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Sample records for biomarker risk score

  1. Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment

    Directory of Open Access Journals (Sweden)

    David Corcoran

    2015-09-01

    Clinical guidelines recommend an early invasive strategy in higher risk NSTE-ACS. The Global Registry of Acute Coronary Events (GRACE risk score is a validated risk stratification tool which has incremental prognostic value for risk stratification compared with clinical assessment or troponin testing alone. In emergency medicine, there has been a limited adoption of the GRACE score in some countries (e.g. United Kingdom, in part related to a delay in obtaining timely blood biochemistry results. Age makes an exponential contribution to the GRACE score, and on an individual patient basis, the risk of younger patients with a flow-limiting culprit coronary artery lesion may be underestimated. The future incorporation of novel cardiac biomarkers into this diagnostic pathway may allow for earlier treatment stratification. The cost-effectiveness of the new diagnostic pathways based on high-sensitivity troponin and copeptin must also be established. Finally, diagnostic tests and risk scores may optimize patient care but they cannot replace patient-focused good clinical judgment.

  2. Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death

    DEFF Research Database (Denmark)

    Ghasemzedah, Nima; Hayek, Salim; Ko, Yi-An

    2017-01-01

    BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a st...

  3. A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection.

    Science.gov (United States)

    Hendriks, Rianne J; van der Leest, Marloes M G; Dijkstra, Siebren; Barentsz, Jelle O; Van Criekinge, Wim; Hulsbergen-van de Kaa, Christina A; Schalken, Jack A; Mulders, Peter F A; van Oort, Inge M

    2017-10-01

    Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. The aim of this study was to determine the association between a novel urinary biomarker-based risk score (SelectMDx), multiparametric MRI (mpMRI) outcomes, and biopsy results for PCa detection. This retrospective observational study used data from the validation study of the SelectMDx score, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. A subset of these patients also underwent a mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy. All mpMRI images were centrally reviewed in 2016 by an experienced radiologist blinded for the urine test results and biopsy outcome. The PI-RADS version 2 was used. In total, 172 patients were included for analysis. Hundred (58%) patients had PCa detected upon prostate biopsy, of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score (P < 0.01). The median SelectMDx score was significantly higher in patients with a suspicious significant lesion on mpMRI compared to no suspicion of significant PCa (P < 0.01). For the prediction of mpMRI outcome, the area-under-the-curve of SelectMDx was 0.83 compared to 0.66 for PSA and 0.65 for PCA3. There was a positive association between SelectMDx score and the final PI-RADS grade. There was a statistically significant difference in SelectMDx score between PI-RADS 3 and 4 (P < 0.01) and between PI-RADS 4 and 5 (P < 0.01). The novel urinary biomarker-based SelectMDx score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx score and mpMRI outcomes, outperforming PCA3. Our results suggest that this risk

  4. Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD.

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    Schultz, Stephanie A; Boots, Elizabeth A; Darst, Burcu F; Zetterberg, Henrik; Blennow, Kaj; Edwards, Dorothy F; Koscik, Rebecca L; Carlsson, Cynthia M; Gallagher, Catherine L; Bendlin, Barbara B; Asthana, Sanjay; Sager, Mark A; Hogan, Kirk J; Hermann, Bruce P; Cook, Dane B; Johnson, Sterling C; Engelman, Corinne D; Okonkwo, Ozioma C

    2017-04-25

    To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers. Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4 , CLU , and ABCA7 , from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. β-Amyloid 42 (Aβ 42 ), Aβ 40 , total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aβ 42 /Aβ 40 and tau/Aβ 42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF. A higher PRS was associated with lower Aβ 42 /Aβ 40 ( p interactions for Aβ 42 /Aβ 40 ( p = 0.003), t-tau/Aβ 42 ( p = 0.003), and p-tau/Aβ 42 ( p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF. In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD. © 2017 American Academy of Neurology.

  5. Clinical Risk Assessment in the Antiphospholipid Syndrome: Current Landscape and Emerging Biomarkers.

    Science.gov (United States)

    Chaturvedi, Shruti; McCrae, Keith R

    2017-07-01

    Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-β2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors. Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-β 2 GPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance. Clinical risk scores may also have value in predicting clinical events. Biomarkers that predict thrombosis risk in patients with antiphospholipid antibodies have been long sought, and several biomarkers have been proposed. Ultimately, integration of biomarkers with established assays and clinical characteristics may offer the best chance of identifying patients at highest risk of APS-related complications.

  6. Clinical risk stratification optimizes value of biomarkers to predict new-onset heart failure in a community-based cohort.

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    Brouwers, Frank P; van Gilst, Wiek H; Damman, Kevin; van den Berg, Maarten P; Gansevoort, Ron T; Bakker, Stephan J L; Hillege, Hans L; van Veldhuisen, Dirk J; van der Harst, Pim; de Boer, Rudolf A

    2014-09-01

    We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction. Thirteen biomarkers reflecting diverse pathophysiologic domains were examined in 8569 HF-free participants in Prevention of Vascular and Renal Endstage Disease (mean age, 49 years; 50% men). Subjects were categorized in 2 risk groups based on cardiovascular history. Incremental value per biomarker was assessed using Harrell C-indices. One hundred sixty-eight subjects (2.4%) were diagnosed with new-onset HF in the low-risk group (n=6915; Framingham Risk Score, 5.9%) and 206 (12.2%) subjects in the high-risk group (n=1654; Framingham Risk Score, 18.6%). The association of natriuretic peptides, adrenomedullin, endothelin, and galectin-3 with new-onset HF was stronger in the high-risk group (all Prisk for new-onset HF between both risk groups. The best model for new-onset HF included the combination of N-terminal pro-B-type natriuretic peptide, troponin-T, and urinary albumin excretion, increasing model accuracy to 0.81 (9.5%, Prisk group. Except for a modest effect of cystatin-C, no biomarker was associated with increased risk for HF with preserved ejection fraction. Risk stratification increases the incremental value per biomarker to predict new-onset HF, especially HF with reduced ejection fraction. We suggest that routine biomarker testing should be limited to the use of natriuretic peptides and troponin-T in patients with increased cardiovascular risk. © 2014 American Heart Association, Inc.

  7. Prominent deep medullary veins: a predictive biomarker for stroke risk from transient ischemic attack?

    Science.gov (United States)

    Duan, Yang; Xu, Zhihua; Li, Hongyi; Cai, Xiaonan; Chang, Cancan; Yang, Benqiang

    2018-05-01

    Background Deep medullary veins (DMVs) are a biomarker of severity and prognosis in patients with acute cerebral infarction. However, their clinical significance remains unclear in patients with transient ischemic attack (TIA). Purpose To determine whether prominent deep medullary veins (PDMVs) are a predictive biomarker for stroke risk after TIA. Material and Methods Clinical and imaging data of 49 patients with TIA and 49 sex- and age-matched controls were studied. PDMVs were defined as DMVs with a score of 3 (TDMVs) or asymmetric DMVs (ADMVs), and the relationship between PDMVs and clinical features was analyzed. The DMV score based on susceptibility weighted imaging (SWI) ranged from 0 (not visible) to 3 (very prominent) and was calculated for both hemispheres separately. A different score in each hemisphere was defined as ADMVs and an equal score was defined as symmetric DMVs. The asymmetry and score of DMVs were compared between the two groups and with respect to the time from TIA onset to imaging analysis. Results Agreement between neuroradiologists for the DMV asymmetry/score on SWI was excellent. The frequency of ADMVs and TDMVs was significantly higher in patients with TIA than controls ( P  0.05); PDMVs were not correlated with age, blood pressure, or diabetes. However, PDMVs were associated with the ABCD2 score (≥4), clinical symptoms, and duration of TIA (≥10 min). Conclusion Prominent deep medullary veins is a predictive biomarker for the risk of stroke in many patients having suffered from TIA.

  8. Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

    Science.gov (United States)

    Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

    2012-12-01

    To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Predicting Risk of Cognitive Decline in Very Old Adults Using Three Models: The Framingham Stroke Risk Profile; the Cardiovascular Risk Factors, Aging, and Dementia Model; and Oxi-Inflammatory Biomarkers.

    Science.gov (United States)

    Harrison, Stephanie L; de Craen, Anton J M; Kerse, Ngaire; Teh, Ruth; Granic, Antoneta; Davies, Karen; Wesnes, Keith A; den Elzen, Wendy P J; Gussekloo, Jacobijn; Kirkwood, Thomas B L; Robinson, Louise; Jagger, Carol; Siervo, Mario; Stephan, Blossom C M

    2017-02-01

    To examine the Framingham Stroke Risk Profile (FSRP); the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score, and oxi-inflammatory load (cumulative risk score of three blood biomarkers-homocysteine, interleukin-6, C-reactive protein) for associations with cognitive decline using three cohort studies of very old adults and to examine whether incorporating these biomarkers with the risk scores can affect the association with cognitive decline. Three longitudinal, population-based cohort studies. Newcastle-upon-Tyne, United Kingdom; Leiden, the Netherlands; and Lakes and Bay of Plenty District Health Board areas, New Zealand. Newcastle 85+ Study participants (n = 616), Leiden 85-plus Study participants (n = 444), and Life and Living in Advanced Age, a Cohort Study in New Zealand (LiLACS NZ Study) participants (n = 396). FSRP, CAIDE risk score, oxi-inflammatory load, FSRP incorporating oxi-inflammatory load, and CAIDE risk score incorporating oxi-inflammatory load. Oxi-inflammatory load could be calculated only in the Newcastle 85+ and the Leiden 85-plus studies. Measures of global cognitive function were available for all three data sets. Domain-specific measures were available for the Newcastle 85+ and the Leiden 85-plus studies. Meta-analysis of pooled results showed greater risk of incident global cognitive impairment with higher FSRP (hazard ratio (HR) = 1.46, 95% confidence interval (CI) = 1.08-1.98), CAIDE (HR = 1.53, 95% CI = 1.09-2.14), and oxi-inflammatory load (HR = 1.73, 95% CI = 1.04-2.88) scores. Adding oxi-inflammatory load to the risk scores increased the risk of cognitive impairment for the FSRP (HR = 1.65, 95% CI = 1.17-2.33) and the CAIDE model (HR = 1.93, 95% CI = 1.39-2.67). Adding oxi-inflammatory load to cardiovascular risk scores may be useful for determining risk of cognitive impairment in very old adults. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  10. A priori-defined diet quality indices, biomarkers and risk for type 2 diabetes in five ethnic groups: the Multiethnic Cohort.

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    Jacobs, Simone; Boushey, Carol J; Franke, Adrian A; Shvetsov, Yurii B; Monroe, Kristine R; Haiman, Christopher A; Kolonel, Laurence N; Le Marchand, Loic; Maskarinec, Gertraud

    2017-08-01

    Dietary indices have been related to risk for type 2 diabetes (T2D) predominantly in white populations. The present study evaluated this association in the ethnically diverse Multiethnic Cohort and examined four diet quality indices in relation to T2D risk, homoeostatic model assessment-estimated insulin resistance (HOMA-IR) and biomarkers of dyslipidaemia, inflammation and adipokines. The T2D analysis included 166 550 white, African American, Native Hawaiian, Japanese American and Latino participants (9200 incident T2D cases). Dietary intake was assessed at baseline using a quantitative FFQ and T2D status was based on three self-reports and confirmed by administrative data. Biomarkers were assessed about 10 years later in a biomarker subcohort (n 10 060). Sex- and ethnicity-specific hazard ratios were calculated for the Healthy Eating Index-2010 (HEI-2010), the alternative HEI-2010 (AHEI-2010), the alternate Mediterranean diet score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). Multivariable-adjusted means of biomarkers were compared across dietary index tertiles in the biomarker subcohort. The AHEI-2010, aMED (in men only) and DASH scores were related to a 10-20 % lower T2D risk, with the strongest associations in whites and the direction of the relationships mostly consistent across ethnic groups. Higher scores on the four indices were related to lower HOMA-IR, TAG and C-reactive protein concentrations, not related to leptin, and the DASH score was directly associated with adiponectin. The AHEI-2010 and DASH were directly related to HDL-cholesterol in women. Potential underlying biological mechanisms linking diet quality and T2D risk are an improved lipid profile and reduced systemic inflammation and, with regards to DASH alone, an improved adiponectin profile.

  11. Application of cardiovascular disease risk prediction models and the relevance of novel biomarkers to risk stratification in Asian Indians.

    Science.gov (United States)

    Kanjilal, S; Rao, V S; Mukherjee, M; Natesha, B K; Renuka, K S; Sibi, K; Iyengar, S S; Kakkar, Vijay V

    2008-01-01

    The increasing pressure on health resources has led to the emergence of risk assessment as an essential tool in the management of cardiovascular disease (CVD). Concern exists regarding the validity of their generalization to all populations. Existing risk scoring models do not incorporate emerging 'novel' risk factors. In this context, the aim of the study was to examine the relevance of British, European, and Framingham predictive CVD risk scores to the asymptomatic high risk Indian population. Blood samples drawn from the participants were analyzed for various 'traditional' and 'novel' biomarkers, and their CVD risk factor profiling was also done. The Framingham model defined only 5% of the study cohort to be at high risk, which appears to be an underestimation of CVD risk in this genetically predisposed population. These subjects at high risk had significantly elevated levels of lipid, pro-inflammatory, pro-thrombotic, and serological markers. It is more relevant to develop risk predictive scores for application to the Indian population. This study substantiates the argument that alternative approaches to risk stratification are required in order to make them more adaptable and applicable to different populations with varying risk factor and disease patterns.

  12. Cardiovascular disease biomarkers on cognitive function in older adults: Joint effects of cardiovascular disease biomarkers and cognitive function on mortality risk.

    Science.gov (United States)

    Loprinzi, Paul D; Crush, Elizabeth; Joyner, Chelsea

    2017-01-01

    Previous research demonstrates an inverse association between age and cardiovascular disease (CVD) biomarkers with cognitive function; however, little is known about the combined associations of CVD risk factors and cognitive function with all-cause mortality in an older adult population, which was the purpose of this study. Data from the 1999-2002 NHANES were used (N=2,097; 60+yrs), with mortality follow-up through 2011. Evaluated individual biomarkers included mean arterial pressure (MAP), high-sensitivity C-reactive protein (CRP), HDL-C, total cholesterol (TC), A1C, and measured body mass index (BMI). Cognitive function was assessed using the Digit Symbol Substitution Test (DSST). Further, 4 groups were created based on CVD risk and cognitive function. Group 1: high cognitive function and low CVD risk; Group 2: high cognitive function and high CVD risk; Group 3: low cognitive function and low CVD risk; Group 4: low cognitive function and high CVD risk. An inverse relationship was observed where those with more CVD risk factors had a lower (worse) cognitive function score. Compared to those in Group 1, only those in Group 3 and 4 had an increase mortality risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Novel biomarkers with potential for cardiovascular risk reclassification.

    Science.gov (United States)

    Mallikethi-Reddy, Sagar; Briasoulis, Alexandros; Akintoye, Emmanuel; Afonso, Luis

    Precise estimation of the absolute risk for CVD events is necessary when making treatment recommendations for patients. A number of multivariate risk models have been developed for estimation of cardiovascular risk in asymptomatic individuals based upon assessment of multiple variables. Due to the inherent limitation of risk models, several novel risk markers including serum biomarkers have been studied in an attempt to improve the cardiovascular risk prediction above and beyond the established risk factors. In this review, we discuss the role of underappreciated biomarkers such as red cell distribution width (RDW), cystatin C (cysC), and homocysteine (Hcy) as well as imaging biomarkers in cardiovascular risk reclassification, and highlight their utility as additional source of information in patients with intermediate risk.

  14. The International Bleeding Risk Score

    DEFF Research Database (Denmark)

    Laursen, Stig Borbjerg; Laine, L.; Dalton, H.

    2017-01-01

    The International Bleeding Risk Score: A New Risk Score that can Accurately Predict Mortality in Patients with Upper GI-Bleeding.......The International Bleeding Risk Score: A New Risk Score that can Accurately Predict Mortality in Patients with Upper GI-Bleeding....

  15. Late-Onset Alzheimer's Disease Polygenic Risk Profile Score Predicts Hippocampal Function.

    Science.gov (United States)

    Xiao, Ena; Chen, Qiang; Goldman, Aaron L; Tan, Hao Yang; Healy, Kaitlin; Zoltick, Brad; Das, Saumitra; Kolachana, Bhaskar; Callicott, Joseph H; Dickinson, Dwight; Berman, Karen F; Weinberger, Daniel R; Mattay, Venkata S

    2017-11-01

    We explored the cumulative effect of several late-onset Alzheimer's disease (LOAD) risk loci using a polygenic risk profile score (RPS) approach on measures of hippocampal function, cognition, and brain morphometry. In a sample of 231 healthy control subjects (19-55 years of age), we used an RPS to study the effect of several LOAD risk loci reported in a recent meta-analysis on hippocampal function (determined by its engagement with blood oxygen level-dependent functional magnetic resonance imaging during episodic memory) and several cognitive metrics. We also studied effects on brain morphometry in an overlapping sample of 280 subjects. There was almost no significant association of LOAD-RPS with cognitive or morphometric measures. However, there was a significant negative relationship between LOAD-RPS and hippocampal function (familywise error [small volume correction-hippocampal region of interest] p risk score based on APOE haplotype, and for a combined LOAD-RPS + APOE haplotype risk profile score (p risk genes on hippocampal function even in healthy volunteers. The effect of LOAD-RPS on hippocampal function in the relative absence of any effect on cognitive and morphometric measures is consistent with the reported temporal characteristics of LOAD biomarkers with the earlier manifestation of synaptic dysfunction before morphometric and cognitive changes. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

  16. Development of an interstitial cystitis risk score for bladder permeability.

    Directory of Open Access Journals (Sweden)

    Laura E Lamb

    Full Text Available Interstitial cystitis/bladder pain syndrome (IC is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function; a subset of IC patients present with Hunner's lesions or ulcers on their bladder walls (UIC. UIC is diagnosed by cystoscopy, which may be quite painful. The objective of this study was to determine if a calculated Bladder Permeability Defect Risk Score (BP-RS based on non-invasive urinary cytokines could discriminate UIC patients from controls and IC patients without Hunner's ulcers.A national crowdsourcing effort targeted IC patients and age-matched controls to provide urine samples. Urinary cytokine levels for GRO, IL-6, and IL-8 were determined using a Luminex assay.We collected 448 urine samples from 46 states consisting of 153 IC patients (147 female, 6 male, of which 54 UIC patients (50 females, 4 male, 159 female controls, and 136 male controls. A defined BP-RS was calculated to classify UIC, or a bladder permeability defect etiology, with 89% validity.The BP-RS Score quantifies UIC risk, indicative of a bladder permeability defect etiology in a subset of IC patients. The Bladder Permeability Defect Risk Score is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome.

  17. III: Use of biomarkers as Risk Indicators in Environmental Risk Assessment of oil based discharges offshore.

    Science.gov (United States)

    Sanni, Steinar; Lyng, Emily; Pampanin, Daniela M

    2017-06-01

    Offshore oil and gas activities are required not to cause adverse environmental effects, and risk based management has been established to meet environmental standards. In some risk assessment schemes, Risk Indicators (RIs) are parameters to monitor the development of risk affecting factors. RIs have not yet been established in the Environmental Risk Assessment procedures for management of oil based discharges offshore. This paper evaluates the usefulness of biomarkers as RIs, based on their properties, existing laboratory biomarker data and assessment methods. Data shows several correlations between oil concentrations and biomarker responses, and assessment principles exist that qualify biomarkers for integration into risk procedures. Different ways that these existing biomarkers and methods can be applied as RIs in a probabilistic risk assessment system when linked with whole organism responses are discussed. This can be a useful approach to integrate biomarkers into probabilistic risk assessment related to oil based discharges, representing a potential supplement to information that biomarkers already provide about environmental impact and risk related to these kind of discharges. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Enhancing the 'real world' prediction of cardiovascular events and major bleeding with the CHA2DS2-VASc and HAS-BLED scores using multiple biomarkers.

