Modest Predictive Value Research Articles

On the Utility of ToxCast™ and ToxPi as Methods for Identifying New Obesogens.

Background:In ToxCast™ Phase I, the U.S. EPA commissioned screening of 320 pesticides, herbicides, fungicides, and other chemicals in a series of high-throughput assays. The agency also developed a toxicological prioritization tool, ToxPi, to facilitate using ToxCast™ assays to predict biological function.Objectives:We asked whether top-scoring PPARγ activators identified in ToxCast™ Phase I were genuine PPARγ activators and inducers of adipogenesis. Next, we identified ToxCast™ assays that should predict adipogenesis, developed an adipogenesis ToxPi, and asked how well the ToxPi predicted adipogenic activity.Methods:We used transient transfection to test the ability of ToxCast™ chemicals to modulate PPARγ and RXRα, and differentiation assays employing 3T3-L1 preadipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to evaluate the adipogenic capacity of ToxCast™ chemicals.Results:Only 5/21 of the top scoring ToxCast™ PPARγ activators were activators in our assays, 3 were PPARγ antagonists, the remainder were inactive. The bona fide PPARγ activators we identified induced adipogenesis in 3T3-L1 cells and mBMSCs. Only 7 of the 17 chemicals predicted to be active by the ToxPi promoted adipogenesis, 1 inhibited adipogenesis, and 2 of the 7 predicted negatives were also adipogenic. Of these 9 adipogenic chemicals, 3 activated PPARγ, and 1 activated RXRα.Conclusions:ToxCast™ PPARγ and RXRα assays do not correlate well with laboratory measurements of PPARγ and RXRα activity. The adipogenesis ToxPi performed poorly, perhaps due to the performance of ToxCast™ assays. We observed a modest predictive value of ToxCast™ for PPARγ and RXRα activation and adipogenesis and it is likely that many obesogenic chemicals remain to be identified.Citation:Janesick AS, Dimastrogiovanni G, Vanek L, Boulos C, Chamorro-García R, Tang W, Blumberg B. 2016. On the utility of ToxCast™ and ToxPi as methods for identifying new obesogens. Environ Health Perspect 124:1214–1226; http://dx.doi.org/10.1289/ehp.1510352

A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study.

BackgroundTo develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents.MethodsWe performed a cross sectional study of 129 overweight adolescents 13–18 yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride content > 5.5 mg/g and quantified using 1H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome.ResultsHepatic steatosis was present in 33 % of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95 % CI: 2.5–10.5), display a higher waist circumference (111 ± 12 vs 100 ± 13 cm, p < 0.001) and have metabolic syndrome (adjusted OR: 5.1; 95 % CI: 1.6–16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95 % CI: 0.70–0.95; p < 0.001) but not girls (AUC = 0.63; 95 % CI: 0.46–0.75, p = 0.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72 %) and specificity (82 %) and positive and negative predictive values of 61 % and 89 % respectively.ConclusionsSerum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

Committee Opinion Summary No. 638: First-Trimester Risk Assessment for Early-Onset Preeclampsia.

Hypertensive disorders with adverse sequelae (including preterm birth, maternal morbidity and mortality, and long-term risk of maternal cardiovascular disease) complicate 5-10% of pregnancies. Early identification of pregnant women at risk of developing early-onset preeclampsia would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease. In practice, however, the effectiveness of such triage would be hindered by the low positive predictive value for early-onset preeclampsia reported in the literature. In spite of the modest predictive value of first-trimester preeclampsia risk assessment and the lack of data demonstrating improved clinical outcomes, commercial tests are being marketed for the prediction of preeclampsia in the first trimester. Taking a detailed medical history to evaluate for risk factors is currently the best and only recommended screening approach for preeclampsia; it should remain the method of screening for preeclampsia until studies show that aspirin or other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests.

Committee Opinion No. 638: First-Trimester Risk Assessment for Early-Onset Preeclampsia.

