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

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

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

Evaluation of Skylab EREP data for land resource management

There are no author-identified significant results in this report

Large parallel and perpendicular electric fields on electron spatial scales in the terrestrial bow shock

Large parallel ($\leq$ 100 mV/m) and perpendicular ($\leq$ 600 mV/m) electric fields were measured in the Earth's bow shock by the vector electric field experiment on the Polar satellite. These are the first reported direct measurements of parallel electric fields in a collisionless shock. These fields exist on spatial scales comparable to or less than the electron skin depth (a few kilometers) and correspond to magnetic field-aligned potentials of tens of volts and perpendicular potentials up to a kilovolt. The perpendicular fields are amongst the largest ever measured in space, with energy densities of $\epsilon_0 E^2/ n k_b T_e$ of order 10%. The measured parallel electric field implies that the electrons can be demagnetized, which may result in stochastic (rather than coherent) electron heating

Cerebral Near Infrared Spectroscopy Monitoring in Term Infants With Hypoxic Ischemic Encephalopathy—A Systematic Review

BACKGROUND: Neonatal hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and morbidity worldwide. Cerebral near infrared spectroscopy (NIRS) can provide cot side continuous information about changes in brain hemodynamics, oxygenation and metabolism in real time. OBJECTIVE: To perform a systematic review of cerebral NIRS monitoring in term and near-term infants with HIE. SEARCH METHODS: A systematic search was performed in Ovid EMBASE and Medline database from inception to November 2019. The search combined three broad categories: measurement (NIRS monitoring), disease condition [hypoxic ischemic encephalopathy (HIE)] and subject category (newborn infants) using a stepwise approach as per PRISMA guidance. SELECTION CRITERIA: Only human studies published in English were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected, assessed the quality, and extracted data from the studies for this review. RESULTS: Forty-seven studies on term and near-term infants following HIE were identified. Most studies measured multi-distance NIRS based cerebral tissue saturation using monitors that are referred to as cerebral oximeters. Thirty-nine studies were published since 2010; eight studies were published before this. Fifteen studies reviewed the neurodevelopmental outcome in relation to NIRS findings. No randomized study was identified. CONCLUSION: Commercial NIRS cerebral oximeters can provide important information regarding changes in cerebral oxygenation and hemodynamics following HIE and can be particularly helpful when used in combination with other neuromonitoring tools. Optical measurements of brain metabolism using broadband NIRS and cerebral blood flow using diffuse correlation spectroscopy add additional pathophysiological information. Further randomized clinical trials and large observational studies are necessary with proper study design to assess the utility of NIRS in predicting neurodevelopmental outcome and guiding therapeutic interventions

Absolute quantification of cerebral tissue oxygen saturation with multidistance broadband NIRS in newborn brain

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO2). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO2 has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO2, however, issues with low measurement accuracy or extracranial tissue signal contamination remain. In this work, we present a novel algorithm to recover StO2 in the neonate, broadband multidistance oximetry (BRUNO), based on a measurement of the gradient of attenuation against distance measured with broadband NIRS. The performance of the algorithm was compared to two other published algorithms, broadband fitting (BF) and spatially resolved spectroscopy (SRS). The median error when recovering StO2 in light transport simulations on a neonatal head mesh was 0.4% with BRUNO, 4.2% with BF and 9.5% with SRS. BRUNO was more sensitive to brain tissue oxygenation changes, shown in layered head model simulations. Comparison of algorithm performance during full oxygenation-deoxygenation cycles in a homogeneous dynamic blood phantom showed significant differences in the dynamic range of the algorithms; BRUNO recovered StO2 over 0–100%, BF over 0–90% and SRS over 39–80%. Recovering StO2 from data collected in a neonate treated at the neonatal intensive care showed different baseline values; mean StO2 was 64.9% with BRUNO, 67.2% with BF and 73.2% with SRS. These findings highlight the effect of StO2 algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex haemodynamic processes occurring during neonatal brain injury