    Science.gov (United States)

    Roldán, Vanessa; Rivera-Caravaca, José Miguel; Shantsila, Alena; García-Fernández, Amaya; Esteve-Pastor, María Asunción; Vilchez, Juan Antonio; Romera, Marta; Valdés, Mariano; Vicente, Vicente; Marín, Francisco; Lip, Gregory Y H

    2018-02-01

    Atrial fibrillation (AF)-European guidelines suggest the use of biomarkers to stratify patients for stroke and bleeding risks. We investigated if a multibiomarker strategy improved the predictive performance of CHA 2 DS 2 -VASc and HAS-BLED in anticoagulated AF patients. We included consecutive patients stabilized for six months on vitamin K antagonists (INRs 2.0-3.0). High sensitivity troponin T, NT-proBNP, interleukin-6, von Willebrand factor concentrations and glomerular filtration rate (eGFR; using MDRD-4 formula) were quantified at baseline. Time in therapeutic range (TTR) was recorded at six months after inclusion. Patients were follow-up during a median of 2375 (IQR 1564-2887) days and all adverse events were recorded. In 1361 patients, adding four blood biomarkers, TTR and MDRD-eGFR, the predictive value of CHA 2 DS 2 -VASc increased significantly by c-index (0.63 vs. 0.65; p = .030) and IDI (0.85%; p originals scores. Addition of biomarkers enhanced the predictive value of CHA 2 DS 2 -VASc and HAS-BLED, although the overall improvement was modest and the added predictive advantage over original scores was marginal. Key Messages Recent atrial fibrillation (AF)-European guidelines for the first time suggest the use of biomarkers to stratify patients for stroke and bleeding risks, but their usefulness in real world for risk stratification is still questionable. In this cohort study involving 1361 AF patients optimally anticoagulated with vitamin K antagonists, adding high sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, interleukin 6, von Willebrand factor, glomerular filtration rate (by the MDRD-4 formula) and time in therapeutic range, increased the predictive value of CHA 2 DS 2 -VASc for cardiovascular events, but not the predictive value of HAS-BLED for major bleeding. Reclassification analyses did not show improvement adding multiple biomarkers. Despite the improvement observed, the added predictive advantage is marginal and

  19. Lead exposure biomarkers and mini-mental status exam scores in older men

    NARCIS (Netherlands)

    Wright, RO; Tsaih, SW; Schwartz, J; Spiro, A; McDonald, K; Weiss, ST; Hu, H

    2003-01-01

    Background: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. Methods:

  20. Lead exposure biomarkers and mini-mental status exam scores in older men

    NARCIS (Netherlands)

    Wright, RO; Tsaih, SW; Schwartz, J; Spiro, A; McDonald, K; Weiss, ST; Hu, H

    Background: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. Methods:

  1. AUC-based biomarker ensemble with an application on gene scores predicting low bone mineral density.

    Science.gov (United States)

    Zhao, X G; Dai, W; Li, Y; Tian, L

    2011-11-01

    The area under the receiver operating characteristic (ROC) curve (AUC), long regarded as a 'golden' measure for the predictiveness of a continuous score, has propelled the need to develop AUC-based predictors. However, the AUC-based ensemble methods are rather scant, largely due to the fact that the associated objective function is neither continuous nor concave. Indeed, there is no reliable numerical algorithm identifying optimal combination of a set of biomarkers to maximize the AUC, especially when the number of biomarkers is large. We have proposed a novel AUC-based statistical ensemble methods for combining multiple biomarkers to differentiate a binary response of interest. Specifically, we propose to replace the non-continuous and non-convex AUC objective function by a convex surrogate loss function, whose minimizer can be efficiently identified. With the established framework, the lasso and other regularization techniques enable feature selections. Extensive simulations have demonstrated the superiority of the new methods to the existing methods. The proposal has been applied to a gene expression dataset to construct gene expression scores to differentiate elderly women with low bone mineral density (BMD) and those with normal BMD. The AUCs of the resulting scores in the independent test dataset has been satisfactory. Aiming for directly maximizing AUC, the proposed AUC-based ensemble method provides an efficient means of generating a stable combination of multiple biomarkers, which is especially useful under the high-dimensional settings. lutian@stanford.edu. Supplementary data are available at Bioinformatics online.

  2. Cardiovascular risk scores for coronary atherosclerosis.

    Science.gov (United States)

    Yalcin, Murat; Kardesoglu, Ejder; Aparci, Mustafa; Isilak, Zafer; Uz, Omer; Yiginer, Omer; Ozmen, Namik; Cingozbay, Bekir Yilmaz; Uzun, Mehmet; Cebeci, Bekir Sitki

    2012-10-01

    The objective of this study was to compare frequently used cardiovascular risk scores in predicting the presence of coronary artery disease (CAD) and 3-vessel disease. In 350 consecutive patients (218 men and 132 women) who underwent coronary angiography, the cardiovascular risk level was determined using the Framingham Risk Score (FRS), the Modified Framingham Risk Score (MFRS), the Prospective Cardiovascular Münster (PROCAM) score, and the Systematic Coronary Risk Evaluation (SCORE). The area under the curve for receiver operating characteristic curves showed that FRS had more predictive value than the other scores for CAD (area under curve, 0.76, P MFRS, PROCAM, and SCORE) may predict the presence and severity of coronary atherosclerosis.The FRS had better predictive value than the other scores.

  3. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  4. Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes.

    Science.gov (United States)

    Eapen, Danny J; Manocha, Pankaj; Patel, Riyaz S; Hammadah, Muhammad; Veledar, Emir; Wassel, Christina; Nanjundappa, Ravi A; Sikora, Sergey; Malayter, Dylan; Wilson, Peter W F; Sperling, Laurence; Quyyumi, Arshed A; Epstein, Stephen E

    2013-07-23

    This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI). Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways-high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels-would be a powerful predictor of death and MI. Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score. An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

    Directory of Open Access Journals (Sweden)

    A. J. Reinecke

    2007-09-01

    Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

  6. Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study.

    Directory of Open Access Journals (Sweden)

    Andreas D Kistler

    Full Text Available Treatment options for autosomal dominant polycystic kidney disease (ADPKD will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS, we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI. The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001 with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD.

  7. Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with Biomarkers of Inflammation and Oxidative Balance in Adults.

    Science.gov (United States)

    Whalen, Kristine A; McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Judd, Suzanne; Bostick, Roberd M

    2016-06-01

    Chronic inflammation and oxidative balance are associated with poor diet quality and risk of cancer and other chronic diseases. A diet-inflammation/oxidative balance association may relate to evolutionary discordance. We investigated associations between 2 diet pattern scores, the Paleolithic and the Mediterranean, and circulating concentrations of 2 related biomarkers, high-sensitivity C-reactive protein (hsCRP), an acute inflammatory protein, and F2-isoprostane, a reliable marker of in vivo lipid peroxidation. In a pooled cross-sectional study of 30- to 74-y-old men and women in an elective outpatient colonoscopy population (n = 646), we created diet scores from responses on Willett food-frequency questionnaires and measured plasma hsCRP and F2-isoprostane concentrations by ELISA and gas chromatography-mass spectrometry, respectively. Both diet scores were calculated and categorized into quintiles, and their associations with biomarker concentrations were estimated with the use of general linear models to calculate and compare adjusted geometric means, and via unconditional ordinal logistic regression. There were statistically significant trends for decreasing geometric mean plasma hsCRP and F2-isoprostane concentrations with increasing quintiles of the Paleolithic and Mediterranean diet scores. The multivariable-adjusted ORs comparing those in the highest with those in the lowest quintiles of the Paleolithic and Mediterranean diet scores were 0.61 (95% CI: 0.36, 1.05; P-trend = 0.06) and 0.71 (95% CI: 0.42, 1.20; P-trend = 0.01), respectively, for a higher hsCRP concentration, and 0.51 (95% CI: 0.27, 0.95; P-trend 0.01) and 0.39 (95% CI: 0.21, 0.73; P-trend = 0.01), respectively, for a higher F2-isoprostane concentration. These findings suggest that diets that are more Paleolithic- or Mediterranean-like may be associated with lower levels of systemic inflammation and oxidative stress in humans. © 2016 American Society for Nutrition.

  8. Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: Clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients.

    Science.gov (United States)

    Blaha, Michael J; Silverman, Michael G; Budoff, Matthew J

    2014-03-01

    Although risk factors have proven to be useful therapeutic targets, they are poor predictors of risk. Traditional risk scores are moderately successful in predicting future CHD events and can be a starting place for general risk categorization. However, there is substantial heterogeneity between traditional risk and actual atherosclerosis burden, with event rates predominantly driven by burden of atherosclerosis. Serum biomarkers have yet to show any clinically significant incremental value to the FRS and even when combined cannot match the predictive value of atherosclerosis imaging. As clinicians, are we willing to base therapy decisions on risk models that lack optimum-achievable accuracy and limit personalization? The decision to treat a patient in primary prevention must be a careful one because the benefit of therapy in an asymptomatic patient must clearly outweigh the potential risk. CAC, in particular, provides a personalized assessment of risk and may identify patients who will be expected to derive the most, and the least, net absolute benefit from treatment. Emerging evidence hints that CAC may also promote long-term adherence to aspirin, exercise, diet, and statin therapy. When potentially lifelong treatment decisions are on the line, clinicians must arm their patients with the most accurate risk prediction tools, and subclinical atherosclerosis testing with CAC is, at the present time, superior to any combination of risk factors and serum biomarkers.

  9. Role of biomarkers in predicting CVD risk in the setting of HIV infection?

    DEFF Research Database (Denmark)

    Worm, Signe W; Hsue, Priscilla

    2010-01-01

    with risk of CVD. Biomarkers associated with inflammation such as C-reactive protein and interleukin-6 have been suggested to improve risk stratification among intermediate-risk persons; however, their routine use is not recommended in the general population. Both biomarkers have recently been reported......-infected population and will increase as this population continues to age. Identification of intermediate-risk individuals using biomarkers will be an important tool for clinicians in the future to be able to treat HIV-infected individuals aggressively. Future studies of biomarkers among individuals with HIV...

  10. Comparison of Accuracy of Diabetes Risk Score and Components of the Metabolic Syndrome in Assessing Risk of Incident Type 2 Diabetes in Inter99 Cohort

    DEFF Research Database (Denmark)

    Shafizadeh, Tracy B; Moler, Edward J; Kolberg, Janice A

    2011-01-01

    developed diabetes risk score, PreDxH Diabetes Risk Score (DRS). DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. Methodology/Principal Findings: DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged......Background: Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM); factors of metabolic syndrome (MetS) and a previously...... 30–60) for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity...

  11. Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

    Science.gov (United States)

    Ionescu, E M; Nicolaie, T; Ionescu, M A; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

    2015-01-01

    DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating

  12. Support Vector Hazards Machine: A Counting Process Framework for Learning Risk Scores for Censored Outcomes.

    Science.gov (United States)

    Wang, Yuanjia; Chen, Tianle; Zeng, Donglin

    2016-01-01

    Learning risk scores to predict dichotomous or continuous outcomes using machine learning approaches has been studied extensively. However, how to learn risk scores for time-to-event outcomes subject to right censoring has received little attention until recently. Existing approaches rely on inverse probability weighting or rank-based regression, which may be inefficient. In this paper, we develop a new support vector hazards machine (SVHM) approach to predict censored outcomes. Our method is based on predicting the counting process associated with the time-to-event outcomes among subjects at risk via a series of support vector machines. Introducing counting processes to represent time-to-event data leads to a connection between support vector machines in supervised learning and hazards regression in standard survival analysis. To account for different at risk populations at observed event times, a time-varying offset is used in estimating risk scores. The resulting optimization is a convex quadratic programming problem that can easily incorporate non-linearity using kernel trick. We demonstrate an interesting link from the profiled empirical risk function of SVHM to the Cox partial likelihood. We then formally show that SVHM is optimal in discriminating covariate-specific hazard function from population average hazard function, and establish the consistency and learning rate of the predicted risk using the estimated risk scores. Simulation studies show improved prediction accuracy of the event times using SVHM compared to existing machine learning methods and standard conventional approaches. Finally, we analyze two real world biomedical study data where we use clinical markers and neuroimaging biomarkers to predict age-at-onset of a disease, and demonstrate superiority of SVHM in distinguishing high risk versus low risk subjects.

  13. A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone

    OpenAIRE

    Rakovitch, Eileen; Nofech-Mozes, Sharon; Hanna, Wedad; Baehner, Frederick L.; Saskin, Refik; Butler, Steven M.; Tuck, Alan; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A.; Bonin, Michel; Chang, Martin C.; Robertson, Susan J.; Slodkowska, Elzbieta; Fong, Cindy

    2015-01-01

    Validated biomarkers are needed to improve risk assessment and treatment decision-making for women with ductal carcinoma in situ (DCIS) of the breast. The Oncotype DX? DCIS Score (DS) was shown to predict the risk of local recurrence (LR) in individuals with low-risk DCIS treated by breast-conserving surgery (BCS) alone. Our objective was to confirm these results in a larger population-based cohort of individuals. We used an established population-based cohort of individuals diagnosed with DC...

  14. Risk score for first-screening of prevalent undiagnosed chronic kidney disease in Peru: the CRONICAS-CKD risk score.

    Science.gov (United States)

    Carrillo-Larco, Rodrigo M; Miranda, J Jaime; Gilman, Robert H; Medina-Lezama, Josefina; Chirinos-Pacheco, Julio A; Muñoz-Retamozo, Paola V; Smeeth, Liam; Checkley, William; Bernabe-Ortiz, Antonio

    2017-11-29

    Chronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables. Cross-sectional study. We used two population-based studies: one for developing and internal validation (CRONICAS), and another (PREVENCION) for external validation. Risk factors included clinical- and laboratory-based variables, among others: sex, age, hypertension and obesity; and lipid profile, anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR anemia were strongly associated with undiagnosed CKD. In the external validation, at a cut-off point of 2, the complete and laboratory-free risk scores performed similarly well with a ROC area of 76.2% and 76.0%, respectively (P = 0.784). The best assessment parameter of these risk scores was their negative predictive value: 99.1% and 99.0% for the complete and laboratory-free, respectively. The developed risk scores showed a moderate performance as a screening test. People with a score of ≥ 2 points should undergo further testing to rule out CKD. Using the laboratory-free risk score is a practical approach in developing countries where laboratories are not readily available and undiagnosed CKD has significant morbidity and mortality.

  15. Significant relationships between a simple marker of redox balance and lifestyle behaviours; Relevance to the Framingham risk score.

    Directory of Open Access Journals (Sweden)

    Neda Seyedsadjadi

    Full Text Available Oxidative stress has been closely linked to the progressive cell damage associated with emerging non-communicable disease (NCDs. Early detection of these biochemical abnormalities before irreversible cell damage occurs may therefore be useful in identifying disease risk at an individual level. In order to test this hypothesis, this study assessed the relationship between a simple measure of redox status and lifestyle risk factors for NCDs, and the population-based risk score of Framingham. In a cross-sectional study design, 100 apparently healthy middle-aged males (n = 48 and females (n = 52 were asked to complete a comprehensive lifestyle assessment questionnaire, followed by body fat percentage and blood pressure measurements, and blood collection. The ratio of plasma total antioxidant capacity to hydroperoxide (TAC/HPX was used as an index of redox balance. One-way ANOVA and multiple linear regression analysis were performed to analyse the association between TAC/HPX, lifestyle components and other plasma biomarkers. The TAC/HPX ratio was higher in males compared to females (t96 = 2.34, P = 0.021. TAC/HPX was also lower in participants with poor sleep quality (t93 = 2.39, P = 0.019, with high sleep apnoea risk (t62.2 = 3.32, P = 0.002, with high caffeine (F(2, 93 = 3.97, P = 0.022 and red meat intake (F(2, 93 = 5.55, P = 0.005. These associations were independent of gender. Furthermore, the TAC/HPX ratio decreased with increasing body fat percentage (F(2, 95 = 4.74, P = 0.011 and depression score (t94 = 2.38, P = 0.019, though these associations were dependent on gender. Importantly, a negative association was observed between TAC/HPX levels and the Framingham risk score in both males (r(45 = -0.39, P = 0.008 and females (r(50 = -0.33, P = 0.019 that was independent of other Framingham risk score components. Findings from this study suggests that a relatively simple measure of redox balance such as the TAC/HPX ratio may be a sensitive

  16. Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

    Science.gov (United States)

    Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

    2003-05-07

    Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated

  17. Self-perceived quality of life predicts mortality risk better than a multi-biomarker panel, but the combination of both does best

    Directory of Open Access Journals (Sweden)

    Nauck Matthias

    2011-07-01

    Full Text Available Abstract Background Associations between measures of subjective health and mortality risk have previously been shown. We assessed the impact and comparative predictive performance of a multi-biomarker panel on this association. Methods Data from 4,261 individuals aged 20-79 years recruited for the population-based Study of Health in Pomerania was used. During an average 9.7 year follow-up, 456 deaths (10.7% occurred. Subjective health was assessed by SF-12 derived physical (PCS-12 and mental component summaries (MCS-12, and a single-item self-rated health (SRH question. We implemented Cox proportional-hazards regression models to investigate the association of subjective health with mortality and to assess the impact of a combination of 10 biomarkers on this association. Variable selection procedures were used to identify a parsimonious set of subjective health measures and biomarkers, whose predictive ability was compared using receiver operating characteristic (ROC curves, C-statistics, and reclassification methods. Results In age- and gender-adjusted Cox models, poor SRH (hazard ratio (HR, 2.07; 95% CI, 1.34-3.20 and low PCS-12 scores (lowest vs. highest quartile: HR, 1.75; 95% CI, 1.31-2.33 were significantly associated with increased risk of all-cause mortality; an association independent of various covariates and biomarkers. Furthermore, selected subjective health measures yielded a significantly higher C-statistic (0.883 compared to the selected biomarker panel (0.872, whereas a combined assessment showed the highest C-statistic (0.887 with a highly significant integrated discrimination improvement of 1.5% (p Conclusion Adding biomarker information did not affect the association of subjective health measures with mortality, but significantly improved risk stratification. Thus, a combined assessment of self-reported subjective health and measured biomarkers may be useful to identify high-risk individuals for intensified monitoring.

  18. Lowering risk score profile during PCI in multiple vessel disease is associated with low adverse events: The ERACI risk score.

    Science.gov (United States)

    Rodriguez, Alfredo E; Fernandez-Pereira, Carlos; Mieres, Juan; Pavlovsky, Hernan; Del Pozo, Juan; Rodriguez-Granillo, Alfredo M; Antoniucci, David

    2018-02-13

    In recent years angiographic risk scores have been introduced in clinical practice to stratify different levels of risk after percutaneous coronary interventions (PCI). The SYNTAX score included all intermediate lesions in vessels ≥1.5 mm, consequently, multiple stent implantation was required. Four years ago, we built a new angiographic score in order to guide PCI strategy avoiding stent deployment both in intermediate stenosis as in small vessels, therefore these were not scored (ERACI risk score). The purpose of this mini review is to validate the strategy of PCI guided by this scoring, taking into account long term follow up outcomes of two observational and prospective registries where this policy was used. With this new risk score we have modified risk profile of our patient's candidates for PCI or coronary artery bypass surgery lowering the risk and PCI. The simple exclusion of small vessels and intermediate stenosis from the revascularization approach resulted in clinical outcome comparable with the one of fractional flow reserve guided revascularization. Low events rate at late follow up observed in both studies was also in agreement with guided PCI by functional lesion assessment observed by Syntax II registry, where investigators found lower events rate in spite of a few number of stents implanted per patient. use of ERACI risk scores may significantly reclassify patients into a lower risk category and be associated with low adverse events rate. Copyright © 2018. Published by Elsevier Inc.

  19. Combined use of aortic dissection detection risk score and D-dimer in the diagnostic workup of suspected acute aortic dissection.

    Science.gov (United States)

    Nazerian, Peiman; Morello, Fulvio; Vanni, Simone; Bono, Alessia; Castelli, Matteo; Forno, Daniela; Gigli, Chiara; Soardo, Flavia; Carbone, Federica; Lupia, Enrico; Grifoni, Stefano

    2014-07-15

    Acute aortic dissection (AD) represents a diagnostic conundrum. Validated algorithms are particularly needed to identify patients where AD could be ruled out without aortic imaging. We evaluated the diagnostic accuracy of a strategy combining the aortic dissection detection (ADD) risk score with D-dimer, a sensitive biomarker of AD. Patients from two clinical centers with suspected AD were prospectively enrolled in a registry, from January 2008 to March 2013. The ADD risk score was calculated by retrospective blinded chart review. For D-dimer, a cutoff of 500 ng/ml was applied. AD was diagnosed in 233 of 1035 (22.5%) patients. The ADD risk score was 0 in 322 (31.1%), 1 in 508 (49.1%) and >1 in 205 (19.8%) patients. The sensitivity and the failure rate of D-dimer were 100% and 0% in patients with ADD score 0, versus 97.5% (95% CI 91.4-99.6%) and 4.2% (95% CI 0.7-12.5%) in patients with ADD risk score >1. In patients with ADD risk score ≤ 1, the sensitivity and the failure rate of D-dimer were 98.7% (95% CI 95.3-99.8%) and 0.8% (95% CI 0.1-2.6%). The diagnostic efficiency of D-dimer in patients with ADD risk score 0 and ≤ 1 was 8.9% (95% CI 7.2-10.7%) and 23.6% (95% CI 21.1-26.2%) respectively. In a large cohort of patients with suspected AD, the presence of ADD risk score 0 or ≤ 1 combined with a negative D-dimer accurately and efficiently ruled out AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Credit scores, cardiovascular disease risk, and human capital.

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  1. Aerobic exercise reduces biomarkers related to cardiovascular risk among cleaners

    DEFF Research Database (Denmark)

    Korshøj, Mette; Ravn, Marie Højbjerg; Holtermann, Andreas

    2016-01-01

    PURPOSE: Blue-collar workers have an increased risk of cardiovascular disease. Accordingly, elevated levels of biomarkers related to risk of cardiovascular disease, such as high-sensitive C-reactive protein, have been observed among blue-collar workers. The objective was to examine whether...... an aerobic exercise worksite intervention changes the level of inflammation biomarkers among cleaners. METHODS: The design was a cluster-randomized controlled trial with 4-month worksite intervention. Before the 116 cleaners aged 18-65 years were randomized, they signed an informed consent form...

  2. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH.

    Science.gov (United States)

    Meijers, Wouter C; de Boer, Rudolf A; van Veldhuisen, Dirk J; Jaarsma, Tiny; Hillege, Hans L; Maisel, Alan S; Di Somma, Salvatore; Voors, Adriaan A; Peacock, W Frank

    2015-12-01

    Traditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. This analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180 days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (± SD) age was 71 (± 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180 days (OR 8.1, 95% confidence interval 1.06-50.0, P = 0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P = 0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of

  3. Biomarkers, lactate, and clinical scores as outcome predictors in systemic poisons exposures.

    Science.gov (United States)

    Lionte, C; Sorodoc, V; Tuchilus, C; Cimpoiesu, D; Jaba, E

    2017-07-01

    Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted a prospective study on adults acutely exposed to systemic poisons. We determined the PSS, Glasgow Coma Scale (GCS), and we performed electrocardiogram, laboratory tests, lactate and cardiac biomarkers (which were reassessed 4 h, respectively 6 h later). Of 120 patients included, 45% developed complications, 19.2% had a poor outcome, and 5% died. Multivariate logistic regression sustained lactate (odds ratio (OR) 1.58; confidence interval (CI) 95%: 0.97-2.59; p 0.066), MB isoenzyme of creatine kinase (6h-CKMB; OR 1.08; CI 95%: 1.02-1.16; p 0.018) as predictors for a poor outcome. A GCS poisons exposure. Receiver operating characteristic analysis showed that brain natriuretic peptide (area under the curve (AUC), 0.96; CI 95%: 0.92-0.99; p poisons exposure.

  4. Risk scores-the modern Oracle of Delphi?

    Science.gov (United States)

    Kronenberg, Florian; Schwaiger, Johannes P

    2017-03-01

    Recently, 4 new risk scores for the prediction of mortality and cardiovascular events were especially tailored for hemodialysis patients; these scores performed much better than previous scores. Tripepi et al. found that these risk scores were even more predictive for all-cause and cardiovascular death than the measurement of the left ventricular mass index was. Nevertheless, the investigation of left ventricular mass and function has its own place for other reasons. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Emergency Medicine Evaluation of Community-Acquired Pneumonia: History, Examination, Imaging and Laboratory Assessment, and Risk Scores.

    Science.gov (United States)

    Long, Brit; Long, Drew; Koyfman, Alex

    2017-11-01

    Pneumonia is a common infection, accounting for approximately one million hospitalizations in the United States annually. This potentially life-threatening disease is commonly diagnosed based on history, physical examination, and chest radiograph. To investigate emergency medicine evaluation of community-acquired pneumonia including history, physical examination, imaging, and the use of risk scores in patient assessment. Pneumonia is the number one cause of death from infectious disease. The condition is broken into several categories, the most common being community-acquired pneumonia. Diagnosis centers on history, physical examination, and chest radiograph. However, all are unreliable when used alone, and misdiagnosis occurs in up to one-third of patients. Chest radiograph has a sensitivity of 46-77%, and biomarkers including white blood cell count, procalcitonin, and C-reactive protein provide little benefit in diagnosis. Biomarkers may assist admitting teams, but require further study for use in the emergency department. Ultrasound has shown utility in correctly identifying pneumonia. Clinical gestalt demonstrates greater ability to diagnose pneumonia. Clinical scores including Pneumonia Severity Index (PSI); Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, age 65 score (CURB-65); and several others may be helpful for disposition, but should supplement, not replace, clinical judgment. Patient socioeconomic status must be considered in disposition decisions. The diagnosis of pneumonia requires clinical gestalt using a combination of history and physical examination. Chest radiograph may be negative, particularly in patients presenting early in disease course and elderly patients. Clinical scores can supplement clinical gestalt and assist in disposition when used appropriately. Published by Elsevier Inc.

  6. Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0328 TITLE: Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk PRINCIPAL INVESTIGATOR: Dr...4. TITLE AND SUBTITLE Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk 5b. GRANT NUMBER W81XWH 16-1-0328 5c. PROGRAM...devise a non-invasive airway based exhaled microRNA metric for lung cancer risk, initial work to be tested in a case control study. We expanded the

  7. Coronary artery disease-associated genetic variants and biomarkers of inflammation

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh; Larsen, Sanne Bøjet; Nyegaard, Mette

    2017-01-01

    score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. RESULTS:The minor allele (G) (CAD risk allele) of rs2075650......INTRODUCTION:Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD...

  8. Developing points-based risk-scoring systems in the presence of competing risks.

    Science.gov (United States)

    Austin, Peter C; Lee, Douglas S; D'Agostino, Ralph B; Fine, Jason P

    2016-09-30

    Predicting the occurrence of an adverse event over time is an important issue in clinical medicine. Clinical prediction models and associated points-based risk-scoring systems are popular statistical methods for summarizing the relationship between a multivariable set of patient risk factors and the risk of the occurrence of an adverse event. Points-based risk-scoring systems are popular amongst physicians as they permit a rapid assessment of patient risk without the use of computers or other electronic devices. The use of such points-based risk-scoring systems facilitates evidence-based clinical decision making. There is a growing interest in cause-specific mortality and in non-fatal outcomes. However, when considering these types of outcomes, one must account for competing risks whose occurrence precludes the occurrence of the event of interest. We describe how points-based risk-scoring systems can be developed in the presence of competing events. We illustrate the application of these methods by developing risk-scoring systems for predicting cardiovascular mortality in patients hospitalized with acute myocardial infarction. Code in the R statistical programming language is provided for the implementation of the described methods. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

  9. Increased prevalence of cardiovascular disease and risk biomarkers in patients with unknown type 2 diabetes visiting cardiology specialists: results from the DIASPORA study.

    Science.gov (United States)

    Schöndorf, Thomas; Lübben, Georg; Karagiannis, Efstrathios; Erdmann, Erland; Forst, Thomas; Pfützner, Andreas

    2010-04-01

    Patients with diabetes mellitus and IGT have a high risk for cardiovascular events. It is tempting to speculate that these patients are often first seen by cardiologists. This cross-sectional study investigates the diabetes prevalence in cardiology care units and the correlated metabolic conditions as assessed by several circulating biomarkers. Patients aged 55 or older with suspected or overt coronary heart disease were eligible for trial participation. Fasting blood samples were drawn from patients to determine HOMA score, glycaemic and lipid profile, and several risk biomarkers. An OGTT was performed in patients without known diabetes. We enrolled 530 patients (181 male, 349 female, mean age, 68+/-7 years) in this study from 22 German cardiology centres; 156 patients (29.4%) had known diabetes and OGTT revealed that 184 patients (34.7%) had no diabetes, 106 patients (20.0%) had IGT or IFG and 84 patients (15.9%) were newly diagnosed with diabetes. Increased cardiovascular risk as reflected by increased hsCRP, ICAM and MMP-9 values was observed in diabetes patients. A higher cardiovascular biomarkers risk profile was seen in the IGT/IFG cohort. This study confirms the observation that one third of patients of a cardiologic care unit suffer from impaired glucose regulation. Furthermore, the cardiology patients with previously unknown glucose homeostasis abnormalities had a higher prevalence of macrovacular disease and an impaired biomarker risk profile. This study underlines the importance of joint treatment efforts by cardiologists in concert with diabetologists for treatment of this patient group at high risk for cardiovascular events.

  10. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  11. Blood-borne biomarkers of mortality risk: systematic review of cohort studies.

    Directory of Open Access Journals (Sweden)

    Evelyn Barron

    Full Text Available Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.Four databases (Medline, Embase, Scopus, Web of Science were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033, N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001 and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001. There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of

  12. Digital imaging biomarkers feed machine learning for melanoma screening.

    Science.gov (United States)

    Gareau, Daniel S; Correa da Rosa, Joel; Yagerman, Sarah; Carucci, John A; Gulati, Nicholas; Hueto, Ferran; DeFazio, Jennifer L; Suárez-Fariñas, Mayte; Marghoob, Ashfaq; Krueger, James G

    2017-07-01

    We developed an automated approach for generating quantitative image analysis metrics (imaging biomarkers) that are then analysed with a set of 13 machine learning algorithms to generate an overall risk score that is called a Q-score. These methods were applied to a set of 120 "difficult" dermoscopy images of dysplastic nevi and melanomas that were subsequently excised/classified. This approach yielded 98% sensitivity and 36% specificity for melanoma detection, approaching sensitivity/specificity of expert lesion evaluation. Importantly, we found strong spectral dependence of many imaging biomarkers in blue or red colour channels, suggesting the need to optimize spectral evaluation of pigmented lesions. © 2016 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

  13. The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic Cardiovascular Disease Score for Applied Use.

    Science.gov (United States)

    Sussman, Jeremy B; Wiitala, Wyndy L; Zawistowski, Matthew; Hofer, Timothy P; Bentley, Douglas; Hayward, Rodney A

    2017-09-01

    Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients' risk of developing CVD. We created a cohort using all patients ages 45-80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007-2011. We then developed a series of recalibrated scores, including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different scores using standard measures of prediction quality. For the 1,512,092 patients in the study, the Atherosclerotic cardiovascular disease risk score had similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in women), but the Atherosclerotic cardiovascular disease model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system's electronic health record and can be more readily updated.

  14. Developing risk prediction models for kidney injury and assessing incremental value for novel biomarkers.

    Science.gov (United States)

    Kerr, Kathleen F; Meisner, Allison; Thiessen-Philbrook, Heather; Coca, Steven G; Parikh, Chirag R

    2014-08-07

    The field of nephrology is actively involved in developing biomarkers and improving models for predicting patients' risks of AKI and CKD and their outcomes. However, some important aspects of evaluating biomarkers and risk models are not widely appreciated, and statistical methods are still evolving. This review describes some of the most important statistical concepts for this area of research and identifies common pitfalls. Particular attention is paid to metrics proposed within the last 5 years for quantifying the incremental predictive value of a new biomarker. Copyright © 2014 by the American Society of Nephrology.

  15. Risk scoring for the primary prevention of cardiovascular disease.

    Science.gov (United States)

    Karmali, Kunal N; Persell, Stephen D; Perel, Pablo; Lloyd-Jones, Donald M; Berendsen, Mark A; Huffman, Mark D

    2017-03-14

    The current paradigm for cardiovascular disease (CVD) emphasises absolute risk assessment to guide treatment decisions in primary prevention. Although the derivation and validation of multivariable risk assessment tools, or CVD risk scores, have attracted considerable attention, their effect on clinical outcomes is uncertain. To assess the effects of evaluating and providing CVD risk scores in adults without prevalent CVD on cardiovascular outcomes, risk factor levels, preventive medication prescribing, and health behaviours. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 2), MEDLINE Ovid (1946 to March week 1 2016), Embase (embase.com) (1974 to 15 March 2016), and Conference Proceedings Citation Index-Science (CPCI-S) (1990 to 15 March 2016). We imposed no language restrictions. We searched clinical trial registers in March 2016 and handsearched reference lists of primary studies to identify additional reports. We included randomised and quasi-randomised trials comparing the systematic provision of CVD risk scores by a clinician, healthcare professional, or healthcare system compared with usual care (i.e. no systematic provision of CVD risk scores) in adults without CVD. Three review authors independently selected studies, extracted data, and evaluated study quality. We used the Cochrane 'Risk of bias' tool to assess study limitations. The primary outcomes were: CVD events, change in CVD risk factor levels (total cholesterol, systolic blood pressure, and multivariable CVD risk), and adverse events. Secondary outcomes included: lipid-lowering and antihypertensive medication prescribing in higher-risk people. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data using 95% confidence intervals. We used a fixed-effects model when heterogeneity (I²) was at least 50% and a random-effects model for substantial heterogeneity

  16. Biomarkers for Risk Stratification of Neoplastic Progression in Barrett Esophagus

    Directory of Open Access Journals (Sweden)

    Marjon Kerkhof

    2007-01-01

    Full Text Available Barrett esophagus (BE is caused by chronic gastroesophageal reflux and predisposes to the development of esophageal adenocarcinoma through different grades of dysplasia. Only a subset of BE patients will finally develop esophageal adenocarcinoma. The majority will therefore not benefit from an endoscopic surveillance program, based on the histological identification of dysplasia. Several studies have been performed to find additional biomarkers that can be used to detect the subgroup of patients with an increased risk of developing malignancy in BE. In this review, we will summarize the most promising tissue biomarkers, i.e. proliferation/cell cycle proteins, tumor suppressor genes, adhesion molecules, DNA ploidy status and inflammation associated markers, that can be used for risk stratification in BE, and discuss their respective clinical application.

  17. Comparing Bleeding Risk Assessment Focused on Modifiable Risk Factors Only Versus Validated Bleeding Risk Scores in Atrial Fibrillation

    DEFF Research Database (Denmark)

    Guo, Yutao; Zhu, Hang; Chen, Yundai

    2018-01-01

    BACKGROUNDThere is uncertainty whether a focus on modifiable bleeding risk factors offers better prediction of major bleeding than other existing bleeding risk scores.METHODSThis study compared a score based on numbers of the modifiable bleeding risk factors recommended in the 2016 European...... guidelines ("European risk score") versus other published bleeding risk scores that have been derived and validated in atrial fibrillation subjects (HEMORR2HAGES, HAS-BLED, ATRIA, and ORBIT) in a large hospital-based cohort of Chinese inpatients with atrial fibrillation.RESULTSThe European score had modest...... predictive ability for major bleeding (c-index 0.63, 95% confidence interval 0.56-0.69) and intracranial hemorrhage (0.72, 0.65-0.79) but nonsignificantly (and poorly) predicted extracranial bleeding (0.55, 0.54-0.56; P = .361). The HAS-BLED score was superior to predict bleeding events compared...

  18. Predictive value of NT-proBNP for 30-day mortality in patients with non-ST-elevation acute coronary syndromes: a comparison with the GRACE and TIMI risk scores.

    Science.gov (United States)

    Schellings, Dirk Aam; Adiyaman, Ahmet; Dambrink, Jan-Henk E; Gosselink, At Marcel; Kedhi, Elvin; Roolvink, Vincent; Ottervanger, Jan Paul; Van't Hof, Arnoud Wj

    2016-01-01

    The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts outcome in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Whether NT-proBNP has incremental prognostic value beyond established risk strategies is still questionable. To evaluate the predictive value of NT-proBNP for 30-day mortality over and beyond the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores in patients with NSTE-ACS. Patients included in our ACS registry were candidates. NT-proBNP levels on admission were measured and the GRACE and TIMI risk scores were assessed. We compared the predictive value of NT-proBNP to both risk scores and evaluated whether NT-proBNP improves prognostication by using receiver operator curves and measures of discrimination improvement. A total of 1324 patients were included and 50 patients died during follow-up. On logistic regression analysis NT-proBNP and the GRACE risk score (but not the TIMI risk score) both independently predicted mortality at 30 days. The predictive value of NT-proBNP did not differ significantly compared to the GRACE risk score (area under the curve [AUC]) 0.85 vs 0.87 p =0.67) but was considerably higher in comparison to the TIMI risk score (AUC 0.60 p risk score by adding NT-proBNP did not improve prognostication: AUC 0.86 ( p =0.57), integrated discrimination improvement 0.04 ( p =0.003), net reclassification improvement 0.12 ( p =0.21). In patients with NSTE-ACS, NT-proBNP and the GRACE risk score (but not the TIMI risk score) both have good and comparable predictive value for 30-day mortality. However, incremental prognostic value of NT-proBNP beyond the GRACE risk score could not be demonstrated.

  19. Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment

    DEFF Research Database (Denmark)

    Pories, Susan E; Zurakowski, David; Roy, Roopali

    2008-01-01

    Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk statu...

  20. The HAT Score-A Simple Risk Stratification Score for Coagulopathic Bleeding During Adult Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Lonergan, Terence; Herr, Daniel; Kon, Zachary; Menaker, Jay; Rector, Raymond; Tanaka, Kenichi; Mazzeffi, Michael

    2017-06-01

    The study objective was to create an adult extracorporeal membrane oxygenation (ECMO) coagulopathic bleeding risk score. Secondary analysis was performed on an existing retrospective cohort. Pre-ECMO variables were tested for association with coagulopathic bleeding, and those with the strongest association were included in a multivariable model. Using this model, a risk stratification score was created. The score's utility was validated by comparing bleeding and transfusion rates between score levels. Bleeding also was examined after stratifying by nadir platelet count and overanticoagulation. Predictive power of the score was compared against the risk score for major bleeding during anti-coagulation for atrial fibrillation (HAS-BLED). Tertiary care academic medical center. The study comprised patients who received venoarterial or venovenous ECMO over a 3-year period, excluding those with an identified source of surgical bleeding during exploration. None. Fifty-three (47.3%) of 112 patients experienced coagulopathic bleeding. A 3-variable score-hypertension, age greater than 65, and ECMO type (HAT)-had fair predictive value (area under the receiver operating characteristic curve [AUC] = 0.66) and was superior to HAS-BLED (AUC = 0.64). As the HAT score increased from 0 to 3, bleeding rates also increased as follows: 30.8%, 48.7%, 63.0%, and 71.4%, respectively. Platelet and fresh frozen plasma transfusion tended to increase with the HAT score, but red blood cell transfusion did not. Nadir platelet count less than 50×10 3 /µL and overanticoagulation during ECMO increased the AUC for the model to 0.73, suggesting additive risk. The HAT score may allow for bleeding risk stratification in adult ECMO patients. Future studies in larger cohorts are necessary to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Novel biomarkers for risk stratification in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Thomas Zelniker

    2015-10-01

    Full Text Available Risk stratification in pulmonary arterial hypertension (PAH is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT, pro-atrial natriuretic peptide (proANP, growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4% patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR 1.91, hsTnT (HR 1.41, echocardiographic right ventricular impairment (HR 1.30 and 6-min walk test (HR 0.97 per 10 m remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

  2. Functional Movement Screen: Pain versus composite score and injury risk.

    Science.gov (United States)

    Alemany, Joseph A; Bushman, Timothy T; Grier, Tyson; Anderson, Morgan K; Canham-Chervak, Michelle; North, William J; Jones, Bruce H

    2017-11-01

    The Functional Movement Screen (FMS™) has been used as a screening tool to determine musculoskeletal injury risk using composite scores based on movement quality and/or pain. However, no direct comparisons between movement quality and pain have been quantified. Retrospective injury data analysis. Male Soldiers (n=2154, 25.0±1.3years; 26.2±.7kg/m 2 ) completed the FMS (scored from 0 points (pain) to 3 points (no pain and perfect movement quality)) with injury data over the following six months. The FMS is seven movements. Injury data were collected six months after FMS completion. Sensitivity, specificity, receiver operator characteristics and positive and negative predictive values were calculated for pain occurrence and low (≤14 points) composite score. Risk, risk ratios (RR) and 95% confidence intervals were calculated for injury risk. Pain was associated with slightly higher injury risk (RR=1.62) than a composite score of ≤14 points (RR=1.58). When comparing injury risk between those who scored a 1, 2 or 3 on each individual movement, no differences were found (except deep squat). However, Soldiers who experienced pain on any movement had a greater injury risk than those who scored 3 points for that movement (pmovements in which pain occurrence increased, so did injury risk (p<0.01). Pain occurrence may be a stronger indicator of injury risk than a low composite score and provides a simpler method of evaluating injury risk compared to the full FMS. Published by Elsevier Ltd.

  3. Beyond Statistics: The Economic Content of Risk Scores

    Science.gov (United States)

    Einav, Liran; Finkelstein, Amy; Kluender, Raymond

    2016-01-01

    “Big data” and statistical techniques to score potential transactions have transformed insurance and credit markets. In this paper, we observe that these widely-used statistical scores summarize a much richer heterogeneity, and may be endogenous to the context in which they get applied. We demonstrate this point empirically using data from Medicare Part D, showing that risk scores confound underlying health and endogenous spending response to insurance. We then illustrate theoretically that when individuals have heterogeneous behavioral responses to contracts, strategic incentives for cream skimming can still exist, even in the presence of “perfect” risk scoring under a given contract. PMID:27429712

  4. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

    Science.gov (United States)

    Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

    2016-06-01

    then showed how the clinical information apps combined with the 50 validated biomarkers into a broad predictor (UP-Suicide), our apriori primary end point, predicts suicidality in women. UP-Suicide had a receiver-operating characteristic (ROC) area under the curve (AUC) of 82% for predicting SI and an AUC of 78% for predicting future hospitalizations for suicidality. Some of the individual components of the UP-Suicide showed even better results. SASS had an AUC of 81% for predicting SI, CFI-S had an AUC of 84% and the combination of the two apps had an AUC of 87%. The top biomarker from our sequential discovery, prioritization and validation steps, BCL2, predicted future hospitalizations due to suicidality with an AUC of 89%, and the panel of 50 validated biomarkers (BioM-50) predicted future hospitalizations due to suicidality with an AUC of 94%. The best overall single blood biomarker for predictions was PIK3C3 with an AUC of 65% for SI and an AUC of 90% for future hospitalizations. Finally, we sought to understand the biology of the biomarkers. BCL2 and GSK3B, the top CFG scoring validated biomarkers, as well as PIK3C3, have anti-apoptotic and neurotrophic effects, are decreased in expression in suicidality and are known targets of the anti-suicidal mood stabilizer drug lithium, which increases their expression and/or activity. Circadian clock genes were overrepresented among the top markers. Notably, PER1, increased in expression in suicidality, had an AUC of 84% for predicting future hospitalizations, and CSNK1A1, decreased in expression, had an AUC of 96% for predicting future hospitalizations. Circadian clock abnormalities are related to mood disorder, and sleep abnormalities have been implicated in suicide. Docosahexaenoic acid signaling was one of the top biological pathways overrepresented in validated biomarkers, which is of interest given the potential therapeutic and prophylactic benefits of omega-3 fatty acids. Some of the top biomarkers from the current

  5. Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. The Murcia Atrial Fibrillation Project.

