| 1. |
- Castro-Giner, F., et al.
(författare)
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Joint effect of obesity and TNFA variability on asthma : two international cohort studies
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 33:5, s. 1003-1009
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
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| 2. |
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| 3. |
- Castro-Giner, F, et al.
(författare)
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TNFA -308G>A in two international population-based cohorts and risk of asthma
- 2008
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Ingår i: European Respiratory Journal. - Sheffield : European respiratory society journals. - 0903-1936 .- 1399-3003. ; 32:2, s. 350-361
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
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| 4. |
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| 5. |
- Burney, P., et al.
(författare)
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A case-control study of the relation between plasma selenium and asthma in European populations : a GAL2EN project
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:7, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.
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| 6. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 7. |
- Shaheen, S., et al.
(författare)
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The relation between paracetamol use and asthma : a GA2LEN European case-control study
- 2008
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 32:5, s. 1231-1236
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Tidskriftsartikel (refereegranskat)abstract
- Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20-45 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.
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| 8. |
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| 9. |
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| 10. |
- Harrop, J., et al.
(författare)
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Eczema, atopy and allergen exposure in adults : a population-based study
- 2007
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 37:4, s. 526-535
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. Objective: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. Methods: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. Results: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. Conclusions: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Cerveri, I, et al.
(författare)
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What defines airflow obstruction in asthma?
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 34:3, s. 568-573
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Tidskriftsartikel (refereegranskat)abstract
- Asthma guidelines from the Global Initiative for Asthma (GINA) and from the National Heart, Lung, and Blood Institute provide conflicting definitions of airflow obstruction, suggesting a fixed forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) cut-off point and the lower limit of normality (LLN), respectively. The LLN was recommended by the recent American Thoracic Society/European Respiratory Society guidelines on lung function testing. The problem in using fixed cut-off points is that they are set regardless of age and sex in an attempt to simplify diagnosis at the expense of misclassification. The sensitivity and specificity of fixed FEV(1)/FVC ratios of 0.70, 0.75 and 0.80 versus the LLN were evaluated in 815 subjects (aged 20-44 yrs) with a diagnosis of asthma within the framework of the European Community Respiratory Health Survey. In males, the 0.70 ratio showed 76.5% sensitivity and 100.0% specificity, the 0.75 ratio 100.0% sensitivity and 92.4% specificity, and the 0.80 ratio 100.0% sensitivity but 58.1% specificity. In females, the 0.70 ratio showed 57.3% sensitivity and 100.0% specificity, the 0.75 ratio 91.5% sensitivity and 95.9% specificity, and the 0.80 ratio 100.0% sensitivity but 72.9% specificity. The fixed cut-off points cause a lot of misidentification of airflow obstruction in young adults, with overestimation with the 0.80 ratio and underestimation with the 0.70 ratio. In conclusion, the GINA guidelines should change their criteria for defining airflow obstruction.
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| 16. |
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| 17. |
- Chinn, S., et al.
(författare)
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Incidence of asthma and net change in symptoms in relation to changes in obesity
- 2006
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 28:4, s. 763-771
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.
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| 18. |
- Ellison-Loschmann, L., et al.
(författare)
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Socioeconomic status, asthma and chronic bronchitis in a large community-based study
- 2007
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 29:5, s. 897-905
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the relationship between socioeconomic status, using measures of occupational class and education level, and the prevalence and incidence of asthma (with and without atopy) and chronic bronchitis using data from the European Community Respiratory Health Survey (ECRHS). Asthma and chronic bronchitis were studied prospectively within the ECRHS (n=9,023). Incidence analyses comprised subjects with no history of asthma or bronchitis at baseline. Asthma symptoms were also assessed as a continuous score. Bronchitis risk was associated with low educational level (prevalence odds ratio (POR) 1.9; 95% confidence interval (CI) 1.4-2.8) and occupatsional class (1.8; 1.2-2.7). Incident bronchitis also increased with low educational level (risk ratio (RR) 2.8; 95%CI 1.5-5.4). Prevalent and incident asthma with no atopy were associated with low educational level. Subjects in the low occupational class (incident risk ratio (IRR) 1.4; 95%CI 1.2-1.7) and education group (IRR 1.3; 95% CI 1.1-1.6) had higher mean asthma scores than those in higher socioeconomic groups. Lower educational level was associated with increased risk of prevalent and incident chronic bronchitis and asthma with no atopy. Lower socioeconomic groups tended to have a higher prevalence and incidence of asthma, particularly higher mean asthma scores. Adjustment for variables associated with asthma and bronchitis explained little of the observed health differences by socioeconomic status.
