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Biomedical subjects

A Oden

Publications and source records attributed to A Oden.

At least 19 recordsLinked to original sources
PubMed2006

The use of multiple sites for the diagnosis of osteoporosis.

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.

Absorptiometry, Photon↗
PubMed2005

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.

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.

Aged↗
PubMed2004

Ten-year probabilities of clinical vertebral fractures according to phalangeal quantitative ultrasonography.

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.

Absorptiometry, Photon↗
PubMed2004

Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study.

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 postmenopausal women without prior vertebral fractures was 18,000 pounds, 23,000 pounds , 18,000 pounds and 21,000 pounds at 50, 60, 70 and 80 years of age. Corresponding estimates for women with prior vertebral fractures were 10,000 pounds, 24,000 pounds, 18,000 pounds and 20,000 pounds. 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.

Adult↗
PubMed2004

The burden of hospitalised fractures in Sweden.

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.

Age Distribution↗
PubMed2004

Smoking and fracture risk: a meta-analysis.

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.

Age Distribution↗
PubMed2004

A meta-analysis of previous fracture and subsequent fracture risk.

Previous fracture is a well-documented 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 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture 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 by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Adolescent↗
PubMed2004

A family history of fracture and fracture risk: a meta-analysis.

The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.

Age Factors↗
PubMed2003

The Ki67 index a prognostic marker in medullary thyroid carcinoma.

Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.

Adult↗
PubMed2003

The risk and burden of vertebral fractures in Sweden.

The aim of this study was to determine the risk and burden of vertebral fractures judged as those coming to clinical attention and as morphometric fractures. Incidence and utility loss were computed from data from Malmo, Sweden. Clinical fractures accounted for 23% of all vertebral deformities in women and for 42% in men. The average 10-year fracture probability for morphometric fractures increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4 at the age of 85 years (26.7% in women). As expected, probabilities increased with decreasing T-score for hip BMD. Cumulative utility loss from a clinical vertebral fracture was substantial and was 50-62% of that due to a hip fracture depending on age. When incidence of fractures in the population was weighted by disutility, all spine fractures accounted for more morbidity than hip fracture up to the age of 75 years. We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis.

Age Distribution↗
PubMed2003

The components of excess mortality after hip fracture.

A high excess mortality is well described after hip fracture. Deaths are in part related to comorbidity and in part due directly or indirectly to the hip fracture event itself (causally related deaths). The aim of this study was to examine the quantum and pattern of mortality following hip fracture. We studied 160,000 hip fractures in men and women aged 50 years or more, in 28.8 million person-years from the patient register of Sweden, using Poisson models applied to hip fracture patients and the general population. At all ages the risk of death was markedly increased compared with population values immediately after the event. Mortality subsequently decreased over a period of 6 months, but thereafter remained higher than that of the general population. The latter function was assumed to account for deaths related to comorbidity and the residuum assumed to be due to the hip fracture. Causally related deaths comprised 17-32% of all deaths associated with hip fracture (depending on age) and accounted for more than 1.5% of all deaths in the population aged 50 years or more. Hip fracture was a more common cause for mortality than pancreatic or stomach cancer. Thus, interventions that decreased hip fracture rate by, say, 50% would avoid 0.75% or more of all deaths.

Aged↗
PubMed2002

Uncertain future of trials in osteoporosis.

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate since proven treatments are available. In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves.

Clinical Trials as Topic↗
PubMed2002

Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies.

Bone mineral density (BMD) measurements are widely used to estimate the risk of osteoporotic fractures. In addition, many other risk factors have been identified, some of which are known to add to the risk independently of BMD measurements. The combination of BMD with such risk factors increases the gradient of risk/standard deviation (SD) than that achieved by BMD alone. In this paper, we report the fracture probabilities according to age, gender, and relative risk, and have investigated the effects of changes in the gradient of risk for osteoporotic fractures on the sensitivity and specificity of assessments, modeled on the population of Sweden. Ten-year risks of hip, clinical vertebral, forearm, or proximal humeral fracture were computed with increments in gradient of risk that varied from 1.5 to 6.0 per SD change in skeletal risk. The identification of high-risk groups had little effect on the specificity of assessments, but increased the sensitivity over a wide range of assumptions. The inclusion of all four fracture types had little effect on sensitivity, but increased the positive predictive value of the test. Positive predictive value also increased with age, so that values greater than 50% were obtained testing women at the age of 65 years with modest gradient of risk of 2.0-2.5/SD when small segments of the population were targeted (0.5-5%). Screening of women to direct intervention at the age of 65 years and targeting 25% of the population could save up to 23% of all fractures in women over the next 10 years by the use of multiple tests with a moderate gradient of risk (RR = 2.0/SD). Such gradients might be achieved with the use of multiple risk factors to identify patients at risk.

Age Factors↗
PubMed2002

Optimal age for preventing osteoporosis after menopause depends on effects of stopping treatment.

The aim of this study was to model the effect of short (3 year) treatments for osteoporosis at different times after menopause on the risk of osteoporotic fracture and to assess the impact of strategies to target high-risk individuals. Treatment efficacy for hip, proximal forearm, shoulder, and spine fracture were computed from the relationship between bone mineral density (BMD) and fracture in women from Sweden. Treatment that increased hip bone mineral density by 6% over untreated women saved 126 vertebral, hip, proximal humerus, and forearm fractures per 1000 women at the age of 50 years, provided that the effects of treatment persisted. Targeting women with osteoporosis at this age would save an additional 50% of fractures. With age, the number of fractures saved decreased moderately. At the age of 70 years, 133 fractures would be saved in women with osteoporosis compared to 198 in women with osteoporosis at the age of 50 years. Where the effect of treatment was assumed to wear off over 20 years after stopping treatment, the efficacy of treatment was reduced at all ages, but most markedly at the age of 50 years. Where all women aged 50 years were treated, the number of fractures saved per 1000 women decreased from 127 to 15 and, in the case of targeting women with osteoporosis, decreased from 198 to 27 per 1000 women. By contrast, with a persisting effect of treatment, the number of fractures saved increased markedly with advancing age. If all women were targeted at the age of 50 years, 15 fractures would be saved, whereas this increased to 55 per 1000 women at the age of 70 years. When treatment effects wore off more rapidly with an offset half-time of 2.5 years only 5 fractures were saved per 1000 women at the age of 50 years. This figure rose to 23 per 1000 at the age of 70 years. We conclude that, although uncertainty exists concerning the offset of effect of treatments, treatments should be optimally given to women without prior fractures in later life.

Age Factors↗
PubMed2002

Intervention thresholds for osteoporosis.

The aim of this study was to determine the threshold of fracture probability at which interventions become cost-effective. We modeled the effects of a treatment costing $500/year, given for 5 years, that decreased the risk of all osteoporotic fractures by 35%, followed by a waning of effect for 5 years. Sensitivity analyses included a range of effectiveness (10%-50%) and a range of intervention costs (200-500 dollars/year). Data on costs and risks were from Sweden. Costs included direct costs and costs in added years of life, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of 60,000 dollars per quality-adjusted life-year (QALY) gained was used. Costs of added years were excluded in a sensitivity analysis for which a threshold value of 30,000 dollars per QALY was used. In the base case, intervention was cost-effective when treatment was targeted to women at average risk at age of >or=65 years. Irrespective of the efficacy modeled (10%-50%) or of cost of intervention (200-500 dollars/year) segments of the population at average risk could be targeted cost-effectively: The lower the intervention cost and the higher the effectiveness, the lower the age at which intervention was cost-effective. With the base case (500 dollars/year; 35% efficacy) treatment in women was cost-effective with a 10 year hip fracture probability that ranged from 1.4% at the age of 50 years to 4.4% at the age of 65 years. The exclusion of osteoporotic fractures other than hip fracture would increase the threshold to a 9%-11% 10 year probability because of the substantial morbidity from fractures other than hip fracture, 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 cost-effectively targeted to individuals at moderately increased risk.

Aged↗
PubMed2001

Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds.

The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in Malmö, Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes.

Age Factors↗