra under various experimental conditions have been observed and compared with the theoretical calculations.Comment: RevTex, 4 pages, 6 figures, Email address: [email protected]

Do Large Language Model Chatbots perform better than established patient information resources in answering patient questions?:A comparative study on melanoma

BACKGROUND: Large Language Models (LLMs) have a potential role in providing adequate patient information.OBJECTIVES: To compare the quality of LLMs' responses with established Dutch patient information resources (PIRs) in answering patient questions regarding melanoma.METHODS: Responses from ChatGPT versions 3.5 and 4.0, Gemini, and three leading Dutch melanoma PIRs to 50 melanoma-specific questions were examined at baseline and for LLMs again after eight months. Outcomes included (medical) accuracy, completeness, personalisation, readability, and additionally reproducibility for LLMs. Comparative analyses were performed within LLMs and PIRs using Friedman's ANOVA, and between best-performing LLMs and gold-standard PIR using Wilcoxon Signed Ranks test.RESULTS: Within LLMs, ChatGPT-3.5 demonstrated the highest accuracy (p=0.009). Gemini performed best in completeness (p&lt;0.001), personalisation (p=0.007), and readability (p&lt;0.001). PIRs were consistent in accuracy and completeness, with the general practitioner's website excelling in personalisation (p=0.013) and readability (p&lt;0.001). The best-performing LLMs outperformed the gold-standard PIR on all criteria except accuracy. Over time, response reproducibility decreased for all LLMs, showing variability across outcomes.CONCLUSIONS: Although LLMs show potential in providing highly personalised and complete responses to patient questions regarding melanoma, improving and safeguarding accuracy, reproducibility and accessibility is crucial before they can replace or complement conventional PIRs.This study compared the quality of responses from Large Language Models (LLMs) with established Dutch patient information resources (PIRs) for melanoma-related patient questions. Results showed LLMs provided highly personalised and complete answers, often surpassing PIRs. However, improving and safeguarding accuracy, reproducibility and accessibility is crucial before they can replace or complement conventional PIRs.</p

Optically written waveguide in an atomic vapor

We present the first demonstration of an optically written waveguide in an atomic vapor. By strongly pumping one rubidium transition, we are able to waveguide a weak probe beam at a different rubidium transition. These effects can be understood with reference to a model of the refractive index for a V system. [S0031-9007(99)08495-1]

Seasonal variation of anti-PD-1 outcome in melanoma—Results from a Dutch patient cohort

Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long-term) benefit from these treatments. There is evidence that the exposome, an accumulation of host-extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with BRAF wild-type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host-extrinsic factor influences the response to ICI-treatment. Analysis and support of clinical decision makin

Trends in survival and costs in metastatic melanoma in the era of novel targeted and immunotherapeutic drugs

BACKGROUND: The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs. MATERIALS AND METHODS: Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan–Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis. RESULTS: Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million. CONCLUSION: Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma