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Träfflista för sökning "WFRF:(Hein Alexander) ;lar1:(uu)"

Sökning: WFRF:(Hein Alexander) > Uppsala universitet

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  • Bhatt, Deepak L., et al. (författare)
  • Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
  • 2019
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
  • Tidskriftsartikel (refereegranskat)abstract
    • In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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  • Connolly, Stuart J, et al. (författare)
  • Dronedarone in High-Risk Permanent Atrial Fibrillation
  • 2011
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:24, s. 2268-2276
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular anti-arrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. Methods We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. Results After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). Conclusions Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients.
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  • Hedman, Linnea, et al. (författare)
  • Receiving support to quit smoking and quit attempts among smokers with and without smoking related diseases : Findings from the EUREST-PLUS ITC Europe Surveys
  • 2018
  • Ingår i: Tobacco Induced Diseases. - Heraklion : European Publishing. - 1617-9625. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION Having a chronic disease either caused or worsened by tobacco smoking does not always translate into quitting smoking. Although smoking cessation is one of the most cost-effective medical interventions, it remains poorly implemented in healthcare settings. The aim was to examine whether smokers with chronic and respiratory diseases were more likely to receive support to quit smoking by a healthcare provider or make a quit attempt than smokers without these diseases.METHODS This population-based study included a sample of 6011 adult smokers in six European countries. The participants were interviewed face-to-face and asked questions on sociodemographic characteristics, current diagnoses for chronic diseases, healthcare visits in the last 12 months and, if so, whether they had received any support to quit smoking. Questions on smoking behavior included nicotine dependence, motivation to quit smoking and quit attempts in the last 12 months. The results are presented as weighted percentages with 95% confidence intervals (CI) and as adjusted odds ratios with 95% CI based on logistic regression analyses.RESULTS Smokers with chronic respiratory disease, those aged 55 years and older, as well as those with one or more chronic diseases were more likely to receive smoking cessation advice from a healthcare professional. Making a quit attempt in the last year was related to younger age, high educational level, higher motivation to quit, lower nicotine dependence and having received advice to quit from a healthcare professional but not with having chronic diseases. There were significant differences between countries with smokers in Romania consistently reporting more support to quit as well as quit attempts.CONCLUSIONS Although smokers with respiratory disease did indeed receive smoking cessation support more often than smokers without disease, many smokers did not receive any advice or support to quit during a healthcare visit.
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  • Irestedt, Martin, 1968-, et al. (författare)
  • A crowd-sourced genomic project to assess hybrid content in a rare avian vagrant (Azure Tit Cyanistes cyanus (Pallas, 1770))
  • 2023
  • Ingår i: Avian Research. - : Elsevier. - 2053-7166. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to correlate plumage variation with the amount of genomic hybrid content in hybrids between Azure Tits Cyanistes cyanus (Pallas, 1770) and European Blue Tit Cyanistes caeruleus (Linnaeus, 1758), by re-sequencing the genomes of museum specimens of non-hybrids and presumed hybrids with varying plumages. The project was funded by crowdsourcing and initiated when two presumed Azure Tits, observed by hundreds of Swedish birdwatchers, were rejected as hybrids based on minor plumage deviations assumed to indicate hybrid contents from the European Blue Tit. The results confirm that hybrids with intermediate plumages, so called Pleske’s Tits, are first generation hybrids (F1 hybrids). Individuals, whose plumages are similar to Azure Tits, but assessed as hybrids based on minor plumage deviations, are all backcrosses but vary in their degree of hybrid content. However, some individuals morphologically recognized as pure Azure Tits expressed similar degrees of hybrid content. The results indicate that: (1) hybrid content may be widespread in Azure Tits in the western part of its habitat distribution; (2) plumage deviation in backcrosses is not linearly correlated with the genetic degree of hybrid origin; and (3) all Azure Tits observed in Europe outside its natural distribution may have some degree of hybrid origin. We therefore suggest that it is very difficult to phenotypically single out hybrids beyond first generation backcrosses. We argue that decreased sequencing costs and improved analytical tools open the doors for museomic crowd-sourced projects that may not address outstanding biological questions but have a major interest for lay citizens such as birdwatchers.
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  • Mueller, Stefanie H., et al. (författare)
  • Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
  • 2023
  • Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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  • Shu, Xiang, et al. (författare)
  • Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
  • 2019
  • Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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  • Torjusen, Hanne, et al. (författare)
  • Reduced risk of pre-eclampsia with organic vegetable consumption : results from the prospective Norwegian Mother and Child Cohort Study
  • 2014
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 4:9, s. e006143-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Design: Prospective cohort study. Setting: Norway, years 2002-2008. Participants: 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Main outcome measure: Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. Results: The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables 'often' or 'mostly' (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported 'never/rarely' or 'sometimes' (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. Conclusions: These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota.
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