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| 19. |
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| 20. |
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| 21. |
- Siroux, V., et al.
(författare)
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Quality-of-life and asthma-severity in general population asthmatics : results of the ECRHS II study
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:5, s. 547-554
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey. METHODS: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL. RESULTS: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively. CONCLUSION: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.
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| 22. |
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| 23. |
- Accordini, S, et al.
(författare)
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The socio-economic burden of asthma is substantial in Europe
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:1, s. 116-124
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.
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| 24. |
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| 25. |
- Björholt, Ingela, 1954, et al.
(författare)
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Principles for the design of the economic evaluation of COLOR II: an international clinical trial in surgery comparing laparoscopic and open surgery in rectal cancer
- 2006
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Ingår i: International journal of technology assessment in health care. - : Cambridge University Press (CUP). - 0266-4623 .- 1471-6348. ; 22:1, s. 130-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective is to describe the principles for the design of the economic evaluation of COLOR II, a randomized, multi-country study comparing laparoscopic and open surgery for rectal cancer. METHODS: By using the experiences gained in a recent economic evaluation in colon cancer, where the same surgical techniques were compared, we could improve the method for identifying and measuring resource use items and also accommodate the use of data from the global study population. RESULTS: In the design of the study, the uncertainty in the resource-use variables was reduced by considering (i) what aspects drive each variable, (ii) what resource use is related to the intervention, (iii) how data from different countries affects the variable. CONCLUSIONS: The aim was to refine the data collection so that the economic research question could be answered in the best possible way, given the circumstances in the clinical study. Thus, (i) some variables were treated as stochastic variables and others as deterministic variables, (ii) aggregate key cost-driving resource items were developed that corresponded to clinical events, and (iii) a surrogate variable was selected, instead of the "obvious variable", to reduce the impact of confounding factors for one particular resource unit.
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| 26. |
- Bousquet, Philippe-Jean, et al.
(författare)
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Geographical distribution of atopic rhinitis in the European Community Respiratory Health Survey I
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:10, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: No large studies in adults has examined geographical variation in the prevalence of nasal allergy/allergic rhinitis in adults or considered the proportion of reported nasal symptoms on exposure to allergen attributable to atopy. The aim of this report was to describe the geographic distribution of subjects with nasal symptoms who are sensitized as determined by skin prick tests, using data from the European Community Respiratory Health Survey I. METHODS: Information on the presence of nasal allergy, nasal symptoms on exposure to allergen and atopy using skin prick tests was collected from 15,394 adults aged 20-44 years living in 35 centres in 15 countries. Age sex standardized prevalence of symptoms and the attributable fraction of IgE sensitization for nasal symptoms on exposure to allergen were determined. RESULTS: The age-sex standardized prevalence of nasal allergy ranged from 11.8% in Oviedo (Spain) to 46.0% in Melbourne (Australia). The prevalence of atopic nasal allergy ranged from 4.6% in Oviedo to 31.8% in Melbourne (analysis limited on 12,566 subjects). The median attributable fraction for atopy on nasal symptoms on exposure ranged between 12.8% and 65.9% (median 27.2%). CONCLUSION: In the general population there is a wide variation in the prevalence of nasal allergy in young adults. Many subjects complaining from nasal symptoms on exposure to allergen are not atopic.
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| 27. |
- Bousquet, P-J, et al.
(författare)
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Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I
- 2007
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 62:3, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many studies have reported the prevalence of sensitization using skin prick tests. However, comparisons between studies and between regions are difficult because the number and the type of allergens tested vary widely. Using the European Community Health Respiratory Survey I data, the geographical variation of sensitization to environmental allergen as measured by skin tests was established. Methods: Adults aged 20-44 years, living in 35 centres in 15 developed countries, underwent skin tests for allergy to nine common aeroallergens: Dermatophagoides pteronyssinus, timothy grass, cat, Cladosporium herbarium, Alternaria alternately birch, Olea europea, common ragweed and Parietaria judaica. The age-sex standardized prevalence of sensitization was determined and centres with high (95% confidence interval above and excluding study median) and low prevalence (95% confidence interval below and excluding study median) of sensitization to each allergen and to any of the nine allergens were identified. Results: There was substantial geographical variation in the prevalence of sensitization to each of the nine allergens tested and in the prevalence of sensitization to any allergen (lowest 17.1%, median 36.8% and highest 54.8%). Sensitization to D. pteronyssinus, grass pollen and cat were usually the most prevalent (median between centre 21.7%, 16.9% and 8.8%, respectively). Timothy grass sensitization was higher than that for any other pollen species. Conclusions: As expected, geographical variations of sensitization to environmental allergen were observed across centres. These findings were compatible for those observed with serum-specific IgE. Skin tests can be used to assess the geographical distribution of allergens in a multicentric epidemiological survey.
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| 28. |
- Cerveri, Isa, et al.
(författare)
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Underestimation of airflow obstruction among young adults using FEV1/FVC<70% as a fixed cut-off : a longitudinal evaluation of clinical and functional outcomes
- 2008
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 63:12, s. 1040-1045
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation.Methods: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20-44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991-1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999-2002.Results: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV1 (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001).Conclusions: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.
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| 29. |
- Chinn, Susan, et al.
(författare)
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Bronchial responsiveness in atopic adults increases with exposure to cat allergen
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 176:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The association of asthma with sensitization and allergen exposure is known to be complex. There have been few studies of bronchial responsiveness in relation to both risk factors in adults. Objectives: To determine the relation of bronchial responsiveness to allergen exposure and IgE sensitization in a community study taking into account the major determinants of bronchial responsiveness in adulthood. Methods: Cross-sectional data were drawn from 1,884 participants in 20 centers in the European Community Respiratory Health Survey follow-up, which included measurement of house dust mite and cat allergen in mattress dust samples, and IgE sensitization to four allergens. Bronchial responsiveness to methacholine was expressed as a continuous variable, and analyzed by multiple regression. Measurements and Main Results: The trend toward greater bronchial responsiveness with increasing exposure to cat allergen was greater in those sensitized to any of the four allergens than those not sensitized (p = 0.001); there was no significant interaction between cat sensitization and Fel d 1 exposure. No trend was found with house dust mite allergen exposure. The difference in bronchial responsiveness between those exposed to the highest levels compared with the lowest was approximately –2.02 doubling doses of PD20 (95% confidence interval, –3.06 to –0.97), and nearly as great in those exposed to more moderate levels. Conclusions: Cat allergen exposure at moderate levels may be harmful to all atopic adults. The clinical implication is that it is insufficient to test patients with asthma for cat sensitization; all atopic individuals may benefit from reduced cat exposure.
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| 30. |
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| 31. |
- Cunningham, Janet Lynn, 1974-
(författare)
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Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored.It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed.In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.
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| 32. |
- de Marco, Roberto, et al.
(författare)
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Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 175:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. Objectives: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. Methods: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV1/FVC ratio ≥ 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV 1/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. Main Results: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). Conclusions: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.
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| 33. |
- de Marco, Roberto, et al.