Hypertensive disorders with adverse sequelae (including preterm birth, maternal morbidity and mortality, and long-term risk of maternal cardiovascular disease) complicate 5-10% of pregnancies. Early identification of pregnant women at risk of developing early-onset preeclampsia would theoretically allow referral for more intensive surveillance or application of preventive therapies to reduce the risk of severe disease. In practice, however, the effectiveness of such triage would be hindered by the low positive predictive value for early-onset preeclampsia reported in the literature. In spite of the modest predictive value of first-trimester preeclampsia risk assessment and the lack of data demonstrating improved clinical outcomes, commercial tests are being marketed for the prediction of preeclampsia in the first trimester. Taking a detailed medical history to evaluate for risk factors is currently the best and only recommended screening approach for preeclampsia; it should remain the method of screening for preeclampsia until studies show that aspirin or other interventions reduce the incidence of preeclampsia for women at high risk based on first-trimester predictive tests.

Dental Students’ Perceived Preparedness to Treat Patients in Clinic After a Fixed Prosthodontics Course: Survey Results of a Case Study

Previous research regarding dental students has found modest predictive value in preclinical didactic course grades in predicting clinical performance, but systematic assessment of students' feedback on their perceived preparedness has received little attention as a preclinical assessment methodology. The aim of this study was to assess the perceptions of the dental students at one U.S. academic dental institution regarding their preparedness for clinical performance following the preclinical fixed prosthodontics course. Third- and fourth-year dental students participated in a survey about their perceived preparedness to diagnose and treat patients with fixed prosthodontics needs in the school's dental clinics. The respondents (79 out of 161 students, for a response rate of 49%) rated each item on a five-point Likert scale. Responses about which preclinical procedures of the course prepared students the least and the best were consistent for the third- and fourth-year students. Less than 60% of all responding students felt prepared for planning complex cases and performing laboratory-related procedures. The findings of this study indicate that improvement is required in teaching students about laboratory procedures and problem-solving to adequately prepare them for clinical treatment of patients with fixed prosthodontics needs.

Clinical Significance of ST Segment Depression in Lead aVR to Predict Culprit Artery in An Acute Inferior Wall Myocardial Infarction

Background and Aims: The main objective of this study is to analyze between left circumflex artery and right coronary artery as a presumptive predictor of a culprit artery in patients with an acute inferior wall ST elevation myocardial infarction according to ST segment change in lead aVR. Methods: This study included 145 consecutive patients who presented with an inferior wall ST elevation myocardial infarction and underwent coronary angiography. Clinical and angiographic findings were compared between patients with and without aVR depression ≥ 0. 1mV. Results: The sensitivity and specificity of ST segment depression in lead aVR to predict left circumflex artery as the culprit artery were 69% and 85%, respectively, and the positive predictive value and negative predictive value to predict left circumflex artery as the culprit arteries were 66% and 87%, respectively. Conclusion: Our study supports, the presence of ST segment depression in lead aVR is associated with good specificity and negative predictive value and modest sensitivity and positive predictive value to determine left circumflex artery as an infarct related artery in an acute ST segment elevation inferior wall myocardial infarction.DOI: http://dx.doi.org/10.3126/njh.v12i1.12324 Nepalese Heart Journal Vol.12(1) 2015: 5-9

Use of a risk nomogram to predict emergency department reattendance in older people after discharge: a validation study.

In older people, revisit to the emergency department (ED) in the short period after discharge is not entirely avoidable, but in a proportion of cases is preventable, and should ideally be minimised. We have previously derived a risk probability nomogram to predict the likelihood of revisit. In this study, we sought to validate the nomogram for use as a general risk stratification tool for use in older people being discharged from ED. We conducted a prospective cohort study, applying the nomogram to consecutive community dwelling discharged patients aged 65 and over. Patients were followed up at 28 days post-discharge to determine whether there had been any unplanned ED revisit in that period. We cross tabulated predicted risk versus revisit rates. In 1143 study subjects, we find the odds of revisit increases progressively with increasing strata of predicted risk, culminating in an OR of 9.7 (95% CI 4.7-19.9) in the highest risk group. The 28-day revisit rates across strata range from 16% through 65%, with the difference between strata being statistically highly significant (p < 0.001). The area under the ROC curve is 0.65. We conclude that the risk nomogram can classify older people discharged from ED into risk strata, and has modest overall predictive value.

A novel coronary angiography index (DILEMMA score) for prediction of functionally significant coronary artery stenoses assessed by fractional flow reserve: A novel coronary angiography index

Angiographic evaluation of diameter stenosis has modest predictive value for functionally significant coronary artery stenoses as assessed by fractional flow reserve (FFR). Lesion length and assessment of area of myocardium at risk (Bypass Angioplasty Revascularization Investigation [BARI] Myocardial Jeopardy Index [MJI]) subtended by the stenotic coronary arteries are also predictors of functionally significant coronary artery stenoses. We sort to assess the diagnostic accuracy of DILEMMA score, which combines minimal lumen diameter (MLD), lesion length, and BARI MJI in prediction of significantly reduced FFR (≤0.8). We assessed patients who underwent coronary angiography and FFR. Lesion length and MLD were assessed by quantitative coronary angiography. Estimation of area of myocardium at risk subtended by coronary stenoses was performed using the BARI MJI. A total of 296 patients (age 64 ± 10.6 years, 68% male, 497 vessels) were included. DILEMMA score was significantly higher in vessels with significant FFR, 6.09 ± 3.23 versus 3.84 ± 2.99 (P < .001). In the derivation cohort, the optimism-adjusted Harrell c statistic for DILEMMA score was 0.82 compared with 0.76 for BARI MJI, 0.75 for lesion length, and 0.7 for MLD. In the validation cohort, the c-statistic for DILEMMA score, BARI MJI, lesion length, and MLD was 0.88, 0.77, 0.81, and 0.72, respectively. The DILEMMA score was a better predictor of FFR ≤0.8 compared with MLD, lesion length, and BARI MJI individually (P < .001, P < .02, and P < .045, respectively) on Bonferroni-adjusted pairwise comparison. DILEMMA score, taking into account MLD, lesion length, and BARI MJI, may have incremental predictive value beyond the individual indices alone for detecting functionally significant coronary artery stenoses.

Serum antimüllerian hormone measurements with second generation assay at two distinct menstrual cycle phases for prediction of cycle cancellation, pregnancy and live birth after in vitro fertilization.

This study investigated the usefulness of serum antimüllerian hormone (AMH) measurements at two distinct menstrual cycle phases to predict in vitro fertilization (IVF) outcomes. This was a prospective observational study enrolling 135 consecutive patients referred for conventional IVF or ICSI in a university hospital. Blood samples were obtained for serum AMH measurements on days 3 and 18-20, while transvaginal ultrasound was performed for antral follicle count (AFC) at day 3 of the menstrual cycle immediately before treatment. AMH was measured with the new Beckman Coulter Generation II (GenII) assay. The main outcome measures were cycle cancellation due to poor ovarian response, clinical pregnancy, and live birth. There was a strong correlation between AMH levels measured at day 3 and day 18-20 of the menstrual cycle (r = 0.837; P < 0.0001). Day 18-20 serum AMH was comparable to day 3 serum AMH and AFC for the prediction of cycle cancellation (areas under the ROC curve were 0.84 for day 3 AMH, 0.89 for day 18-20 AMH, and 0.80 for AFC). Day 18-20 AMH had a modest predictive value for pregnancy or live birth (area under ROC curve 0.71 for both), which was comparable to that of day 3 AMH; however, AFC had no predictive value for these outcomes. Day 18-20 AMH was comparable to day 3 AMH for the prediction of cycle cancellation, clinical pregnancy, and live birth after IVF. Both AMH measurements were accurate for the prediction of cancellation but were significantly less useful for the prediction of pregnancy or live birth.

The Predictive Ability of the CHADS2 and CHA2DS2-VASc Scores for Bleeding Risk in Atrial Fibrillation: The MAQI2 Experience

IntroductionGuidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. Methods2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. Results110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. ConclusionsThe CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well.

