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| 2. |
- Chotiyarnwong, P., et al.
(författare)
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Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- A Summary The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. Introduction The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. Methods The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. Results and Conclusion The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.
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| 4. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 5. |
- Borgstrom, E. W., et al.
(författare)
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CD4(+) T cell proliferative responses to PPD and CFP-10 associate with recent M. tuberculosis infection
- 2020
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Ingår i: Tuberculosis. - : Elsevier BV. - 1472-9792 .- 1873-281X. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-gamma release assays cannot differentiate latent from active tuberculosis (TB), nor identify the recently infected with increased risk of active disease. The objective of this study was to identify biomarkers of recent infection following exposure to tuberculosis, to increase the positive predictive value for incipient TB. Contacts to patients with pulmonary TB were tested repeatedly with interferon-gamma release assays and flow-cytometry. Proliferative CD4(+) T cell responses to purified protein derivative (PPD) and 11 M. tuberculosis antigens were analysed. The individual probability of recent and remote infection was estimated using clinical data in a novel mathematical model and compared with CD4(+) responses in a prediction model. The most specific prediction of recent infection was high CD4(+) proliferative responses to CFP-10 and PPD and a low CD4(+) response to ESAT-6. CD4(+) proliferative responses to Rec85a, Rec85b and Rv1284 were also observed in recent infection, but did not reach significance in the prediction model. Conclusions: High CD4(+) proliferative responses to CFP-10 and PPD and a low response to ESAT-6 may be used as biomarkers to improve positive predictive values for recent LTBI and thus, increased risk of incipient TB. Rec85a, Rec85b and Rv1284 are also of interest to study further in this context.
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| 10. |
- Hammarsten, Ola, et al.
(författare)
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Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the gamma-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results: Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing gamma-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of gamma-H2AX in response to radiation. Conclusions: The combination of the CDA and the gamma-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.
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- Soreskog, E., et al.
(författare)
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Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32, s. 585-594
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Tidskriftsartikel (refereegranskat)abstract
- Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. Purpose To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate ("romosozumab-to-alendronate") compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden. Methods A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), for women treated with romosozumab-to-alendronate or alendronate alone. Patients aged 74 years with a recent major osteoporotic fracture (MOF) were followed from the start of treatment until the age of 100 years or death. Treatment with romosozumab for 12 months was followed by alendronate for up to 48 months or alendronate alone with a maximum treatment duration of 60 months. The analysis had a societal perspective. Efficacy of romosozumab and alendronate were derived from phase III randomized controlled trials. Resource use and unit costs were collected from the literature. Cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) with QALYs as effectiveness measures. Results The base case analysis showed that sequential romosozumab-to-alendronate treatment was associated with 0.089 additional QALYs at an additional cost of euro3002 compared to alendronate alone, resulting in an ICER of euro33,732. At a Swedish reference willingness-to-pay per QALY of euro60,000, romosozumab-to-alendronate had a 97.9% probability of being cost-effective against alendronate alone. The results were most sensitive to time horizon, persistence assumptions, patient age, and treatment efficacy. Conclusion The results of this study indicate that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture.
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| 14. |
- Soreskog, E., et al.
(författare)
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Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study
- 2020
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31:8, s. 1499-1506
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Tidskriftsartikel (refereegranskat)abstract
- Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. Introduction The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. Methods A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. Results Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (286) pound and gained 0.015 QALYs/patient in comparison with usual management arm. Conclusions This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.
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| 19. |
- Bondesson, Eva, et al.
(författare)
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Planar gamma scintigraphy - points to consider when quantifying pulmonary dry powder aerosol deposition
- 2003
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Ingår i: International Journal of Pharmaceutics. - 1873-3476. ; 251:1-2, s. 33-47
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Tidskriftsartikel (refereegranskat)abstract
- Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.
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| 23. |
- Borgstrom, S, et al.
(författare)
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Time-resolved x-ray spectroscopy of optical-field-ionized plasmas
- 1995
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Ingår i: Laser and Particle Beams. - 0263-0346. ; 13:4, s. 459-468
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Tidskriftsartikel (refereegranskat)abstract
- The time-dependent soft X-ray emission of helium and nitrogen plasmas generated by optical-field ionization is reported. The experiments were carried out by focusing pulses of the high-power Ti:sapphire laser of the Lund Institute of Technology (lambda = 796 nm, pulse duration 150 fs, pulse energy 150 mJ) to a 50-mu m diameter spot close to a nozzle, using He and N-2 as target gases. The emission on He+, N4+, and N3+ resonance lines was recorded by means of a flat-field grating spectrometer coupled to an X-ray streak camera. A pronounced difference in the temporal shape of the emission of the Lyman-alpha line of hydrogen-like helium and of the 2p-3d resonance lines of lithium-like and beryllium-like nitrogen was observed. The helium line exhibited an initial spike followed by a slow revival of the emission, whereas the nitrogen lines showed a slow decay after a fast initial rise. These observations are explained with the help of simulations.
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| 27. |
- Dimai, HP, et al.
(författare)
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Epidemiology of hip fractures in Austria: evidence for a change in the secular trend
- 2011
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 22:2, s. 685-692
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Tidskriftsartikel (refereegranskat)
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| 28. |
- Dimai, HP, et al.
(författare)
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Epidemiology of proximal humeral fractures in Austria between 1989 and 2008
- 2013
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 24:9, s. 2413-2421
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Fill, E, et al.
(författare)
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Xuv Spectra of Optical-field-ionized Plasmas
- 1995
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Ingår i: Physical Review E: covering statistical, nonlinear, biological, and soft matter physics. - 1063-651X. ; 51:6, s. 6016-6027
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Tidskriftsartikel (refereegranskat)
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| 30. |
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| 31. |
- Froberg, G, et al.