(författare)
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Long-term outcomes in mild/moderate chronic obstructive pulmonary disease in the European community respiratory health survey
- 2009
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 180:10, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Little is known about the long-term outcomes of individuals with mild/moderate chronic obstructive pulmonary disease (COPD) according to spirometric criteria. OBJECTIVES: To test whether nonsmokers and asymptomatic subjects with a spirometric diagnosis of COPD have a steeper decrease in lung function and higher hospitalization rates than subjects without airway obstruction. METHODS: A total of 5,205 subjects without asthma (20-44 years of age) from the general population, with FEV(1) >or= 50% predicted at baseline, were followed for 9 years in the frame of an international cohort study. Percent decrease in FEV(1) (DeltaFEV(1)%) and the annual hospitalization rate for respiratory causes during the follow-up were assessed for each subject. MEASUREMENTS AND MAIN RESULTS: At baseline, 324 (6.2%) subjects had the prebronchodilator FEV(1)/FVC ratio less than the lower limit of normal (LLN-COPD), and 105 (2.0%) subjects had the same ratio less than 0.70 (modified GOLD-COPD). At follow-up, smokers with LLN-COPD (n = 205) had a greater mean DeltaFEV(1)% (1.7%; 95% confidence interval [CI], 0.8-2.7) and a higher hospitalization rate (rate ratio [RR], 2.52; 95% CI, 1.65-3.86) than normal subjects. Similarly, symptomatic subjects with LLN-COPD (n = 104) had DeltaFEV(1)% (2.0%; 95% CI, 0.8-3.3) and the hospitalization rate (RR, 4.18; 95% CI, 2.43-7.21) higher than the reference group. By contrast, nonsmokers and asymptomatic subjects with LLN-COPD had outcomes that were similar or even better than normal subjects. Among subjects with LLN-COPD, the association of symptoms with DeltaFEV(1)% varied according to smoking habits (P = 0.007); it was particularly strong in symptomatic smokers and disappeared in symptomatic nonsmokers. Similar results were found with the modified GOLD classification. CONCLUSIONS: In relatively young populations, COPD is associated with poor long-term outcomes in smokers and in symptomatic subjects only.
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| 34. |
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| 35. |
- Gromada, Jesper, et al.
(författare)
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Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic beta cells through activation of phosphatidylinositol 4-kinase beta
- 2005
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:29, s. 10303-8
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Tidskriftsartikel (refereegranskat)abstract
- Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic beta cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic beta cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase beta activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in beta cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic beta cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase beta, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.
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| 36. |
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| 37. |
- Gu, M., et al.
(författare)
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One-step purification of resveratrol and polydatin from Polygonum cuspidatum (Sieb. & Zucc.) by isocratic hydrogen bond adsorption chromatography on cross-linked 12% agarose
- 2006
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Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 64:11-12, s. 701-704
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Tidskriftsartikel (refereegranskat)abstract
- Resveratrol and polydatin (piceid), the major active components of the traditional Chinese medicinal herb Polygonum cuspidatum (Sieb. & Zucc.), have been separated and purified from crude root extracts in one step by isocratic hydrogen bond adsorption chromatography on cross-linked 12% agarose (Superose™ 12 HR 10/30). Separation was achieved by step-wise elution with mobile phases composed of mixtures of ethanol and acetic acid: 0–75 mL, 10% ethanol, 10% acetic acid; 75–150 mL, 20% ethanol, 20% acetic acid; 150–250 mL, 30% ethanol, 30% acetic acid. At a sample load of 40 mg crude extract dissolved in 0.5 mL mobile phase (corresponding to a load of 1.7 mg mL−1 gel) a resveratrol purity of about 96% with a recovery of 61% was obtained by proper peak cutting.
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| 38. |
- Gu, M., et al.
(författare)
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The Separation of Polyphenols by Isocratic Hydrogen Bond Adsorption Chromatography on a Cross-Linked 12% Agarose Gel
- 2006
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Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 64:5-6, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- The highly cross-linked 12% agarose gel, Superose™ 12 HR 10/30 is shown to possess hydrogen bond acceptor properties suitable for the separation of polyphenolic solutes such as phenolic acids, flavonols and flavonoids. The separation is achieved isocratically in the presence of solvent mixtures of acetic acid and ethanol. The extent of hydrogen bond adsorption is reviewed based on data obtained from the elution behaviour of a variety of simple polyphenolic solutes including dihydroxybenzoic acids.
