| 71. |
- Talseth, Arne, et al.
(författare)
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Quality of life and psychological and gastrointestinal symptoms after cholecystectomy : a population-based cohort study
- 2017
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Ingår i: BMJ Open Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2054-4774.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The study aims to examine gastrointestinal symptoms, quality of life and the risk of psychological symptoms after cholecystectomy. DESIGN: This is a prospective population-based cohort study based on the Nord-Trondelag Health Study (HUNT) Norway. HUNT is a repeated health survey of the county population and includes a wide range of health-related items. In the present study, all 3 HUNT surveys were included, performed between 1984 and 2008. Selected items were scores on quality of life, the Hospital Anxiety and Depression Scale (HADS) and selected gastrointestinal symptoms. Participants who underwent cholecystectomy for gallstone disease between 1 January 1990 and until 1 year before attending HUNT3 were compared with the remaining non-operated cohort. Associations between cholecystectomy and the postoperative scores and symptoms were assessed by multivariable regression models. RESULTS: Participants in HUNT1, HUNT2 and HUNT3 were 77 212 (89.4% of those invited), 65 237 (69.5%) and 50 807 (54.1%), respectively. In the study period, 931 participants were operated with cholecystectomy. Cholecystectomy was associated with an increased risk of diarrhoea and stomach pain postoperatively. In addition, cholecystectomy was associated with an increased risk of nausea postoperatively in men. We found no associations between cholecystectomy and quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation following surgery. CONCLUSIONS: In this large population-based cohort study, cholecystectomy was associated with postoperative diarrhoea and stomach pain. Cholecystectomy for gallstone colic was associated with nausea in men. There were no associations between quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation.
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| 72. |
- Talseth, Arne, et al.
(författare)
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Risk factors of having cholecystectomy for gallstone disease in a prospective population-based cohort study
- 2016
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Ingår i: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The relationship between different lifestyle factors and the risk of needing cholecystectomy for gallstone disease is not clear. This study aimed to assess the association between anthropometric, lifestyle and sociodemographic risk factors and the subsequent risk of requiring cholecystectomy for gallstone disease during long-term follow-up in a defined population cohort. METHODS: Data from a large population-based cohort study performed from 1995 to 1997 were used (the second Norwegian Nord-Trondelag health study, HUNT2). Following HUNT2, from 1998 to 2011, all patients operated on for gallstone disease with cholecystectomy at the two hospitals in the county, Levanger Hospital and Namsos Hospital, were identified. A Cox proportional hazards model was used for multivariable risk analysis. RESULTS: The HUNT2 cohort included 65 237 individuals (69.5 per cent response rate), aged 20-99 years. During a median follow-up of 15.3 (range 0.6-16.4) years, 1162 cholecystectomies were performed. In multivariable analysis, overweight individuals (body mass index (BMI) 25.0-29.9 kg/m(2) ) had a 58 per cent increased risk of cholecystectomy compared with individuals with normal weight (BMI less than 25.0 kg/m(2) ). Obese individuals (BMI 30 kg/m(2) or above) had a twofold increased risk. Increasing waist circumference independently increased the risk of cholecystectomy. In women, current hormone replacement therapy (HRT) increased the risk, whereas hard physical activity and higher educational level were associated with reduced risk of cholecystectomy. CONCLUSION: High BMI and waist circumference increased the risk of having cholecystectomy for both sexes. In women, the risk was increased by HRT, and decreased by hard physical activity and higher educational level.
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| 73. |
- Theofylaktopoulou, Despoina, et al.
(författare)
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Impaired functional vitamin B6 status is associated with increased risk of lung cancer
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:12, s. 2425-2434
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Tidskriftsartikel (refereegranskat)abstract
- Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
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| 74. |
- Trenkwalder, Teresa, et al.
(författare)
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Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.
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| 75. |
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| 76. |
- Ueda, Peter, et al.
(författare)
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Use of DPP4 Inhibitors and GLP-1 Receptor Agonists and Risk of Intestinal Obstruction: Scandinavian Cohort Study
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - 1542-3565 .- 1542-7714.
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. Methods: Using data from nationwide registers in Sweden, Denmark, and Norway, 2013–2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors). Results: Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6–2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4–1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96–1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4–1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4–1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69–1.01). Conclusions: In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.
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| 77. |
- van Duijnhoven, Fraenzel J. B., et al.
(författare)
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Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:6, s. 1189-1201
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-TrOndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D-2 and 25(OH)D-3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of 25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
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| 78. |
- van Ommen, Gert-Jan B, et al.
(författare)
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BBMRI-ERIC as a resource for pharmaceutical and life science industries : the development of biobank-based Expert Centres
- 2015
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23:7, s. 893-900
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Tidskriftsartikel (refereegranskat)abstract
- Biological resources (cells, tissues, bodily fluids or biomolecules) are considered essential raw material for the advancement of health-related biotechnology, for research and development in life sciences, and for ultimately improving human health. Stored in local biobanks, access to the human biological samples and related medical data for transnational research is often limited, in particular for the international life science industry. The recently established pan-European Biobanking and BioMolecular resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) aims to improve accessibility and interoperability between academic and industrial parties to benefit personalized medicine, disease prevention to promote development of new diagnostics, devices and medicines. BBMRI-ERIC is developing the concept of Expert Centre as public-private partnerships in the precompetitive, not-for-profit field to provide a new structure to perform research projects that would face difficulties under currently established models of academic-industry collaboration. By definition, Expert Centres are key intermediaries between public and private sectors performing the analysis of biological samples under internationally standardized conditions. This paper presents the rationale behind the Expert Centres and illustrates the novel concept with model examples.
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| 79. |
- Wang, Ying, et al.
(författare)
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Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts
- 2023
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.
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| 80. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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