    Science.gov (United States)

    Esteve-Pastor, María Asunción; Rivera-Caravaca, José Miguel; Roldan, Vanessa; Vicente, Vicente; Valdés, Mariano; Marín, Francisco; Lip, Gregory Y H

    2017-10-05

    Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better than HAS-BLED score in a clinical trial cohort but has not been externally validated. The aim of this study was to analyze the predictive performance of the ABC-Bleeding score compared to HAS-BLED score in an independent "real-world" anticoagulated AF patients with long-term follow-up. We enrolled 1,120 patients stable on vitamin K antagonist treatment. The HAS-BLED and ABC-Bleeding scores were quantified. Predictive values were compared by c-indexes, IDI, NRI, as well as decision curve analysis (DCA). Median HAS-BLED score was 2 (IQR 2-3) and median ABC-Bleeding was 16.5 (IQR 14.3-18.6). After 6.5 years of follow-up, 207 (2.84 %/year) patients had major bleeding events, of which 65 (0.89 %/year) had intracranial haemorrhage (ICH) and 85 (1.17 %/year) had gastrointestinal bleeding events (GIB). The c-index of HAS-BLED was significantly higher than ABC-Bleeding for major bleeding (0.583 vs 0.518; p=0.025), GIB (0.596 vs 0.519; p=0.017) and for the composite of ICH-GIB (0.593 vs 0.527; p=0.030). NRI showed a significant negative reclassification for major bleeding and for the composite of ICH-GIB with the ABC-Bleeding score compared to HAS-BLED. Using DCAs, the use of HAS-BLED score gave an approximate net benefit of 4 % over the ABC-Bleeding score. In conclusion, in the first "real-world" validation of the ABC-Bleeding score, HAS-BLED performed significantly better than the ABC-Bleeding score in predicting major bleeding, GIB and the composite of GIB and ICH.

  6. Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH

    NARCIS (Netherlands)

    Meijers, Wouter C.; de Boer, Rudolf A.; van Veldhuisen, Dirk J.; Jaarsma, Tiny; Hillege, Hans L.; Maisel, Alan S.; Di Somma, Salvatore; Voors, Adriaan A.; Peacock, W. Frank

    2015-01-01

    AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating

  7. MODELING CREDIT RISK THROUGH CREDIT SCORING

    OpenAIRE

    Adrian Cantemir CALIN; Oana Cristina POPOVICI

    2014-01-01

    Credit risk governs all financial transactions and it is defined as the risk of suffering a loss due to certain shifts in the credit quality of a counterpart. Credit risk literature gravitates around two main modeling approaches: the structural approach and the reduced form approach. In addition to these perspectives, credit risk assessment has been conducted through a series of techniques such as credit scoring models, which form the traditional approach. This paper examines the evolution of...

  8. Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.

    Science.gov (United States)

    Biener, Moritz; Giannitsis, Evangelos; Kuhner, Manuel; Zelniker, Thomas; Mueller-Hennessen, Matthias; Vafaie, Mehrshad; Stoyanov, Kiril M; Neumann, Franz-Josef; Katus, Hugo A; Hochholzer, Willibald; Valina, Christian Marc

    2018-01-01

    To evaluate the prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) compared with the ESC-SCORE. We included low-risk outpatients with stable cardiovascular (CV) disease categorised into need for non-secondary and secondary prevention. The prognostication of hs-cTnT at index visit was compared with the European Society of Cardiology-Systematic COronary Risk Evaluation (ESC-SCORE) with respect to all-cause mortality (ACM) and two composite endpoints (ACM, acute myocardial infarction (AMI) and stroke and ACM, AMI, stroke and rehospitalisation for acute coronary syndrome (ACS) and decompensated heart failure (DHF)). Within a median follow-up of 796 days, a total of 16 deaths, 32 composite endpoints of ACM, AMI and stroke and 83 composite endpoints of ACM, AMI, stroke, rehospitalisation for ACS and DHF were observed among 693 stable low-risk outpatients. Using C-statistics, measurement of hs-cTnT alone outperformed the ESC-SCORE for the prediction of ACM in the entire study population (Δarea under the curve (AUC) 0.221, p=0.0039) and both prevention groups (non-secondary: ΔAUC 0.164, p=0.0208; secondary: ΔAUC 0.264, p=0.0134). For the prediction of all other secondary endpoints, hs-cTnT was at least as effective as the ESC-SCORE, both in secondary and non-secondary prevention. Using continuous and categorical net reclassification improvement and integrated discrimination improvement, hs-cTnT significantly improved reclassification regarding all endpoints in the entire population and in the secondary prevention cohort. In non-secondary prevention, hs-cTnT improved reclassification only for ACM. The results were confirmed in an independent external cohort on 2046 patients. Hs-cTnT is superior to the multivariable ESC-SCORE for the prediction of ACM and a composite endpoint in stable outpatients with and without relevant CV disease. NCT01954303; Pre-results.

  9. Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial.

    Science.gov (United States)

    Sparks, Jeffrey A; Iversen, Maura D; Yu, Zhi; Triedman, Nellie A; Prado, Maria G; Miller Kroouze, Rachel; Kalia, Sarah S; Atkinson, Michael L; Mody, Elinor A; Helfgott, Simon M; Todd, Derrick J; Dellaripa, Paul F; Bermas, Bonnie L; Costenbader, Karen H; Deane, Kevin D; Lu, Bing; Green, Robert C; Karlson, Elizabeth W

    2017-10-12

    To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions. We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans-theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intent-to-treat analyses using generalized estimating equations for the binary outcome. Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18). Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health

  10. Assessment of three risk evaluation systems for patients aged ≥70 in East China: performance of SinoSCORE, EuroSCORE II and the STS risk evaluation system.

    Science.gov (United States)

    Shan, Lingtong; Ge, Wen; Pu, Yiwei; Cheng, Hong; Cang, Zhengqiang; Zhang, Xing; Li, Qifan; Xu, Anyang; Wang, Qi; Gu, Chang; Zhang, Yangyang

    2018-01-01

    To assess and compare the predictive ability of three risk evaluation systems (SinoSCORE, EuroSCORE II and the STS risk evaluation system) in patients aged ≥70, and who underwent coronary artery bypass grafting (CABG) in East China. Three risk evaluation systems were applied to 1,946 consecutive patients who underwent isolated CABG from January 2004 to September 2016 in two hospitals. Patients were divided into two subsets according to their age: elderly group (age ≥70) with a younger group (age evaluation system were 0.78(0.64)%, 1.43(1.14)% and 0.78(0.77)%, respectively. SinoSCORE achieved the best discrimination (the area under the receiver operating characteristic curve (AUC) = 0.829), followed by the STS risk evaluation system (AUC = 0.790) and EuroSCORE II (AUC = 0.769) in the entire cohort. In the elderly group, the observed mortality rate was 4.82% while it was 1.38% in the younger group. SinoSCORE (AUC = .829) also achieved the best discrimination in the elderly group, followed by the STS risk evaluation system (AUC = .730) and EuroSCORE II (AUC = 0.640) while all three risk evaluation systems all had good performances in the younger group. SinoSCORE, EuroSCORE II and the STS risk evaluation system all achieved positive calibrations in the entire cohort and subsets. The performance of the three risk evaluation systems was not ideal in the entire cohort. In the elderly group, SinoSCORE appeared to achieve better predictive efficiency than EuroSCORE II and the STS risk evaluation system.

  11. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

    Science.gov (United States)

    Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L

    2012-09-25

    Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (Pstatistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

  12. Risk score for contrast induced nephropathy following percutaneous coronary intervention

    International Nuclear Information System (INIS)

    Ghani, Amal Abdel; Tohamy, Khalid Y.

    2009-01-01

    Contrast-induced nephropathy (CIN) is an important cause of acute renal failure. Identification of risk factors of CIN and creating a simple risk scoring for CIN after percutaneous coronary intervention (PCI) is important. A prospective single center study was conducted in Kuwait chest disease hospital. All patients admitted to chest disease hospital for PCI from March to May 2005 were included in the study. Total of 247 patients were randomly assigned for the development dataset and 100 for the validation set using the simple random method. The overall occurrence of CIN in the development set was 5.52%. Using multivariate analysis; basal Serum creatinine, shock, female gender, multivessel PCI, and diabetes mellitus were identified as risk factors. Scores assigned to different variables yielded basal creatinine > 115 micron mol/L with the highest score(7), followed by shock (3), female gender, multivessel PCI and diabetes mellitus had the same score (2). Patients were further risk stratified into low risk score ( 1 2). The developed CIN model demonstrated good discriminative power in the validation population. In conclusion, use of a simple risk score for CIN can predict the probability of CIN after PCI; this however needs further validation in larger multicenter trials. (author)

  13. A summary risk score for the prediction of Alzheimer disease in elderly persons.

    Science.gov (United States)

    Reitz, Christiane; Tang, Ming-Xin; Schupf, Nicole; Manly, Jennifer J; Mayeux, Richard; Luchsinger, José A

    2010-07-01

    To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles. A longitudinal, community-based study. New York, New York. Patients One thousand fifty-one Medicare recipients aged 65 years or older and residing in New York who were free of dementia or cognitive impairment at baseline. We separately explored the associations of several vascular risk factors with late-onset Alzheimer disease (LOAD) using Cox proportional hazards models to identify factors that would contribute to the risk score. Then we estimated the score values of each factor based on their beta coefficients and created the LOAD vascular risk score by summing these individual scores. Risk factors contributing to the risk score were age, sex, education, ethnicity, APOE epsilon4 genotype, history of diabetes, hypertension or smoking, high-density lipoprotein levels, and waist to hip ratio. The resulting risk score predicted dementia well. According to the vascular risk score quintiles, the risk to develop probable LOAD was 1.0 for persons with a score of 0 to 14 and increased 3.7-fold for persons with a score of 15 to 18, 3.6-fold for persons with a score of 19 to 22, 12.6-fold for persons with a score of 23 to 28, and 20.5-fold for persons with a score higher than 28. While additional studies in other populations are needed to validate and further develop the score, our study suggests that this vascular risk score could be a valuable tool to identify elderly individuals who might be at risk of LOAD. This risk score could be used to identify persons at risk of LOAD, but can also be used to adjust for confounders in epidemiologic studies.

  14. Thrombotic risk assessment in APS: the Global APS Score (GAPSS).

    Science.gov (United States)

    Sciascia, S; Bertolaccini, M L

    2014-10-01

    Recently, we developed a risk score for antiphospholipid syndrome (APS) (Global APS Score or GAPSS). This score derived from the combination of independent risk factors for thrombosis and pregnancy loss, taking into account the antiphospholipid antibodies (aPL) profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors, and the autoimmune antibodies profile. We demonstrate that risk profile in APS can be successfully assessed, suggesting that GAPSS can be a potential quantitative marker of APS-related clinical manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

    Science.gov (United States)

    Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

    2017-09-01

    Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

  16. The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer.

    Science.gov (United States)

    Reeh, Matthias; Metze, Johannes; Uzunoglu, Faik G; Nentwich, Michael; Ghadban, Tarik; Wellner, Ullrich; Bockhorn, Maximilian; Kluge, Stefan; Izbicki, Jakob R; Vashist, Yogesh K

    2016-02-01

    Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.

  17. The ERICE-score: the new native cardiovascular score for the low-risk and aged Mediterranean population of Spain.

    Science.gov (United States)

    Gabriel, Rafael; Brotons, Carlos; Tormo, M José; Segura, Antonio; Rigo, Fernando; Elosua, Roberto; Carbayo, Julio A; Gavrila, Diana; Moral, Irene; Tuomilehto, Jaakko; Muñiz, Javier

    2015-03-01

    In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11800 people (6387 women) representing 107915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic=0.789 in men and C=0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  18. The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk.

    Science.gov (United States)

    Warren Andersen, Shaneda; Trentham-Dietz, Amy; Gangnon, Ronald E; Hampton, John M; Figueroa, Jonine D; Skinner, Halcyon G; Engelman, Corinne D; Klein, Barbara E; Titus, Linda J; Newcomb, Polly A

    2013-07-01

    We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score's highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67-2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.

  19. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

    Science.gov (United States)

    Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

    2011-09-01

    Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

  20. Fish bioaccumulation and biomarkers in environmental risk assessment : a review

    NARCIS (Netherlands)

    van der Oost, Ron; Beyer, Jonny; Vermeulen, Nico P E

    In this review, a wide array of bioaccumulation markers and biomarkers, used to demonstrate exposure to and effects of environmental contaminants, has been discussed in relation to their feasibility in environmental risk assessment (ERA). Fish bioaccumulation markers may be applied in order to

  1. Quest for biomarkers of treatment-resistant depression: shifting the paradigm toward risk

    DEFF Research Database (Denmark)

    Smith, Donald F.

    2013-01-01

    have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk ofTRD. Particular ttention in future studies should be on shifting the experimental paradigm oward procedures that can determine the risk for developing treatment...

  2. Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

    Science.gov (United States)

    Miralbell, Júlia; López-Cancio, Elena; López-Oloriz, Jorge; Arenillas, Juan Francisco; Barrios, Maite; Soriano-Raya, Juan José; Galán, Amparo; Cáceres, Cynthia; Alzamora, Maite; Pera, Guillem; Toran, Pere; Dávalos, Antoni; Mataró, Maria

    2013-01-01

    Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA

  3. [Risk scores for community acquired pneumonia in elderly and geriatric patients].

    Science.gov (United States)

    Pflug, M A; Wesemann, T; Heppner, H J; Thiem, U

    2015-10-01

    Community-acquired pneumonia (CAP) is still an important and serious disease for elderly and geriatric patients. For epidemiological and clinical reasons it is important to collate the frequencies of the various degrees of severity of CAP and to obtain information on the spread and degree of the threat to the various risk groups by CAP. In outpatient treatment a simple to execute prognosis score can be used to objectify the assessment of the clinical status of a patient and to support therapeutic decision-making. For this purpose knowledge of the appropriate instruments should be available to potential users. Since the 1990s a variety of risk scores for stratification of CAP have been developed and evaluated. This article presents the content and value of the available risk scores whereby the advantages and disadvantages of the individual scores are critically compared. Special emphasis is placed on the importance of the risk scores for geriatric patients. At present the decision about outpatient or inpatient treatment is primarily based on the risk score CRB-65. Criteria for intensive care unit admissions are provided by the modified American Thoracic Society (ATS) set of criteria. Overall, risk scores are less reliable for elderly patients than for younger adults. For treatment decisions for the elderly, functional aspects should also be considered in addition to the aspects of risk scores discussed here. In particular, the decision about inpatient admission for elderly, geriatric CAP patients should be made on an individual basis taking the benefit-risk relationship into consideration.

  4. What does my patient's coronary artery calcium score mean? Combining information from the coronary artery calcium score with information from conventional risk factors to estimate coronary heart disease risk

    Directory of Open Access Journals (Sweden)

    Pletcher Mark J

    2004-08-01

    Full Text Available Abstract Background The coronary artery calcium (CAC score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information. Methods We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios. Results Among 9341 asymptomatic study participants (age 35–88 years, 40% female, we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham to 6–9%; if her score were over 100, however (a 17% chance, her risk estimate would be markedly higher (25–51% in 10 years. In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management. Conclusion Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy.

  5. Prostate cancer staging with extracapsular extension risk scoring using multiparametric MRI

    DEFF Research Database (Denmark)

    Boesen, Lars; Chabanova, Elizaveta; Løgager, Vibeke

    2015-01-01

    OBJECTIVES: To evaluate the diagnostic performance of preoperative multiparametric MRI with extracapsular extension (ECE) risk-scoring in the assessment of prostate cancer tumour stage (T-stage) and prediction of ECE at final pathology. MATERIALS AND METHODS: Eighty-seven patients with clinically....../87 (36 %) patients. ECE risk-scoring showed an AUC of 0.65-0.86 on ROC-curve for both readers, with sensitivity and specificity of 81 % and 78 % at best cutoff level (reader A), respectively. When tumour characteristics were influenced by personal opinion, the sensitivity and specificity for prediction...... technique for preoperative prostate cancer staging • ECE risk scoring predicts extracapsular tumour extension at final pathology • ECE risk scoring shows an AUC of 0.86 on the ROC-curve • ECE risk scoring shows a moderate inter-reader agreement (K = 0.45) • Multiparametric MRI provides essential knowledge...

  6. Weighing of risk factors for penetrating keratoplasty graft failure: application of Risk Score System

    Directory of Open Access Journals (Sweden)

    Abdo Karim Tourkmani

    2017-03-01

    Full Text Available AIM: To analyze the relationship between the score obtained in the Risk Score System (RSS proposed by Hicks et al with penetrating keratoplasty (PKP graft failure at 1y postoperatively and among each factor in the RSS with the risk of PKP graft failure using univariate and multivariate analysis. METHODS: The retrospective cohort study had 152 PKPs from 152 patients. Eighteen cases were excluded from our study due to primary failure (10 cases, incomplete medical notes (5 cases and follow-up less than 1y (3 cases. We included 134 PKPs from 134 patients stratified by preoperative risk score. Spearman coefficient was calculated for the relationship between the score obtained and risk of failure at 1y. Univariate and multivariate analysis were calculated for the impact of every single risk factor included in the RSS over graft failure at 1y. RESULTS: Spearman coefficient showed statistically significant correlation between the score in the RSS and graft failure (P0.05 between diagnosis and lens status with graft failure. The relationship between the other risk factors studied and graft failure was significant (P<0.05, although the results for previous grafts and graft failure was unreliable. None of our patients had previous blood transfusion, thus, it had no impact. CONCLUSION: After the application of multivariate analysis techniques, some risk factors do not show the expected impact over graft failure at 1y.

  7. The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

    Science.gov (United States)

    Lassere, Marissa N

    2008-06-01

    There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

  8. Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

    LENUS (Irish Health Repository)

    Zannad, Faiez

    2012-04-01

    The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A(2) , genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

  9. The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30 824 Europeans

    DEFF Research Database (Denmark)

    Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G

    2015-01-01

    .8 years of follow-up, 339 individuals died of CVD. In the SCORE target population (age 40-65; n = 30,824), fewer individuals were at baseline categorized as high risk (≥5% 10-year risk of fatal CVD) using SCORE-HDL compared with SCORE (10 vs. 17% in men, 1 vs. 3% in women). SCORE-HDL did not improve...... with SCORE, but deteriorated risk classification based on NRI. Future guidelines should consider lower decision thresholds and prioritize CVD morbidity and people above age 65....

  10. Recalibration of the ACC/AHA Risk Score in Two Population-Based German Cohorts.

    Science.gov (United States)

    de Las Heras Gala, Tonia; Geisel, Marie Henrike; Peters, Annette; Thorand, Barbara; Baumert, Jens; Lehmann, Nils; Jöckel, Karl-Heinz; Moebus, Susanne; Erbel, Raimund; Meisinger, Christine; Mahabadi, Amir Abbas; Koenig, Wolfgang

    2016-01-01

    The 2013 ACC/AHA guidelines introduced an algorithm for risk assessment of atherosclerotic cardiovascular disease (ASCVD) within 10 years. In Germany, risk assessment with the ESC SCORE is limited to cardiovascular mortality. Applicability of the novel ACC/AHA risk score to the German population has not yet been assessed. We therefore sought to recalibrate and evaluate the ACC/AHA risk score in two German cohorts and to compare it to the ESC SCORE. We studied 5,238 participants from the KORA surveys S3 (1994-1995) and S4 (1999-2001) and 4,208 subjects from the Heinz Nixdorf Recall (HNR) Study (2000-2003). There were 383 (7.3%) and 271 (6.4%) first non-fatal or fatal ASCVD events within 10 years in KORA and in HNR, respectively. Risk scores were evaluated in terms of calibration and discrimination performance. The original ACC/AHA risk score overestimated 10-year ASCVD rates by 37% in KORA and 66% in HNR. After recalibration, miscalibration diminished to 8% underestimation in KORA and 12% overestimation in HNR. Discrimination performance of the ACC/AHA risk score was not affected by the recalibration (KORA: C = 0.78, HNR: C = 0.74). The ESC SCORE overestimated by 5% in KORA and by 85% in HNR. The corresponding C-statistic was 0.82 in KORA and 0.76 in HNR. The recalibrated ACC/AHA risk score showed strongly improved calibration compared to the original ACC/AHA risk score. Predicting only cardiovascular mortality, discrimination performance of the commonly used ESC SCORE remained somewhat superior to the ACC/AHA risk score. Nevertheless, the recalibrated ACC/AHA risk score may provide a meaningful tool for estimating 10-year risk of fatal and non-fatal cardiovascular disease in Germany.

  11. From differences in means between cases and controls to risk stratification: a business plan for biomarker development.

    Science.gov (United States)

    Wentzensen, Nicolas; Wacholder, Sholom

    2013-02-01

    Researchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior. Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case–control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage.

  12. Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

    Science.gov (United States)

    Parks, Anna L; Fang, Margaret C

    2017-07-01

    Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands.

    Science.gov (United States)

    Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Umans, Victor A; Kietselaer, Bas; Schotborgh, Carl; Ronner, Eelko; Lenderink, Timo; Liem, Anho; Haitsma, David; van der Harst, Pim; Asselbergs, Folkert W; Maas, Arthur; Oude Ophuis, Anton J; Ilmer, Ben; Dijkgraaf, Rene; de Winter, Robbert-Jan; The, S Hong Kie; Wardeh, Alexander J; Hermans, Walter; Cramer, Etienne; van Schaik, Ron H; Hoefer, Imo E; Doevendans, Pieter A; Simoons, Maarten L; Boersma, Eric

    2016-12-23

    Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should

  14. Scores for post-myocardial infarction risk stratification in the community.

    Science.gov (United States)

    Singh, Mandeep; Reeder, Guy S; Jacobsen, Steven J; Weston, Susan; Killian, Jill; Roger, Véronique L

    2002-10-29

    Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification. MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3+/-4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity. In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.

  15. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.