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| 39. |
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| 40. |
- Gudmundsson, Gunnar, et al.
(författare)
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Mortality in COPD patients discharged from hospital : the role of treatment and co-morbidity
- 2006
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 7, s. 109-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to analyse mortality and associated risk factors, with special emphasis on health status, medications and co-morbidity, in patients with chronic obstructive pulmonary disease ( COPD) that had been hospitalized for acute exacerbation.Methods: This prospective study included 416 patients from each of the five Nordic countries that were followed for 24 months. The St. George's Respiratory Questionnaire (SGRQ) was administered. Information on treatment and co-morbidity was obtained.Results: During the follow-up 122 (29.3%) of the 416 patients died. Patients with diabetes had an increased mortality rate [HR = 2.25 (1.28 - 3.95)]. Other risk factors were advanced age, low FEV1 and lower health status. Patients treated with inhaled corticosteroids and/or long-acting beta-2-agonists had a lower risk of death than patients using neither of these types of treatment.Conclusion: Mortality was high after COPD admission, with older age, decreased lung function, lower health status and diabetes the most important risk factors. Treatment with inhaled corticosteroids and long-acting bronchodilators may be associated with lower mortality in patients with COPD.
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| 41. |
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| 42. |
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| 43. |
- Intarasiri, S., et al.
(författare)
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RBS and ERDA determinations of depth distributions of high-dose carbon ions implanted in silicon for silicon-carbide synthesis study
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 249, s. 859-864
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Tidskriftsartikel (refereegranskat)abstract
- For ion beam synthesis of silicon carbide (SiC), a knowledge of the depth distribution of implanted carbon ions in silicon is crucial for successful development. Based on its simplicity and availability, we selected Rutherford backscattering spectrometry (RBS) as an analysis technique for this purpose. A self-developed computer program dedicated to extract depth profiles of lighter impurities in heavier matrix is established. For control, calculated results are compared with an other ion beam analysis (IBA) technique superior for studying lighter impurity in heavier substrate i.e. elastic recoil detection analysis (ERDA). The RBS was performed with a 1.7-MV Tandetron accelerator using He2+ as the probe ions. The ERDA was performed with a 5-MV Pelletron accelerator using I8+ as the probe ions. This work shows that the RBS-extracted data had no significant deviations from those of ERDA and simulations by SRIM2003 and SIMPL computer codes. We also found that annealing at temperatures as high as 1000 degrees C had quite limited effect on the redistribution of carbon in silicon.
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| 44. |
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| 45. |
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| 46. |
- Janson, Christer, et al.
(författare)
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Characteristics of hospitalised patients with COPD in the Nordic countries
- 2006
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 100, s. S10-S16
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to examine differences in the characteristics and management of hospitalised patients with chronic obstructive pulmonary disease (COPD) and to determine factors related to the duration of the hospital stay in the Nordic countries. The study comprised 416 patients from five University Hospitals (Bergen, Reykjavik, Uppsala, Tampere and Copenhagen). The patients were interviewed and spirometry was performed. Psychological status was assessed with the Hospital Anxiety and Depression questionnaire and quality of life with the St. Georges' Hospital Respiratory Questionnaire. The mean age was 69 years, 51% were women. The majority of the patients (76%) had severe COPD (GOLD stage III and IV) and 24% were on tong-term oxygen therapy. Forty five % of the patients had cardio-vascutar disease and 11 % diabetes. In Bergen, Uppsala and Tampere over half of the patients had anxiety and depression but the prevalence of psychiatric co-morbidity was lower in Reykjavik and Copenhagen. The median length of the hospitalisation was 7-8 days in four of the five centres but two times higher in Reykjavik. The independent predictors for a longer hospitatisation was living atone (+3 days), being on long-term oxygen (+8 days) and having diabetes (+5 days). In conclusion, this study revealed substantial differences in the characteristics and management of hospitalised COPD patients between departments of respiratory disease in five Nordic university hospitals. Living alone, concurrent diseases like diabetes and long-term oxygen therapy are predictors of more prolonged hospitalisation periods.