C0523: Venous Thromboembolism in Special Populations-Findings from the Riete Registry

Background: Bleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. Methods: We retrospectively included adult patients on vitamin K antagonists (VKAs) for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-nonmajor-bleeding (CRNMB). Results: 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (±3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HASBLED showed the best predictive value for bleeding complications during the first three months of treatment (AUC 0.68, 95%CI 0.59– 0.78), while only the ACCP showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51–0.72). These two scores had also the highest sensitivity and the highest negative predictive value. Conclusions: Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.

Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays.

Early detection of residual disease may benefit management strategies in patients undergoing transsphenoidal surgery for acromegaly. This requires establishing objective thresholds for early postoperative growth hormone (GH) assays, and incorporating these parameters into a scale for outcome prediction. We analyzed a database containing the records of 86 patients who had undergone gross total transsphenoidal resection of GH-secreting pituitary adenomas. Early postoperative biochemical testing included a morning fasting basal GH assay on the first postoperative day (POD1) and a second GH assay following suppression with 100 g of oral glucose on the seventh postoperative day (POD7). Remission was defined as a normal IGF-1 with either a GH nadir <0.4 ng/ml following suppression with oral glucose or a basal fasting GH <1 ng/ml on follow-up dated >3 months after surgery. Receiver operator characteristic (ROC) curves identified optimal thresholds for all biochemical parameters. Logistic regression analysis assessed the statistical significance of factors associated with cure. A point system was developed, employing regression coefficients obtained from the multivariate statistical model to quantify the impact of each predictor on cure. Remission was achieved in 34.6 % of patients and was associated with smaller, non-invasive tumors with lower preoperative, POD1 and POD7 GH levels. Optimal thresholds obtained from the ROC analysis suggested that lower POD1 and POD7 GH values provided good sensitivity and specificity for cure, despite modest predictive values. The model with the best ability to predict outcome included size, POD1 GH and POD7 GH levels, with a score of ≥95 demonstrating high specificity for prediction of remission. Early postoperative GH assays are highly sensitivity and specific. The scoring system that we propose provided excellent predictive value and requires further validation in larger cohorts and in different populations. The model may help guide the intensity of follow-up and enable early identification of residual disease.

Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.

Cervical length in asymptomatic twin pregnancies: prospective multicenter comparison of predictive indicators

Objective: To determine whether cervical shortening between 22 and 27 weeks predicts spontaneous preterm delivery before 34 weeks better than a single cervical length (CL) measurement at 22 or 27 weeks in asymptomatic twins.Methods: Prospective 13-center study over a 2-year-period. CL was measured in 120 asymptomatic twin pregnancies. The area under the ROC curve was calculated for each parameter and the cutoff point providing the best diagnostic performance, sensitivity and specificity for predicting spontaneous delivery <34 weeks was defined too.Results: About 13/116 women gave birth before 34 weeks. The three ROC curves differed significantly at the 0.05 level. The best cutoff points were CL ≤35 mm at 22 weeks, CL ≤25 mm at 27 weeks and cervical shortening ≥20%. For equal sensitivity values for each, specificity for CL ≤25 mm at 27 weeks was 87.5%, significantly better.Conclusions: The performance of cervical shortening for the prediction of preterm delivery of asymptomatic twins before 34 weeks does not differ from that of CL measurements at 22 or 27 weeks. The modest predictive value of CL at 22 weeks and of cervical shortening is an argument against recommending routine CL measurements

A prospective analysis of false positive events in a National Colon Cancer Surveillance Program

