Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to ...the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels.
An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 52.8 million ...Swedish kronor (SEK) (5.15 million pounds), compared with SEK 36.0 million (3.51 million pounds) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16.8 million (1.6 million pounds) or SEK 7560 (738 pounds) per patient. The net cost per patient for the duration of the study (5.4 years) was SEK 13,540 (1324 pounds). Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56,400 (5502 pounds). Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion. The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.
A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low ...predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.
The objective of this study was to analyze the problem of interpreting change scores of ordinal health status measures for clinical research or practice. Methods used included exploration of the ...generation of change scores in the physical ability scale of the SF-36, one of the most widely used generic health status instruments. Resulting data are presented as the ranking of items according to baseline score; a percentage of patients with severe difficulty and Rasch analysis provided the same rank order of item difficulty. On the interval scale provided by the Rasch model a concentration of items reflecting moderate difficulty occurred. This “inflates” numerical gains for patients with moderate disability compared to patients with very severe or minor physical disability. Calibration of change scores using patient perception of the level of change in function showed important variation of numerical gains with baseline.
We conclude that numerically equal gains may differ in their meaning depending on baseline health status. It is recommended that distribution of baseline health status measures and distribution of responders by baseline status be reported in evaluative studies.
Objective
To measure the willingness to pay for a reduction in the number of micturitions and urinary leakages for patients with urge incontinence.
Patients and methods
A self‐administered ...questionnaire with a binary willingness‐to‐pay question was administered to 541 patients in Sweden with urge or mixed incontinence; 461 questionnaires were returned. The reduction in micturitions and urinary leakages valued in the willingness‐to‐pay question was varied randomly between 25% and 50% in two different subsamples. Information was also collected about the number of micturitions and urinary leakages, health‐related quality of life and socio‐economic characteristics of the patients in the study.
Results
Quality of life was significantly related to the severity of the symptoms and was worse than that of the sex‐ and age‐matched general Swedish population. The median (mean) willingness to pay per month was 240 (530) Swedish krona (SEK, £1=SEK 11.50) for a 25% reduction in micturitions and leakages and SEK 470 (1030) for a 50% reduction in micturitions and leakages. As hypothesized, the willingness to pay was significantly related to the size of the reduction in micturitions and leakages, the initial number of micturitions and leakages, and income.
Conclusions
Patients with incontinence problems are willing to pay substantial amounts for a reduction in the number of micturitions and leakages.
Environmental levels of airborne carcinogenic and related substances are comparatively better known than individual exposure and its determinants. We report on a personal monitoring program involving ...five Swedish urban populations. The aim of the program was to investigate personal exposure to benzene, 1,3-butadiene, formaldehyde, and nitrogen dioxide (NO2). The measurements were performed among 40 inhabitants during seven consecutive days, in one urban area each year, during 2000-2008. The estimated population exposure levels were 1.95 μg/m(3) for benzene, 0.56 μg/m(3) for 1,3-butadiene, 19.4 μg/m(3) for formaldehyde, and 14.1 μg/m(3) for NO2. Statistical analysis using a mixed-effects model revealed that time spent in traffic and time outdoors contributed to benzene and 1,3- butadiene exposure. For benzene, refueling a car was an additional determinant influencing the exposure level. Smoking or environmental tobacco smoke were significant determinants of exposure to NO2, benzene, and 1,3-butadiene. Those with a gas stove had higher NO2 exposure. Living in a single-family house increased the exposure to formaldehyde significantly. In a variance component model, the between-subject variance dominated for 1,3-butadiene and formaldehyde, whereas the between-city variance dominated for NO2. For benzene, the between-subject and between-cities variances were similar.
The friction cost method: A comment Johannesson, Magnus; Karlsson, Göran
Journal of health economics,
04/1997, Letnik:
16, Številka:
2
Journal Article
Recenzirano
The friction cost method has been proposed as an alternative to the human-capital approach of estimating indirect costs. We argue that the fricton cost method is based on implausible assumptions not ...supported by neoclassical economic theory. Furthermore consistently applying the friction cost method would mean that the method should also be applied in the estimation of direct costs, which would mean that the costs of health care programmes are substantially decreased. It is concluded that the friction cost method does not seem to be a useful alternative to the human-capital approach in the estimation of indirect costs.
We estimate the income-related inequality in Sweden with respect to life-years and quality-adjusted life-years (QALYs). We use a large data set from Sweden with over 40,000 individuals followed up ...for 10–16 years, to estimate the survival and quality-adjusted survival in different income groups. For both life-years and QALYs, we discover inequalities in health favouring the higher income groups. For men (women) in the youngest age-group (20–29 years), the number of QALYs is 43.7 (45.7) in the lowest income decile and 47.2 (49.0) in the highest income decile.
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