| 1. |
- Baird, Denis A., et al.
(författare)
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Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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| 2. |
- Benetou, V., et al.
(författare)
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Education, marital status, and risk of hip fractures in older men and women : the CHANCES project
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 26:6, s. 1733-1746
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Tidskriftsartikel (refereegranskat)abstract
- The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.
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| 3. |
- Benetou, Vassiliki, et al.
(författare)
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Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women : The CHANCES Project
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 31:9, s. 1743-1752
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Tidskriftsartikel (refereegranskat)abstract
- The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.
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| 4. |
- Benetou, V., et al.
(författare)
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Mediterranean diet and hip fracture incidence among older adults : the CHANCES project
- 2018
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 29:7, s. 1591-1599
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Tidskriftsartikel (refereegranskat)abstract
- The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk.INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults.METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis.RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence.CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.
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| 5. |
- Ekman, Agneta, et al.
(författare)
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Läkemedelsarbete behöver vara integrerat i klinisk utbildning [Preparing for the licence to prescribe in medical school - a questionnaire study on medical students professional confidence in the art of prescribing]
- 2019
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Ingår i: Läkartidningen. - Stockholm, Sweden : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment is a complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills. Acquiring professional confidence in the art of prescribing is essential during medical training. The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.e. the basics of prescribing. The confidence increased by the number of reviews and reports performed, i.e. the extent of practice (correlation coefficients: 0.41 and 0.38, respectively, both pamp;lt;0.0001), as did the extent of the students reflection on important aspects of drug treatment such as adherence, adverse reactions, renal function, dosing, and drug interactions. In multivariate regression analyses, major predictors for confidence in performing medication reviews were extent of practice and extent of clinical supervision. The results suggest that these factors are keys to acquiring professional confidence in the art of prescribing.
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| 6. |
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| 7. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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[Preparing for the licence to prescribe in medical school - a questionnaire study on medical students professional confidence in the art of prescribing]. : Läkemedelsarbete behöver vara integrerat i klinisk utbildning - Att göra många läkemedelsgenomgångar ökar trygghet och reflektion över patientens behandling, visar enkätstudie.
- 2019
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Ingår i: Lakartidningen. - 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- A prerequisite for rational use of medicines is adequate prescribing skills; drug treatment is a complex task requiring diagnostic competence combined with pharmacologic knowledge and patient communication skills. Acquiring professional confidence in the art of prescribing is essential during medical training. The results of this questionnaire study, conducted in four medical schools in Sweden after the course in internal medicine (252 respondents; response rate: 74%; median age: 24 years, 61% female), show that 45% and 62% were confident in performing medication reviews and writing medication summary reports, respectively, i.e. the basics of prescribing. The confidence increased by the number of reviews and reports performed, i.e. the extent of practice (correlation coefficients: 0.41 and 0.38, respectively, both p<0.0001), as did the extent of the students' reflection on important aspects of drug treatment such as adherence, adverse reactions, renal function, dosing, and drug interactions. In multivariate regression analyses, major predictors for confidence in performing medication reviews were extent of practice and extent of clinical supervision. The results suggest that these factors are keys to acquiring professional confidence in the art of prescribing.
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| 8. |
- Hemminki, Kari, et al.
(författare)
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Germline genetics of cancer of unknown primary (CUP) and its specific subtypes
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:16, s. 22140-22149
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Tidskriftsartikel (refereegranskat)abstract
- Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls. In the whole sample set, 6 loci reached an allelic p-value in the range of 10(-7) and were supported by data from the three centers. Three associations were located next to non-coding RNA genes. rs2660852 flanked 5' UTR of LTA4H (leukotriene A4 hydrolase), rs477145 was intronic to TIAM1 (T-cell lymphoma invasion and metastases) and rs2835931 was intronic to KCNJ6 (potassium channel, inwardly rectifying subfamily J, member 6). In analysis of subgroups of CUP patients (smokers, non-smokers and CUP with liver metastases) genome-wide significant associations were noted. For patients with liver metastases associations on chromosome 6 and 11, the latter including a cluster of genes DHCR7 and NADSYN1, encoding key enzymes in cholesterol and NAD synthesis, and KRTAP5-7, encoding a keratin associated protein. This first GWAS on CUP provide preliminary evidence that germline genes relating to inflammation (LTA4H), metastatic promotion (TIAM1) in association with lipid metabolic disturbance (chromosome 11 cluster) may contribute to the risk of CUP.
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| 9. |
- Katsoulis, M, et al.
(författare)
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Excess mortality after hip fracture in elderly persons from Europe and the USA : the CHANCES project.
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:3, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude.METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis.RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years].CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.
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| 10. |
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