Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events (Review)

Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe when used alone or in conjunction with inhaled corticosteroids. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol with inhaled corticosteroids versus the same dose of inhaled corticosteroids alone. Search strategy Trials were identified using the Cochrane Airways Group Specialised Register of trials. Web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol were also checked. The date of the most recent search was October 2008. Selection criteria Controlled parallel design clinical trials on patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol and inhaled corticosteroids, and were of at least 12 weeks duration. Data collection and analysis Two authors independently selected trials for inclusion in the review. Outcome data were independently extracted by two authors. Unpublished data on mortality and serious adverse events were obtained from the sponsors. Main results The review included 14 studies on adults and adolescents (8,028 participants) and seven studies on children and adolescents (2,788 participants). Data on all cause fatal and non-fatal serious adverse events were found for all studies, and the overall risk of bias was low.Four deaths occurred on regular formoterol with inhaled corticosteroids, and none on regular inhaled corticosteroids alone. All the deaths were in adults, and one was reported to be asthma-related. The difference was not statistically significant. Non-fatal serious adverse events of any cause were very similar in adults [Peto Odds Ratio 0.99 (95% CI 0.74 to 1.33)], and an increase in events in children on regular formoterol was not statistically significant [Peto Odds Ratio 1.62 (95% CI 0.80 to 3.28)]. Asthma related serious adverse events on formoterol were lower in adults [Peto Odds Ratio 0.53 (95% CI 0.28 to 1.00)] and although they were higher in children [Peto Odds Ratio 1.49 ( 95% CI 0.48 to 4.61)], this was not statistically significant. Authors' conclusions It is not possible, from the data in this review, to reassure people with asthma that inhaled corticosteroids with regular formoterol carries no risk of increasing mortality in comparison to inhaled corticosteroids alone as all four deaths occurred among 6,594 people using inhaled corticosteroids with formoterol. On the other hand, we have found no conclusive evidence of harm and there was only one asthma related death registered during over 3,000 patient year observation on formoterol. In adults, the decrease in asthma-related serious adverse events on regular formoterol with inhaled corticosteroids was not accompanied by a decrease in all cause serious adverse events. In children the number of events was too small, and consequently the results too imprecise, to determine whether the increase in all cause non-fatal serious adverse events found in the previous meta-analysis on regular formoterol alone is abolished by the additional use of inhaled corticosteroids. Clinical decisions and information for patients regarding regular use of formoterol have to take into account the balance between known symptomatic benefits of formoterol and the degree of uncertainty and concern associated with its potential harmful effects

Diffusion and rheology in a model of glassy materials

We study self-diffusion within a simple hopping model for glassy materials. (The model is Bouchaud's model of glasses [J.-P. Bouchaud, J. Physique I 2, 1705 (1992)], as extended to describe rheological properties [P. Sollich, F. Lequeux, P. Hebraud and M.E. Cates, Phys. Rev. Lett. 78, 2020 (1997)].) We investigate the breakdown, near the glass transition, of the (generalized) Stokes-Einstein relation between self-diffusion of a tracer particle and the (frequency-dependent) viscosity of the system as a whole. This stems from the presence of a broad distribution of relaxation times of which different moments control diffusion and rheology. We also investigate the effect of flow (oscillatory shear) on self-diffusion and show that this causes a finite diffusivity in the temperature regime below the glass transition (where this was previously zero). At higher temperatures the diffusivity is enhanced by a power law frequency dependence that also characterises the rheological response. The relevance of these findings to soft glassy materials (foams, emulsions etc.) as well as to conventional glass-forming liquids is discussed.Comment: 39 page (double spaced), 2 figure

Thermal fluctuations in the lattice Boltzmann method for non-ideal fluids

We introduce thermal fluctuations in the lattice Boltzmann method for non-ideal fluids. A fluctuation-dissipation theorem is derived within the Langevin framework and applied to a specific lattice Boltzmann model that approximates the linearized fluctuating Navier-Stokes equations for fluids based on square-gradient free energy functionals. The obtained thermal noise is shown to ensure equilibration of all degrees of freedom in a simulation to high accuracy. Furthermore, we demonstrate that satisfactory results for most practical applications of fluctuating hydrodynamics can already be achieved using thermal noise derived in the long wavelength-limit.Comment: 15 pages, 5 figure