(författare)
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A new mathematical model to identify contacts with recent and remote latent tuberculosis
- 2019
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis (TB) elimination programmes need to target preventive treatment to groups with an increased risk of TB activation, such as individuals with a latent tuberculosis infection (LTBI) acquired recently. Current diagnostic tests for LTBI have poor predictive values for TB activation and there is, at present, no reference method to evaluate new LTBI diagnostic and prognostic tools. Thus, our objective was to develop a mathematical model, independent of currently available diagnostic tests, to estimate the individual probability of recent and/or remote LTBI.Estimations of recent LTBI were based on the contagiousness of index case, proximity and time of exposure, and environmental factors. Estimation of remote LTBI was based on country of origin, previous stays in high-risk environments or known exposure to TB. Individual probabilities were calculated and compared with tuberculin skin test (TST) and interferon-γ release assay results for 162 contacts of 42 index TB cases.Probabilities of remote LTBI were 16% for European/American contacts and 38% for African/Asian contacts. The probability of recent LTBI was 35% for close contacts to smear microscopy positive index cases. A higher probability of remote LTBI was seen among TST-positive contacts.This model may, with further validation, be used as an independent tool to evaluate new diagnostic markers for recent LTBI.
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| 32. |
- Gauthier, A, et al.
(författare)
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Development and validation of a disease model for postmenopausal osteoporosis
- 2011
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 22:3, s. 771-780
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Tidskriftsartikel (refereegranskat)
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| 41. |
- Johansson, H, et al.
(författare)
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UTILITY LOSS AFTER A SENTINEL FRACTURE
- 2018
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Ingår i: OSTEOPOROSIS INTERNATIONAL. - 0937-941X. ; 29, s. S72-S73
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 42. |
- Jonsson, E., et al.
(författare)
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A health economic simulation model for the clinical management of osteoporosis
- 2018
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:3, s. 545-555
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings.IntroductionThe purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice.MethodsThe analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines.ResultsThe national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382–3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient).ConclusionsThe analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.
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| 49. |
- Kanis, J A, et al.
(författare)
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Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK.
- 2008
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 19:10, s. 1395-408
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: Assessment and intervention thresholds are developed and proposed in men aged over 50 years and postmenopausal women for the UK based on fracture probability from the WHO fracture risk assessment tool (FRAX). INTRODUCTION: The FRAX tool has recently become available to compute the 10-year probability of fractures in men and women from clinical risk factors (CRFs) with or without the measurement of femoral neck bone mineral density (BMD). The aim of this study was to develop a case-finding strategy for men and women from the UK at high risk of osteoporotic fracture by delineating the fracture probabilities at which BMD testing or intervention should be recommended. METHODS: Fracture probabilities were computed using the FRAX tool calibrated to the epidemiology of fracture and death in the UK. The relationship between cost effectiveness and fracture probability used the source data from a prior publication that examined the cost effectiveness of generic alendronate in the UK. An intervention threshold was set by age in men and women, based on the fracture probability equivalent to that of women with a history of a prior osteoporosis related fracture. In addition, assessment thresholds for the use of BMD testing were explored. Assessment thresholds for the measurement of BMD followed current practice guidelines where individuals were considered to be eligible for assessment in the presence of one or more CRF. An upper assessment threshold (i.e. a fracture probability above which patients could be treated without recourse to BMD) was based on optimisation of the positive predictive value of the assessment tool. The consequences of assessment and intervention thresholds on the requirement for BMD test and interventions were assessed using the distribution of clinical risk factors and femoral neck BMD for women in the source cohorts used for the development of the FRAX models RESULTS: Treatment was cost effective at all ages when the 10-year probability of a major fracture exceeded 7%. The intervention threshold at the age of 50 years corresponded to a 10-year probability of a major osteoporotic fracture of 7.5%. This rose progressively with age to 30% at the age of 80 years, so that intervention was cost effective at all ages. Assessment thresholds for testing with BMD (6-9% at the age of 50 years) also rose with age (18-36% at the age of 80 years). The use of these thresholds in a case-finding strategy would identify 6-20% of women as eligible for BMD testing and 23-46% as eligible for treatment, depending on age. The same threshold can be used in men. CONCLUSION: The study provides a method of developing management algorithms for osteoporosis from the estimation of fracture probabilities, rather than those based on BMD alone or BMD with single or multiple CRFs.
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| 50. |
- Kanis, J A, et al.
(författare)
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How to decide who to treat
- 2009
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Ingår i: Best practice & research. Clinical rheumatology. - : Elsevier BV. - 1532-1770 .- 1521-6942. ; 23:6, s. 711-26
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Tidskriftsartikel (refereegranskat)abstract
- Fractures are the clinical consequence of osteoporosis and are a major cause of morbidity and mortality worldwide. Although treatments are available that have been shown to decrease the risk of fracture, problems arise in identifying individuals at high risk of fracture so that intervention can be effectively targeted. Practice guidelines, available in many countries, differ markedly in approach, but generally recommend treatments on the basis of a previous fragility fracture and a defined threshold for bone mineral density (BMD). Recent developments in fracture risk assessment include the availability of the FRAX tool by the World Health Organization (WHO) Collaborating Centre for Metabolic Bone Diseases at Sheffield, UK, that integrates the weight of clinical risk factors for fracture risk with or without information on BMD and computes the 10-year probability of fracture. The tool increases sensitivity without trading specificity and is now being used in the re-appraisal of clinical guidelines.
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