| 1631. |
- Kanis, J. A., et al.
(författare)
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FRAX and fracture prediction without bone mineral density
- 2015
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Ingår i: Climacteric. - : Informa UK Limited. - 1369-7137 .- 1473-0804. ; 18:Suppl. 2, s. 2-9
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Tidskriftsartikel (refereegranskat)abstract
- The major application of FRAX in osteoporosis is to direct pharmacological interventions to those at high risk of fracture. Whereas the efficacy of osteoporosis treatment, with the possible exception of alendronate, is largely independent of baseline bone mineral density (BMD), it remains a widely held perception that osteoporosis therapies are only effective in the presence of low BMD. Thus, the use of FRAX in the absence of BMD to identify individuals requiring therapy remains the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high evidence-based validity to identify a risk responsive to intervention. The selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD and thus identifies a risk that is responsive to pharmacological intervention. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where facilities for BMD testing are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Thus concerns surrounding the use of FRAX in clinical practice without information on BMD are largely misplaced. © 2015 International Menopause Society.
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| 1632. |
- Kanis, J. A., et al.
(författare)
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FRAX Update
- 2017
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 20:3, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- The fracture risk assessment tool, FRAX, was released in 2008 and provides country-specific algorithms for estimating individualized 10-year probability of hip and major osteoporotic fracture (hip, clinical spine, distal forearm, and proximal humerus). Since its release, models are now available for 63 countries, covering 79% of the world population. The website receives approximately 3 million visits annually. Following independent validation, FRAX has been incorporated into more than 80 guidelines worldwide. However, the application of FRAX in guidelines has been heterogeneous with the adoption of several different approaches to setting intervention thresholds. The relationship between FRAX and efficacy of intervention has been explored and is expected to influence treatment guidelines in the future. A more unified approach to setting intervention thresholds with FRAX is a research priority.
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| 1633. |
- Kanis, J. A., et al.
(författare)
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Overview of Fracture Prediction Tools
- 2017
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 20:3, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of risk factors for fracture that contribute significantly to fracture risk, over and above that provided by the bone mineral density, has stimulated the development of risk assessment tools. The more adequately evaluated tools, all available online, include the FRAX (R) tool, the Garvan fracture risk calculator and, in the United Kingdom only, QFracture (R). Differences in the input variables, output, and model construct give rise to marked differences in the computed risks from each calculator. Reasons for the differences include the derivation of fracture probability (FRAX) rather than incidence (Garvan and QFracture), limited calibration (Garvan), and inappropriate source information (QFracture). These differences need to be taken into account in the evaluation of assessment guidelines.
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| 1634. |
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| 1635. |
- Karadenizli, A., et al.
(författare)
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Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012
- 2015
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Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:21
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Tidskriftsartikel (refereegranskat)abstract
- Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.
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| 1636. |
- Karageorgis, Anastassia, et al.
(författare)
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A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury (Dili) is a leading cause of acute liver failure and transplantation. Dili can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s -1 (n = 23) and 11.7 +/- 1.3 s -1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s -1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s -1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic. Conclusion: Rate constants of
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| 1637. |
- Karlsson, Bengt, et al.
(författare)
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A novel method to determine the natural course of unruptured brain arteriovenous malformations without the need for follow-up information
- 2018
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 129, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE There is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture. METHODS The present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy. RESULTS The age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25-60 years). It was concluded to be 3.1% +/- 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years. CONCLUSIONS The present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% +/- 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.
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| 1638. |
- Karlsson, C., et al.
(författare)
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Introduction
- 2010
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Ingår i: Entrepreneurship and Regional Development. - : Edward Elgar Publishing. - 9781847209320 ; , s. 1-27
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Bokkapitel (refereegranskat)
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| 1639. |
- Karlsson, C., et al.
(författare)
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Preface
- 2014
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Ingår i: Knowledge, Innovation and Space. - : Edward Elgar Publishing. - 9781848449015 ; , s. IX-X
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Bokkapitel (refereegranskat)
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| 1640. |
- Karlsson, C., et al.
(författare)
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Preface
- 2012
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Ingår i: Entrepreneurship, Social Capital and Governance. - : Edward Elgar Publishing Ltd.. ; , s. xii-xiii
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Bokkapitel (refereegranskat)
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