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| 47. |
- Janson, C., et al.
(författare)
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Insomnia is more common among subjects living in damp buildings
- 2005
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Ingår i: Occup Environ Med. ; 62:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insomnia is a condition with a high prevalence and a great impact on quality of life. Little is known about the relation between and sleep disturbances and the home environment. AIM: To analyse the association between insomnia and building dampness. METHODS: In a cross-sectional, multicentre, population study, 16 190 subjects (mean age 40 years, 53% women) were studied from Reykjavik in Iceland, Bergen in Norway, Umea, Uppsala, and Goteborg in Sweden, Aarhus in Denmark, and Tartu in Estonia. Symptoms related to insomnia were assessed by questionnaire. RESULTS: Subjects living in houses with reported signs of building dampness (n = 2873) had a higher prevalence of insomnia (29.4 v 23.6%; crude odds ratio 1.35, 95% CI 1.23 to 1.48). The association between insomnia and different indicators of building dampness was strongest for floor dampness: "bubbles or discoloration on plastic floor covering or discoloration of parquet floor" (crude odds ratio 1.96, 95% CI 1.66 to 2.32). The associations remained significant after adjusting for possible confounders such as sex, age, smoking history, housing, body mass index, and respiratory diseases. There was no significant difference between the centres in the association between insomnia and building dampness. CONCLUSION: Insomnia is more common in subjects living in damp buildings. This indicates that avoiding dampness in building constructions and improving ventilation in homes may possibly have a positive effect on the quality of sleep.
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| 48. |
- Janson, M., et al.
(författare)
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Data validation in an economic evaluation of surgery for colon cancer
- 2005
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Ingår i: International journal of technology assessment in health care. - 0266-4623 .- 1471-6348. ; 21:2, s. 246-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to validate the accuracy of data retrieved in a prospective multicenter trial, the purpose of which was an economic evaluation of two techniques of surgery for colon cancer. METHODS: Within the Swedish contribution of the COLOR trial (Colon Cancer Open or Laparoscopic Resection), an economic evaluation of open versus laparoscopic surgical techniques was conducted. Data were collected by case record forms (CRF), patient diaries, and telephone surveys every 2 weeks. The study period was 12 weeks, and the perspective was societal. Data from the first consecutive forty patients to complete the health economic study protocol were validated. Retrieved data were compared with data from medical records and data from local social security offices for agreement. RESULTS: Statistically significant differences were found for duration of anesthesia, length of surgery, number of outpatient consultations by doctors and district nurses, complication rate, and the use of central venous lines. No significant differences were observed concerning length of hospital stay, disposable instruments cost, and time off work, all of which heavily influence total costs. CONCLUSIONS: The present method of data collection regarding resources used in this setting seems to produce accurate data for economic evaluation; however, relative to complication rates, the method did not retrieve accurate data.
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| 49. |
- Janson, M., et al.
(författare)
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Randomized trial of health-related quality of life after open and laparoscopic surgery for colon cancer
- 2007
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Ingår i: Surgical endoscopy. - 1432-2218. ; 21:5, s. 747-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Randomized controlled trials (RCTs) have reported improved or unchanged three-year survival following laparoscopic colon resection (LCR) for colon cancer compared with that following open resection (OCR). The aim of this study was to determine health-related quality of life (HRQL) in patients randomized to laparoscopic or open resection for colon cancer. METHODS: In total, 285 patients (130 LCR, 155 OCR) from seven Swedish centers were included. HRQL was assessed preoperatively and at 2, 4, and 12 weeks postoperatively with the EQ-5D and EORTC QLQ-C30 instruments. RESULTS: The LCR patients did significantly better on the social function component of the EORTC QLQ-C30 at two and four weeks and on the role function component at two weeks. CONCLUSION: Laparoscopic resection for colon cancer improved quality of life during the first postoperative month.
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| 50. |
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