| 1. |
- Försth, Peter, et al.
(författare)
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A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:15, s. 1413-1423
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The efficacy of fusion surgery in addition to decompression surgery in patients who have lumbar spinal stenosis, with or without degenerative spondylolisthesis, has not been substantiated in controlled trials.METHODS We randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomization was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI; which ranges from 0 to 100, with higher scores indicating more severe disability) 2 years after surgery. The primary analysis, which was a per-protocol analysis, did not include the 14 patients who did not receive the assigned treatment and the 5 who were lost to follow-up.RESULTS There was no significant difference between the groups in the mean score on the ODI at 2 years (27 in the fusion group and 24 in the decompression-alone group, P = 0.24) or in the results of the 6-minute walk test (397 m in the fusion group and 405 m in the decompression- alone group, P = 0.72). Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years. The mean length of hospitalization was 7.4 days in the fusion group and 4.1 days in the decompression-alone group (P< 0.001). Operating time was longer, the amount of bleeding was greater, and surgical costs were higher in the fusion group than in the decompression-alone group. During a mean follow-up of 6.5 years, additional lumbar spine surgery was performed in 22% of the patients in the fusion group and in 21% of those in the decompression-alone group.CONCLUSIONS Among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone.
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| 2. |
- 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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| 3. |
- Kanis, John A, et al.
(författare)
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Assessment of fracture risk.
- 2005
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:6, s. 581-9
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Kanis, John A, et al.
(författare)
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Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden.
- 2005
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Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:1, s. 6-14
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in men and women, based on data from Sweden. We modeled the effects of a treatment costing $500 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect for a further 5 years. Sensitivity analyses included a range of effectiveness (10-50%) and a range of intervention costs ($200-500/year). Data on costs and risks were from Sweden. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of approximately $45,000/QALY gained was used. Cost of added years was included in a sensitivity analysis. With the base case ($500 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.2% at the age of 50 years to 7.4% at the age of 80 years. Similar results were observed in men except that the threshold for cost-effectiveness was higher at younger ages than in women (2.0 vs 1.2%, respectively, at the age of 50 years). Intervention thresholds were sensitive to the assumed effectiveness and intervention cost. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age, and that available treatments can be targeted cost-effectively to individuals at moderately increased fracture risk.
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| 7. |
- Kobelt, G, et al.
(författare)
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Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia
- 2003
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Ingår i: BJU International. - 1464-4096. ; 91:3, s. 190-195
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To assess the effect of nocturia on productivity, vitality and utility in a selected group of professionally active individuals with nocturia, compared with matched controls, and investigate the effect of symptom severity, to test the hypothesis that lack of sleep caused by frequent sleep interruptions could reduce an individuals' daytime energy and activity levels. SUBJECTS AND METHODS Subjects (203) were recruited in Sweden through advertisements, and their suitability for the study assessed in a structured interview. Controls (80) matched for age and gender were randomly selected from a market research panel and given the same interview. Both groups completed a productivity questionnaire, a generic quality-of-life questionnaire with a specific domain for vitality and a utility instrument. RESULTS The study group with nocturia had a significantly lower level of vitality and utility, and greater impairment of work and activity, than the control group. Women were more affected than men. Symptom severity correlated with all three measures. CONCLUSIONS In an otherwise healthy and professionally active group of individuals, waking at night to void significantly diminishes their overall well-being, vitality and productivity, leading to a significant level of indirect and intangible costs.
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| 8. |
- 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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| 9. |
- Svanberg, Sune, et al.
(författare)
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Applications of terawatt lasers
- 1994
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Ingår i: LASER SPECTROSCOPY - XITH INTERNATIONAL CONFERENCE. - : AIP. - 1551-7616 .- 0094-243X. - 1563962624 ; :290, s. 264-269
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Konferensbidrag (refereegranskat)
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| 10. |
- Winge, David O., et al.
(författare)
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Optoelectronic III-V nanowire implementation of a neural network in a shared waveguide
- 2020
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Ingår i: 2020 International Conference on Numerical Simulation of Optoelectronic Devices, NUSOD 2020. - 2158-3234. - 9781728160863 ; 2020-September, s. 99-100
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Konferensbidrag (refereegranskat)abstract
- Neural node components consisting of III-V nanowire devices are introduced. This allows for the construction of a small footprint specialized neural network. A broadcasting strategy is developed which removes the need for inter-node wiring. As a model system, an insect brain navigational circuit is chosen and successfully emulated using the introduced nodes and network architecture. The results are based on electronic transport simulations in each device as well as finite-difference time-domain simulations for the broadcasting of optical signals.
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