    Science.gov (United States)

    Borges, Álvaro H; Silverberg, Michael J; Wentworth, Deborah; Grulich, Andrew E; Fätkenheuer, Gerd; Mitsuyasu, Ronald; Tambussi, Giuseppe; Sabin, Caroline A; Neaton, James D; Lundgren, Jens D

    2013-06-01

    To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection. A prospective cohort. HIV-infected patients on continuous antiretroviral therapy (ART) in the control arms of three randomized trials (N=5023) were included in an analysis of predictors of cancer (any type, infection-related or infection-unrelated). Hazard ratios for IL-6, CRP and D-dimer levels (log2-transformed) were calculated using Cox models stratified by trial and adjusted for demographics and CD4+ cell counts and adjusted also for all biomarkers simultaneously. To assess the possibility that biomarker levels were elevated at entry due to undiagnosed cancer, analyses were repeated excluding early cancer events (i.e. diagnosed during first 2 years of follow-up). During approximately 24,000 person-years of follow-up (PYFU), 172 patients developed cancer (70 infection-related; 102 infection-unrelated). The risk of developing cancer was associated with higher levels (per doubling) of IL-6 (hazard ratio 1.38, Passociated with cancer risk when all biomarkers were considered simultaneously. Results for infection-related and infection-unrelated cancers were similar to results for any cancer. Hazard ratios excluding 69 early cancer events were 1.31 (P=0.007), 1.14 (P=0.02) and 1.07 (P=0.49) for IL-6, CRP and D-dimer, respectively. Activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection. This association was stronger for IL-6 and persisted after excluding early cancer. Trials of interventions may be warranted to assess whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive individuals.

  16. Performance of upper gastrointestinal bleeding risk assessment scores in variceal bleeding

    DEFF Research Database (Denmark)

    Ngu, JH; Laursen, Stig Borbjerg; Chin, YK

    2017-01-01

    Performance of upper gastrointestinal bleeding risk assessment scores in variceal bleeding: a prospective international multicenter study.......Performance of upper gastrointestinal bleeding risk assessment scores in variceal bleeding: a prospective international multicenter study....

  17. A scoring system for ascertainment of incident stroke; the Risk Index Score (RISc).

    Science.gov (United States)

    Kass-Hout, T A; Moyé, L A; Smith, M A; Morgenstern, L B

    2006-01-01

    The main objective of this study was to develop and validate a computer-based statistical algorithm that could be translated into a simple scoring system in order to ascertain incident stroke cases using hospital admission medical records data. The Risk Index Score (RISc) algorithm was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christi (BASIC) project, 2000. The validity of RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment by physician and/or abstractor review of hospital admission records. RISc was developed on 1718 randomly selected patients (training set) and then statistically validated on an independent sample of 858 patients (validation set). A multivariable logistic model was used to develop RISc and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analyses. The higher the value of RISc, the higher the patient's risk of potential stroke. The study showed RISc was well calibrated and discriminated those who had potential stroke from those that did not on initial screening. In this study we developed and validated a rapid, easy, efficient, and accurate method to ascertain incident stroke cases from routine hospital admission records for epidemiologic investigations. Validation of this scoring system was achieved statistically; however, clinical validation in a community hospital setting is warranted.

  18. A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone.

    Science.gov (United States)

    Rakovitch, Eileen; Nofech-Mozes, Sharon; Hanna, Wedad; Baehner, Frederick L; Saskin, Refik; Butler, Steven M; Tuck, Alan; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A; Bonin, Michel; Chang, Martin C; Robertson, Susan J; Slodkowska, Elzbieta; Fong, Cindy; Anderson, Joseph M; Jamshidian, Farid; Miller, Dave P; Cherbavaz, Diana B; Shak, Steven; Paszat, Lawrence

    2015-07-01

    Validated biomarkers are needed to improve risk assessment and treatment decision-making for women with ductal carcinoma in situ (DCIS) of the breast. The Oncotype DX DCIS Score (DS) was shown to predict the risk of local recurrence (LR) in individuals with low-risk DCIS treated by breast-conserving surgery (BCS) alone. Our objective was to confirm these results in a larger population-based cohort of individuals. We used an established population-based cohort of individuals diagnosed with DCIS treated with BCS alone from 1994 to 2003 with validation of treatment and outcomes. Central pathology assessment excluded cases with invasive cancer, DCIS < 2 mm or positive margins. Cox model was used to determine the relationship between independent covariates, the DS (hazard ratio (HR)/50 Cp units (U)) and LR. Tumor blocks were collected for 828 patients. Final evaluable population includes 718 cases, of whom 571 had negative margins. Median follow-up was 9.6 years. 100 cases developed LR following BCS alone (DCIS, N = 44; invasive, N = 57). In the primary pre-specified analysis, the DS was associated with any LR (DCIS or invasive) in ER+ patients (HR 2.26; P < 0.001) and in all patients regardless of ER status (HR 2.15; P < 0.001). DCIS Score provided independent information on LR risk beyond clinical and pathologic variables including size, age, grade, necrosis, multifocality, and subtype (adjusted HR 1.68; P = 0.02). DCIS was associated with invasive LR (HR 1.78; P = 0.04) and DCIS LR (HR 2.43; P = 0.005). The DCIS Score independently predicts and quantifies individualized recurrence risk in a population of patients with pure DCIS treated by BCS alone.

  19. The metabolic syndrome, biomarkers, and the acculturation-health relationship among older Mexican Americans.

    Science.gov (United States)

    González, Hector M; Tarraf, Wassim; Haan, Mary N

    2011-10-01

    To examine the acculturation-health relationship using metabolic syndrome biomarkers. Cross-sectional sample data. 1,789 Mexican Americans (60 years and older) from northern California. Biomarkers (waist circumference, blood pressure, fasting plasma glucose, triglycerides, and high-density lipids) were used to construct the metabolic syndrome indicator using American Heart Association criteria. MAIN PREDICTOR: Acculturation Rating Scale for Mexican Americans-II scores. Higher acculturation scores were associated with a significantly lower risk for the metabolic syndrome for foreign-born, but not U.S.-born, Mexican Americans. Immigrant health advantages over U.S.-born Mexican Americans are not evident in older adulthood. Higher acculturation was associated with lowered metabolic syndrome risk among older foreign-born Mexican Americans. This suggests that the prevailing acculturative stress hypothesis may not apply to the health of older adults and that any negative relationship between acculturation and health found in younger adults may yield to different developmental health influences in later adulthood.

  20. Comparison of accuracy of diabetes risk score and components of the metabolic syndrome in assessing risk of incident type 2 diabetes in Inter99 cohort.

    Directory of Open Access Journals (Sweden)

    Tracy B Shafizadeh

    Full Text Available BACKGROUND: Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM; factors of metabolic syndrome (MetS and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS. DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. METHODOLOGY/PRINCIPAL FINDINGS: DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged 30-60 for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity was fixed to match MetS, DRS had a significantly lower false positive rate. Similarly, when the false positive rate was fixed to match MetS, DRS had a significantly higher specificity. In further analyses, subjects were classified by presence of 0-2, 3 or 4-5 risk factors with matching proportions of subjects distributed among three DRS groups. Comparison between the two risk stratification schemes, MetS risk factors and DRS, were evaluated using Net Reclassification Improvement (NRI. Comparing risk stratification by DRS to MetS factors in the total population, the NRI was 0.146 (p = 0.008 demonstrating DRS provides significantly improved stratification. Additionally, the relative risk of T2DM differed by 15 fold between the low and high DRS risk groups, but only 8-fold between the low and high risk MetS groups. CONCLUSIONS/SIGNIFICANCE: DRS provides a more accurate assessment of risk for diabetes than MetS. This improved performance may allow clinicians to focus preventive strategies on those most in need of urgent intervention.

  1. A risk score to predict type 2 diabetes mellitus in an elderly Spanish Mediterranean population at high cardiovascular risk.

    Directory of Open Access Journals (Sweden)

    Marta Guasch-Ferré

    Full Text Available INTRODUCTION: To develop and test a diabetes risk score to predict incident diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk. MATERIALS AND METHODS: A diabetes risk score was derived from a subset of 1381 nondiabetic individuals from three centres of the PREDIMED study (derivation sample. Multivariate Cox regression model ß-coefficients were used to weigh each risk factor. PREDIMED-personal Score included body-mass-index, smoking status, family history of type 2 diabetes, alcohol consumption and hypertension as categorical variables; PREDIMED-clinical Score included also high blood glucose. We tested the predictive capability of these scores in the DE-PLAN-CAT cohort (validation sample. The discrimination of Finnish Diabetes Risk Score (FINDRISC, German Diabetes Risk Score (GDRS and our scores was assessed with the area under curve (AUC. RESULTS: The PREDIMED-clinical Score varied from 0 to 14 points. In the subset of the PREDIMED study, 155 individuals developed diabetes during the 4.75-years follow-up. The PREDIMED-clinical score at a cutoff of ≥6 had sensitivity of 72.2%, and specificity of 72.5%, whereas AUC was 0.78. The AUC of the PREDIMED-clinical Score was 0.66 in the validation sample (sensitivity = 85.4%; specificity = 26.6%, and was significantly higher than the FINDRISC and the GDRS in both the derivation and validation samples. DISCUSSION: We identified classical risk factors for diabetes and developed the PREDIMED-clinical Score to determine those individuals at high risk of developing diabetes in elderly individuals at high cardiovascular risk. The predictive capability of the PREDIMED-clinical Score was significantly higher than the FINDRISC and GDRS, and also used fewer items in the questionnaire.

  2. Effect of Exercise Training on Cardiac Biomarkers in At-Risk Populations: A Systematic Review.

    Science.gov (United States)

    Glenney, Susan Sullivan; Brockemer, Derrick Paul; Ng, Andy C; Smolewski, Michael A; Smolgovskiy, Vladimir M; Lepley, Adam S

    2017-12-01

    Studies have demonstrated beneficial effects of exercise on cardiovascular disease biomarkers for healthy individuals; however, a comprehensive review regarding the effect of exercise on cardiovascular disease biomarkers in at-risk populations is lacking. A literature search was performed to identify studies meeting the following criteria: randomized controlled study, participants with pathology/activity limitations, biomarker outcome (total cholesterol, high-density lipoprotein, low-density lipoprotein, C-reactive protein, insulin, triglycerides, or glucose), and exercise intervention. Means and standard deviations from each biomarker were used to calculate standardized Cohen's d effect sizes with 95% confidence intervals. In total, 37 articles were included. The majority (44/57; 77%) of data points demonstrated moderate to strong effects for the reduction in total cholesterol, triglycerides, and low-density lipoprotein, and elevation in high-density lipoprotein following exercise. The majority of data points demonstrated strong effects for reductions in blood glucose (24/30; 80%) and insulin (23/24; 96%) levels following exercise intervention. Evidence is heterogeneous regarding the influence of exercise on cardiovascular disease biomarkers in at-risk patients, which does not allow a definitive conclusion. Favorable effects include reductions in triglycerides, total cholesterol, low-density lipoprotein, glucose, and insulin, and elevation in high-density lipoprotein following exercise intervention. The strongest evidence indicates that exercise is favorable for the reduction in glucose and cholesterol levels among obese patients, and reduction of insulin regardless of population.

  3. In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

    Directory of Open Access Journals (Sweden)

    Andreia Matos

    2014-01-01

    Full Text Available Preeclampsia (PE may affect the risk for future cardiovascular disease. Haptoglobin (Hp, an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35±5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP, myeloperoxidase (MPO, and nitric oxide metabolites (total and nitrites, and others associated with liver function (AST and ALT and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B. Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT, whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women.

  4. Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort.

    Science.gov (United States)

    Cho, Hyunje G; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Assimes, Themistocles; Han, Jiali; Stefanick, Marcia; Tang, Jean Y; Sarin, Kavita Y

    2018-07-01

    Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk. We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women. Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset. Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma. Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort. Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Hypoadiponectinemia in overweight children contributes to a negative metabolic risk profile 6 years later

    DEFF Research Database (Denmark)

    Kynde, Iben; Heitmann, Berit L; Bygbjerg, Ib C

    2009-01-01

    follow-up data 6 years later (n = 169). Cardiometabolic risk profile was calculated using a continuous composite score derived from summing of 6 factors standardized to the sample means (Z scores): body mass index, homeostasis model assessment of insulin resistance, total serum cholesterol to serum high...... adiponectin at baseline was inversely associated with metabolic risk score 6 years later (P = .04). In childhood, both hypoadiponectinemia and hyperleptinemia accompany a negative metabolic risk profile. In addition, circulating plasma adiponectin may be a useful biomarker to identify overweight children......Prognostic biomarkers are needed to identify children at increased cardiometabolic risk. The objective was to study whether markers of metabolism and inflammation, for example, circulating plasma adiponectin, leptin, interleukin-8, and hepatocyte growth factor, are associated with cardiometabolic...

  6. Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones.

    Science.gov (United States)

    Shieh, Yiwey; Hu, Donglei; Ma, Lin; Huntsman, Scott; Gard, Charlotte C; Leung, Jessica W T; Tice, Jeffrey A; Ziv, Elad; Kerlikowske, Karla; Cummings, Steven R

    2017-11-01

    Models that predict the risk of estrogen receptor (ER)-positive breast cancers may improve our ability to target chemoprevention. We investigated the contributions of sex hormones to the discrimination of the Breast Cancer Surveillance Consortium (BCSC) risk model and a polygenic risk score comprised of 83 single nucleotide polymorphisms. We conducted a nested case-control study of 110 women with ER-positive breast cancers and 214 matched controls within a mammography screening cohort. Participants were postmenopausal and not on hormonal therapy. The associations of estradiol, estrone, testosterone, and sex hormone binding globulin with ER-positive breast cancer were evaluated using conditional logistic regression. We assessed the individual and combined discrimination of estradiol, the BCSC risk score, and polygenic risk score using the area under the receiver operating characteristic curve (AUROC). Of the sex hormones assessed, estradiol (OR 3.64, 95% CI 1.64-8.06 for top vs bottom quartile), and to a lesser degree estrone, was most strongly associated with ER-positive breast cancer in unadjusted analysis. The BCSC risk score (OR 1.32, 95% CI 1.00-1.75 per 1% increase) and polygenic risk score (OR 1.58, 95% CI 1.06-2.36 per standard deviation) were also associated with ER-positive cancers. A model containing the BCSC risk score, polygenic risk score, and estradiol levels showed good discrimination for ER-positive cancers (AUROC 0.72, 95% CI 0.65-0.79), representing a significant improvement over the BCSC risk score (AUROC 0.58, 95% CI 0.50-0.65). Adding estradiol and a polygenic risk score to a clinical risk model improves discrimination for postmenopausal ER-positive breast cancers.

  7. Adding an alcohol-related risk score to an existing categorical risk classification for older adults: sensitivity to group differences.

    Science.gov (United States)

    Wilson, Sandra R; Fink, Arlene; Verghese, Shinu; Beck, John C; Nguyen, Khue; Lavori, Philip

    2007-03-01

    To evaluate a new alcohol-related risk score for research use. Using data from a previously reported trial of a screening and education system for older adults (Computerized Alcohol-Related Problems Survey), secondary analyses were conducted comparing the ability of two different measures of risk to detect post-intervention group differences: the original categorical outcome measure and a new, finely grained quantitative risk score based on the same research-based risk factors. Three primary care group practices in southern California. Six hundred sixty-five patients aged 65 and older. A previously calculated, three-level categorical classification of alcohol-related risk and a newly developed quantitative risk score. Mean post-intervention risk scores differed between the three experimental conditions: usual care, patient report, and combined report (Ptrinary risk classification. The additional clinical value of the risk score relative to the categorical measure needs to be determined.

  8. 'Mechanical restraint-confounders, risk, alliance score'

    DEFF Research Database (Denmark)

    Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise

    2017-01-01

    . AIM: To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical...... restraint. METHODS: The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. RESULTS: The three sub-scales (Confounders......, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. CONCLUSIONS: MR-CRAS contains 18 clinically valid items...

  9. BRAIN NATRIURETIC PEPTIDE (BNP: BIOMARKER FOR RISK STRATIFICATION AND FUNCTIONAL RECOVERY PREDICTION IN ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    STANESCU Ioana

    2015-02-01

    Full Text Available Functional outcome after cardiovascular and cerebrovascular events is traditionally predicted using demographic and clinical variables like age, gender, blood pressure, cholesterol levels, diabetes status, smoking habits or pre-existing morbidity. Identification of new variables will improve the risk stratification of specific categories of patients. Numerous blood-based biomarkers associated with increased cardiovascular risk have been identified; some of them even predict cardiovascular events. Investigators have tried to produce prediction models by incorporating traditional risk factors and biomarkers. (1. Widely-available, rapidly processed and less expensive biomarkers could be used in the future to guide management of complex cerebrovascular patients in order to maximize their recovery (2 Recently, studies have demonstrated that biomarkers can predict not only the risk for a specific clinical event, but also the risk of death of vascular cause and the functional outcome after cardiovascular or cerebrovascular events. Early prediction of fatal outcome after stroke may improve therapeutic strategies (such as the use of more aggressive treatments or inclusion of patients in clinical trials and guide decision-making processes in order to maximize patient’s chances for survival and recovery. (3 Long term functional outcome after stroke is one of the most difficult variables to predict. Elevated serum levels of brain natriuretic peptide (BNP are powerful predictor of outcomes in patients with cardiovascular disease (heart failure, atrial fibrillation. Potential role of BNP in predicting atrial fibrillation occurrence, cardio-embolic stroke and post-stroke mortality have been proved in many studies. However, data concerning the potential role of BNP in predicting short term and long term functional outcomes after stroke remain controversial.

  10. External validation of scoring systems in risk stratification of upper gastrointestinal bleeding.

    Science.gov (United States)

    Anchu, Anna Cherian; Mohsina, Subair; Sureshkumar, Sathasivam; Mahalakshmy, T; Kate, Vikram

    2017-03-01

    The aim of this study was to externally validate the four commonly used scoring systems in the risk stratification of patients with upper gastrointestinal bleed (UGIB). Patients of UGIB who underwent endoscopy within 24 h of presentation were stratified prospectively using the pre-endoscopy Rockall score (PRS) >0, complete Rockall score (CRS) >2, Glasgow Blatchford bleeding scores (GBS) >3, and modified GBS (m-GBS) >3 scores. Patients were followed up to 30 days. Prognostic accuracy of the scores was done by comparing areas under curve (AUC) in terms of overall risk stratification, re-bleeding, mortality, need for intervention, and length of hospitalization. One hundred and seventy-five patients were studied. All four scores performed better in the overall risk stratification on AUC [PRS = 0.566 (CI: 0.481-0.651; p-0.043)/CRS = 0.712 (CI: 0.634-0.790); p0.001); m-GBS = 0.802 (CI: 0.734-0.871; pbleed [AUC-0.679 (CI: 0.579-0.780; p = 0.003)]. All the scoring systems except PRS were found to be significantly better in detecting 30-day mortality with a high AUC (CRS = 0.798; p-0.042)/GBS = 0.833; p-0.023); m-GBS = 0.816; p-0.031). All four scores demonstrated significant accuracy in the risk stratification of non-variceal patients; however, only GBS and m-GBS were significant in variceal etiology. Higher cutoff scores achieved better sensitivity/specificity [RS > 0 (50/60.8), CRS > 1 (87.5/50.6), GBS > 7 (88.5/63.3), m-GBS > 7(82.3/72.6)] in the risk stratification. GBS and m-GBS appear to be more valid in risk stratification of UGIB patients in this region. Higher cutoff values achieved better predictive accuracy.

  11. Recurrent Stroke: The Value of the CHA2DS2VASc Score and the Essen Stroke Risk Score in a Nationwide Stroke Cohort.

    Science.gov (United States)

    Andersen, Søren Due; Gorst-Rasmussen, Anders; Lip, Gregory Y H; Bach, Flemming W; Larsen, Torben Bjerregaard

    2015-09-01

    The CHA2DS2VASc score and the Essen Stroke Risk Score are respectively used for risk stratification in patients with atrial fibrillation and in patients with cerebrovascular incidents. We aimed to test the ability of the 2 scores to predict stroke recurrence, death, and cardiovascular events (stroke, transient ischemic attack, myocardial infarction, or arterial thromboembolism) in a nationwide Danish cohort study, among patients with incident ischemic stroke and no atrial fibrillation. We conducted a registry-based study in patients with incident ischemic stroke and no atrial fibrillation. Patients were stratified according to the CHA2DS2VASc score and the Essen Stroke Risk Score and were followed up until stroke recurrence or death. We estimated stratified incidence rates and hazard ratios and calculated the cumulative risks. 42 182 patients with incident ischemic stroke with median age 70.1 years were included. The overall 1-year incidence rates of recurrent stroke, death, and cardiovascular events were 3.6%, 10.5%, and 6.7%, respectively. The incidence rates, the hazard ratios, and the cumulative risk of all outcomes increased with increasing risk scores. C-statistics for both risk scores were around 0.55 for 1-year stroke recurrence and cardiovascular events and correspondingly for death around 0.67 for both scores. In this cohort of non-atrial fibrillation patients with incident ischemic stroke, increasing CHA2DS2VASc score and Essen Stroke Risk Score was associated with increasing risk of recurrent stroke, death, and cardiovascular events. Their discriminatory performance was modest and further refinements are required for clinical application. © 2015 American Heart Association, Inc.

