The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD

Background: The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV 1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (COPD). Methods. Thirty-nine (27 males and 12 females) stable COPD patients (GOLD stages I and II) inhaled a maximum of six sequential doses of histamine according to ERS standards until one of these provocative doses produced a 20% decrease in FEV 1 (PD 20). The effects on the FEV 1, the forced inspiratory volume in one second (FIV 1), inspiratory capacity (IC), forced inspiratory flow at 50% of the vital capacity (FIF50), peak inspiratory flow (PIF) and dyspnea score by a visual analogue scale (VAS) were measured and investigated after each dose step. Results: After each dose of histamine, declines in all of the lung function parameters were detected; the largest decrease was observed in the FEV 1. At the PD 20 endpoint, more FEV 1 responders than ILP responders were found. Among the ILPs, the FIV 1 and IC best predicted which patients would reach the PD 20 endpoint. No significant correlations were found between any of the lung function parameters and the VAS results. Conclusions: In COPD patients, the FEV 1 and ILPs declined after each dose of inhaled histamine. FEV 1 was more sensitive to histamine than the ILPs. Of the ILPs, FIV 1 and IC were the best predictors of reaching the PD 20 endpoint. No statistically significant correlations were found between the lung function parameters and the degree of dyspnea

Adverse Selection in Private Annuity Markets and the Role of Mandatory Social Annuitization

We study the effects on the macroeconomic equilibrium, the wealth distribution, and welfare of adverse selection in private annuity markets in a closed economy inhabited by overlapping generations of heterogeneous agents who are distinguished by their health status. If an agent's health type is private information there will be a pooling equilibrium in the private annuity market. We also study the implications for the macro-economy and welfare of a social security system with mandatory contributions that are constant across health types. These social annuities are immune to adverse selection and therefore offer a higher rate of return than private annuities do. However, they have a negative effect on the steady-state capital intensity and welfare. The positive effect of a fair pooled rate of return on a fixed part of savings and a higher return on capital in equilibrium is outweighed by the negative consequences of increased adverse selection in the private annuity market and a lower wage rate

Entry and fiscal policy effectiveness in a small open economy within a Monetary Union

In this article I develop an imperfectly competitive dynamic general equilibrium model for a small open economy integrated in a monetary union. Here, the type of entry in the non-traded goods’ sector affects fiscal policy effectiveness. Fiscal policy effectiveness is enlarged when aggregate demand stimuli increase intra-industrial competition (case I). This is due to the counter-cyclical mark-up mechanism generated by entry. Such a mechanism is absent in the usual monopolistic competition where entry only has a sharing effect (case II).info:eu-repo/semantics/publishedVersio

Population pharmacokinetics of the von Willebrand factor-factor VIII interaction in patients with von Willebrand disease

Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels outside of prespecified target levels necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain target levels of both VWF and FVIII, application of an integrated population PK model describing both VWF activity (VWF:Act) and FVIII levels may improve dosing and quality of care. In total, 695 VWF:Act and 894 FVIII level measurements from 118 patients (174 surgeries) who were treated perioperatively with the VWF/FVIII concentrate were used to develop this population PK model using nonlinear mixed-effects modeling. VWF:Act and FVIII levels were analyzed simultaneously using a turnover model. The protective effect of VWF:Act on FVIII clearance was described with an inhibitory maximum effect function. An average perioperative VWF:Act level of 1.23 IU/mL decreased FVIII clearance from 460 mL/h to 264 mL/h, and increased FVIII half-life from 6.6 to 11.4 hours. Clearly, in the presence of VWF, FVIII clearance decreased with a concomitant increase of FVIII half-life, clarifying the higher FVIII levels observed after repetitive dosing with this concentrate. VWF:Act and FVIII levels during perioperative treatment were described adequately by this newly developed integrated population PK model. Clinical application of this model may facilitate more accurate targeting of VWF:Act and FVIII levels during perioperative treatment with this specific VWF/FVIII concentrate (Humate P/Haemate P).Thrombosis and Hemostasi

Macroeconomic Implications of Demography for the Environment: A Life-Cycle Perspective

This article studies how demography affects the outcome of the environmental policy in a macro-economic perspective, incorporating age-earning profiles in an OLG model à la Blanchard (1985) to capture the age structure effect of the demographic shocks. It first demonstrates, conversely to previous works of the related literature that a decrease in the birth rate may lower the steady-state per capita stock of physical capital even if the aggregate labor supply is exogenous. It also demonstrates that the ageing of population influences the macro-economic impact of the environmental policy according to the cause of the ageing and the life-cycle earnings assumption. Thus, with decreasing age-earning profiles, a lower birth rate reduces the detrimental impact of the environmental policy on the steady-state per capita stock of physical capital for low values of this birth rate, while a reduction of the mortality rate reinforces the negative outcome of the environmental policy. When earnings profiles are independent of age, ageing always strengthens the negative impact of the environmental policy

Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument

Contains fulltext : 80284.pdf (publisher's version ) (Closed access)PURPOSE: To compose a battery of instruments that provides a detailed assessment of health status (HS) in COPD but that is applicable and clinically meaningful in routine care. METHODS: In a previous study, we developed the Nijmegen Integral Assessment Framework (NIAF) that organizes existing tests and instruments by the sub-domains of HS they measure. Based on clinical and statistical criteria (correlation coefficients and Cronbach alpha's) we selected for each sub-domain instruments from the NIAF. A COPD-study group was used to determine c-scores, and two control groups were used to determine the score ranges indicating normal functioning versus clinically relevant problems for each sub-domain. Existing questionnaire completion software (TestOrganiser) was adapted to enhance clinical applicability. RESULTS: The NCSI measures eleven sub-domains of physiological functioning, symptoms, functional impairment, and quality of life. The TestOrganiser automatically processes the data and produces the graphical PatientProfileChart, which helps to easily interpret results. This envisages the problem areas and discrepancies between the different sub-domains. CONCLUSION: The NCSI provides a valid and detailed picture of a patient's HS within 15-25 min. In combination with the PatientProfileChart, the NCSI can be used perfectly in routine care as screening instrument and as a guide in patient-tailored treatment