He Started the Whole World Singing a Song

Throughout history, people from a variety of backgrounds have commented on the relationship between music and language. Several say that music transcends language; some refer to music as being another language; others believe music actually speaks. In spite of a diversity of responses, there is still a collective sense that music and language are intriguingly related—a profound, intuitive awareness of some type of bonding agent between the two. Music has also been perceived throughout history to possess meaning and power, both on a grand, cosmic level and an anthropic, human level. For the Greek philosopher Plato, music acted as something that “[implanted] cosmic harmony into the soul of humans,” while in the Old Testament of the Bible, “[w]henever the spirit from God troubled Saul, David would pick up his harp and play, and Saul would then be relieved, feel better.” Music moves listeners powerfully and communicates meaning in ways that are often difficult or impossible to express in words. In this paper, I wish to explore the essence of these musical moments and attempt to articulate why they occur from a theological framework. This framework will consist of demonstrating a connection between language and music, discussing how music is able to possess meaning, and showing that throughout the Bible, people have responded to the transcendent and immanent presence of the Triune God working in and through creation musically. With this framework in place, I will conclude this paper by discussing how music has the capacity to reveal three essential qualities of what it means to be fully human in a world where God is fully present: hope, faith, and love

On the Power of Music: Using \u27Cosmos\u27 and \u27Anthropos\u27 to Articulate a Holistic Approach to Discussing the Power of Music

Throughout history music has played an integral role in shaping both societies at large and individuals who are a part of these societies. Many of these individuals have sought not only to enjoy music by listening to it from an aesthetic paradigm, but by understanding it from a metaphysical one, probing its sonic depths and studying its emotive qualities, starting with the doctrines of music proposed by ancient Greek philosophers. However, from the doctrines of music in the ancient era up to the doctrines of music in the baroque era, one can observe a shift in the way music was perceived metaphysically. In spite of this shift, there remained a unifying idea: music moves. In this paper, I will attempt to show where this shift in musical thought occurred in history and explain its significance for present day lovers of music. By understanding the impact of this paradigm shift and having a more accurate way of approaching the perception of music in general, one is able to be more effective in realizing and appreciating the power of music in everyday life

On the Power of Music: Using \u27Cosmos\u27 and \u27Anthropos\u27 to Articulate a Holistic Approach to Discussing the Power of Music

Music is an experience that is universal to all of mankind, no matter one’s race, gender, culture, or socioeconomic status. Whether it’s beholding one of Mahler’s symphonies in Carnegie Hall or listening to the “No. 1 Top Single” on iTunes using headphones, one truth is evident: music moves. The statement “music moves” inherently possesses an implication of the \u27cosmic\u27 and the \u27anthropic’ nature of music – a holistic union of both mystery and humanity. This one truth has been the subject of an ongoing 2,000 year-old discussion that attempts to articulate the powerful reaction that results from experiencing music in all forms, beginning with the ancient Greeks of antiquity who possessed a cosmologically-grounded explanation to the power of music. However, as time moved forward, this cosmological, mysterious paradigm of the power of music slowly began to incorporate explainable and tangible anthropological articulations of the power of the music with respect to the human emotions, senses, and thoughts. This incorporation of anthropos reached a climax in the Renaissance era with the ushering in of humanism, which stripped away the mysterious and replaced the cosmologically-grounded explanation of music with the anthropologically-grounded view of naturalism. Since this profound departure from cosmos, society seems to be at a loss in articulating accurate reactions to music. This paper offers two proposals with respect to musical thought, one for society at large and one for the individual. I assert in this paper that society, in general, needs to return to an appreciation of the cosmos, the answerable, and the mysterious in nature, and that the individual needs to commence thinking holistically with respect to music—incorporating both cosmic and anthropic thought. I have reached my conclusions, assertions, and propositions based on this thesis by critically analyzing both primary and secondary resources in the form of the historical documentation methodology