  12. A score for measuring health risk perception in environmental surveys.

    Science.gov (United States)

    Marcon, Alessandro; Nguyen, Giang; Rava, Marta; Braggion, Marco; Grassi, Mario; Zanolin, Maria Elisabetta

    2015-09-15

    In environmental surveys, risk perception may be a source of bias when information on health outcomes is reported using questionnaires. Using the data from a survey carried out in the largest chipboard industrial district in Italy (Viadana, Mantova), we devised a score of health risk perception and described its determinants in an adult population. In 2006, 3697 parents of children were administered a questionnaire that included ratings on 7 environmental issues. Items dimensionality was studied by factor analysis. After testing equidistance across response options by homogeneity analysis, a risk perception score was devised by summing up item ratings. Factor analysis identified one latent factor, which we interpreted as health risk perception, that explained 65.4% of the variance of five items retained after scaling. The scale (range 0-10, mean ± SD 9.3 ± 1.9) had a good internal consistency (Cronbach's alpha 0.87). Most subjects (80.6%) expressed maximum risk perception (score = 10). Italian mothers showed significantly higher risk perception than foreign fathers. Risk perception was higher for parents of young children, and for older parents with a higher education, than for their counterparts. Actual distance to major roads was not associated with the score, while self-reported intense traffic and frequent air refreshing at home predicted higher risk perception. When investigating health effects of environmental hazards using questionnaires, care should be taken to reduce the possibility of awareness bias at the stage of study planning and data analysis. Including appropriate items in study questionnaires can be useful to derive a measure of health risk perception, which can help to identify confounding of association estimates by risk perception. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Polygenic risk scores for smoking: predictors for alcohol and cannabis use?

    NARCIS (Netherlands)

    Vink, J.M.; de Geus, E.J.C.; Willemsen, G.; Neale, M.C.; Furberg, H.; Boomsma, D.I.

    2014-01-01

    Background and Aims: A strong correlation exists between smoking and the use of alcohol and cannabis. This paper uses polygenic risk scores to explore the possibility of overlapping genetic factors. Those scores reflect a combined effect of selected risk alleles for smoking. Methods: Summary-level

  14. Validation of an imaging based cardiovascular risk score in a Scottish population.

    Science.gov (United States)

    Kockelkoren, Remko; Jairam, Pushpa M; Murchison, John T; Debray, Thomas P A; Mirsadraee, Saeed; van der Graaf, Yolanda; Jong, Pim A de; van Beek, Edwin J R

    2018-01-01

    A radiological risk score that determines 5-year cardiovascular disease (CVD) risk using routine care CT and patient information readily available to radiologists was previously developed. External validation in a Scottish population was performed to assess the applicability and validity of the risk score in other populations. 2915 subjects aged ≥40 years who underwent routine clinical chest CT scanning for non-cardiovascular diagnostic indications were followed up until first diagnosis of, or death from, CVD. Using a case-cohort approach, all cases and a random sample of 20% of the participant's CT examinations were visually graded for cardiovascular calcifications and cardiac diameter was measured. The radiological risk score was determined using imaging findings, age, gender, and CT indication. Performance on 5-year CVD risk prediction was assessed. 384 events occurred in 2124 subjects during a mean follow-up of 4.25 years (0-6.4 years). The risk score demonstrated reasonable performance in the studied population. Calibration showed good agreement between actual and 5-year predicted risk of CVD. The c-statistic was 0.71 (95%CI:0.67-0.75). The radiological CVD risk score performed adequately in the Scottish population offering a potential novel strategy for identifying patients at high risk for developing cardiovascular disease using routine care CT data. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Validation of the Rockall risk scoring system in upper gastrointestinal bleeding

    NARCIS (Netherlands)

    Vreeburg, E. M.; Terwee, C. B.; Snel, P.; Rauws, E. A.; Bartelsman, J. F.; Meulen, J. H.; Tytgat, G. N.

    1999-01-01

    Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study. To assess internal and

  16. Skin autofluorescence as proxy of tissue AGE accumulation is dissociated from SCORE cardiovascular risk score, and remains so after 3 years.

    Science.gov (United States)

    Tiessen, Ans H; Jager, Willemein; ter Bogt, Nancy C W; Beltman, Frank W; van der Meer, Klaas; Broer, Jan; Smit, Andries J

    2014-01-01

    Skin autofluorescence (SAF), as a proxy of AGE accumulation, is predictive of cardiovascular (CVD) complications in i.a. type 2 diabetes mellitus and renal failure, independently of most conventional CVD risk factors. The present exploratory substudy of the Groningen Overweight and Lifestyle (GOAL)-project addresses whether SAF is related to Systematic COronary Risk Evaluation (SCORE) risk estimation (% 10-year CVD-mortality risk) in overweight/obese persons in primary care, without diabetes/renal disease, and if after 3-year treatment of risk factors (change in, Δ) SAF is related to ΔSCORE. In a sample of 65 participants from the GOAL study, with a body mass index (BMI) >25-40 kg/m2, hypertension and/or dyslipidemia, but without diabetes/renal disease, SAF and CVD risk factors were measured at baseline, and after 3 years of lifestyle and pharmaceutical treatment. At baseline, the mean SCORE risk estimation was 3.1±2.6%, mean SAF 2.04±0.5AU. In multivariate analysis SAF was strongly related to age, but not to other risk factors/SCORE. After 3 years ΔSAF was 0.34±0.45 AU (phistory of CVD compared to 54 persons without CVD (p=0.002). Baseline and 3-year-Δ SAF are not related to (Δ)SCORE, or its components, except age, in the studied population. ΔSAF was negatively related to Δweight. As 3-year SAF was higher in persons with CVD, these results support a larger study on SAF to assess its contribution to conventional risk factors/SCORE in predicting CVD in overweight persons with low-intermediate cardiovascular risk.

  17. Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

    Science.gov (United States)

    Baena-Díez, José Miguel; Subirana, Isaac; Ramos, Rafael; Gómez de la Cámara, Agustín; Elosua, Roberto; Vila, Joan; Marín-Ibáñez, Alejandro; Guembe, María Jesús; Rigo, Fernando; Tormo-Díaz, María José; Moreno-Iribas, Conchi; Cabré, Joan Josep; Segura, Antonio; Lapetra, José; Quesada, Miquel; Medrano, María José; González-Diego, Paulino; Frontera, Guillem; Gavrila, Diana; Ardanaz, Eva; Basora, Josep; García, José María; García-Lareo, Manel; Gutiérrez-Fuentes, José Antonio; Mayoral, Eduardo; Sala, Joan; Dégano, Irene R; Francès, Albert; Castell, Conxa; Grau, María; Marrugat, Jaume

    2018-04-01

    To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  18. A risk prediction score for invasive mold disease in patients with hematological malignancies.

    Directory of Open Access Journals (Sweden)

    Marta Stanzani

    Full Text Available BACKGROUND: A risk score for invasive mold disease (IMD in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. METHODS: We retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008 to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012. RESULTS: Of the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of 5% of IMD, with a negative predictive value (NPV of 0.99, (95% CI 0.98-0.99. During 2009-2012, patients with a calculated risk score at admission of 6 (0.9% vs. 10.6%, P <0.001. CONCLUSION: An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate "screening-out" of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis.

  19. Using 3–6 differences in essential fatty acids rather than 3/6 ratios gives useful food balance scores

    Directory of Open Access Journals (Sweden)

    Lands Bill

    2012-05-01

    Full Text Available Abstract Background The vitamin-like omega-3 and omega-6 essential fatty acids are converted in the body to a large family of hormones which act at selective receptors that occur on nearly every cell and tissue. A relative omega-3 deficit allows overabundant actions of omega-6 hormones to develop into health disorders. People need simple, explicit information on the balance of essential fatty acids in their foods to avoid accumulating unintended imbalances in their tissue omega-3 and omega-6 fatty acids. Results We developed an Omega 3–6 Balance Food Score that summarizes in a single value the balance among eleven omega-3 and omega-6 essential fatty acids in a food. The value allows a quantitative estimate of the impact of each food item on the proportions of omega-3 and omega-6 that will accumulate in the 20- and 22-carbon highly unsaturated fatty acids of blood, which is an important health risk assessment biomarker. Conclusions The impact of an individual food item upon a useful health risk assessment biomarker is easily evident in a simple, explicit value for the balance among eleven essential fatty acids nutrients. Foods with more positive Omega 3–6 Balance Food Scores will increase the percent of omega-3 in the biomarker, whereas those with more negative Scores will increase the percent of omega-6 in the biomarker.

  20. Biomarkers of threat and reward sensitivity demonstrate unique associations with risk for psychopathology.

    Science.gov (United States)

    Nelson, Brady D; McGowan, Sarah Kate; Sarapas, Casey; Robison-Andrew, E Jenna; Altman, Sarah E; Campbell, Miranda L; Gorka, Stephanie M; Katz, Andrea C; Shankman, Stewart A

    2013-08-01

    Two emotional/motivational constructs that have been posited to underlie anxiety and depressive disorders are heightened sensitivity to threat and reduced sensitivity to reward, respectively. It is unclear, though, whether these constructs are only epiphenomena or also connote risk for these disorders (and relatedly, whether they connote risk for separate disorders). Using family history of psychopathology as an indicator of risk, the present study examined whether biomarkers of sensitivity to threat (startle potentiation) and reward (frontal EEG asymmetry) were associated with similar or different familial liabilities. In addition, the present study examined whether these biomarkers were associated with risk independent of proband DSM-IV diagnosis. One-hundred and seventy-three individuals diagnosed with panic disorder (PD), early onset major depressive disorder (MDD), both (comorbids), or controls completed two laboratory paradigms assessing sensitivity to predictable/unpredictable threat (measured via startle response) and reward (measured via frontal EEG asymmetry during a gambling task). Results indicated that across all participants: (a) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was associated with family history of MDD (but not PD). Additionally, both measures continued to be associated with family history of psychopathology after controlling for proband DSM-IV diagnosis. Results suggest that the proposed biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant validity and may add to the predictive validity of the DSM-IV defined constructs of PD and MDD, respectively. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  1. Risk-adjusted scoring systems in colorectal surgery.

    Science.gov (United States)

    Leung, Edmund; McArdle, Kirsten; Wong, Ling S

    2011-01-01

    Consequent to recent advances in surgical techniques and management, survival rate has increased substantially over the last 25 years, particularly in colorectal cancer patients. However, post-operative morbidity and mortality from colorectal cancer vary widely across the country. Therefore, standardised outcome measures are emphasised not only for professional accountability, but also for comparison between treatment units and regions. In a heterogeneous population, the use of crude mortality as an outcome measure for patients undergoing surgery is simply misleading. Meaningful comparisons, however, require accurate risk stratification of patients being analysed before conclusions can be reached regarding the outcomes recorded. Sub-specialised colorectal surgical units usually dedicated to more complex and high-risk operations. The need for accurate risk prediction is necessary in these units as both mortality and morbidity often are tools to justify the practice of high-risk surgery. The Acute Physiology And Chronic Health Evaluation (APACHE) is a system for classifying patients in the intensive care unit. However, APACHE score was considered too complex for general surgical use. The American Society of Anaesthesiologists (ASA) grade has been considered useful as an adjunct to informed consent and for monitoring surgical performance through time. ASA grade is simple but too subjective. The Physiological & Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and its variant Portsmouth POSSUM (P-POSSUM) were devised to predict outcomes in surgical patients in general, taking into account of the variables in the case-mix. POSSUM has two parts, which include assessment of physiological parameters and operative scores. There are 12 physiological parameters and 6 operative measures. The physiological parameters are taken at the time of surgery. Each physiological parameter or operative variable is sub-divided into three or four levels with

  2. Improvement of Risk Prediction After Transcatheter Aortic Valve Replacement by Combining Frailty With Conventional Risk Scores.

    Science.gov (United States)

    Schoenenberger, Andreas W; Moser, André; Bertschi, Dominic; Wenaweser, Peter; Windecker, Stephan; Carrel, Thierry; Stuck, Andreas E; Stortecky, Stefan

    2018-02-26

    This study sought to evaluate whether frailty improves mortality prediction in combination with the conventional scores. European System for Cardiac Operative Risk Evaluation (EuroSCORE) or Society of Thoracic Surgeons (STS) score have not been evaluated in combined models with frailty for mortality prediction after transcatheter aortic valve replacement (TAVR). This prospective cohort comprised 330 consecutive TAVR patients ≥70 years of age. Conventional scores and a frailty index (based on assessment of cognition, mobility, nutrition, and activities of daily living) were evaluated to predict 1-year all-cause mortality using Cox proportional hazards regression (providing hazard ratios [HRs] with confidence intervals [CIs]) and measures of test performance (providing likelihood ratio [LR] chi-square test statistic and C-statistic [CS]). All risk scores were predictive of the outcome (EuroSCORE, HR: 1.90 [95% CI: 1.45 to 2.48], LR chi-square test statistic 19.29, C-statistic 0.67; STS score, HR: 1.51 [95% CI: 1.21 to 1.88], LR chi-square test statistic 11.05, C-statistic 0.64; frailty index, HR: 3.29 [95% CI: 1.98 to 5.47], LR chi-square test statistic 22.28, C-statistic 0.66). A combination of the frailty index with either EuroSCORE (LR chi-square test statistic 38.27, C-statistic 0.72) or STS score (LR chi-square test statistic 28.71, C-statistic 0.68) improved mortality prediction. The frailty index accounted for 58.2% and 77.6% of the predictive information in the combined model with EuroSCORE and STS score, respectively. Net reclassification improvement and integrated discrimination improvement confirmed that the added frailty index improved risk prediction. This is the first study showing that the assessment of frailty significantly enhances prediction of 1-year mortality after TAVR in combined risk models with conventional risk scores and relevantly contributes to this improvement. Copyright © 2018 American College of Cardiology Foundation

  3. Pneumonia Risk Stratification Scores for Children in Low-Resource Settings: A Systematic Literature Review.

    Science.gov (United States)

    Deardorff, Katrina V; McCollum, Eric D; Ginsburg, Amy Sarah

    2017-12-22

    Pneumonia is the leading infectious cause of death among children less than five years of age. Predictive tools, commonly referred to as risk scores, can be employed to identify high-risk children early for targeted management to prevent adverse outcomes. This systematic review was conducted to identify pediatric pneumonia risk scores developed, validated, and implemented in low-resource settings. We searched CAB Direct, Cochrane Reviews, Embase, PubMed, Scopus, and Web of Science for studies that developed formal risk scores to predict treatment failure or mortality among children less than five years of age diagnosed with a respiratory infection or pneumonia in low-resource settings. Data abstracted from articles included location and study design, sample size, age, diagnosis, score features and model discrimination. Three pediatric pneumonia risk scores predicted mortality specifically, and two treatment failure. Scores developed using World Health Organization recommended variables for pneumonia assessment demonstrated better predictive fit than scores developed using alternative features. Scores developed using routinely collected healthcare data performed similarly well as those developed using clinical trial data. No score has been implemented in low-resource settings. While pediatric pneumonia-specific risk scores have been developed and validated, it is yet unclear if implementation is feasible, what impact, if any, implemented scores may have on child outcomes, or how broadly scores may be generalized. To increase the feasibility of implementation, future research should focus on developing scores based on routinely collected data.

  4. Candidate biomarker discovery and selection for ‘Granny Smith' superficial scald risk management and diagnosis, poster board

    Science.gov (United States)

    Discovery of candidate biomarkers for superficial scald, a peel disorder that develops during storage of susceptible apple cultivars, is part of a larger project aimed at developing biomarker-based risk-management and diagnostic tools for multiple apple postharvest disorders (http://www.tfrec.wsu.ed...

  5. Association of mallampatti score as a risk factor for obstructive sleep apnea

    International Nuclear Information System (INIS)

    Naqvi, S.U.; Shahab, A.; Zia, S.; Adil, S.O.; Tariq, S.

    2017-01-01

    Objectives: To determine the association of Mallampatti Score as a risk factor for Obstructive Sleep Apnea (OSA). Methodology: This is a prospective questionnaire based survey included 103 individuals Results: Mean BMI of patients was 23.83+-6.03 kg/m2. There were 28 (27.2%) overweight and 22 (21.4%) obese patients. High risk on Berlin questionnaire was found in 12 (11.7%) patients. Both Berlin Questionnaire and Epworth questioner showed a negative association with Mallampati; the low risk group of these variables in our study with a p-value of 0.034 and 0.016 respectively i.e they are good for exclusion of OSA if found negative. Comparison of general characteristics with Mallampatti score and snoring showed significant association among patients with >25 years of age (p=0.02), low risk of Berlin score (p=0.034) and normal Epworth Sleep Score (p=0.016). Fifteen (14.5%) of overweight and obese individuals had higher Mallampatti score III and lV but the P-values were not significant (0.283 and 0.386). Conclusion: There is strong association between high Mallampatti score and O.S.A. Therefore we suggest that high mallampatti can be taken as a risk factor / screening tool limitation for O.S.A. (author)

  6. [Cardiovascular risk by Framingham and SCORE in patients 40-65 years old].

    Science.gov (United States)

    González, Carmen; Rodilla, Enrique; Costa, José A; Justicia, Jorge; Pascual, José M

    2006-04-15

    The aim of this study was to compare the clinical and treatment implications of 2 cardiovascular risk stratification systems in a population of patients 40-65 years old. 929 non diabetic patients (40-65 years old) (51% female) with no evidence of previous cardiovascular disease were included in the study. The risk of cardiovascular death was assessed with the charts of the Systematic Coronary Risk Evaluation (SCORE), and coronary risk by the Framingham function (National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults -NCEP-ATP-III-). Patients were considered of high risk if risk of cardiovascular death was >or= 5% and coronary risk was > 20%, respectively. 4.1% of patients were considered as high risk by SCORE and 2.5% by Framingham. Only 0.2% of females were classified as high risk with either system. 8.2% and 4.8% of male population were considered as high risk by SCORE and Framingham, respectively. There was a low level of concordance between both systems. Patients classified as high risk by SCORE but not by Framingham were older, smoke less and had a better lipid profile. According to European Guidelines 28% of male and 23% of female were candidates to hypolipemic treatment, that proportion was higher, 43% of males and 28% of females, by NCEP-ATP-III guidelines. In Spanish patients 40-65 years old, SCORE charts almost duplicate the number of high risk individuals compared to Framingham. although the number of patients candidates to hypolipemic treatment is lower with the European than ATP-III guidelines. Differences were more evident in male.

  7. Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes

    NARCIS (Netherlands)

    Beulens, J.W.J.; Schouw, van der Y.T.; Moons, K.G.M.; Boshuizen, H.C.; A, van der D.L.; Groenwold, R.H.H.

    2013-01-01

    Purpose Moderate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol–biomarker

  8. Classification for longevity potential: the use of novel biomarkers

    Directory of Open Access Journals (Sweden)

    Marian Beekman

    2016-10-01

    Full Text Available Background: In older people chronological age may not be the best predictor of residual lifespan and mortality, because with age the heterogeneity in health is increasing. Biomarkers for biological age and residual lifespan are being developed to predict disease and mortality better at an individual level than chronological age. In the current paper we aim to classify a group of older people into those with longevity potential or controls.Methods: In the Leiden Longevity Study participated 1671 offspring of nonagenarian siblings, as the group with longevity potential, and 744 similarly aged controls. Using known risk factors for cardiovascular disease, previously reported markers for human longevity and other physiological measures as predictors, classification models for longevity potential were constructed with multiple logistic regression of the offspring-control status.Results: The Framingham Risk Score is predictive for longevity potential (AUC = 64.7. Physiological parameters involved in immune responses and glucose, lipid and energy metabolism further improve the prediction performance for longevity potential (AUCmale = 71.4, AUCfemale = 68.7.Conclusion: Using the Framingham Risk Score, the classification of older people in groups with longevity potential and controls is moderate, but can be improved to a reasonably good classification in combination with markers of immune response, glucose, lipid and energy metabolism. We show that individual classification of older people for longevity potential may be feasible using biomarkers from a wide variety of different biological processes.

  9. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  10. The fracture risk assessment tool (FRAX® score in subclinical hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Polovina Snežana

    2015-01-01

    Full Text Available Background/Aim. The Fracture Risk Assessment Tool (FRAX® score is the 10-year estimated risk calculation tool for bone fracture that includes clinical data and hip bone mineral density measured by dual-energy x-ray absorptiometry (DXA. The aim of this cross-sectional study was to elucidate the ability of the FRAX® score in discriminating between bone fracture positive and negative pre- and post-menopausal women with subclinical hyperthyroidism. Methods. The bone mineral density (by DXA, thyroid stimulating hormone (TSH level, free thyroxine (fT4 level, thyroid peroxidase antibodies (TPOAb titre, osteocalcin and beta-cross-laps were measured in 27 pre- and post-menopausal women with newly discovered subclinical hyperthyroidism [age 58.85 ± 7.83 years, body mass index (BMI 27.89 ± 3.46 kg/m2, menopause onset in 46.88 ± 10.21 years] and 51 matched euthyroid controls (age 59.69 ± 5.72 years, BMI 27.68 ± 4.66 kg/m2, menopause onset in 48.53 ± 4.58 years. The etiology of subclinical hyperthyroisims was autoimmune thyroid disease or toxic goiter. FRAX® score calculation was performed in both groups. Results. In the group with subclinical hyperthyroidism the main FRAX® score was significantly higher than in the controls (6.50 ± 1.58 vs 4.35 ± 1.56 respectively; p = 0.015. The FRAX® score for hip was also higher in the evaluated group than in the controls (1.33 ± 3.92 vs 0.50 ± 0.46 respectively; p = 0.022. There was no correlations between low TSH and fracture risk (p > 0.05. The ability of the FRAX® score in discriminating between bone fracture positive and negative pre- and postmenopausal female subjects (p < 0.001 is presented by the area under the curve (AUC plotted via ROC analysis. The determined FRAX score cut-off value by this analysis was 6%, with estimated sensitivity and specificity of 95% and 75.9%, respectively. Conclusion. Pre- and postmenopausal women with subclinical hyperthyroidism have higher FRAX® scores and thus

  11. Fibrosis-Related Biomarkers and Risk of Total and Cause-Specific Mortality

    Science.gov (United States)

    Agarwal, Isha; Glazer, Nicole L.; Barasch, Eddy; Biggs, Mary L.; Djoussé, Luc; Fitzpatrick, Annette L.; Gottdiener, John S.; Ix, Joachim H.; Kizer, Jorge R.; Rimm, Eric B.; Siscovick, David S.; Tracy, Russell P.; Zieman, Susan J.; Mukamal, Kenneth J.

