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1.
  • Kanis, J A, et al. (författare)
  • The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women.
  • 2007
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 18:8, s. 1033-46
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMMARY: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. METHODS: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). RESULTS: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. CONCLUSIONS: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.
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3.
  • Kanis, J A, et al. (författare)
  • Smoking and fracture risk: a meta-analysis.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:2, s. 155-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
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4.
  • Kanis, J A, et al. (författare)
  • The use of multiple sites for the diagnosis of osteoporosis.
  • 2006
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 17:4, s. 527-34
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: It has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T-score should be taken for the purpose of diagnosing osteoporosis. PURPOSE: The aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination for fracture prediction. METHODS: We studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately. Results of the different studies were merged using weighted beta-coefficients. RESULTS: The gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined, the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI)=1.42-1.61] per standard deviation (SD) decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI=1.38-1.56). Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45-1.64). Higher gradients of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10-2.87), with lumbar BMD was 1.57 (95% CI=1.36-1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95% CI=1.81-2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of specificity. Thus, the same effect could be achieved by using a less stringent T-score for the diagnosis of osteoporosis. CONCLUSIONS: Since taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis of osteoporosis is low.
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5.
  • Jivegård, Lennart, 1950, et al. (författare)
  • Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.
  • 2005
  • Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 29:2, s. 190-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.
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6.
  • Johnell, Olof, et al. (författare)
  • Predictive value of BMD for hip and other fractures.
  • 2005
  • Ingår i: Journal of bone and mineral research. - 0884-0431 .- 1523-4681. ; 20:7, s. 1185-94
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.
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7.
  • Kanis, John A, et al. (författare)
  • A meta-analysis of milk intake and fracture risk: low utility for case finding.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:7, s. 799-804
  • Tidskriftsartikel (refereegranskat)abstract
    • A low intake of calcium is widely considered to be a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the effect of age, gender and bone mineral density (BMD) on this risk. We studied 39,563 men and women (69% female) from six prospectively studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000 person-years. The effect of calcium intake as judged by the intake of milk on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture. There was no difference in risk ratio between men and women. When both sexes were combined there was a small but non-significant increase in the risk of osteoporotic and of hip fracture. There was also a small increase in the risk of an osteoporotic fracture with age which was significant at the age of 80 years (RR = 1.15; 95% CI = 1.02-1.30) and above. The association was no longer significant after adjustment for BMD. No significant relationship was observed by age for low milk intake and hip fracture risk. We conclude that a self-reported low intake of milk is not associated with any marked increase in fracture risk and that the use of this risk indicator is of little or no value in case-finding strategies.
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8.
  • Kanis, John A, et al. (författare)
  • Alcohol intake as a risk factor for fracture.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:7, s. 737-42
  • Tidskriftsartikel (refereegranskat)abstract
    • High intakes of alcohol have adverse effects on skeletal health, but evidence for the effects of moderate consumption are less secure. The aim of this study was to quantify this risk on an international basis and explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and 11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and the Rotterdam Study. Cohorts were followed for a total of 75,433 person-years. The effect of reported alcohol intake on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined included age and BMD. The results of the different studies were merged using weighted beta-coefficients. Alcohol intake was associated with a significant increase in osteoporotic and hip fracture risk, but the effect was nonlinear. No significant increase in risk was observed at intakes of 2 units or less daily. Above this threshold, alcohol intake was associated with an increased risk of any fracture (risk ratio [RR] = 1.23; 95% CI, 1.06-1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16-1.65), or hip fracture (RR = 1.68; 95% CI, 1.19-2.36). There was no significant interaction with age, BMD, or time since baseline assessment. Risk ratios were moderately but not significantly higher in men than in women, and there was no evidence for a different threshold for effect by gender. We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in case-finding strategies.
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10.
  • Tsang, S W Y, et al. (författare)
  • Ten-year fracture probability in Hong Kong Southern Chinese according to age and BMD femoral neck T-scores
  • 2009
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 20:11, s. 1939-45
  • Tidskriftsartikel (refereegranskat)abstract
    • This study estimated the 10-year probability of osteoporotic fracture in Hong Kong Southern Chinese based on a simplified model of the recently developed WHO fracture risk prediction tool (FRAX). Thus, the data provides further insights into potential development of a population-specific FRAX model for Hong Kong in the future. INTRODUCTION: The purpose of this paper was to estimate the 10-year probability of osteoporotic fracture in Hong Kong (HK) Southern Chinese according to age and bone mineral density (BMD) T-score at the femoral neck based on the methodology of the FRAX risk assessment tool calibrated to the epidemiology of HK. METHODS: Hip fracture data was obtained from the Clinical Data Analysis Reporting System (CDAS) of the Hospital Authority of HK and population size and death rates were taken from the HK Government Census and Statistics Department. Fracture probability was calculated using the cut-off values for T-scores derived from the NHANES III data for Caucasian women aged 20-29 years for BMD at the femoral neck. RESULTS: In this study, the 10-year probability of osteoporotic fracture in HK Southern Chinese increased markedly with increasing age and decreasing femoral neck BMD T-scores in both women and men. Interestingly, at low T-scores, the increase in 10-year probability of osteoporotic fracture in women with age was greater than in men. Fracture probabilities were substantially higher than those from mainland China. CONCLUSIONS: Based on this evidence, and until we have HK Southern Chinese population-specific information, we recommend the application of the Caucasian risk profile to calculate the absolute fracture risk for HK Southern Chinese subjects.
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11.
  • Borgström, F, et al. (författare)
  • The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX(R).
  • 2009
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965.
  • Tidskriftsartikel (refereegranskat)abstract
    • The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of pound30,000. INTRODUCTION: The aim of this study was to assess the cost-effectiveness of risedronate for the prevention and treatment in a UK setting using the FRAX(R) algorithm for fracture risk assessment. A further aim was to establish intervention thresholds with risedronate treatment. METHODS: The cost-effectiveness of risedronate was compared to no treatment in post-menopausal women with clinical risk factors for fracture using a Markov cohort model populated with data relevant for the UK. The model incorporated the features of FRAX(R) (the WHO risk assessment tool). The analysis had a health care perspective and quality adjusted life years was used as the main outcome measure. RESULTS: Treatment was cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of pound30,000. Treatment was also cost-effective at all ages in women who had previously sustained a fragility fracture or in women with a parental history of hip fracture with a bone mineral density set at the threshold of osteoporosis. At the pound30,000 threshold value for a QALY, risedronate was on average found to cost-effective below the 10-year probability of a major osteoporotic fractures of 13.0%. CONCLUSIONS: Risedronate is a cost-effective agent for the treatment of established osteoporosis (osteoporosis and a prior fragility fracture) in women from the age of 50 years and older and above 65 years in women with osteoporosis alone. The results support the treatment recommendations in recent UK guidelines for osteoporosis.
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12.
  • Brohall, Gerhard, 1952, et al. (författare)
  • Carotid artery intima-media thickness in patients with Type 2 diabetes mellitus and impaired glucose tolerance: a systematic review
  • 2006
  • Ingår i: Diabet Med. - : Wiley. - 0742-3071. ; 23:6, s. 609-16
  • Forskningsöversikt (refereegranskat)abstract
    • AIMS: To review the difference in carotid artery intima media thickness (IMT) between patients with Type 2 diabetes (DM) or impaired glucose tolerance (IGT), and control subjects. METHODS: Systematic reviews were made in order to identify cross-sectional studies using the ultrasound method. The differences between IMT in DM or IGT and control subjects were calculated. Meta-analysis using random-effects modelling was used to calculate summary measures. RESULTS: Twenty-three studies included 24,111 subjects; 4019 with DM and 1110 with IGT. In 20 of 21 studies, the diabetic patients had greater carotid artery IMT than the subjects in the control groups. The estimated mean difference in IMT was 0.13 (95% CI: 0.12-0.14) mm. Heterogeneity was observed and likely sources of variation were study size, diabetes duration, and ultrasound method. In three out of nine studies, the IGT patients had significant greater carotid artery IMT than the subjects in the control groups. The estimated mean difference in IMT was 0.04 (95% CI: 0.014-0.071) mm. CONCLUSIONS: Type 2 diabetes was associated with an 0.13 mm increase in IMT compared with control subjects. In patients with IGT, the increase in IMT was about one-third of that observed in diabetes. The observed difference in IMT can be interpreted as if the diabetes patients were more than 10 years older than the control groups, and that the relative risks of myocardial infarction and stroke were increased by almost 40%, respectively.
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13.
  • De Laet, Chris, et al. (författare)
  • The impact of the use of multiple risk indicators for fracture on case-finding strategies: a mathematical approach.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:3, s. 313-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The value of bone mineral density (BMD) measurements to stratify fracture probability can be enhanced in a case-finding strategy that combines BMD measurement with independent clinical risk indicators. Putative risk indicators include age and gender, BMI or weight, prior fracture, the use of corticosteroids, and possibly others. The aim of the present study was to develop a mathematical framework to quantify the impact of using combinations of risk indicators with BMD in case finding. Fracture probability can be expressed as a risk gradient, i.e. a relative risk (RR) of fracture per standard deviation (SD) change in BMD. With the addition of other continuous or categorical risk indicators a continuous distribution of risk indicators is obtained that approaches a normal distribution. It is then possible to calculate the risk of individuals compared with the average risk in the population, stratified by age and gender. A risk indicator with a gradient of fracture risk of 2 per SD identified 36% of the population as having a higher than average fracture risk. In individuals so selected, the risk was on average 1.7 times that of the general population. Where, through the combination of several risk indicators, the gradient of risk of the test increased to 4 per SD, a smaller proportion (24%) was identified as having a higher than average risk, but the average risk in this group was 3.1 times that of the population, which is a much better performance. At higher thresholds of risk, similar phenomena were found. We conclude that, whereas the change of the proportion of the population detected to be at high risk is small, the performance of a test is improved when the RR per SD is higher, indicated by the higher average risk in those identified to be at risk. Case-finding strategies that combine clinical risk indicators with BMD have increased efficiency, while having a modest impact on the number of individuals requiring treatment. Therefore, the cost-effectiveness is enhanced.
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  • Fahlén, M, et al. (författare)
  • Optimization of basal insulin delivery in Type 1 diabetes: a retrospective study on the use of continuous subcutaneous insulin infusion and insulin glargine.
  • 2005
  • Ingår i: Diabetic medicine : a journal of the British Diabetic Association. - : Wiley. - 0742-3071. ; 22:4, s. 382-6
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To compare the effects on glycaemic control after using continuous subcutaneous insulin infusion (CSII) or insulin glargine. METHODS: Data were obtained from 17 diabetes outpatient clinics in Sweden, employing the same diabetes data management system. Type 1 diabetic patients using multiple dose injections were included prior to starting on either CSII (n = 563) or glargine (n = 513). The median duration of therapy was 25 months for CSII and 6 months for glargine. The comparison between the treatment modalities was carried out by multiple regression analysis and logistic regression analysis in an attempt at reducing the influence of confounding factors. RESULTS: The mean HbA1c decrease was 0.59 +/- 1.19% for CSII and 0.20 +/- 1.07% for glargine (P < 0.001, when assessed by logistic regression). An additional 0.1% lower HbA1c would be expected if glargine had been optimized with basal insulin 40-60% of the daily dose. The more pronounced effect of CSII was achieved with a lower daily dosage of insulin. In a multiple regression analysis with a change of HbA1c as the dependent variable, the following variables were significant: choice of treatment (P < 0.001), HbA1c prior to treatment (P < 0.001) and BMI prior to treatment (P < 0.01). CONCLUSION: Both regimes improved metabolic control, but CSII resulted in significantly higher reduction in HbA1c than after insulin glargine treatment, particularly in those individuals who had higher levels of HbA1c at baseline.
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  • Fujiwara, S, et al. (författare)
  • Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX).
  • 2008
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:4, s. 429-35
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMMARY: The present study estimated the 10-year probability using the Japanese version of WHO fracture risk assessment tool (FRAX) in order to determine fracture probabilities that correspond to intervention thresholds currently used in Japan and to resolve some issues for its use in Japan. INTRODUCTION: The objective of the present study was to evaluate a Japanese version of the WHO fracture risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic fracture in Japanese men and women. Since lumbar spine bone mineral density (BMD) is used preferentially as a site for assessment, and densitometers use Japanese reference data, a second aim was to investigate the suitability and impact of this practice in Japan. METHODS: Fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention thresholds currently used in Japan. The difference between T-scores derived from international reference data and that using Japanese-specific normal ranges was estimated from published sources. The gradient of risk of BMD for fracture in Japan was compared to that for BMD at the lumbar spine in the Hiroshima cohort. RESULTS: The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine. There were small differences in T-scores between those used for the model and those derived from a Japanese reference population. CONCLUSIONS: The FRAX mark tool has been used to determine possible thresholds for therapeutic intervention, based on equivalence of risk with current guidelines. The approach will need to be supported by appropriate health economic analyses. Femoral neck BMD is suitable for the prediction of fracture risk among Japanese. However, when applying the FRAX model to Japan, T-scores and Z-scores should be converted to those derived from the international reference.
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16.
  • Gjertsson, Peter, 1961, et al. (författare)
  • Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis
  • 2005
  • Ingår i: J Thorac Cardiovasc Surg. - : Elsevier BV. - 0022-5223. ; 129:4, s. 890-6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We studied long-term outcomes in severe aortic stenosis and the importance of prosthesis type (mechanical vs biologic) and size, preoperative left ventricular ejection fraction, diastolic function, and left ventricular mass. METHODS: Patients undergoing valve replacement from 1991 to 1993 (n = 399, 45% women) were included. The diastolic function was evaluated by integrating mitral and pulmonary venous flow data with Doppler echocardiography. The patients were classified as having either normal diastolic function to mild diastolic dysfunction or moderate to severe diastolic dysfunction. Left ventricular ejection fraction and the diastolic function category were incorporated together with age, sex, and time since operation into a Poisson regression model with death as the end point. Prosthesis type and size and left ventricular mass were also investigated. RESULTS: The age (mean +/- SD) was 71 +/- 9 years, and the overall survival after 12 years was 50%. Although markedly reduced during the initial 6-month period, mortality risk subsequently increased more than could be explained by age (hazard ratio of 1-year difference = 1.12, P = .0005). The moderate to severe diastolic dysfunction pattern independently predicted late mortality (hazard ratio = 1.72, P = .0038), whereas left ventricular ejection fraction did not (hazard ratio = 0.99, P = .18). The prognostic importance of moderate to severe diastolic dysfunction did not diminish with time; on the contrary, it tended to increase. Mortality after 12 years was not predicted by left ventricular mass (P = .66), prosthesis type (P = .57), or prosthesis size (P = .58). CONCLUSION: This study reveals that moderate to severe diastolic dysfunction in patients with aortic stenosis is an independent predictor of late mortality after valve replacement and that its importance does not decrease with time. Our findings may suggest that moderate to severe diastolic dysfunction implies nonreversible myocardial changes that negatively affect survival.
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19.
  • Johansson, C. A., et al. (författare)
  • A comparison of experiences of training emergency care in military exercises and competences among conscript nurses with different levels of education
  • 2007
  • Ingår i: Military Medicine. - : Association of Military Surgeons. - 0026-4075 .- 1930-613X. ; 172:10, s. 1046-1052
  • Tidskriftsartikel (refereegranskat)abstract
    • The military emergency care education of nurses is primarily concerned with the treatment of soldiers with combat-related injuries. Even though great progress has been made in military medicine, there is still the pedagogical question of what emergency care education for military nurses should contain and how it should be taught. The aim of this study was to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education. A descriptive study was performed to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education in nursing. There were statistical differences between nurses with general nursing education and nurses with a general nursing education and supplementary education. A reasonable implication of the differences is that the curriculum must be designed differently depending on the educational background of the students. Hence, there is an interaction between background characteristics, e.g., the level of previous education and differences pertaining to clinical experience of the participants, and the impact of the exercise itself.
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20.
  • Johansson, Helena, 1981, et al. (författare)
  • BMD, clinical risk factors and their combination for hip fracture prevention
  • 2009
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 20:10, s. 1675-1682
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examined the effects of the use of clinical risk factors (CRFs) alone, BMD alone or the combination using the FRAXA (R) tool for the detection of women at risk of hip fracture. BMD tests alone selected women at higher risk and a greater number of hip fracture cases were identified compared to the use of CRFs alone. The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone, but with a higher hip fracture risk and thus had the more favourable positive predictive value (PPV) and number needed to treat (NNT). Algorithms have recently become available for the calculation of hip fracture probability from CRFs with and without information on femoral neck BMD. The aim of this study was to examine the effects of the use of CRFs alone, BMD alone or their combination using the FRAXA (R) tool for the detection of women at risk of hip fracture. Data from 10 prospective population based cohorts, in which BMD and CRFs were documented, were used to compute the 10-year probabilities of hip fracture calibrated to the fracture and death hazards of the UK. The effects of the use of BMD tests were examined in simulations where BMD tests were used alone, CRFs alone or their combined use. The base case examined the effects in women at the age of 65 years. The principal outcome measures were the number of women identified above an intervention threshold, the number of hip fracture cases that would be identified, the positive predicted value and the NNT to prevent a hip fracture during a hypothetical treatment with an effectiveness of 35% targeted to those above the threshold fracture risk. We also examined BMD values in women selected for treatment. Sensitivity analysis examined the effect of age and limited use of BMD resources. BMD tests alone selected women at higher risk of hip fracture than the use of CRFs alone (6.1% versus 5.3%). BMD tests alone also identified a greater number of hip fracture cases (219/1,000) compared to the use of CRFs alone (140/1,000). The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone (168/1,000 versus 219/1,000, respectively), but with a higher hip fracture risk (PPV, 8.6% versus 6.1%), and consequently a lower number needed to treat (NNT) (33 versus 47). In sensitivity analyses, the PPV and NNT were always better for the combination than either BMD or CRFs alone across all ages studied (50-70 years). The use of FRAXA (R) in combination with BMD increases the performance characteristics of fracture risk assessment.
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21.
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22.
  • Johnell, Olof, et al. (författare)
  • The burden of hospitalised fractures in Sweden.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:2, s. 222-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to characterise the hospital burden of fractures in the Swedish population by age and gender. The number of patients and number of fractures were documented according to site of fracture, age, sex and duration of hospital stay for the whole population of Sweden in 1996. Fractures were additionally classified as osteoporotic according to fracture site. In 1996 there were 54,000 admissions for fracture in men and women aged 50 years or more, accounting for 600,000 hospital-bed days. Hip fractures accounted for 63% of admissions for fracture in men and 72% in women, for 69% and 73% of hospital-bed days, respectively. Fractures considered to be osteoporotic accounted for 84% of all hospital-bed days due to fracture in men, and 93% in women. More hospital-bed days were due to osteoporotic fracture than to breast cancer and prostate cancer combined. The number of hospital-bed days due to osteoporotic fracture was between the amount due to ischaemic heart disease and the amount due to stroke.
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23.
  • Kanis, John A, et al. (författare)
  • A reference standard for the description of osteoporosis.
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 42:3, s. 467-75
  • Tidskriftsartikel (refereegranskat)abstract
    • In 1994, the World Health Organization published diagnostic criteria for osteoporosis. Since then, many new technologies have been developed for the measurement of bone mineral at multiple skeletal sites. The information provided by each assessment will describe the clinical characteristics, fracture risk and epidemiology of osteoporosis differently. Against this background, there is a need for a reference standard for describing osteoporosis. In the absence of a true gold standard, this paper proposes that the reference standard should be based on bone mineral density (BMD) measurement made at the femoral neck with dual-energy X-ray absorptiometry (DXA). This site has been the most extensively validated, and provides a gradient of fracture risk as high as or higher than that of many other techniques. The recommended reference range is the NHANES III reference database for femoral neck measurements in women aged 20-29 years. A similar cut-off value for femoral neck BMD that is used to define osteoporosis in women can be used for the diagnosis of osteoporosis in men - namely, a value for BMD 2.5 SD or more below the average for young adult women. The adoption of DXA as a reference standard provides a platform on which the performance characteristics of less well established and new methodologies can be compared.
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24.
  • Kanis, John A, et al. (författare)
  • Approaches to the targeting of treatment for osteoporosis
  • 2009
  • Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 5:8, s. 425-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Fractures are a clinical consequence of osteoporosis, and represent a major cause of morbidity and mortality worldwide. Several treatments have been shown to decrease the risk of fracture, but problems arise in identifying individuals at high fracture risk so that treatments can be effectively targeted. The case for widespread population screening using bone mineral density testing is weak, as these tests lack sensitivity. Case-finding algorithms are available in many countries, but differ markedly in their approaches. Recent developments in fracture risk assessment include the availability of the FRAX (WHO Collaborating Center for Bone Metabolic Disease, Sheffield, UK) tool, which integrates the weight of clinical risk factors for fracture risk with or without information on bone mineral density, and computes the 10-year probability of fracture. The tool increases sensitivity without trading specificity, and is now being used in the reappraisal of clinical guidelines.
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25.
  • Kanis, John A, et al. (författare)
  • Assessment of fracture risk
  • 2009
  • Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 71:3, s. 392-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Fractures are a common complication of osteoporosis. Although osteoporosis is defined by bone mineral density at the femoral neck, other sites and validated techniques can be used for fracture prediction. Several clinical risk factors contribute to fracture risk independently of BMD. These include age, prior fragility fracture, smoking, excess alcohol, family history of hip fracture, rheumatoid arthritis and the use of oral glucocorticoids. These risk factors in conjunction with BMD can be integrated to provide estimates of fracture probability using the FRAX tool. Fracture probability rather than BMD alone can be used to fashion strategies for the assessment and treatment of osteoporosis.
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26.
  • Kanis, John A, et al. (författare)
  • Assessment of fracture risk.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:6, s. 581-9
  • 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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27.
  • Kanis, John A, et al. (författare)
  • Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX
  • 2009
  • Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 44:6, s. 1049-54
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Bazedoxifene has been shown to significantly decrease the risk of vertebral fractures in postmenopausal women. No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture. AIMS: The aim of this study was to re-evaluate the efficacy of bazedoxifene on fracture outcomes avoiding subgroup analysis by examining the efficacy of intervention as a function of fracture risk. METHODS: The phase III study was a double-blind, randomised, placebo- and raloxifene-controlled randomised 3-year multinational study that enrolled 7492 osteoporotic women aged 55 years or more (mean age=66 years). For the present analysis, women taking raloxifene were excluded (n=1849), and we compared the effects of two doses of bazedoxifene (20 and 40 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture. The risk of a major osteoporotic fracture was assessed using region specific FRAX algorithms, and the relationship between pre hoc 10-year fracture probabilities and efficacy examined by Poisson regression. RESULTS: Overall, bazedoxifene was associated with a significant 39% decrease in incident morphometric vertebral fractures (hazard ratio HR=0.61; 95% CI=0.43-0.86; p=0.005) and a non-statistically significant 16% decrease in all clinical fractures (hazard ratio HR=0.84; 95% CI=0.67-1.06; p=0.14) compared to placebo. Hazard ratios for the effect of bazedoxifene on all clinical fractures decreased with increasing fracture probability. In patients with 10-year fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the risk of all clinical fractures. The 16% probability threshold corresponded to the 80th percentile of the study population. Hazard ratios for the effect of bazedoxifene on morphometric vertebral fractures also decreased with increasing fracture probability. In patients with 10-year fracture probabilities above 6.9% (corresponding to the 41st percentile), bazedoxifene was associated with a significant decrease in the risk of morphometric vertebral fractures. At equivalent fracture probability percentiles, the treatment effect of bazedoxifene was greater on vertebral fracture risk than on the risk of all clinical fractures. For example, at the 90th percentile of FRAX probability, bazedoxifene was associated with a relative risk reduction of 33% (95% CI=7-51%) for all clinical fractures and 51% reduction (95% CI=21-69%) for morphometric vertebral fractures. The findings were robust to several sensitivity analyses. CONCLUSION: Bazedoxifene (20 and 40 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX based fracture probability threshold. These results, consistent with the previous subgroup analysis, suggest that bazedoxifene should be targeted preferentially to women at high fracture risk.
  •  
28.
  • Kanis, J A, et al. (författare)
  • Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK.
  • 2008
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 19:10, s. 1395-408
  • 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.
  •  
29.
  • Kanis, John A, et al. (författare)
  • FRAX and its applications to clinical practice
  • 2009
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:5, s. 734-43
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of the WHO FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well validated risk factors for fracture with or without the use of BMD. Its use in fracture risk prediction poses challenges for patient assessment, the development of practice guidelines, the evaluation of drug efficacy and reimbursement, as well as for health economics which are the topics outlined in this review.
  •  
30.
  • Kanis, J A, et al. (författare)
  • FRAX and the assessment of fracture probability in men and women from the UK.
  • 2008
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:4, s. 385-97
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMMARY: A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. INTRODUCTION: The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. METHODS: Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. RESULTS: Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. CONCLUSION: The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.
  •  
31.
  • Kanis, J A, et al. (författare)
  • How to decide who to treat
  • 2009
  • Ingår i: Best practice & research. Clinical rheumatology. - : Elsevier BV. - 1532-1770 .- 1521-6942. ; 23:6, s. 711-26
  • 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.
  •  
32.
  • Kanis, John A, et al. (författare)
  • Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:1, s. 6-14
  • 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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33.
  • Kanis, JA, et al. (författare)
  • Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study
  • 2005
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 16:1, s. 15-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Raloxifene treatment has been shown to reduce the risk of vertebral fractures and breast cancer in postmenopausal women. The long-term economic implications of treatment with raloxifene have not yet been investigated. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women in the UK with raloxifene. A previously developed computer simulation model was used to estimate the cost-effectiveness of osteoporotic treatments with extra skeletal benefits. The model was populated with epidemiological data and cost data relevant for a UK female population. Data on the effect of treatment were taken from the Multiple Outcomes of Raloxifene (MORE) study., which recruited women with low bone mineral density or with a prior vertebral fracture. Cost-effectiveness was estimated using Quality Adjusted Life Years (QALYs) and life years gained as primary outcome measures. The cost per QALY gained of treating post menopausal women without prior vertebral fractures was pound18,000, pound23,000, pound18,000 and pound21,000 at 50. 60, 70 and SO years of age. Corresponding estimates for women with prior vertebral fractures were pound10,000, pound24,000, pound18,000 and pound20,000. In relation to threshold values that are recommended in the UK. the analysis suggests that raloxifene is cost-effective in the treatment of postmenopausal women at an increased risk of vertebral fractures.
  •  
34.
  • Kanis, JA, et al. (författare)
  • Intervention thresholds for osteoporosis in the UK
  • 2005
  • Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 36:1, s. 22-32
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in women based on data from the UK. We modelled the effects of an intervention costing pound350 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect (offset time) for a further 5 years. Sensitivity analyses included a range of treatment duration (3-10 years), intervention costs (pound300-400/year) and offset times (0-15 years). Data on costs and risks were from the UK. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of pound30,000/QALY gained was used. With the base case (pound350 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.1% at the age of 50 years to 9.0% at the age of 85 years. Intervention thresholds were sensitive to the assumed costs and offset time. 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. Cost-effective scenarios were found for women at the threshold for osteoporosis from the age of 60 years. Treatment of established osteoporosis was cost-effective irrespective of age. 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 from the UK at moderately increased fracture risk.
  •  
35.
  • Kanis, JA, et al. (författare)
  • Ten-year probabilities of clinical vertebral fractures according to phalangeal quantitative ultrasonography
  • 2005
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 16:9, s. 1065-1070
  • Tidskriftsartikel (refereegranskat)abstract
    • The objectives of the present study were to estimate 10-year probabilities of clinical vertebral fractures in women, according to age and bone mineral assessment using phalangeal quantitative ultrasound (QUS). Risks were computed from UK derived data on the incidence of a first symptomatic vertebral fracture and mortality rates for each year of age using Poisson models. The 10-year probability of vertebral fracture was determined as the proportion of individuals fracture-free at that site from the age of 45 years. We assumed that the risk of fracture increased with decreasing QUS as assessed by an independent re-analysis of a previously published, multicenter cross-sectional study. For amplitude-dependent speed of sound (AD-SoS) information was available from 8,502 women, and vertebral fracture risk increased 1.7-fold for each SD decrease in measurement. For fast wave amplitude (FWA), available in 6,573 women, the risk gradient was 2.4/SD. In a subset of the population ( n =1,572) in whom bone mineral density was measured at the lumbar spine, the gradient of risk was 2.3/SD, with similar gradients of risk noted for AD-SoS (1.8/SD) and FWA (2.6/SD). Ten-year probabilities increased with age and decreasing Z -score. The use of absolute risk permits information from different types of bone mineral measurements to be applied for the assessment of patients, either alone or in combination with other independent risk factors.
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36.
  • Kayan, K, et al. (författare)
  • Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate
  • 2009
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965.
  • Tidskriftsartikel (refereegranskat)abstract
    • Fall risk does not significantly impact on the efficacy of the bisphosphonate clodronate in reducing the incidence of fracture. INTRODUCTION: The debate about the efficacy of skeletal therapies on fracture risk in women at increased risk of falling continues. We determined whether fall risk impeded the efficacy of clodronate to reduce osteoporotic fracture incidence. METHODS: This is a post hoc analysis of a 3-year placebo-controlled study of bisphosphonate clodronate involving 5,212 women aged 75 years or more. At entry, self-reported multiple falls in the previous month and ability to rise from a chair were documented. Their interaction with treatment efficacy was examined using Poisson regression. RESULTS: Oral doses of clodronate at 800 mg daily reduced osteoporotic fracture incidence by 24% (hazard ration (HR) 0.76, 95% confidence interval 0.63-0.93). The efficacy was similar in women with recent multiple falls compared to those without (HR 0.61 vs. 0.77, p value for interaction >0.30) or impaired ability in rising compared to those with no impairment (HR 0.79 vs. 0.74, respectively; p value > 0.30). CONCLUSION: Fall risk does not significantly impact on the anti-fracture efficacy of clodronate. If confirmed with other agents, fall risk may be incorporated into risk assessment tools designed to target skeletal therapies.
  •  
37.
  •  
38.
  • Khorram-Manesh, Amir, 1958, et al. (författare)
  • Long-term outcome of a large series of patients surgically treated for pheochromocytoma
  • 2005
  • Ingår i: Journal of internal medicine. - 0954-6820. ; 258:1, s. 55-66
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
  •  
39.
  •  
40.
  • Lindahl, Hans, 1950, et al. (författare)
  • Risk factors for failure after treatment of a periprosthetic fracture of the femur
  • 2006
  • Ingår i: J Bone Joint Surg Br. - 0301-620X. ; 88:1, s. 26-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Periprosthetic fracture of the femur is an uncommon complication after total hip replacement, but appears to be increasing. We undertook a nationwide observational study to determine the risk factors for failure after treatment of these fractures, examining patient- and implant-related factors, the classification of the fractures and the outcome.Between 1979 and 2000, 1049 periprosthetic fractures of the femur were reported to the Swedish National Hip Arthroplasty Register. Of these, 245 had a further operation after failure of their initial management. Data were collected from the Register and hospital records. The material was analysed by the use of Poisson regression models.It was found that the risk of failure of treatment was reduced for Vancouver type B2 injuries (p = 0.0053) if revision of the implant was undertaken (p = 0.0033) or revision and open reduction and internal fixation (p = 0.0039) were performed. Fractures classified as Vancouver type B1 had a significantly higher risk of failure (p = 0.0001). The strongest negative factor was the use of a single plate for fixation (p = 0.001). The most common reasons for failure in this group were loosening of the femoral prosthesis, nonunion and re-fracture.It is probable that many fractures classified as Vancouver type B1 (n = 304), were in reality type B2 fractures with a loose stem which were not recognised. Plate fixation was inadequate in these cases. The difficulty in separating type B1 from type B2 fractures suggests that the prosthesis should be considered as loose until proven otherwise.
  •  
41.
  • McCloskey, Eugene V, et al. (författare)
  • From relative risk to absolute fracture risk calculation: the FRAX algorithm.
  • 2009
  • Ingår i: Current osteoporosis reports. - 1544-2241 .- 1544-1873. ; 7:3, s. 77-83
  • Tidskriftsartikel (refereegranskat)abstract
    • FRAX is a computer-based algorithm that provides models for the assessment of fracture probability in men and women (http://www.shef.ac.uk/FRAX). The approach uses easily obtained clinical risk factors to estimate 10-year fracture probability, with or without femoral neck bone mineral density (BMD), to enhance fracture risk prediction. It has been constructed using primary data from population-based cohorts around the world. The gradients of fracture risk have been validated in independent cohorts with a similar geographic distribution. The FRAX tool should not be considered as a gold standard, but rather as a platform technology on which to build as new validated risk indicators become available. Notwithstanding, the present models provide an aid to enhance patient assessment by the integration of clinical risk factors alone and/or in combination with BMD. This article describes the steps undertaken in the development of FRAX.
  •  
42.
  • McCloskey, E V, et al. (författare)
  • Ten-year fracture probability identifies women who will benefit from clodronate therapy--additional results from a double-blind, placebo-controlled randomised study
  • 2009
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 20:5, s. 811-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy. INTRODUCTION: Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX). METHODS: Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos) daily over 3 years. Baseline clinical risk factors were entered in the FRAX model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression. RESULTS: In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58-0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46-0.84). CONCLUSIONS: The estimation of an individual's 10-year probability of fracture by the FRAX algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.
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43.
  • Mellström, Dan, 1945, et al. (författare)
  • Older men with low serum estradiol and high serum SHBG have an increased risk of fractures
  • 2008
  • Ingår i: J Bone Miner Res. - : Wiley. - 1523-4681 .- 0884-0431. ; 23:10, s. 1552-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p
  •  
44.
  • Mouzon, Johanne, et al. (författare)
  • Fabrication of transparent yttria by HIP and the glass-encapsulation method
  • 2009
  • Ingår i: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219 .- 1873-619X. ; 29:2, s. 311-316
  • Tidskriftsartikel (refereegranskat)abstract
    • This method consists of a combination of vacuum sintering at 1600 °C followed by hot isostatic pressing (HIP) at 1500 °C of a highly agglomerated commercial powder. The use of evacuated glass capsules to perform HIP treatment allowed samples that showed open porosity after vacuum sintering to be sintered to transparency. The sintering response of the investigated powder was studied by careful microstructural observations using scanning electron microscopy and optical microscopy both in reflection and transmission. The successful key of this method was to keep porosity intergranular during pre-sintering, so that it can be removed subsequently by HIP treatment. It was found that agglomerates of closely packed particles are helpful to reach that purpose, since they densify fully and leave only intergranular porosity. However, performing HIP treatment at 1625 °C was found to result in opaque samples. This was attributed to the diffusion of argon inside the capsule. Contamination at different steps of processing was also investigated by inductively coupled plasma mass spectrometry (ICP-MS).
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45.
  • Müller, Lennart, 1959, et al. (författare)
  • Ultrasound assessment of detrusor thickness in children and young adults with myelomeningocele
  • 2006
  • Ingår i: J Urol. - 0022-5347. ; 175:2
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We determine by ultrasonography the range of dT in carefully treated and followed children with myelomeningocele, and evaluate the role of such measurements for the understanding of bladder abnormalities in these patients. MATERIALS AND METHODS: We studied 66 children and young adults with MMC (34 males and 32 females, median age 8.1 years, range 1.1 to 20.1). Detrusor thickness was measured with a previously established ultrasonographic technique and the results were compared to those in normal children. The variation in detrusor thickness with degree of bladder dysfunction as well as with bladder wall trabeculation, kidney function and anticholinergic treatment was studied. RESULTS: The detrusor of the ventral wall was slightly thinner in children with MMC compared to normal. No significant variation in dT was found for different degrees of bladder dysfunction, bladder wall trabeculation, kidney function or anticholinergic treatment. Boys had thicker detrusor of the ventral wall than girls. CONCLUSIONS: Children with MMC, followed closely and treated according to international standards, do not acquire detrusor thickening as measured by ultrasonography. The detrusor thickness did not correlate with the degree of bladder dysfunction or renal function, or with anticholinergic treatment. Bladder wall trabeculation at VCU was not associated with bladder wall thickening on ultrasonography. We postulate that in a closely monitored and actively treated population of patients with MMC muscular hypertrophy and the development of connective tissue in the bladder wall is kept to a minimum.
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46.
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47.
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48.
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49.
  • Rexius, Helena, 1967, et al. (författare)
  • A simple score to assess mortality risk in patients waiting for coronary artery bypass grafting
  • 2006
  • Ingår i: Ann Thorac Surg. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:2, s. 577-82
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Independent risk factors for death in patients waiting for elective coronary artery bypass surgery have previously been identified. A prioritization where these factors are considered may potentially reduce waiting list mortality. A simple score based on the risk factors was constructed and validated. METHODS: A scoring system based on risk factors in 5,864 consecutive patients operated from 1995 to 1999 was constructed. The following factors were included in the score: unstable angina (3 points [p]), left main stenosis (2p), concomitant aortic valve disease (2p), operative risk (0-2p), left ventricular ejection fraction (0-2p), and male gender (1p). The score was retrospectively validated in 5,167 new patients operated from 1999 to 2003. Based on the sum of risk score points, the patients were divided into three risk groups: low risk (0-2p), intermediate risk (3-5p) and high risk (> or = 6p). The risk groups were related to waiting list mortality and clinical priority (imperative, urgent, and routine). RESULTS: Median waiting time was 33 days. Forty-two patients (0.8%) died while waiting for surgery (5.2 deaths/100 waiting years). Of the patients, 2,406 (47%) were low risk, 1,990 (38%) intermediate risk, and 771 (15%) high risk. Mortality incidence in the high-risk group was fivefold higher than in the intermediate group and 25-fold higher than in the low-risk group (32, 7, and 1.3 deaths/100 waiting years, respectively, p < 0.001 between all groups). Twenty-three percent of the patients in the high-risk group had not been given imperative clinical priority. CONCLUSIONS: The score system identifies patients with increased risk of death while waiting for coronary artery bypass grafting. The score may be used to facilitate and improve the prioritization process.
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50.
  • Rexius, Helena, 1967, et al. (författare)
  • Waiting time and mortality after elective coronary artery bypass grafting
  • 2005
  • Ingår i: Ann Thorac Surg. - 1552-6259. ; 79:2, s. 538-43
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Limited resources for coronary artery bypass grafting (CABG) results in waiting times, prioritization between patients, and to mortality among the patients on the waiting list. Waiting time is an independent predictor for mortality on the waiting list, but it is not clear if the waiting time also influences outcome after CABG. METHODS: The study population was 5453 consecutive CABG patients who were prioritized at acceptance into three groups: imperative (CABG intended within 2 weeks), urgent (within 12 weeks), and routine (within 6 months). Postoperative mortality was compared between patients operated on within or after the intended waiting time in their respective groups. A multivariate Poisson regression model was used to further determine the effect of waiting time on postoperative mortality. Mean follow up was 24 +/- 15 months. RESULTS: Median waiting time was 55 days. Fifty-five percent of the patients were operated on within the intended waiting time. Postoperative mortality during follow-up was higher in patients operated on after the intended time (8.0 vs 6.2%, p = 0.014), but after correction for age, gender, operative risk, and angina symptoms, waiting time was not an independent predictor for postoperative death (risk ratio, 0.98 per waiting month; 95% confidence interval, 0.97 to 1.00; p = 0.44). CONCLUSIONS: The results suggest that mortality after CABG is not influenced by prolonged waiting time. The result does not exclude subgroups of patients that might benefit from a shorter waiting time.
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