Combination Of Clinical Risk Factors Research Articles

Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis

The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate. Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated. A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation. At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was-irrespective of age-cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20%. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32%, respectively. FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate.

The micro-architecture estimation by TBS discriminate women with and without osteoporotic fracture independently of age, BMI and BMD: The osteo-mobile vaud cohort study

Introduction: « Osteo-Mobile Vaud » is a mobile osteoporosis (OP) screening program. The women > 60 years living in the region Vaud will be offered OP screening with new equipment installed in a bus. The main goal is to evaluate the fracture risk with the combination of clinical risk factors (CRF) and informations extracted by a single DXA: bone mineral density (BMD), vertebral fracture assessment (VFA), and micro-architecture (MA) evaluation. MA is yet evaluable in daily practice by the Trabecular Bone Score (TBS) measure. TBS is a novel grey-level texture measurement reflecting bone MA based on the use of experimental variograms of 2D projection images. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis value, partially independent of CRF and BMD. A 55-years follow- up is planned. Method: The Osteo-Mobile Vaud cohort (1500 women, > 60 years, living in the region Vaud) started in July 2010. CRF for OP, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded. Preliminary results are reported. Results: In July 31th, we evaluated 510 women: mean age 67 years, BMI 26 kg/m². 72 women had one or more fragility fractures, 39 had vertebral fracture (VFx) grade 2/3. TBS decreases with age (-0.005 / year, p<0.001), and with BMI (-0.011 per kg/m², p<0.001). Correlation between BMD and site matched TBS is low (r=0.4, p<0.001). For the lowest T-score BMD, odds ratio (OR, 95% CI) for VFx grade 2/3 and clinical OP Fx are 1.8 (1.1-2.9) and 2.3 (1.5-3.4). For TBS, age-, BMI- and BMD adjusted ORs (per SD decrease) for VFx grade 2/3 and clinical OP Fx are 1.9 (1.2-3.0) and 1.8 (1.2-2.7). The TBS added value was independent of lumbar spine BMD or the lowest T-score (femoral neck, total hip or lumbar spine). Conclusion: As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS and BMD may increase significantly the identification of women with prevalent OP Fx. For the first time we are able to have complementary information about fracture (VFA), density (BMD), and micro-architecture (TBS) from a simple, low ionizing radiation and cheap device: DXA. The value of such informations in a screening program will be evaluated.

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.

Abstract 147: Weighted Insurance Reimbursement Strategies For Cardiac Imaging Based On Appropriateness Criteria

Rising use of medical imaging has been a major driver in escalating health care costs. As reimbursement for imaging has declined, it is likely that some effort to expand volume into lower risk populations has occurred. Consequently, insurance payouts based on pre-test likelihood of disease can be restructured to promote effective use in intermediate risk populations where uncertainty about disease presence is highest (50%). Objective: to analyze the incidence of normal result imaging over 5 years and to construct insurance payout schemes that will result in a net reduction in cost while simultaneously promoting the effective use of imaging. Methods .This is a retrospective study of patients (pts) who underwent stress nuclear perfusion scans to detect coronary artery disease (CAD). The study is in 2 parts. Part 1: Specific years were randomly sampled: 2006 (n=2894), 2008 (n= 2843) and 2010 (n=2550) as to whether results were normal or had some abnormality in perfusion suggesting CAD. Part 2: The years 2010 and 2011 (n=2486) were then combined to fit different models of reimbursement based on the pre-test likelihood of CAD. All patients without known CAD referred for imaging were included. A risk score derived from combination of clinical risk factors known to be associated with CAD and available to all clinicians was calculated for each patient. This score was further weighted by the resting ECG status and the presence or absence of symptoms. Three appropriateness classifications were assigned based on this score (1=inappropriate (1-10% risk),2=probably appropriate (10-40% risk and more than 60%) and 3= appropriate (40-60% risk) derived from a national expert panel of physicians. The cost of imaging was set at $2000, which is an approximate national median charge Results: There was a significant increase in the incidence of normal imaging results with time: 2006=66%, 2008=69%, 2010=76%, p&lt;0.0001). The median pretest risk score for CAD in the test cohort (n=2486) was 13.5% with 43% of pts tested having a risk score of &lt;10%. Applying a weighted reimbursement scheme such that class 1 received 75% of payment, class 2=full payment and class 3=125% of payment, the following payout structure is generated(see table): The total cost of imaging the group without weighting was $5.0 million. Consequently, weighted reimbursement produced a 9% savings. Conclusion: This approach, based on established pretest criteria, is highly flexible and produces immediate savings. More importantly, it provides incentive to reshape ordering behavior in the future but may need to be complemented with tort reform.

Surgery and cardiovascular outcomes: an untapped public health benefit that potentially saves lives

Surgery and cardiovascular outcomes: an untapped public health benefit that potentially saves lives

A functional variant in ANGPT1 and the risk of pregnancies with hypertensive disorders and small-for-gestational-age infants

Pregnancies complicated by pre-eclampsia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-eclampsia [P = 0.01, adjusted odds ratio (aOR), 0.5; 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5; 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7; 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6; 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-eclampsia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.

Risk Factor and Prediction Modeling for Sudden Cardiac Death in Women With Coronary Artery Disease

To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD. The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed. Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n=683), 1 (n=1224), 2 (n=610), and 3 plus (n=246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P<.001). Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.

Discriminative value of FRAX for fracture prediction in a cohort of Chinese postmenopausal women

We followed 2,266 postmenopausal Chinese women for 4.5 years to determine which model best predicts osteoporotic fracture. A model that contains ethnic-specific risk factors, some of which reflect frailty, performed as well as or better than the well-established FRAX model. Clinical risk assessment, with or without T-score, can predict fractures in Chinese postmenopausal women although it is unknown which combination of clinical risk factors is most effective. This prospective study sought to compare the accuracy for fracture prediction using various models including FRAX, our ethnic-specific clinical risk factors (CRF) and other simple models. This study is part of the Hong Kong Osteoporosis Study. A total of 2,266 treatment naïve postmenopausal women underwent clinical risk factor and bone mineral density assessment. Subjects were followed up for outcome of major osteoporotic fracture and receiver operating characteristic (ROC) curves for different models were compared. The percentage of subjects in different quartiles of risk according to various models who actually fractured was also compared. The mean age at baseline was 62.1 ± 8.5 years and mean follow-up time was 4.5 ± 2.8 years. A total of 106 new major osteoporotic fractures were reported, of which 21 were hip fractures. Ethnic-specific CRF with T-score performed better than FRAX with T-score (based on both Chinese normative and National Health and Nutrition Examination Survey (NHANES) databases) in terms of AUC comparison for prediction of major osteoporotic fracture. The two models were similar in hip fracture prediction. The ethnic-specific CRF model had a 10% higher sensitivity than FRAX at a specificity of 0.8 or above. CRF related to frailty and differences in lifestyle between populations are likely to be important in fracture prediction. Further work is required to determine which and how CRF can be applied to develop a fracture prediction model in our population.

Prophylaxis, empirical and preemptive treatment of invasive candidiasis

Invasive candidiasis remains an important infection for ICU patients, associated with poor clinical outcomes. It has been increasingly recognized that the traditional paradigm of culture-directed antifungal treatment is unsatisfactory, and that earlier antifungal intervention strategies, such as prophylaxis, preemptive therapy, and empiric therapy, are required to improve patient outcomes. The purpose of this review is to summarize the recent supportive evidence for such strategies and to highlight the current challenges in their implementation. Despite new antifungal agents and classes, the mortality from invasive candidiasis remains high. Antifungal prophylaxis remains the best-studied early antifungal intervention strategy; however, unless targeted to patients at highest risk, is inefficient. Recent data suggests that although risk predictive models, using a combination of clinical risk factors and Candida colonization parameters, may be a relatively simple and practical approach to guide prophylaxis or preemptive therapy, further validation of these models is required. A single trial has demonstrated that empiric antifungal therapy is not of benefit when instituted to patients with antibiotic-refractory fever alone. On the basis of current knowledge, it is difficult to universally recommend antifungal prophylaxis, apart from patient groups with a known very high risk, such as those with necrotising pancreatitis or recurrent gastrointestinal perforations. Antifungal prophylaxis may also be reasonable where local incidence rates and epidemiology are compelling. Among stable patients with multifocal Candida colonization and/or a multitude of clinical-risk factors, preemptive therapy is currently not indicated, although the development of better risk predictive models may assist with such patients. Among patients with refractory fever despite broad-spectrum antibacterial therapy, empiric antifungal therapy may be reasonable where local incidence rates are high (e.g. >10%); however, a thorough search for alternate causes must be instituted.

Prediction of Preeclampsia and Delivery of Small for Gestational Age Babies Based on a Combination of Clinical Risk Factors in High-Risk Women

Objective. To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women. Methods. Individual risk scores based on clinical risk factors were calculated using logistic regression and validated in 1687 women with obesity in first pregnancy, chronic hypertension, or previous preeclampsia. Results. The risk of preeclampsia varied from 7% in obese primiparae without hypertension to 30% when previous preeclampsia and chronic hypertension occurred together. A prediction model incorporating these risk factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks' gestation. Conclusion. Multiple clinical risk factors increase the risk of preeclampsia and SGA.

FRAX ® and its applications in health economics—Cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example

Background An important aspect of cost-effectiveness analysis of osteoporosis is to accurately model the fracture risk and mortality related to the patient groups in the analysis. The estimation of fracture risk is based on a number of factors, such as the level of general risk of the normal population, the effect of treatment and the prevalence of clinical risk factors (CRFs) for fracture. Fracture risk has traditionally been calculated with risk adjustments based on age, bone mineral density and prior vertebral fracture. The treatment effect has been derived from clinical trials and, in the absence of subgroup analyses, the same efficacy has been assumed irrespective of the fracture risk of the population. The FRAX ® tool enables the estimation of risk based on a wider range of risk factors, and treatment efficacy that is dependent on the level of risk in the analyzed population. The objective was to describe the implementation of the FRAX ® algorithms into health economic osteoporosis models and to highlight how it differs from traditional risk assessment. Methods The selective estrogen receptor modulator, bazedoxifene, was evaluated in a Swedish setting with traditional and FRAX ®-based risk assessment in a previously developed Markov model that included fractures and thromboembolic events, and also was adapted to accommodate risk-dependent efficacy, which is available for bazedoxifene. Results The traditional approach gave lower ICERs at ages up to 60 years compared to the FRAX ® method when only considering age, BMD and prior fracture. At 70 years and older and when adding more CRFs with the FRAX ® approach, the FRAX ® ICER decreased and fell below the traditional approach. The risk dependant efficacy was the main reason for lower ICERs with FRAX ® in women at higher risk of fracture. Discussion FRAX ® applied in cost-effectiveness analyses is a more granular method for the estimation of fracture risk, mortality and efficacy compared to previous approaches that can also improve case finding. Furthermore, it facilitates the estimation of cost-effectiveness for various types of patients with different combinations of CRFs, which more closely matches patients in clinical practice.

Importance of bone mineral density measurements in evaluating fragility bone fracture risk in Asian Indian men

We evaluated the effect of BMD on fracture risk prediction using FRAX® among Asian Indian men when used in conjunction with clinical risk factors. A majority of our subjects were either osteopenic or osteoporotic, and their fracture risk increased when FRAX® was used in conjunction with femur neck T-scores. Asian Indian men living in the United States may represent a population that is at high and underappreciated risk for fragility bone fractures. To evaluate the effect of BMD on fracture risk prediction using FRAX® among Asian Indian men when used in conjunction with clinical risk factors. Forty four Asian Indian men (mean age 64.9 (±8.4) years) who had lived in the United States for an average of 33.6 (±10.6) years underwent BMD measurement at the proximal femur. Subjects were subjected to a general physical exam and history of fracture, hip fracture in a parent, current smoking and alcohol use, and diagnosis of inflammatory arthritis was obtained. Data from each subject were entered into the FRAX® algorithm and 10-year fracture probabilities were calculated using clinical risk factors (CRFs) alone and in combination with femur neck T-scores. Thirteen subjects (29.5%) had femur neck T-scores ≥ -1.0, 28 (63.6%) T-scores between -1.0 and -2.5, and three (6.8%) T-scores < -2.5. The 10-year probability of a major osteoporotic fracture based on a combination of clinical risk factors and femur neck T-scores was significantly higher than the fracture probability based on clinical risk factors alone (t(43) = 2.58, p = 0.01). Among Asian Indian men, the 10-year probability of a major osteoporotic fracture increases when femur neck T-scores are added to clinical risk factors in the FRAX® algorithm, and this population have a high fracture probability even in the absence of clinical risk factors.

The effects of a FRAX® revision for the USA

A revision (version 3.0) of the fracture risk assessment tool (FRAX) is developed based on an update of epidemiological information for the USA. With the revised tool, there were strong correlations (r > 0.99) between versions 2.0 and 3.0 for FRAX estimates of fracture probability, but the revised models gave lower probability estimates. The aim of this study was to determine the effects of a revision of the epidemiological data used to compute fracture probabilities in the USA with FRAX. Models were constructed to compute fracture probabilities based on updated fracture incidence and mortality rates in the USA. The models comprised the ten-year probability of hip fracture and the ten-year probability of a major osteoporotic fracture, both including femoral neck bone mineral density (BMD). For each model, fracture and death hazards were computed as continuous functions. The effect of the revised rates on fracture probability was examined by piecewise linear regression using multiple combinations of clinical risk factors and BMD. At all ages, there was a strong correlation (r > 0.99) between version 2.0 and revised FRAX estimates of fracture probability. For a major osteoporotic fracture, the revised model gave lower median probabilities by 13% to 24% in men, depending on age, and by 19% to 24% in women. For hip fracture probability, the revised model gave lower median fracture probabilities by 40% and 27% at the ages of 50 and 60 years in men and by 43% and 30%, respectively, in women. At the ages of 70 years and older the revised model gave similar hip fracture probabilities as version 2.0 in both men and women. The revised FRAX model for the USA (version 3.0) does not alter the ranking of fracture probabilities but provides lower probability estimates than version 2.0, particularly, in younger women and men.

Intermediate Dose Intravenous Methotrexate (MTX) Dramatically Reduces the Risk of Secondary Central Nervous System (CNS) Lymphoma.

Secondary CNS lymphoma (SCNSL) is a rare complication of diffuse large B cell non-Hodgkins lymphoma (DLBCL) which is almost universally fatal. Several groups have analyzed risk factors for the development of SCNSL and published risk estimates for both individual anatomic sites of DLBCL as well as combinations of clinical risk factors. Although the rates of SCNSL for all DLBCL patients range from 2.5% to 5% subgroups can be identified with risks as high as 33%. High risk scenarios where CNS prophylaxis is most commonly offered include either a combination of an elevated LDH and more than one extranodal site of disease, or disease involving the bone marrow, testicle, sinus, orbit, or a para-spinal location. The type of prophylaxis used varies widely from intrathecal to high-dose intravenous methotrexate as well as intrathecal use of cytarabine. Despite the advances made in the systemic therapy of DLBCL there is very limited data on the efficacy of these chemopreventive regimens in SCNSL. We undertook a retrospective review at our institution of all patients with DLBCL treated with inpatient intermediate dose methotrexate (3.5 grams per meter squared) followed by leucovorin rescue between 2002 and 2006 for CNS prophylaxis. We found 37 patients. Of 15 patients initially evaluated with diagnostic lumbar punctures (LP), no patient had a positive CSF cytology. The median age of the patients was 59 (26–79). The average IPI was 3. All patients were tested for HIV and 3 were found to be positive. The indications for CNS prophylaxis were primarily an elevated LDH and more than 1 extranodal site of disease (20) but also included patients with bone marrow (9), testicular (3), orbital (5), para-spinal (2) and sinus (6) involvement, with 6 patients having more than one site of involvement. All patients received an anthracycline containing chemotherapy regimen with curative intent. Thirty-six patients received rituximab. Patients received a median of 6 cycles of systemic chemotherapy and 3 courses of MTX given on day 15 of alternating cycles (usually 2, 4 and 6). In addition 2 patients received a single dose of 12 mg of intrathecal methotrexate at the time of their initial LP and 5 patients received intrathecal liposomal cytarabine. We calculated the expected number of cases of SCNSL using the estimates from van Besien et al. Blood ‘98, Hollender et al. Ann Onc ‘02, and Boehme et al. Ann Onc ‘06 as appropriate depending on the sites of disease for each patient. For this population the expected number of cases of SCNSL was 7.98 and the observed number of cases was 1 (p=.002 two-sided binomial probability). In this population of 37 patients with an elevated risk of SCNSL, the use of intravenous intermediate dose methotrexate substantially reduced their risk of this fatal complication.

Development of a nomogram for individualizing hip fracture risk in men and women

Until now there has been no published prognostic tool available for predicting of hip fracture to primary care settings. We have developed a nomogram for predicting the absolute risk of hip fracture for any individual by using clinical factors, including age, prior fracture and fall, in addition to BMD that was based on a 15-year follow-up cohort study. Bone mineral density or clinical risk factors alone are useful but limited tools for the identification of individuals with high-risk of hip fracture. It is hypothesized that the combination of clinical risk factors and BMD can improve the accuracy of fracture prediction. This study was aimed at developing a nomogram which combines these factors for predicting 5-year and 10-year risk of hip fracture for an individual. The study, designed as a epidemiologic, community-based prospective study, included 1,208 women and 740 men aged 60+ years with median duration of follow-up of 13 years (inter-quartile range, IQR: 6-14) for both women and men, yielding 10,523 and 7,586 person-years of observation, respectively. Main outcome measures were incidence of hip fractures and risk factors were femoral neck bone mineral density (FNBMD), prior fracture, history of fall, postural sway and quadriceps strength. Femoral neck BMD was measured by DXA (GE-LUNAR Corp, Madison, Wisconsin, USA). Cox's proportional hazards model was used to estimate the risk of fracture for individuals, and a nomogram was constructed for predicting hip fracture risk. Between 1989 and 2004, 127 individuals (96 women) sustained a hip fracture. Advancing age, low femoral neck BMD, prior fracture and history of falls were independent predictors of hip fracture. The area under the receiver operating characteristic curve for the model was 0.85 for both sexes. A nomogram was constructed for predicting hip fracture risk for an individual. Among those aged 75 or older with BMD T-scores < or = -2.5, the risk of hip fracture in men was comparable to or higher than in women; however, in younger age groups, the risk was higher in women than in men. The combination of BMD and non-invasive clinical risk factors in a nomogram could be useful for identifying high-risk individuals for intervention to reduce the risk of hip fracture.

The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women

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. 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). 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. 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.

Type and crossmatch of the trauma patient.

To identify a population of trauma patients in the emergency department (ED) that do not require emergent blood transfusion via a combination of clinical risk factors that are readily accessible and easily obtained. A review of trauma patients was conducted for a 6-month period. Crossmatched patients were identified and examined for clinical characteristics and whether transfusion was performed. Risk factors for transfusion were identified and a model was developed for predicting likelihood of transfusion. Six hundred fifty-four patients were crossmatched, with emergent transfusion occurring in 81 (12.4%). Four risk factors were identified: systolic blood pressure < 90 mm Hg, Glasgow Coma Scale score < 9, pulse > 120 beats/min, and high-risk injury (trauma to the chest between the midclavicular lines, abdominal injury with diffuse tenderness, survival of a fatal vehicular crash, ejection from a vehicle, or stab or gunshot wound to the trunk). Patients with no risk factors were shown to have a 2.2% incidence of transfusion with no emergent transfusions occurring in the ED. Trauma patients with no risk factors at presentation were less likely to require emergent blood transfusion, especially in the setting of the ED.

Detection of small for gestational age fetuses by the combination of clinical risk factors and ultrasonography

Clinical risk factors of fetal growth retardation and targeted ultrasound examinations were combined to detect small for gestational age (SGA) fetuses below the 10th percentile weight for age in 1122 unselected singleton pregnancies, in which the true gestational age was confirmed by ultrasonography at 18 weeks. The prevalence of SGA infants was 6.0% in this population. A risk group of 236 (21%) mothers was referred for an ultrasound examination of fetal growth by the midwives of maternity welfare centers on the basis of low symphysis-fundal height or five other major maternal risk factors (pregnancy associated hypertension, loss of weight gain, a previous SGA infant, pre-pregnancy weight below 50 kg, any smoking during pregnancy). The sensitivity and positive predictive value of the clinical part of the study were 83.6 and 23.7%, respectively. Fetal growth was assessed by measuring both biparietal diameter (BPD) and transverse abdominal diameter. In the clinically selected risk group, 83.9% of the SGA fetuses could be detected by this method using a cutoff level of −1 standard deviation (SD). The two-step screening combining clinical and ultrasonographic methods in the detection of SGA fetuses in general population showed a sensitivity of 70.1%, a specificity of 95.5%, a positive predictive value of 49.5%, and a negative predictive value of 98.1%. After ultrasound examination, the definitive risk group for SGA was 8.5% of the total material of 1122. Although the total number of ultrasound examinations was decreased by about half, the ability of the screening to detect SGA fetuses was in this study even better than that of a routine screening performed twice during pregnancy with the same ultrasound method.