    2014-01-01

    Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996–2010). We measured circulating TGF-β and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-β and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-β and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-β and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-β and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death. PMID:24771724

  12. A Posterior Circulation Ischemia Risk Score System to Assist the Diagnosis of Dizziness.

    Science.gov (United States)

    Chen, Ru; Su, Rui; Deng, Mingzhu; Liu, Jia; Hu, Qing; Song, Zhi

    2018-02-01

    We aimed to establish a risk score system without radio-image examination, which could help clinicians to differentiate patients with vertigo and posterior circulation ischemia (PCI) rapidly from the other dizzy patients. We analyzed 304 patients with vertigo (50% PCI). The attributes with more significant contributions were selected as the risk factors for the PCI risk score system, and every one of them was assigned a value according to their respective odds ratio values. We also compared the respective receiver operating characteristic curves of the 3 diagnostic methods (PCI score system, ABCD 2 , and Essen score systems) to evaluate their prediction effectiveness. Nine risk factors were ultimately selected for PCI score system, including high blood pressure (1'), diabetes mellitus (1'), ischemic stroke (1'), rotating and rocking (-1'), difficulty in speech (5'), tinnitus (-5'), limb and sensory deficit (5'), gait ataxia (1'), and limb ataxia (5'). According to their respective PCI risk scores, the patients were divided into 3 subgroups: low risk (≤0', risk 95.0%). When 0' was selected as a cutoff point for differentiating the patients with PCI from patients without PCI, the sensitivity was 94.1%, with a specificity of 41.4%. The areas under the receiver operator curve value of PCI score system was .82 (P = .000), much higher than the areas under the receiver operator curve value of ABCD 2 (.69, P = .000) and that of the Essen system (.67, P = .000) CONCLUSION: The PCI score system could help clinicians to differentiate patients with vertigo and PCI rapidly from the other dizzy patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

    Science.gov (United States)

    Kim, Hwi Young; Lee, Dong Hyeon; Lee, Jeong-Hoon; Cho, Young Youn; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

    2018-03-20

    Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values). This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

  14. External validation of the NOBLADS score, a risk scoring system for severe acute lower gastrointestinal bleeding.

    Directory of Open Access Journals (Sweden)

    Tomonori Aoki

    Full Text Available We aimed to evaluate the generalizability of NOBLADS, a severe lower gastrointestinal bleeding (LGIB prediction model which we had previously derived when working at a different institution, using an external validation cohort. NOBLADS comprises the following factors: non-steroidal anti-inflammatory drug use, no diarrhea, no abdominal tenderness, blood pressure ≤ 100 mmHg, antiplatelet drug use, albumin < 3.0 g/dL, disease score ≥ 2, and syncope.We retrospectively analyzed 511 patients emergently hospitalized for acute LGIB at the University of Tokyo Hospital, from January 2009 to August 2016. The areas under the receiver operating characteristic curves (ROCs-AUCs for severe bleeding (continuous and/or recurrent bleeding were compared between the original derivation cohort and the external validation cohort.Severe LGIB occurred in 44% of patients. Several clinical factors were significantly different between the external and derivation cohorts (p < 0.05, including background, laboratory data, NOBLADS scores, and diagnosis. The NOBLADS score predicted the severity of LGIB with an AUC value of 0.74 in the external validation cohort and one of 0.77 in the derivation cohort. In the external validation cohort, the score predicted the risk for blood transfusion need (AUC, 0.71, but was not adequate for predicting intervention need (AUC, 0.54. The in-hospital mortality rate was higher in patients with a score ≥ 5 than in those with a score < 5 (AUC, 0.83.Although the external validation cohort clinically differed from the derivation cohort in many ways, we confirmed the moderately high generalizability of NOBLADS, a clinical risk score for severe LGIB. Appropriate triage using this score may support early decision-making in various hospitals.

  15. Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

    Science.gov (United States)

    Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

    2017-12-31

    To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

  16. Performance of Surgical Risk Scores to Predict Mortality after Transcatheter Aortic Valve Implantation

    Directory of Open Access Journals (Sweden)

    Leonardo Sinnott Silva

    2015-01-01

    Full Text Available Abstract Background: Predicting mortality in patients undergoing transcatheter aortic valve implantation (TAVI remains a challenge. Objectives: To evaluate the performance of 5 risk scores for cardiac surgery in predicting the 30-day mortality among patients of the Brazilian Registry of TAVI. Methods: The Brazilian Multicenter Registry prospectively enrolled 418 patients undergoing TAVI in 18 centers between 2008 and 2013. The 30-day mortality risk was calculated using the following surgical scores: the logistic EuroSCORE I (ESI, EuroSCORE II (ESII, Society of Thoracic Surgeons (STS score, Ambler score (AS and Guaragna score (GS. The performance of the risk scores was evaluated in terms of their calibration (Hosmer–Lemeshow test and discrimination [area under the receiver–operating characteristic curve (AUC]. Results: The mean age was 81.5 ± 7.7 years. The CoreValve (Medtronic was used in 86.1% of the cohort, and the transfemoral approach was used in 96.2%. The observed 30-day mortality was 9.1%. The 30-day mortality predicted by the scores was as follows: ESI, 20.2 ± 13.8%; ESII, 6.5 ± 13.8%; STS score, 14.7 ± 4.4%; AS, 7.0 ± 3.8%; GS, 17.3 ± 10.8%. Using AUC, none of the tested scores could accurately predict the 30-day mortality. AUC for the scores was as follows: 0.58 [95% confidence interval (CI: 0.49 to 0.68, p = 0.09] for ESI; 0.54 (95% CI: 0.44 to 0.64, p = 0.42 for ESII; 0.57 (95% CI: 0.47 to 0.67, p = 0.16 for AS; 0.48 (95% IC: 0.38 to 0.57, p = 0.68 for STS score; and 0.52 (95% CI: 0.42 to 0.62, p = 0.64 for GS. The Hosmer–Lemeshow test indicated acceptable calibration for all scores (p > 0.05. Conclusions: In this real world Brazilian registry, the surgical risk scores were inaccurate in predicting mortality after TAVI. Risk models specifically developed for TAVI are required.

  17. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Stanley, Adrian J; Laine, Loren; Dalton, Harry R

    2017-01-01

    OBJECTIVE: To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. DESIGN: International multicentre prospective study. SETTING: Six large hospitals in Europe, North America, Asia, and Oceania...... clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined...... accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited...

  18. Personalized Risk Scoring for Critical Care Prognosis Using Mixtures of Gaussian Processes.

    Science.gov (United States)

    Alaa, Ahmed M; Yoon, Jinsung; Hu, Scott; van der Schaar, Mihaela

    2018-01-01

    In this paper, we develop a personalized real-time risk scoring algorithm that provides timely and granular assessments for the clinical acuity of ward patients based on their (temporal) lab tests and vital signs; the proposed risk scoring system ensures timely intensive care unit admissions for clinically deteriorating patients. The risk scoring system is based on the idea of sequential hypothesis testing under an uncertain time horizon. The system learns a set of latent patient subtypes from the offline electronic health record data, and trains a mixture of Gaussian Process experts, where each expert models the physiological data streams associated with a specific patient subtype. Transfer learning techniques are used to learn the relationship between a patient's latent subtype and her static admission information (e.g., age, gender, transfer status, ICD-9 codes, etc). Experiments conducted on data from a heterogeneous cohort of 6321 patients admitted to Ronald Reagan UCLA medical center show that our score significantly outperforms the currently deployed risk scores, such as the Rothman index, MEWS, APACHE, and SOFA scores, in terms of timeliness, true positive rate, and positive predictive value. Our results reflect the importance of adopting the concepts of personalized medicine in critical care settings; significant accuracy and timeliness gains can be achieved by accounting for the patients' heterogeneity. The proposed risk scoring methodology can confer huge clinical and social benefits on a massive number of critically ill inpatients who exhibit adverse outcomes including, but not limited to, cardiac arrests, respiratory arrests, and septic shocks.

  19. Interrater reliability of Violence Risk Appraisal Guide scores provided in Canadian criminal proceedings.

    Science.gov (United States)

    Edens, John F; Penson, Brittany N; Ruchensky, Jared R; Cox, Jennifer; Smith, Shannon Toney

    2016-12-01

    Published research suggests that most violence risk assessment tools have relatively high levels of interrater reliability, but recent evidence of inconsistent scores among forensic examiners in adversarial settings raises concerns about the "field reliability" of such measures. This study specifically examined the reliability of Violence Risk Appraisal Guide (VRAG) scores in Canadian criminal cases identified in the legal database, LexisNexis. Over 250 reported cases were located that made mention of the VRAG, with 42 of these cases containing 2 or more scores that could be submitted to interrater reliability analyses. Overall, scores were skewed toward higher risk categories. The intraclass correlation (ICCA1) was .66, with pairs of forensic examiners placing defendants into the same VRAG risk "bin" in 68% of the cases. For categorical risk statements (i.e., low, moderate, high), examiners provided converging assessment results in most instances (86%). In terms of potential predictors of rater disagreement, there was no evidence for adversarial allegiance in our sample. Rater disagreement in the scoring of 1 VRAG item (Psychopathy Checklist-Revised; Hare, 2003), however, strongly predicted rater disagreement in the scoring of the VRAG (r = .58). (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. A Soft Intelligent Risk Evaluation Model for Credit Scoring Classification

    Directory of Open Access Journals (Sweden)

    Mehdi Khashei

    2015-09-01

    Full Text Available Risk management is one of the most important branches of business and finance. Classification models are the most popular and widely used analytical group of data mining approaches that can greatly help financial decision makers and managers to tackle credit risk problems. However, the literature clearly indicates that, despite proposing numerous classification models, credit scoring is often a difficult task. On the other hand, there is no universal credit-scoring model in the literature that can be accurately and explanatorily used in all circumstances. Therefore, the research for improving the efficiency of credit-scoring models has never stopped. In this paper, a hybrid soft intelligent classification model is proposed for credit-scoring problems. In the proposed model, the unique advantages of the soft computing techniques are used in order to modify the performance of the traditional artificial neural networks in credit scoring. Empirical results of Australian credit card data classifications indicate that the proposed hybrid model outperforms its components, and also other classification models presented for credit scoring. Therefore, the proposed model can be considered as an appropriate alternative tool for binary decision making in business and finance, especially in high uncertainty conditions.

  1. Prospects for using risk scores in polygenic medicine

    Directory of Open Access Journals (Sweden)

    Cathryn M. Lewis

    2017-11-01

    Full Text Available Editorial summary Genome-wide association studies have made strides in identifying common variation associated with disease. The modest effect sizes preclude risk prediction based on single genetic variants, but polygenic risk scores that combine thousands of variants show some predictive ability across a range of complex traits and diseases, including neuropsychiatric disorders. Here, we consider the potential for translation to clinical use.

  2. The HEART score is useful to predict cardiovascular risks and reduces unnecessary cardiac imaging in low-risk patients with acute chest pain.

    Science.gov (United States)

    Dai, Siping; Huang, Bo; Zou, Yunliang; Guo, Jianbin; Liu, Ziyong; Pi, Dangyu; Qiu, Yunhong; Xiao, Chun

    2018-06-01

    The present study was to investigate whether the HEART score can be used to evaluate cardiovascular risks and reduce unnecessary cardiac imaging in China.Acute coronary syndrome patients with the thrombosis in myocardial infarction risk score risk HEART score group and 2 patients (1.5%) in the high risk HEART score group had cardiovascular events. The sensitivity of HEART score to predict cardiovascular events was 100% and the specificity was 46.7%. The potential unnecessary cardiac testing was 46.3%. Cox proportional hazards regression analysis showed that per one category increase of the HEART score was associated with nearly 1.3-fold risk of cardiovascular events.In the low-risk acute chest pain patients, the HEART score is useful to physicians in evaluating the risk of cardiovascular events within the first 30 days. In addition, the HEART score is also useful in reducing the unnecessary cardiac imaging.

  3. MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

    Science.gov (United States)

    Hiura, Kazuya; Shiraishi, Akiko; Suzuki, Chinami; Takamura, Kei; Yamamoto, Makoto; Komori, Hitoshi; Watanabe, Yasuhiro; Iwaki-Egawa, Sachiko

    2015-01-01

    Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

  4. Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort

    DEFF Research Database (Denmark)

    Kolberg, Janice A; Jørgensen, Torben; Gerwien, Robert W

    2009-01-01

    who did not were tested. An ultrasensitive immunoassay was used to measure of 58 candidate biomarkers in multiple diabetes-associated pathways, along with six routine clinical variables. Statistical learning methods and permutation testing were used to select the most informative biomarkers. Risk....... This model has a bootstrap-estimated area under the curve of 0.76, which is greater than that for A1C, fasting plasma glucose, fasting serum insulin, BMI, sex-adjusted waist circumference, a model using fasting glucose and insulin, and a noninvasive clinical model. CONCLUSIONS: A model incorporating six...... circulating biomarkers provides an objective and quantitative estimate of the 5-year risk of developing type 2 diabetes, performs better than single risk indicators and a noninvasive clinical model, and provides better stratification than fasting plasma glucose alone....

  5. Evaluation of Cardiovascular Risk Scores Applied to NASA's Astronant Corps

    Science.gov (United States)

    Jain, I.; Charvat, J. M.; VanBaalen, M.; Lee, L.; Wear, M. L.

    2014-01-01

    In an effort to improve cardiovascular disease (CVD) risk prediction, this analysis evaluates and compares the applicability of multiple CVD risk scores to the NASA Astronaut Corps which is extremely healthy at selection.

  6. Alzheimer Disease and Its Growing Epidemic: Risk Factors, Biomarkers, and the Urgent Need for Therapeutics.

    Science.gov (United States)

    Hickman, Richard A; Faustin, Arline; Wisniewski, Thomas

    2016-11-01

    Alzheimer disease (AD) represents one of the greatest medical challenges of this century; the condition is becoming increasingly prevalent worldwide and no effective treatments have been developed for this terminal disease. Because the disease manifests at a late stage after a long period of clinically silent neurodegeneration, knowledge of the modifiable risk factors and the implementation of biomarkers is crucial in the primary prevention of the disease and presymptomatic detection of AD, respectively. This article discusses the growing epidemic of AD and antecedent risk factors in the disease process. Disease biomarkers are discussed, and the implications that this may have for the treatment of this currently incurable disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Aerobic fitness is associated with low cardiovascular disease risk: the impact of lifestyle on early risk factors for atherosclerosis in young healthy Swedish individuals – the Lifestyle, Biomarker, and Atherosclerosis study

    Directory of Open Access Journals (Sweden)

    Fernström M

    2017-03-01

    Full Text Available Maria Fernström,1,* Ulrika Fernberg,2,* Gabriella Eliason,1 Anita Hurtig-Wennlöf1 1Department of Medical Diagnostics, Medical Faculty, School of Health Sciences, 2Medical Faculty, School of Medical Sciences, Örebro University, Örebro, Sweden *These authors contributed equally to this work Background: The progression of cardiovascular disease (CVD and atherosclerosis is slow and develops over decades. In the cross-sectional Swedish Lifestyle, Biomarker, and Atherosclerosis study, 834 young, self-reported healthy adults aged 18.0–25.9 years have been studied to identify early risk factors for atherosclerosis.Purpose: The aims of this study were to 1 assess selected cardiometabolic biomarkers, carotid intima–media thickness (cIMT as a marker of subclinical atherosclerosis, and lifestyle-related indicators (food habits, handgrip strength, and oxygen uptake, VO2 max; 2 analyze the assofciations between cIMT and lifestyle factors; and 3 identify subjects at risk of CVD using a risk score and to compare the characteristics of subjects with and without risk of CVD.Method: Blood samples were taken in a fasting state, and food habits were reported through a questionnaire. cIMT was measured by ultrasound, and VO2 max was measured by ergometer bike test. The risk score was calculated according to Wildman.Result: cIMT (mean ± standard deviation was 0.50±0.06 mm, and VO2 max values were 37.8±8.5 and 42.9±9.9 mL/kg/min, in women and men, respectively. No correlation was found between aerobic fitness expressed as VO2 max (mL/kg/min and cIMT. Using Wildman’s definition, 12% of the subjects were classified as being at risk of CVD, and 15% had homeostasis model assessment of insulin resistance. A total of 35% of women and 25% of men had lower high-density lipoprotein cholesterol than recommended. Food habits did not differ between those at risk and those not at risk. However, aerobic fitness measured as VO2 max (mL/kg/min differed; 47% of the

  8. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

    Science.gov (United States)

    Van Neste, Leander; Partin, Alan W; Stewart, Grant D; Epstein, Jonathan I; Harrison, David J; Van Criekinge, Wim

    2016-09-01

    Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. Low DNA-methylation levels in PCa-negative biopsies led

  9. Clinical Risk Stratification Optimizes Value of Biomarkers to Predict New-Onset Heart Failure in a Community-Based Cohort

    NARCIS (Netherlands)

    Brouwers, Frank P.; van Gilst, Wiek H.; Damman, Kevin; van den Berg, Maarten P.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Hillege, Hans L.; van Veldhuisen, Dirk J.; van der Harst, Pim; de Boer, Rudolf A.

    Background-We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction. Methods and

  10. A Clinical Risk Score for Atrial Fibrillation in a Biracial Prospective Cohort (From the Atherosclerosis Risk in Communities (ARIC) Study)

    OpenAIRE

    Chamberlain, Alanna M.; Agarwal, Sunil K.; Folsom, Aaron R.; Soliman, Elsayed Z.; Chambless, Lloyd E.; Crow, Richard; Ambrose, Marietta; Alonso, Alvaro

    2011-01-01

    A risk score for AF has been developed by the Framingham Heart Study; however the applicability of this risk score, derived from whites, to predict new-onset AF in non-whites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF using risk factors commonly measured in clinical practice using 14,546 individuals from the Atherosclerosis Risk in Communities study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 5...

  11. The "polyenviromic risk score": Aggregating environmental risk factors predicts conversion to psychosis in familial high-risk subjects.

    Science.gov (United States)

    Padmanabhan, Jaya L; Shah, Jai L; Tandon, Neeraj; Keshavan, Matcheri S

    2017-03-01

    Young relatives of individuals with schizophrenia (i.e. youth at familial high-risk, FHR) are at increased risk of developing psychotic disorders, and show higher rates of psychiatric symptoms, cognitive and neurobiological abnormalities than non-relatives. It is not known whether overall exposure to environmental risk factors increases risk of conversion to psychosis in FHR subjects. Subjects consisted of a pilot longitudinal sample of 83 young FHR subjects. As a proof of principle, we examined whether an aggregate score of exposure to environmental risk factors, which we term a 'polyenviromic risk score' (PERS), could predict conversion to psychosis. The PERS combines known environmental risk factors including cannabis use, urbanicity, season of birth, paternal age, obstetric and perinatal complications, and various types of childhood adversity, each weighted by its odds ratio for association with psychosis in the literature. A higher PERS was significantly associated with conversion to psychosis in young, familial high-risk subjects (OR=1.97, p=0.009). A model combining the PERS and clinical predictors had a sensitivity of 27% and specificity of 96%. An aggregate index of environmental risk may help predict conversion to psychosis in FHR subjects. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Relationship between framingham risk score and coronary artery calcium score in asymptomatic Korean individuals

    International Nuclear Information System (INIS)

    Heo, So Young; Park, Noh Hyuck; Park, Chan Sub; Seong, Su Ok

    2016-01-01

    We explored the association between Framingham risk score (FRS) and coronary artery calcium score (CACS) in asymptomatic Korean individuals. We retrospectively analyzed 2216 participants who underwent routine health screening and CACS using the 64-slice multidetector computed tomography between January 2010 and June 2014. Relationship between CACS and FRS, and factors associated with discrepancy between CACS and FRS were analyzed. CACS and FRS were positively correlated (p < 0.0001). However, in 3.7% of participants with low coronary event risk and high CACS, age, male gender, smoker, hypertension, total cholesterol, diabetes mellitus, and body mass index (BMI; ≥ 35) were associated with the discrepancy. In the diagnostic prediction model for discrepancy, the receiver operating characteristic curve including factors associated with FRS, diastolic blood pressure (≥ 75 mm Hg), diabetes mellitus, and BMI (≥ 35) showed that the area under the curve was 0.854 (95% confidence interval, 0.819–0.890), indicating good sensitivity. Diabetes mellitus or obesity (BMI ≥ 35) compensate for the weakness of FRS and may be potential indicators for application of CACS in asymptomatic Koreans with low coronary event risk

  13. Relationship between framingham risk score and coronary artery calcium score in asymptomatic Korean individuals

    Energy Technology Data Exchange (ETDEWEB)

    Heo, So Young; Park, Noh Hyuck; Park, Chan Sub; Seong, Su Ok [Dept. of Radiology, Myongji Hospital, Seonam University College of Medicine, Goyang (Korea, Republic of)

    2016-02-15

    We explored the association between Framingham risk score (FRS) and coronary artery calcium score (CACS) in asymptomatic Korean individuals. We retrospectively analyzed 2216 participants who underwent routine health screening and CACS using the 64-slice multidetector computed tomography between January 2010 and June 2014. Relationship between CACS and FRS, and factors associated with discrepancy between CACS and FRS were analyzed. CACS and FRS were positively correlated (p < 0.0001). However, in 3.7% of participants with low coronary event risk and high CACS, age, male gender, smoker, hypertension, total cholesterol, diabetes mellitus, and body mass index (BMI; ≥ 35) were associated with the discrepancy. In the diagnostic prediction model for discrepancy, the receiver operating characteristic curve including factors associated with FRS, diastolic blood pressure (≥ 75 mm Hg), diabetes mellitus, and BMI (≥ 35) showed that the area under the curve was 0.854 (95% confidence interval, 0.819–0.890), indicating good sensitivity. Diabetes mellitus or obesity (BMI ≥ 35) compensate for the weakness of FRS and may be potential indicators for application of CACS in asymptomatic Koreans with low coronary event risk.

