Estimating the cost-effectiveness of fluticasone propionate for treating chronic obstructive pulmonary disease in the presence of missing data

Objectives: To explore the cost-effectiveness of fluticasone propionate (FP) for the treatment of chronic obstructive pulmonary disease (COPD), we estimated costs and qualityadjusted life-years (QALYs) over 3 years, based on an economic appraisal of a previously reported clinical trial (Inhaled Steroids in Obstructive Lung Disease in Europe [ISOLDE]). Methods: Seven hundred forty-two patients enrolled in the ISOLDE trial who received either FP or placebo had data available on health-care costs and quality of life over the period of the study. The SF-36-based utility scores for quality of life were used to calculate QALYs. A combined imputation and bootstrapping procedure was employed to handle missing data and to estimate statistical uncertainty in the estimated cumulative costs and QALYs over the study period. The imputation approach was based on propensity scoring and nesting this approach within the bootstrap ensured that multiple imputations were performed such that statistical estimates included imputation uncertainty. Results: Complete data were available on mortality within the follow-up period of the study and a nonsignificant trend toward improved survival of 0.06 (95% confidence interval [CI] –0.01 to 0.15) life-years was observed. In an analysis based on a propensity scoring approach to missing data we estimated the incremental costs of FP versus placebo to be £1021 (95% CI £619–1338) with an additional effect of 0.11 QALYs (CI 0.04–0.20). Cost-effectiveness estimates for the within-trial period of £17,700 per life-year gained (£6900 to ∞) and £9500 per QALY gained (CI £4300–26,500) were generated that include uncertainty due to the imputation process. An alternative imputation approach did not materially affect these estimates. Conclusions: Previous analyses of the ISOLDE study showed significant improvement on disease-specific health status measures and a trend toward a survival advantage for treatment with FP. This analysis shows that joint considerations of quality of life and survival result in a substantial increase in QALYs favoring treatment with FP. Based on these data, the inhaled corticosteroid FP appears costeffective for the treatment of COPD. Confirmation or refutation of this result may be achieved once the Towards a Revolution in COPD Health (TORCH) study reports, a large randomized controlled trial powered to detect mortality changes associated with the use of FP alone, or in combination with salmeterol, which is also collecting resource use and utility data suitable for estimating cost-effectiveness

Magnetic fluctuation power near proton temperature anisotropy instability thresholds in the solar wind

The proton temperature anisotropy in the solar wind is known to be constrained by the theoretical thresholds for pressure anisotropy-driven instabilities. Here we use approximately 1 million independent measurements of gyroscale magnetic fluctuations in the solar wind to show for the first time that these fluctuations are enhanced along the temperature anisotropy thresholds of the mirror, proton oblique firehose, and ion cyclotron instabilities. In addition, the measured magnetic compressibility is enhanced at high plasma beta ($\beta_\parallel \gtrsim 1$) along the mirror instability threshold but small elsewhere, consistent with expectations of the mirror mode. The power in this frequency (the 'dissipation') range is often considered to be driven by the solar wind turbulent cascade, an interpretation which should be qualified in light of the present results. In particular, we show that the short wavelength magnetic fluctuation power is a strong function of collisionality, which relaxes the temperature anisotropy away from the instability conditions and reduces correspondingly the fluctuation power.Comment: 4 pages, 4 figure

Kline, Homer B. - The Spirit of Otterbein From A Personal Perspective

https://digitalcommons.otterbein.edu/archives_spirit/1004/thumbnail.jp

Evaluation of Skylab EREP data for land resource management

There are no author-identified significant results in this report

Kinetic Scale Density Fluctuations in the Solar Wind

We motivate the importance of studying kinetic scale turbulence for understanding the macroscopic properties of the heliosphere, such as the heating of the solar wind. We then discuss the technique by which kinetic scale density fluctuations can be measured using the spacecraft potential, including a calculation of the timescale for the spacecraft potential to react to the density changes. Finally, we compare the shape of the density spectrum at ion scales to theoretical predictions based on a cascade model for kinetic turbulence. We conclude that the shape of the spectrum, including the ion scale flattening, can be captured by the sum of passive density fluctuations at large scales and kinetic Alfven wave turbulence at small scales

Impact of third-order dispersion on the evolution of parabolic pulses

We present a perturbation analysis that describes the effect of third-order dispersion on the similariton pulse solution of the nonlinear Schrödinger equation in a fibre gain medium. The theoretical model predicts with sufficient accuracy the pulse structural changes induced, which are observed through direct numerical simulations

From Jöbsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase

Near-infrared spectroscopy (NIRS) measurements of cytochrome-c-oxidase (CCO) have the potential to yield crucial information about cerebral metabolism at the patient bedside. Developments in instrumentation and the analytical methods used to resolve changes in CCO have led to many clinical applications of the measurement since its first demonstration in 1977 by Jöbsis. There is a substantial literature of work on measures of CCO in animal and in vitro studies; however, this review focuses on translational studies. Almost 40 years from the advent of the first measurement of CCO using NIRS, this signal continues to hold significant interest in our understanding of the human brain in health and disease. We discuss methodologies for obtaining NIRS measurements of CCO in the clinic and review studies in neonates and adults

The critical role of intracavity dynamics in high-power mode-locked fiber lasers

We present a theoretical description of the generation of ultra-short, high-energy pulses in two laser cavities driven by periodic spectral filtering or dispersion management. Critical in driving the intra-cavity dynamics is the nontrivial phase profiles generated and their periodic modification from either spectral filtering or dispersion management. For laser cavities with a spectral filter, the theory gives a simple geometrical description of the intra-cavity dynamics and provides a simple and efficient method for optimizing the laser cavity performance. In the dispersion managed cavity, analysis shows the generated self-similar behavior to be governed by the porous media equation with a rapidly-varying, mean-zero diffusion coefficient whose solution is the well-known Barenblatt similarity solution with parabolic profile

Parabolic pulse propagation in mean-zero, dispersion-managed transmission systems and mode-locked laser cavities

Self-similarity is a ubiquitous concept in the physical sciences used to explain a wide range of spatial- or temporalstructures observed in a broad range of applications and natural phenomena. Indeed, they have been predicted or observed in the context of Raman scattering, spatial soliton fractals, propagation in the normal dispersion regime with strong nonlinearity, optical amplifiers, and mode-locked lasers. These self-similar structures are typically long-time transients formed by the interplay, often nonlinear, of the underlying dominant physical effects in the system. A theoretical model shows that in the context of the universal Ginzburg-Landau equation with rapidly-varying, mean-zero dispersion, stable and attracting self-similar pulses are formed with parabolic profiles: the zero-dispersion similariton. The zero-dispersion similariton is the final solution state of the system, not a long-time, intermediate asymptotic behavior. An averaging analysis shows the self-similarity to be governed by a nonlinear diffusion equation with a rapidly-varying, mean-zero diffusion coefficient. Indeed, the leadingorder behavior is shown to be governed by the porous media (nonlinear diffusion) equation whose solution is the well-known Barenblatt similarity solution which has a parabolic, self-similar profile. The alternating sign of the diffusion coefficient, which is driven by the dispersion fluctuations, is critical to supporting the zero-dispersion similariton which is, to leading-order, of the Barenblatt form. This is the first analytic model proposing a mechanism for generating physically realizable temporal parabolic pulses in the Ginzburg-Landau model. Although the results are of restricted analytic validity, the findings are suggestive of the underlying physical mechanism responsible for parabolic (self-similar) pulse formation in lightwave transmission and observed in mode-locked laser cavities