BackgroundThe survival benefits of colon cancer surveillance programs are well delineated, but less is known about the magnitude of false positive testing. The objective of this study was to estimate the false positive rate and positive predictive value of testing as part of a surveillance program based on national guidelines, and to estimate the degree of testing and resource use needed to identify a curable recurrence.MethodsAnalysis of clinically significant events leading to suspicion of cancer recurrence, false positive events, true cancer recurrences, time to confirmation of diagnosis, and resource use (radiology, blood samples, colonoscopies, consultations) among patients included in a randomised colon cancer surveillance trial.Results110 patients surgically treated for colon cancer were followed according to national guidelines for 1884 surveillance months. 1105 tests (503 blood samples, 278 chest x-rays, 209 liver ultrasounds, 115 colonoscopies) and 1186 health care consultations were performed. Of the 48 events leading to suspicion of cancer recurrence, 34 (71%) represented false positives. Thirty-one (65%) were initiated by new symptoms, and 17 (35%) were initiated by test results. Fourteen patients had true cancer recurrence; 7 resections of recurrent disease were performed, 4 of which were successful R0 metastasis Resections. 276 tests and 296 healthcare consultations were needed per R0 resection; the cost per R0 surgery was £ 103207. There was a 29% probability (positive predictive value) of recurrent cancer when a diagnostic work-up was initiated based on surveillance testing or patient complaints.ConclusionWe observed a high false positive rate and low positive predictive value for significant clinical events suggestive of possible colorectal cancer relapse in the setting of a post-treatment surveillance program based on national guidelines. Providers and their patients should have an appreciation for the modest positive predictive value inherent in colorectal cancer surveillance programs in order to make informed choices, which maximize quality of life during survivorship. Better means of tailoring surveillance programs based on patient risk would likely lead to more effective and cost-effective post-treatment follow-up.Trial registrationClinicalTrials.gov identifier NCT00572143. Date of trial registration: 11th of December 2007.

Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA

The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY). This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection. Data analysis was completed using sequence reads unique to the chromosomes of interest. A total of 3430 patients were analyzed for demographic characteristics and medical history. There were 137 fetuses with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13 for a prevalence rate of the common autosomal trisomies of 5.8%. There were no false-negative results for trisomy 21, 3 for trisomy 18, and 2 for trisomy 13; all 3 false-positive results were for trisomy 21. The positive predictive values for trisomies 18 and 13 were 100% and 97.9% for trisomy 21. A total of 8.6% of the pregnancies were 21 weeks or beyond; there were no aneuploid fetuses in this group. All 15 of the common sex chromosome aneuploidies in this population were identified, although there were 11 false-positive results for 45,X. Taken together, the positive predictive value for the sex chromosome aneuploidies was 48.4% and the negative predictive value was 100%. Our prospective study demonstrates that noninvasive prenatal analysis of cell-free deoxyribonucleic acid from maternal plasma is an accurate advanced screening test with extremely high sensitivity and specificity for trisomy 21 (>99%) but with less sensitivity for trisomies 18 and 13. Despite high sensitivity, there was modest positive predictive value for the small number of common sex chromosome aneuploidies because of their very low prevalence rate.

Abstract T P354: The Role of Lindegaard Ratio on TCD for Predicting Angiographic Vasospasm Following Aneurysmal Subarachnoid Haemorrhage

Background and objective: Middle cerebral artery (MCA) Lindegaard ratio (LR) has been used as indicator of moderate to severe vasospasm (VSP) following subarachnoid hemorrhage (SAH). However there have been many criticisms about the ability to detect impending vasospasm using Transcranial Doppler (TCD). The purpose of this study was to determine the correlation between TCD Mean Flow Velocities (MFV) and angiographic VSP after aneurysmal SAH using LR of several anterior circulation vessels. Methods: The study population included prospective collected data of 134 patients with aneurysmal SAH admitted to University of Alberta hospital from January 2006 to December 2008. Complete TCD was performed daily from day 2 to 14 from symptoms onset. All patients underwent cerebral angiography on admission and within 7 days following onset of symptoms. The M1, M2 MCA, ACA and intracranial ICA/ipsilateral extra cranial ICA velocity ratios (LR) were calculated and correlation was made with the presence of angiographic vasospasm (defined as more than one-third luminal narrowing). Then, anterior circulation LR was defined as the highest LR in the ipsilateral anterior circulation arteries. Moderate to severe VSP was defined as LR &gt; 3. Results: Results are shown in table. The probability of VSP in the presence of one anterior circulation vessel LR &gt; 3 is 14 % (2/14), 2 vessels LR &gt;3 (4/16. 16 %), 3 vessels LR &gt; 3 (3/6, 50 %) and 4 vessels LR &gt;3 (5/5 = 100 %). (P&lt; 0.001) Conclusion: LR of M2 MCA has higher sensitivity compared to other vessels and ACA LR has less sensitivity but more specificity whereas the rest of anterior circulation LR had modest predictive value. The likelihood of VSP increases as more number of vessels in anterior circulation shows LR&gt;3. LR should not be interpreted in a blind fashion to the rest of TCD MFV numbers.

Abstract T MP59: Texas Stroke Intervention Pre-Hospital Stroke Severity Scale (aka LEGS score): A Triaging Tool for Interventional Stroke Therapy

Introduction: A pre-hospital stroke severity scale that correlates well with an NIHSS of 10 or greater as well as with large vessel occlusions, but is easier and faster to perform than full NIHSS, would be a very useful triaging tool to emergency medical services (EMS). The LEGS score (Lower extremity strength, Eyes/visual fields, Gaze deviation, Speech difficulty) is a 16-point pre-hospital stroke severity scale that is a shortened NIHSS-5. Hypothesis: We assessed the hypothesis that the LEGS score was a useful pre-hospital stroke severity scoring system to identify large vessel acute ischemic strokes. Methods: The LEGS score (0-16) and NIHSS (0-42) were performed in the emergency department over a 6-month period. We retrospectively reviewed those charts for correlation to an NIHSS of 10 or greater and evidence of large-vessel occlusion on either CT or MR Angiography within 48 hours of last known normal. Results: A total of 181 consecutive ischemic stroke patients were evaluated. LEGS score 4 or greater was a good predictor of an NIHSS of 10 or greater (59/181; positive predictive value 92%; and specificity 95%) and false positives noted was 5/181. LEGS score of less than 4 was a good predictor of an NIHSS of less than 10 (108/181; negative predictive value 91%; and sensitivity 95%) and false negatives noted was 10/181. Of those patients 155 underwent intracranial vascular imaging. LEGS score of less than 4 was a good test to rule-out large vessel occlusion (negative predictive value of 86%; 89/103), but had modest sensitivity (69%; 31/45) and positive predictive value (60%; 31/52). The LEGS score of 4 or greater, however, was fairly specific for determining large-vessel occlusions at 81% (89/110). Conclusions: LEGS score of 4 or greater has good correlation with an NIHSS of 10 or greater as well as modest correlation with large vessel occlusion on CT or MR Angiography. This shortened NIHSS-5 may be a useful pre-hospital indicator of patients who may benefit from endovascular intervention.

Abstract T MP37: Fractional Anisotropy Changes in the Acute Stroke Phase Only Modestly Predict Motor Outcome at 3 Months

Background: A decrease in fractional anisotropy (FA) of the ipsilesional corticospinal tract (CST) distal to ischemic stroke lesions in chronic stroke patients has been associated with poor motor outcome, but in the acute phase no clear FA trends have been observed or used to make outcome predictions. Methods: This study followed 40 patients with first-ever ischemic stroke, measuring motor impairment with the Upper Extremity Fugl-Meyer (UE-FM) acutely and at 3 months. Images obtained &lt;3 days after stroke, including FA, were overlaid with a probabilistic CST (blue in Figure 1) derived from healthy subjects to define a cerebral peduncle region of interest ROI and a “nearest slice” ROI (green line in Figure 1), the second slice downstream from the stroke lesion (red in Figure 1). Ipsilesional and contralesional CST FA values as well as Apparent Diffusion Coefficient (ADC) values of regions of interests were compared using a laterality index and related to 3-month motor outcome. Results: Asymmetry between ipsilesional and contralesional CST FA values was significant different between patients with bad motor outcome and good outcome, with lower FA of the ipsilesional CST in the bad outcome group. No such asymmetry was seen for the cerebral peduncle ROI using either FA or ADC values. The FA laterality index for the nearest slice ROI was a significant but modest predictor of 3-month motor outcome (R2=0.186, p=.02), with the best predictive value offered by the combination of this imaging variable and the initial motor impairment (R2=0.696, p=.01). Conclusion: FA changes of the CST can be detected near the ischemic lesion in the acute phase after stroke, but these changes offer only modest predictive value for eventual motor outcome.

Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study.

Bleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59-0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51-0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.