Pharmacoeconomic analysis of prostaglandin and prostamide therapy for patients with glaucoma or ocular hypertension

BACKGROUND: To determine monthly cost and cost effectiveness of bilateral prostaglandin/prostamide therapy for lowering intraocular pressure (IOP) in patients taking bimatoprost 0.03% (Lumigan(®), Allergan, Inc.), latanoprost 0.005% (Xalatan(®), Pfizer, Inc.), or travoprost 0.004% (Travatan(®), Alcon Laboratories, Inc.). METHODS: Drops in five new 2.5-mL bottles were counted and then averaged for each drug. Average retail price was determined by surveys of pharmacies. Drop count, average retail price, average wholesale price, and IOP reduction data were used to compute annual cost, and cost effectiveness (annual cost-per-mm Hg of IOP reduction) of the three drugs. RESULTS: Drops per 2.5-mL bottle averaged 113 for bimatoprost 0.03%, 84 for latanoprost 0.005%, and 83 for travoprost 0.004%. Average retail cost (2005) per bottle was $69.99 for bimatoprost 0.03$61.69 for latanoprost 0.005%, and $66.37 for travoprost 0.004$37.92 for bimatoprost 0.03%, $44.75 for latanoprost 0.005$49.25 for travoprost 0.004%. Cost effectiveness ranges were $57 to$65 per mm Hg reduction in IOP per year for bimatoprost, 0.03%, $67 to$90 per mm Hg for latanoprost 0.005%, and $74 to$84 per mm Hg for travoprost 0.004%. CONCLUSION: Bimatoprost 0.03% had the lowest monthly and annual costs and the greatest cost effectiveness for lowering IOP compared with latanoprost 0.005% and travoprost 0.004%

Hyperbaric oxygen therapy for the treatment of radiation-induced macular ischemia

Shamim A Haji1,2, Ronald EP Frenkel1,2,31Eye Research Foundation, Stuart, FL, USA; 2East Florida Eye Institute, Stuart, FL, USA; 3Bascom Palmer Eye Institute, Miami, FL, USAPurpose: To report a case of radiation-induced macular ischemia where vision and macular perfusion improved after hyperbaric oxygen (HBO) therapy.Methods: A 62-year-old male patient developed radiation-induced macular ischemia after he was treated with radiation for brain glioma. The patient presented with best spectacle-corrected visual acuity (BSCVA) acuity of 20/400 in his right eye. Optical coherence tomography (OCT) showed central macular thickness of 468 μm. The patient received focal laser, intravitreal triamcinolone, and HBO therapy.Results: The patient’s vision improved from 20/400 to 20/100 after focal laser and intravitreal triamcinolone. His central macular thickness improved from 468 μm to 132 μm. After receiving HBO therapy, his VA improved to 20/50 and fluorescein angiography showed improvement in macular perfusion.Conclusion: HBO therapy improves macular perfusion in patients with radiation-induced macular ischemia.Keywords: macular ischemia, visual acuity, hyperbaric oxygen therapy, macular perfusio

Time separation as a hidden variable to the Copenhagen school of quantum mechanics

The Bohr radius is a space-like separation between the proton and electron in the hydrogen atom. According to the Copenhagen school of quantum mechanics, the proton is sitting in the absolute Lorentz frame. If this hydrogen atom is observed from a different Lorentz frame, there is a time-like separation linearly mixed with the Bohr radius. Indeed, the time-separation is one of the essential variables in high-energy hadronic physics where the hadron is a bound state of the quarks, while thoroughly hidden in the present form of quantum mechanics. It will be concluded that this variable is hidden in Feynman's rest of the universe. It is noted first that Feynman's Lorentz-invariant differential equation for the bound-state quarks has a set of solutions which describe all essential features of hadronic physics. These solutions explicitly depend on the time separation between the quarks. This set also forms the mathematical basis for two-mode squeezed states in quantum optics, where both photons are observable, but one of them can be treated a variable hidden in the rest of the universe. The physics of this two-mode state can then be translated into the time-separation variable in the quark model. As in the case of the un-observed photon, the hidden time-separation variable manifests itself as an increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be published in one of the AIP Conference Proceedings serie

SL(2,R) Chern-Simons, Liouville, and Gauge Theory on Duality Walls

We propose an equivalence of the partition functions of two different 3d gauge theories. On one side of the correspondence we consider the partition function of 3d SL(2,R) Chern-Simons theory on a 3-manifold, obtained as a punctured Riemann surface times an interval. On the other side we have a partition function of a 3d N=2 superconformal field theory on S^3, which is realized as a duality domain wall in a 4d gauge theory on S^4. We sketch the proof of this conjecture using connections with quantum Liouville theory and quantum Teichmuller theory, and study in detail the example of the once-punctured torus. Motivated by these results we advocate a direct Chern-Simons interpretation of the ingredients of (a generalization of) the Alday-Gaiotto-Tachikawa relation. We also comment on M5-brane realizations as well as on possible generalizations of our proposals.Comment: 53+1 pages, 14 figures; v2: typos corrected, references adde

N=2 gauge theories on toric singularities, blow-up formulae and W-algebrae

We compute the Nekrasov partition function of gauge theories on the (resolved) toric singularities C2/\u393 in terms of blow-up formulae. We discuss the expansion of the partition function in the e1,e2 \u2192 0 limit along with its modular properties and how to derive them from the M-theory perspective. On the two-dimensional conformal field theory side, our results can be interpreted in terms of representations of the direct sum of Heisenberg plus W_N -algebrae with suitable central charges, which can be computed from the fan of the resolved toric variety. We provide a check of this correspondence by computing the central charge of the two-dimensional theory from the anomaly polynomial of M5-brane theory. Upon using the AGT correspondence our results provide a candidate for the conformal blocks and three-point functions of a class of the two-dimensional CFTs which includes parafermionic theories

Megascopic Quantum Phenomena. A Critical Study of Physical Interpretations

A megascopic revalidation is offered providing responses and resolutions of current inconsistencies and existing contradictions in present-day quantum theory. As the core of this study we present an independent proof of the Goldstone theorem for a quantum field formulation of molecules and solids. Along with phonons two types of new quasiparticles appear: rotons and translons. In full analogy with Lorentz covariance, combining space and time coordinates, a new covariance is necessary, binding together the internal and external degrees of freedom, without explicitly separating the centre-of-mass, which normally applies in both classical and quantum formulations. The generally accepted view regarding the lack of a simple correspondence between the Goldstone modes and broken symmetries, has significant consequences: an ambiguous BCS theory as well as a subsequent Higgs mechanism. The application of the archetype of the classical spontaneous symmetry breaking, i.e. the Mexican hat, as compared to standard quantum relations, i.e. the Jahn-Teller effect, superconductivity or the Higgs mechanism, becomes a disparity. In short, symmetry broken states have a microscopic causal origin, but transitions between them have a teleological component. The different treatments of the problem of the centre of gravity in quantum mechanics and in field theories imply a second type of Bohr complementarity on the many-body level opening the door for megascopic representations of all basic microscopic quantum axioms with further readings for teleonomic megascopic quantum phenomena, which have no microscopic rationale: isomeric transitions, Jahn-Teller effect, chemical reactions, Einstein-de Haas effect, superconductivity-superfluidity, and brittle fracture.Comment: 117 pages, 17 sections, final revised version from 20 May 2019 but uploaded after the DOI was know

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe