Economic evaluation of adverse events of dabrafenib plus trametinib versus nivolumab in patients with advanced BRAF-mutant cutaneous melanoma for adjuvant therapy in Germany

Background: Adjuvant treatment options have become the standard therapy for stage III and IV resectable cutaneous melanoma. Two recent studies led to the registration of dabrafenib and trametinib as targeted therapies for BRAF-mutated melanoma, and of immunotherapy with nivolumab irrespective of BRAF-mutation status. Both therapies have different spectrums of adverse events. Objective: To estimate the financial impact of side effects from the perspective of the German statutory sick funds to compare both therapeutic options and to relate the burden to the overall costs of the treatment. Study design and setting: Thirty-six adverse event categories for the combination of dabrafenib and trametinib (‘combi treatment’) and for nivolumab were extracted from the original publications of the studies named COMBI-AD and CheckMate 238. Patients and intervention: For all event categories a diagnosis and therapy recommendation were determined according to current national or international guidelines or from leading German textbooks. Main outcome measure: The resulting diagnostic steps, treatments, and therapies were evaluated with unit costs based on the German fee schedule for ambulatory physicians, the German G-DRG scheme, and the German drug price list. Results: The number of events with nivolumab per one hundred treatments amounted to 3.8 mandatory hospitalizations, 3.5 emergency care events and 0.8 life-threatening events. For the combi treatment, the respective number of events per one hundred treatments was 2.7, 1.8, and 0.5. The overall cost burden was calculated as €899 for nivolumab and €861 for combi-treatment. Conclusion: The treatment of adverse events resulting from adjuvant melanoma therapy showed comparable costs for both therapies

Electrostatic Interactions of Asymmetrically Charged Membranes

We predict the nature (attractive or repulsive) and range (exponentially screened or long-range power law) of the electrostatic interactions of oppositely charged and planar plates as a function of the salt concentration and surface charge densities (whose absolute magnitudes are not necessarily equal). An analytical expression for the crossover between attractive and repulsive pressure is obtained as a function of the salt concentration. This condition reduces to the high-salt limit of Parsegian and Gingell where the interaction is exponentially screened and to the zero salt limit of Lau and Pincus in which the important length scales are the inter-plate separation and the Gouy-Chapman length. In the regime of low salt and high surface charges we predict - for any ratio of the charges on the surfaces - that the attractive pressure is long-ranged as a function of the spacing. The attractive pressure is related to the decrease in counter-ion concentration as the inter-plate distance is decreased. Our theory predicts several scaling regimes with different scaling expressions for the pressure as function of salinity and surface charge densities. The pressure predictions can be related to surface force experiments of oppositely charged surfaces that are prepared by coating one of the mica surfaces with an oppositely charged polyelectrolyte

Evidence that the a0(980) and f0(980) are not elementary particles

We study the interesting problem of whether it is possible to distinguish composite from elementary particles. In particular we generalize a model-independent approach of S. Weinberg to the case of unstable particles. This allows us to apply our formalism to the case of the a0(980) and f0(980) resonances and to address the question whether these particles are predominantly genuine, confined quark states (of $\bar q q$ or $qq\bar q\bar q$ structure) or governed by mesonic components.Comment: 15 pages, 4 Figure

Supportive Care in Older Adults with Cancer: Across the Continuum

Supportive care is an essential component of anti-cancer treatment regardless of age or treatment intent. As the number of older adults with cancer increases, and supportive care strategies enable more patients to undergo treatment, greater numbers of older patients will become cancer survivors. These patients may have lingering adverse effects from treatment and will need continued supportive care interventions. Older adults with cancer benefit from geriatric assessment (GA)-guided supportive care interventions. This can occur at any stage across the cancer treatment continuum. As a GA commonly uncovers issues potentially unrelated to anti-cancer treatment, it could be argued that the assessment is essentially a supportive care strategy. Key aspects of a GA include identification of comorbidities, assessing for polypharmacy, screening for cognitive impairment and delirium, assessing functional status, and screening for psychosocial issues. Treatment-related issues of particular importance in older adults include recognition of increased bone marrow toxicity, management of nausea and vomiting, identification of anemia, and prevention of neurotoxicity. The role of physical therapy and cancer rehabilitation as a supportive care strategy in older adults is important regardless of treatment stage or intent

Bethe-Salpeter equation and a nonperturbative quark-gluon vertex

A Ward-Takahashi identity preserving Bethe-Salpeter kernel can always be calculated explicitly from a dressed-quark-gluon vertex whose diagrammatic content is enumerable. We illustrate that fact using a vertex obtained via the complete resummation of dressed-gluon ladders. While this vertex is planar, the vertex-consistent kernel is nonplanar and that is true for any dressed vertex. In an exemplifying model the rainbow-ladder truncation of the gap and Bethe-Salpeter equations yields many results; e.g., pi- and rho-meson masses, that are changed little by including higher-order corrections. Repulsion generated by nonplanar diagrams in the vertex-consistent Bethe-Salpeter kernel for quark-quark scattering is sufficient to guarantee that diquark bound states do not exist.Comment: 16 pages, 12 figures, REVTEX

New Results in Sasaki-Einstein Geometry

This article is a summary of some of the author's work on Sasaki-Einstein geometry. A rather general conjecture in string theory known as the AdS/CFT correspondence relates Sasaki-Einstein geometry, in low dimensions, to superconformal field theory; properties of the latter are therefore reflected in the former, and vice versa. Despite this physical motivation, many recent results are of independent geometrical interest, and are described here in purely mathematical terms: explicit constructions of infinite families of both quasi-regular and irregular Sasaki-Einstein metrics; toric Sasakian geometry; an extremal problem that determines the Reeb vector field for, and hence also the volume of, a Sasaki-Einstein manifold; and finally, obstructions to the existence of Sasaki-Einstein metrics. Some of these results also provide new insights into Kahler geometry, and in particular new obstructions to the existence of Kahler-Einstein metrics on Fano orbifolds.Comment: 31 pages, no figures. Invited contribution to the proceedings of the conference "Riemannian Topology: Geometric Structures on Manifolds"; minor typos corrected, reference added; published version; Riemannian Topology and Geometric Structures on Manifolds (Progress in Mathematics), Birkhauser (Nov 2008