Search

Rationale: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited. Objectives: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF. Methods: The study population included all 1,156 randomized patients in two clinical trials of IFN-[gamma]1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID. Measurements and Main Results: Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%. Conclusions: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference. [ABSTRACT FROM AUTHOR]

Rationale: The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated. Objectives: To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. Methods: The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. Measurements and Main Results: Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m. Conclusions: The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF. [ABSTRACT FROM AUTHOR]

The mastery of the use of lightweight rocks in concrete as a means of controlling the thrusts of large-scale vaults was among the most important contributions of the Roman builders to the development of vaulted architecture. The string of volcanoes along the Tyrrhenian coast of Italy produced a variety of lightweight rocks, which allowed the builders in Rome to develop highly sophisticated ways of manipulating form and mass to create stable structures. The use of lighter rocks in vaults and heavier in foundations occurs from the mid-first centurybc in Rome, but the systematic use of imported lightweight rocks only began in the early second centuryad under Trajan ( Lancaster 2005 , 59-64). Soon thereafter, the technique of using lightweight stones to build large vaults spread throughout the empire, usually to areas that had a local source of lightweight volcanic material. However, there was also a seaborne trade in lightweight rocks to areas that did not have local sources of such material. The intention of our analysis is to determine as precisely as possible the provenance of the lightweight stones used in vaulting of two areas of the Mediterranean, modern Turkey (ancient Cilicia) and Tunisia (ancient Africa Proconsularis), and thus to provide a better understanding of the nature of this trade. [ABSTRACT FROM AUTHOR]