Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios

Numerical solution to the hermitian Yang-Mills equation on the Fermat quintic

We develop an iterative method for finding solutions to the hermitian Yang-Mills equation on stable holomorphic vector bundles, following ideas recently developed by Donaldson. As illustrations, we construct numerically the hermitian Einstein metrics on the tangent bundle and a rank three vector bundle on P^2. In addition, we find a hermitian Yang-Mills connection on a stable rank three vector bundle on the Fermat quintic.Comment: 25 pages, 2 figure

Hyperholomorpic connections on coherent sheaves and stability

Let $M$ be a hyperkaehler manifold, and $F$ a torsion-free and reflexive coherent sheaf on $M$. Assume that $F$ (outside of its singularities) admits a connection with a curvature which is invariant under the standard SU(2)-action on 2-forms. If the curvature is square-integrable, then $F$ is stable and its singularities are hyperkaehler subvarieties in $M$. Such sheaves (called hyperholomorphic sheaves) are well understood. In the present paper, we study sheaves admitting a connection with SU(2)-invariant curvature which is not necessarily square-integrable. This situation arises often, for instance, when one deals with higher direct images of holomorphic bundles. We show that such sheaves are stable.Comment: 37 pages, version 11, reference updated, corrected many minor errors and typos found by the refere

Small bound for birational automorphism groups of algebraic varieties (with an Appendix by Yujiro Kawamata)

We give an effective upper bound of |Bir(X)| for the birational automorphism group of an irregular n-fold (with n = 3) of general type in terms of the volume V = V(X) under an ''albanese smoothness and simplicity'' condition. To be precise, |Bir(X)| < d_3 V^{10}. An optimum linear bound |Bir(X)|-1 < (1/3)(42)^3 V is obtained for those 3-folds with non-maximal albanese dimension. For all n > 2, a bound |Bir(X)| < d_n V^{10} is obtained when alb_X is generically finite, alb(X) is smooth and Alb(X) is simple.Comment: Mathematische Annalen, to appea

Knaster's problem for (Z2)k(Z_2)^k-symmetric subsets of the sphere S2k−1S^{2^k-1}

We prove a Knaster-type result for orbits of the group $(Z_2)^k$ in $S^{2^k-1}$, calculating the Euler class obstruction. Among the consequences are: a result about inscribing skew crosspolytopes in hypersurfaces in $\mathbb R^{2^k}$, and a result about equipartition of a measures in $\mathbb R^{2^k}$ by $(Z_2)^{k+1}$-symmetric convex fans

Use of traditional and complementary medicine as self-care strategies in community health centers

In China, Community Health Centers (CHCs) are major providers of primary care services, but their potential in empowering patients’ self-management capacity has not been assessed. This study aims to describe self-care practice patterns amongst CHC attendees in urban China. In this cross-sectional quantitative study, 3360 CHC patients from 6 cities within the Pearl Delta Region were sampled using multistage cluster sampling. Thirty-seven per cent had used with over-the-counter Chinese herbal medicines (OTC CHMs) in the past year and majority of respondents found OTC CHMs effective. OTC CHMs were more popular amongst those who needed to pay out of pocket for CHC services. Less than 10% used vitamins and minerals, and those with a lower socioeconomic background have a higher propensity to consume. Although doubts on their usefulness are expressed, their use by the vulnerable population may reflect barriers to access to conventional health care, cultural affinity, or a defense against negative consequences of illnesses. About 25% performed physical exercise, but the prevalence is lower amongst women and older people. Taiji seems to be an alternative for these populations with promising effectiveness, but overall only 6% of CHC attendees participated. These results suggest that CHCs should start initiatives in fostering appropriate use of OTC CHM, vitamins, and minerals. Engaging community pharmacists in guiding safe and effective use of OTC CHM amongst the uninsured is essential given their low accessibility to CHC services. Prescription of Taiji instead of physical exercises to women and older people could be more culturally appropriate, and the possibility of including this as part of the CHC services worth further exploration

K\"{a}hler-Einstein metrics on strictly pseudoconvex domains

The metrics of S. Y. Cheng and S.-T. Yau are considered on a strictly pseudoconvex domains in a complex manifold. Such a manifold carries a complete K\"{a}hler-Einstein metric if and only if its canonical bundle is positive. We consider the restricted case in which the CR structure on $\partial M$ is normal. In this case M must be a domain in a resolution of the Sasaki cone over $\partial M$. We give a condition on a normal CR manifold which it cannot satisfy if it is a CR infinity of a K\"{a}hler-Einstein manifold. We are able to mostly determine those normal CR 3-manifolds which can be CR infinities. Many examples are given of K\"{a}hler-Einstein strictly pseudoconvex manifolds on bundles and resolutions.Comment: 30 pages, 1 figure, couple corrections, improved a couple example

Nuclear Octupole Correlations and the Enhancement of Atomic Time-Reversal Violation

We examine the time-reversal-violating nuclear ``Schiff moment'' that induces electric dipole moments in atoms. After presenting a self-contained derivation of the form of the Schiff operator, we show that the distribution of Schiff strength, an important ingredient in the ground-state Schiff moment, is very different from the electric-dipole-strength distribution, with the Schiff moment receiving no strength from the giant dipole resonance in the Goldhaber-Teller model. We then present shell-model calculations in light nuclei that confirm the negligible role of the dipole resonance and show the Schiff strength to be strongly correlated with low-lying octupole strength. Next, we turn to heavy nuclei, examining recent arguments for the strong enhancement of Schiff moments in octupole-deformed nuclei over that of 199Hg, for example. We concur that there is a significant enhancement while pointing to effects neglected in previous work (both in the octupole-deformed nuclides and 199Hg) that may reduce it somewhat, and emphasizing the need for microscopic calculations to resolve the issue. Finally, we show that static octupole deformation is not essential for the development of collective Schiff moments; nuclei with strong octupole vibrations have them as well, and some could be exploited by experiment.Comment: 25 pages, 4 figures embedded in tex

Ebola virus disease

Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case–fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013–2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients