Validated risk rule using computerized data to identify males at high risk for fracture

Summary  

Absolute risk assessment is now the preferred approach to guide osteoporosis treatment decisions. Data collected passively during routine healthcare operations can be used to develop discriminative absolute risk assessment rules in male veterans. These rules could be used to develop computerized clinical decision support tools that might improve fracture prevention.     

Relationship of glycosylated hemoglobin to oral glucose tolerance. Implications for diabetes screening

The oral glucose tolerance test (OGTT) for diagnosis of diabetes is inconvenient and requires a great deal of patient cooperation. Glycosylated hemoglobin (GHb), an index of long-term glycemic control, could offer several practical advantages over the OGTT for diabetes screening. We evaluated GHb as a screen for diabetes in 381 adults from a population with a high prevalence of non-insulin-dependent diabetes (Pima Indians). All individuals underwent a standard OGTT (75 g) and were separated into one of three groups: normal (N), impaired glucose tolerance (IGT), or diabetes mellitus (D) based on World Health Organization criteria. HbA1c, a GHb, was measured by highly precise high-performance liquid chromatography (interassay C.V. less than 4%). The normal range for HbA1c was 4.07-6.03% based on the 95% confidence interval for a nondiabetic, mostly Caucasian population. Compared with OGTT, HbA1c was highly specific (91%); an elevated HbA1c usually indicated D or IGT (sensitivity = 85 and 30%, respectively). A normal HbA1c did not, however, exclude a diagnosis of D or IGT. Based on previous epidemiological studies relating plasma glucose to chronic diabetic complications, GHb as measured in this study would properly identify the vast majority of subjects at risk. Long-term studies are necessary to determine the actual risk of complications in individuals with persistently normal HbA1c and D or IGT (based on OGTT).     

Optimization of BMD measurements to identify high risk groups for treatment--a test analysis.

INTRODUCTION: The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy. We studied 2113 women > or = 75 years of age randomly selected from Sheffield, UK, and adjacent regions. Baseline assessment included hip BMD and clinical risk factors. Outcomes included death and fracture in women followed for 6723 person-years. MATERIALS AND METHODS: Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities. Women were categorized by fracture probability with and without a BMD assessment. A 10-year fracture probability threshold of 35% was taken as an intervention threshold. Discordance in categorization of risk (i.e., above or below the threshold probability) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification. Age, prior fracture, use of corticosteroids, and low body mass index were identified as significant clinical risk factors. RESULTS: A total of 16.8% of women were classified as high risk based on these clinical risk factors. The average BMD in these patients was approximately 1 SD lower than in low-risk women; 21.5% of women were designated to be at high risk with the addition of BMD. Fifteen percent of all women were reclassified after adding BMD to clinical risk factors, most of whom lay near the intervention threshold. When a high probability of reclassification was accepted (without a BMD test) for high risk to low risk (p1< or = 0.8) and a low probability accepted for low to high risk (P2 < or = 0.2), BMD tests would be required in only 21% of the population. CONCLUSION: We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD. BMD testing is required, however, in a minority of women--a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen. These findings need to be validated in other cohorts at different ages and from different regions of the world.     

Impedance analysis to identify the at risk femorodistal graft.

Computer-assisted impedance analysis is a newly developed technique to identify femoropopliteal and distal vein graft stenoses before failure. Pulsatile flow is measured from the proximal and distal graft by use of an 8Mhz Doppler velocimeter. A pulse volume recorder measures pulsatile pressure within the thigh and calf. Fourier transfer analysis is performed on paired Doppler pulse volume recorder waveforms and an impedance score derived for the thigh and calf, respectively. In a retrospective review of 50 nonreversed femoropopliteal/distal grafts performed for limb salvage, postoperative biplanar intraarterial digital subtraction arteriography was compared with impedance analysis. Arteriography showed graft or runoff stenoses in 22 grafts (at risk) and 28 normal grafts (controls). Impedance scores were significantly higher in the at risk group (0.58 + [0.43 to 0.72]*), when compared with the controls (0.34 + [0.30 to 0.38], p less than 0.001*). A thigh or calf impedance score of greater than 0.45 was able to detect 20 of 22 stenoses, including 6 lesions in grafts with normal resting and postexercise ankle pressures. This score was then applied prospectively and compared with serial biplanar digital subtraction arteriography in a further 56 femoropopliteal/distal bypasses for limb salvage. Thirty-three of 34 lesions were successfully predicted and impedance scores were significantly higher in the at risk limbs (0.56 + [0.44 to 0.68]*) when compared with the controls (0.38 + [0.35 to 0.41], p less than 0.001*). In this series impedance analysis proved more sensitive than resting or stressed ankle pressures and, unlike Duplex scanning, was able to detect runoff as well as graft stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of electronic medical records to identify patients at risk for prostate cancer in an academic institution

One purported advantage of electronic medical records (EMRs) is to improve patient care. This study uses a search of EMR to identify patients at risk for prostate cancer who were not evaluated by an urologist. The University of Texas Southwestern Medical Center (UTSW) has an institutional outpatient EMR that is used by all providers in all specialties. Since March 2009, all PSA tests were reported with specific interpretative comments including a recommendation for referral to urology for a PSA >2.5 ng ml(-1). All PSA tests were performed on campus since institution of these recommendations were analyzed, and charts reviewed for all patients not seen in urology with a serum PSA >2.5 ng ml(-1). Of the 2884 non-urology patients that had a serum PSA drawn between March 2009 and February 2010 at UTSW, 293 patients had a serum PSA >2.5 ng ml(-1). Of these, 39 patients had known prostate cancer and were seeing an oncologist. There were 59 patients seeing urologists outside the institution. A total of 195 patients were not seen by an urologist and only 11 patients were recommended to see one but did not make an appointment. There were 151 patients with more than one PSA in the system, and of these 103 had a rise in PSA with a median rise of 0.53 ng ml(-1) per year. EMR allows identification of patients at increased risk of prostate cancer who are not evaluated. Prospective studies are needed to identify ways to improve appropriate evaluation and detection of prostate cancer.     

Use of the Valsalva manoeuvre to identify haemodialysis patients at risk of congestive heart failure

Background: In the presence of elevated cardiac filling pressures, the decline of blood pressure (BP) during the straining phase of a Valsalva manoeuvre is blunted or absent. We compared the use of non-invasively measured BP response to a Valsalva manoeuvre with clinical assessment and bioimpedance measurements to identify haemodialysis patients at risk of acute congestive heart failure (CHF). Methods: Continuous BP response (Finapres) to a Valsalva manoeuvre, clinical assessment by nephrologists, and bioimpedance estimations of extracellular fluid volume were determined before and after haemodialysis, once every week during a 5-week period. Acute CHF was defined according to preset clinical and radiological criteria. Results: Participants (age 60±19 years, six females, nine males) had an average predialysis weight of 66.8±11.8 kg. Patients were dialysed for 3.8±0.8 h with a mean ultrafiltration of 2.4±1.1 litres. Valsalva systolic BP ratios (phase 2 to 1) decreased significantly during dialysis from 0.81±0.11 to 0.73±0.10 (P<0.05). Five patients experienced an episode of acute CTF. The Valsalva BP ratios for these patients before and after dialysis (0.89±0.05 and 0.78±0.05 respectively) were higher than for the remaining ten patients (0.77±0.10 and 0.70±0.11, respectively) (P<0.05). A cutoff Valsalva BP ratio of 0.82 resulted in positive and negative predictive values for CHF of 62 and 100% respectively. No differences in clinical assessment or bioimpedance parameters were found, with the exception of postdialysis diastolic BP and predialysis ankle oedema. After treatment of CHF, Valsalva BP ratios decreased significantly without changes in the other hydration parameters. Conclusions: Non-invasive assessment of the BP response to a Valsalva manoeuvre appears to be a potential tool for identifying patients at risk of acute CHF during maintenance haemodialysis.     

Magnesium deficiency in IDDM related to level of glycosylated hemoglobin

Magnesium and potassium were analyzed in plasma, erythrocytes, and urine collected during 24 h and in muscle biopsies from 25 subjects with insulin-dependent, type I diabetes mellitus (IDDM). Magnesium was also measured in mononuclear cells. The results were compared with those of 28 healthy controls, and were also correlated with the degree of diabetic control as estimated by analysis of the level of glycosylated hemoglobin (HbA1c). Subjects with IDDM had significantly lower muscle (P less than 0.01) and plasma (P less than 0.001) concentrations of magnesium compared with those of healthy controls. The HbA1c levels correlated significantly with the concentrations of magnesium in muscle (r = -0.62, P less than 0.001), plasma (r = -0.62, P less than 0.001), and mononuclear cells (r = -0.47, P less than 0.05). The results indicate that some patients with IDDM have lowered contents of magnesium in striated muscular and/or plasma, and that those parameters are dependent on the degree of diabetic control.     

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection

BACKGROUND: Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. METHODS: Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. RESULTS: On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). CONCLUSION: On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.     

The B-APNEIC score: distilling the STOP-Bang questionnaire to identify patients at high risk for severe obstructive sleep apnoea

The STOP-Bang questionnaire is an established clinical screening tool to identify the risk of having mild, moderate or severe obstructive sleep apnoea using eight variables. It is unclear whether all eight variables contribute equally to the risk of clinically significant obstructive sleep apnoea. We analysed each variable for its contribution to detecting obstructive sleep apnoea; based on the results, we investigated whether the STOP-Bang questionnaire could be abbreviated to identify patients at high risk for severe obstructive sleep apnoea. We recruited patients with suspected obstructive sleep apnoea who were referred for overnight polysomnography. We used multivariable logistic regression to investigate the association of STOP-Bang parameters with severe obstructive sleep apnoea based on clinical and polysomnography data. Regression estimates were used to select variables to create the novel B-APNEIC score. We constructed receiver operating characteristic curves for the STOP-Bang questionnaire and B-APNEIC scores to identify patients with severe obstructive sleep apnoea and compared the areas under the curve using the DeLong method. Of the 275 patients enrolled, 32% (n = 88) had severe obstructive sleep apnoea. Logistic regression demonstrated that neck circumference (OR 2.20; 95%CI 1.10–4.40, p = 0.03) was the only variable independently associated with severe obstructive sleep apnoea. Observed apnoea during sleep, blood pressure and body mass index were the three next most closely trending predictors of severe obstructive sleep apnoea and were included along with neck circumference in the B-APNEIC score. Receiver operating curves demonstrated that the areas under the curve for STOP-Bang vs. B-APNEIC were comparable for identifying patients with severe obstructive sleep apnoea (OR 0.75; 95%CI 0.68-0.81 vs. OR 0.75; 95%CI 0.68–0.81: p = 0.99, respectively). Our results suggest that the B-APNEIC score is a simplified adaptation of the STOP-Bang questionnaire with equivalent effectiveness in identifying patients with severe obstructive sleep apnoea. Further studies are needed to validate and build on our findings.     

Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy

Introduction and hypothesis Over half of all fractures among post-menopausal women occur in those who do not have osteoporosis by bone density criteria. Measurement of bone turnover may cost-effectively identify a subset of women with T-score >−2.5 for whom anti-resorptive drug therapy is cost-effective. Methods Using a Markov model, we estimated the cost per quality adjusted life year (QALY) for five years of oral bisphosphonate compared to no drug therapy for osteopenic post-menopausal women aged 60 to 80 years with a high (top quartile) or low (bottom 3 quartiles) level of a bone turnover marker. Results For women with high bone turnover, the cost per QALY gained with alendronate compared to no drug therapy among women aged 70 years with T-scores of −2.0 or −1.5 were $58,000 and $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also reduced the risk of non-vertebral fractures by 20% among osteopenic women with high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for women age 70 with high bone turnover and T-scores of −2.0 and −1.5, respectively. Conclusion Measurement of bone turnover markers has the potential to identify a subset of post-menopausal women without osteoporosis by bone density criteria for whom bisphosphonate therapy to prevent fracture is cost-effective. The size of that subset highly depends on the assumed efficacy of bisphosphonates for fracture risk reduction among women with both a T-score >−2.5 and high bone turnover and the cost of bisphosphonate treatment.     

Bimodality of glycosylated hemoglobin distribution in Pima Indians: relationship to fasting hyperglycemia.

Glycosylated hemoglobin (HbA1) concentrations were determined in 300 Pima Indians aged 15 yr and older. Frequency distributions of HbA1 were unimodal in the 15--24-yr-old age group, but were bimodal in those aged 25 yr and over. The bimodality indicated that the subpopulation with diabetes could be identified by the presence of elevated HbA1 levels. This group was comprised primarily of subjects who also had fasting plasma glucose levels of less than or equal to 140 mg/dl, but subjects with impaired glucose tolerance without fasting hyperglycemia had HbA1 levels that were not significantly higher than those with normal glucose tolerance. The prevalence of diabetic retinopathy was much higher in the subgroup with elevated HbA1 levels and increased with increasing HbA1 level. HbA1 levels and triglyceride concentrations showed only a modest association. HbA1 determinations provided no advantage over fasting or post challenge glucose levels in the diagnosis of diabetes.     

Use of clinical risk factors to identify postmenopausal women with vertebral fractures

Introduction and hypothesis Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. Methods Women aged 65–75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. Results Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the subgroup of 13 patients with two or more VFs, which revealed that in this instance, the Margolis back pain score and rib-pelvis distance were associated with the presence of multiple VFs (P=0.022 and 0.026, respectively). Moreover, the predictive value as reflected by the ROC curve area was improved: 0.80 (BMD), 0.88 (the four most predictive clinical risk factors consisting of the height loss, past NVF, Margolis back pain score and rib-pelvis distance) and 0.91 (clinical risk factors + BMD). Conclusions Evaluation of additional risk factors from detailed one-to-one assessment does not improve the predictive value of risk factors for one or more prevalent vertebral deformities in postmenopausal women. However, the use of factors such as the Margolis back pain score and rib-pelvis distance may be helpful in identifying postmenopausal women at high risk of multiple prevalent VFs. This project was funded by Procter and Gamble UK.     

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport.

Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)