  14. The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery.

    Science.gov (United States)

    Klein, A A; Collier, T; Yeates, J; Miles, L F; Fletcher, S N; Evans, C; Richards, T

    2017-09-01

    A simple and accurate scoring system to predict risk of transfusion for patients undergoing cardiac surgery is lacking. We identified independent risk factors associated with transfusion by performing univariate analysis, followed by logistic regression. We then simplified the score to an integer-based system and tested it using the area under the receiver operator characteristic (AUC) statistic with a Hosmer-Lemeshow goodness-of-fit test. Finally, the scoring system was applied to the external validation dataset and the same statistical methods applied to test the accuracy of the ACTA-PORT score. Several factors were independently associated with risk of transfusion, including age, sex, body surface area, logistic EuroSCORE, preoperative haemoglobin and creatinine, and type of surgery. In our primary dataset, the score accurately predicted risk of perioperative transfusion in cardiac surgery patients with an AUC of 0.76. The external validation confirmed accuracy of the scoring method with an AUC of 0.84 and good agreement across all scores, with a minor tendency to under-estimate transfusion risk in very high-risk patients. The ACTA-PORT score is a reliable, validated tool for predicting risk of transfusion for patients undergoing cardiac surgery. This and other scores can be used in research studies for risk adjustment when assessing outcomes, and might also be incorporated into a Patient Blood Management programme. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  15. CAN TIMI RISK SCORE PREDICT ANGIOGRAPHIC INVOLVEMENT IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION?

    Directory of Open Access Journals (Sweden)

    Allahyar Golabchi

    2010-11-01

    Full Text Available BACKGROUND: In most studies, the agreeable risk scores for ST-elevation myocardial infarction (STEMI consist of thrombolytic in myocardial infarction (TIMI risk score and modified Gensini risk score. Researchers showed significant relations between TIMI with angiography scores in patients with UA/NSTEMI. We studied this relation in patients with STEMI.    METHODS: We studied CCU patients with STEMI hospitalized in several hospitals of Isfahan, Iran from September 2007 to June 2008. Sampling method of 240 patients was random and simple. Exclusion criteria were incomplete history, nonspecific electrocardiogram changes, left bundle branch block and not accomplished angiography or accomplished angiography after 2 months of STEMI. Questionnaire indices collected on the basis of TIMI (0-14 points. Echocardiography and angiography were done and then, we used Gensini (0-400 points to review films of angiography. Spearman`s rank test and Pearson correlation coefficient were used to study the relation between these scores.    RESULTS: One hundred and sixty one patients were male and their average age was 60.02 years. Averages of TIMI and Gensini scores were 6.30 ± 2.5 and 120.77 ± 50.4, respectively. Study showed significant relation between TIMI, age and LVEF (P <0.001, r=-0.46. Also, between Gensini and age, gender and LVEF significant relation was found (P <0.001. But, a meaningful correlation didn’t exist between TIMI and the gender (P =0.08. Our study proved direct relation between TIMI risk scores and modified Gensini scores (P <0.001, r=0.55.     CONCLUSION: We may decide quickly and correctly in emergency room to distinguish which patients with STEMI could derive a benefit from invasive strategies using TIMI score. Also, TIMI risk score can be a good predictor to determine the extension of coronary artery disease in patients with STEMI. As a result, we suggest determination of TIMI score for any patient entered emergency room. Also

  16. Effects of Positive Psychology Interventions on Risk Biomarkers in Coronary Patients: A Randomized, Wait-List Controlled Pilot Trial.

    Science.gov (United States)

    Nikrahan, Gholam Reza; Laferton, Johannes A C; Asgari, Karim; Kalantari, Mehrdad; Abedi, Mohammad Reza; Etesampour, Ali; Rezaei, Abbas; Suarez, Laura; Huffman, Jeff C

    2016-01-01

    Among cardiac patients, positive psychologic factors are consistently linked with superior clinical outcomes and improvement in key markers of inflammation and hypothalamic-pituitary-adrenal axis functioning. Further, positive psychology interventions (PPI) have effectively increased psychologic well-being in a wide variety of populations. However, there has been minimal study of PPIs in cardiac patients, and no prior study has evaluated their effect on key prognostic biomarkers of cardiac outcome. Accordingly, we investigated the effect of 3 distinct PPIs on risk biomarkers in cardiac patients. In an exploratory trial, 69 patients with recent coronary artery bypass graft surgery or percutaneous intervention were randomized to (1) one of three 6-week in-person PPIs (based on the work of Seligman, Lyubomirsky, or Fordyce) or (2) a wait-list control group. Risk biomarkers were assessed at baseline, postintervention (7 weeks), and at 15-week follow-up. Between-group differences in change from baseline biomarker levels were examined via random effects models. Compared with the control group, participants randomized to the Seligman (B = -2.06; p = 0.02) and Fordyce PPI (B = -1.54; p = 0.04) had significantly lower high-sensitivity C-reactive protein levels at 7 weeks. Further, the Lyubomirsky PPI (B = -245.86; p = 0.04) was associated with a significantly lower cortisol awakening response at 7 weeks when compared with control participants. There were no other significant between-group differences. Despite being an exploratory pilot study with multiple between-group comparisons, this initial trial offers the first suggestion that PPIs might be effective in reducing risk biomarkers in high-risk cardiac patients. Copyright © 2016 The Academy of Psychosomatic Medicine. All rights reserved.

  17. A Novel Risk Scoring System Reliably Predicts Readmission Following Pancreatectomy

    Science.gov (United States)

    Valero, Vicente; Grimm, Joshua C.; Kilic, Arman; Lewis, Russell L.; Tosoian, Jeffrey J.; He, Jin; Griffin, James; Cameron, John L.; Weiss, Matthew J.; Vollmer, Charles M.; Wolfgang, Christopher L.

    2015-01-01

    Background Postoperative readmissions have been proposed by Medicare as a quality metric and may impact provider reimbursement. Since readmission following pancreatectomy is common, we sought to identify factors associated with readmission in order to establish a predictive risk scoring system (RSS). Study Design A retrospective analysis of 2,360 pancreatectomies performed at nine, high-volume pancreatic centers between 2005 and 2011 was performed. Forty-five factors strongly associated with readmission were identified. To derive and validate a RSS, the population was randomly divided into two cohorts in a 4:1 fashion. A multivariable logistic regression model was constructed and scores were assigned based on the relative odds ratio of each independent predictor. A composite Readmission After Pancreatectomy (RAP) score was generated and then stratified to create risk groups. Results Overall, 464 (19.7%) patients were readmitted within 90-days. Eight pre- and postoperative factors, including prior myocardial infarction (OR 2.03), ASA Class ≥ 3 (OR 1.34), dementia (OR 6.22), hemorrhage (OR 1.81), delayed gastric emptying (OR 1.78), surgical site infection (OR 3.31), sepsis (OR 3.10) and short length of stay (OR 1.51), were independently predictive of readmission. The 32-point RAP score generated from the derivation cohort was highly predictive of readmission in the validation cohort (AUC 0.72). The low (0-3), intermediate (4-7) and high risk (>7) groups correlated to 11.7%, 17.5% and 45.4% observed readmission rates, respectively (preadmission following pancreatectomy. Identification of patients with increased risk of readmission using the RAP score will allow efficient resource allocation aimed to attenuate readmission rates. It also has potential to serve as a new metric for comparative research and quality assessment. PMID:25797757

  18. Antioxidant vitamins and cancer risk: is oxidative damage to DNA a relevant biomarker?

    DEFF Research Database (Denmark)

    Loft, Steffen; Møller, Peter; Cooke, Marcus S

    2008-01-01

    -dihydroguanine (8-oxodG) are increasingly being regarded as reliable biomarkers of oxidative stress and they may have a predictive value of cancer risk, although this needs to be established independently in several cohort studies. A survey of intervention studies of the ingestion of antioxidant-containing foods...

  19. [Clinical scores for the risk of bleeding with or without anticoagulation].

    Science.gov (United States)

    Junod, Alain

    2016-09-14

    The assessment of hemorragic risk related to therapeutic anticoagulation is made difficult because of the variety of existing drugs, the heterogeneity of treatment strategies and their duration. Six prognostic scores have been analyzed. For three of them, external validations have revealed a marked decrease in the discrimination power. One British study, Qbleed, based on the data of more than 1 million of ambulatory patients, has repeatedly satisfied quality criteria. Two scores have also studied the bleeding risk during hospital admission for acute medical disease. The development of new and effective anticoagulants with fewer side-effects is more likely to solve this problem than the production of new clinical scores.

  20. Does simplicity compromise accuracy in ACS risk prediction? A retrospective analysis of the TIMI and GRACE risk scores.

    Directory of Open Access Journals (Sweden)

    Krishna G Aragam

    Full Text Available BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI risk scores for Unstable Angina/Non-ST-elevation myocardial infarction (UA/NSTEMI and ST-elevation myocardial infarction (STEMI and the Global Registry of Acute Coronary Events (GRACE risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems. METHODOLOGY/PRINCIPAL FINDINGS: ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753 and STEMI (n = 698 subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%, and among the survivors, 234 (7.4% died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81-0.89, versus 0.54, 95% CI: 0.48-0.60; p<0.01 and 6-month (C = 0.79, 95% CI: 0.76-0.83, versus 0.56, 95% CI: 0.52-0.60; p<0.01 mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78-0.90 versus 0.83, 95% CI: 0.78-0.89; p = 0.83 and 6-month (C = 0.72, 95% CI: 0.63-0.81, versus 0.71, 95% CI: 0.64-0.79; p = 0.79 mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution

  1. Risk stratification with the risk chart from the European Society of Hypertension compared with SCORE in the general population

    DEFF Research Database (Denmark)

    Sehestedt, Thomas; Jeppesen, Jørgen; Hansen, Tine W

    2009-01-01

    to higher-risk categories than SCORE (P smokers. However, ESH risk chart agreed with ESC guidelines for antihypertensive treatment using SCORE in 89% (634/713) of the patients recommended treatment and produced...... similar sensitivities (79 vs. 79%), specificities (46 vs. 50%), positive (14 vs. 15%) and negative (95 vs. 96%) predictive values for CEP. CONCLUSION: Although SCORE did not use subclinical organ damage, the guidelines by ESH and ESC using SCORE recommended antihypertensive treatment in almost the same...

  2. A validated risk score to estimate mortality risk in patients with dementia and pneumonia: barriers to clinical impact

    NARCIS (Netherlands)

    van der Steen, J.T.; Albers, G.; Strunk, E.; Muller, M.T.; Ribbe, M.W.

    2011-01-01

    Background: The clinical impact of risk score use in end-of-life settings is unknown, with reports limited to technical properties. Methods: We conducted a mixed-methods study to evaluate clinical impact of a validated mortality risk score aimed at informing prognosis and supporting clinicians in

  3. Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery.

    Science.gov (United States)

    Xing, Xue-Zhong; Wang, Hai-Jun; Huang, Chu-Lin; Yang, Quan-Hui; Qu, Shi-Ning; Zhang, Hao; Wang, Hao; Gao, Yong; Xiao, Qing-Ling; Sun, Ke-Lin

    2012-01-01

    Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care. The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors. The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI (PAbelha's AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422-0.592) for Abelha's AKI risk score. Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.

  4. A Danish diabetes risk score for targeted screening: the Inter99 study.

    Science.gov (United States)

    Glümer, Charlotte; Carstensen, Bendix; Sandbaek, Annelli; Lauritzen, Torsten; Jørgensen, Torben; Borch-Johnsen, Knut

    2004-03-01

    To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (Pscreening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.

  5. In-hospital outcome of acute myocardial infarction in correlation with 'thrombolysis in myocardial infarction' risk score

    International Nuclear Information System (INIS)

    Masood, A.; Naqvi, M.A.; Jafar, S.S.

    2009-01-01

    Effective risk stratification is integral to management of acute coronary syndromes (ACS). The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI) is a simple integer score based on 8 high-risk parameters that can be used at the bedside for risk stratification of patients at presentation with STEMI. To evaluate the prognostic significance of TIMI risk score in a local population group of acute STEMI. The study included 160 cases of STEMI eligible for thrombolysis. TIMI risk score was calculated for each case at the time of presentation and were then followed during their hospital stay for the occurrence of electrical and mechanical complications as well as mortality. The patients were divided into three risk groups, namely 'low risk', 'moderate-risk' and 'high-risk' based on their TIMI scores (0-4 low-risk, 5-8 moderate-risk, 9-14 high risk). The frequencies of complications and deaths were compared among the three risk groups. Post MI arrhythmias were noted in 2.2%, 16% and 50%; cardiogenic shock in 6.7%, 16% and 60%; pulmonary edema in 6.7%, 20% and 80%; mechanical complications of MI in 0%, 8% and 30%; death in 4.4%, 8%, and 60% of patients belonging to low-risk, moderate-risk and high-risk groups respectively. Frequency of complications and death correlated well with TIMI risk score (p=0.001). TIMI risk score correlates well with the frequency of electrical or mechanical complications and death after STEMI. (author)

  6. B-type Natriuretic Peptide and RISK-PCI Score in the Risk Assessment in Patients with STEMI Treated by Primary Percutaneous Coronary Intervention.

    Science.gov (United States)

    Asanin, Milika; Mrdovic, Igor; Savic, Lidija; Matic, Dragan; Krljanac, Gordana; Vukcevic, Vladan; Orlic, Dejan; Stankovic, Goran; Marinkovic, Jelena; Stankovic, Sanja

    2016-01-01

    RISK-PCI score is a novel score for risk stratification of patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). The aim of this study was to evaluate the role of B-type natriuretic peptide (BNP) and the RISK-PCI score for early risk assessment in patients with STEMI treated by pPCI. In 120 patients with STEMI treated by pPCI, BNP was measured on admission before pPCI. The primary end point was 30-day mortality. The ROC curve analysis revealed that the most powerful predictive factors of 30-day mortality were the plasma level of BNP ≥ 206.6 pg/mL with the sensitivity of 75% and specificity of 87.5% and the RISK-PCI score ≥ 5.25 with the sensitivity of 75% and specificity of 85.7%. Thirty-day mortality was 6.7%. After multivariate adjustment, admission BNP (≥ 206.6 pg/mL) (OR 2.952, 95% CI 1.072 - 8.133, p = 0.036) and the RISK-PCI score (≥ 5.25) (OR 2.284, 95% CI 1.140-4.578, p = 0.020) were independent predictors of 30-day mortality. The area under the ROC curve using the RISK-PCI score and BNP to detect mortality was 0.828 (p = 0.002) and 0.903 (p PCI score increased the area under the ROC to 0.949 (p PCI score for 30-day mortality. BNP on admission and the RISK-PCI score were the independent predictors of 30-day mortality in patients with the STEMI treated by pPCI. BNP in combination with the RISK-PCI score showed the way to more accurate risk assessment in patients with STEMI treated by pPCI.

  7. Prognostic biomarkers in osteoarthritis

    Science.gov (United States)

    Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

    2013-01-01

    Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

  8. Validation of the German Diabetes Risk Score within a population-based representative cohort.

    Science.gov (United States)

    Hartwig, S; Kuss, O; Tiller, D; Greiser, K H; Schulze, M B; Dierkes, J; Werdan, K; Haerting, J; Kluttig, A

    2013-09-01

    To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle (CARLA) study. The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10⁻¹²). The area under the receiver-operator characteristic curve (AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76-0.86) or HbA(1c) concentration (AUC 0.84; 95% CI 0.80-0.91) was found to peform better. Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes

  9. Construction of an Exome-Wide Risk Score for Schizophrenia Based on a Weighted Burden Test.

    Science.gov (United States)

    Curtis, David

    2018-01-01

    Polygenic risk scores obtained as a weighted sum of associated variants can be used to explore association in additional data sets and to assign risk scores to individuals. The methods used to derive polygenic risk scores from common SNPs are not suitable for variants detected in whole exome sequencing studies. Rare variants, which may have major effects, are seen too infrequently to judge whether they are associated and may not be shared between training and test subjects. A method is proposed whereby variants are weighted according to their frequency, their annotations and the genes they affect. A weighted sum across all variants provides an individual risk score. Scores constructed in this way are used in a weighted burden test and are shown to be significantly different between schizophrenia cases and controls using a five-way cross-validation procedure. This approach represents a first attempt to summarise exome sequence variation into a summary risk score, which could be combined with risk scores from common variants and from environmental factors. It is hoped that the method could be developed further. © 2017 John Wiley & Sons Ltd/University College London.

  10. Serum biomarkers predictive of depressive episodes in panic disorder.

    Science.gov (United States)

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2016-02-01

    Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Imaging primary prostate cancer with 11C-Choline PET/CT: relation to tumour stage, Gleason score and biomarkers of biologic aggressiveness

    International Nuclear Information System (INIS)

    Chen, Ji; Zhao, Yong; Li, Xin; Sun, Peng; Wang, Muwen; Wang, Ridong; Jin, Xunbo

    2012-01-01

    As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness. Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed. Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax. Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer

  12. Quasi-linear score for capturing heterogeneous structure in biomarkers.

    Science.gov (United States)

    Omae, Katsuhiro; Komori, Osamu; Eguchi, Shinto

    2017-06-19

    Linear scores are widely used to predict dichotomous outcomes in biomedical studies because of their learnability and understandability. Such approaches, however, cannot be used to elucidate biodiversity when there is heterogeneous structure in target population. Our study was focused on describing intrinsic heterogeneity in predictions. Because heterogeneity can be captured by a clustering method, integrating different information from different clusters should yield better predictions. Accordingly, we developed a quasi-linear score, which effectively combines the linear scores of clustered markers. We extended the linear score to the quasi-linear score by a generalized average form, the Kolmogorov-Nagumo average. We observed that two shrinkage methods worked well: ridge shrinkage for estimating the quasi-linear score, and lasso shrinkage for selecting markers within each cluster. Simulation studies and applications to real data show that the proposed method has good predictive performance compared with existing methods. Heterogeneous structure is captured by a clustering method. Quasi-linear scores combine such heterogeneity and have a better predictive ability compared with linear scores.

  13. Development of a self-assessment score for metabolic syndrome risk in non-obese Korean adults.

    Science.gov (United States)

    Je, Youjin; Kim, Youngyo; Park, Taeyoung

    2017-03-01

    There is a need for simple risk scores that identify individuals at high risk for metabolic syndrome (MetS). Therefore, this study was performed to develop and validate a self-assessment score for MetS risk in non-obese Korean adults. Data from the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2007-2009 were used to develop a MetS risk score. We included a total of 5,508 non-obese participants aged 19-64 years who were free of a self-reported diagnosis of diabetes, hyperlipidemia, hypertension, stroke, angina, or cancer. Multivariable logistic regression model coefficients were used to assign each variable category a score. The validity of the score was assessed in an independent population survey performed in 2010 and 2011, KNHANES V (n=3,892). Age, BMI, physical activity, smoking, alcohol consumption, dairy consumption, dietary habit of eating less salty and food insecurity were selected as categorical variables. The MetS risk score value varied from 0 to 13, and a cut-point MetS risk score of >=7 was selected based on the highest Youden index. The cut-point provided a sensitivity of 81%, specificity of 61%, positive predictive value of 14%, and negative predictive value of 98%, with an area under the curve (AUC) of 0.78. Consistent results were obtained in the validation data sets. This simple risk score may be used to identify individuals at high risk for MetS without laboratory tests among non-obese Korean adults. Further studies are needed to verify the usefulness and feasibility of this score in various settings.

  14. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Torp-Pedersen, Christian; Hansen, Morten Lock

    2012-01-01

    associated with increasing CHA2DS2-VASc score was estimated in Cox regression models adjusted for year of inclusion and antiplatelet therapy. The value of adding the extra CHA2DS2-VASc risk factors to the CHADS2 score was evaluated by c-statistics, Net Reclassification Improvement (NRI) and Integrated......DS2-VASc score significantly improved the predictive value of the CHADS2 score alone and a CHA2DS2-VASc score=0 could clearly identify 'truly low risk' subjects. Use of the CHA2DS2-VASc score would significantly improve classification of AF patients at low and intermediate risk of stroke, compared......North American and European guidelines on atrial fibrillation (AF) are conflicting regarding the classification of patients at low/intermediate risk of stroke. We aimed to investigate if the CHA2DS2-VASc score improved risk stratification of AF patients with a CHADS2 score of 0-1. Using individual...

  15. Soy Food Intake and Biomarkers of Breast Cancer Risk: Possible Difference in Asian Women?

    Science.gov (United States)

    Maskarinec, Gertraud; Ju, Dan; Morimoto, Yukiko; Franke, Adrian A; Stanczyk, Frank Z

    2017-01-01

    Soy foods may protect against breast cancer in Asian but not in Western populations. We examined if the levels of various markers of breast cancer risk and inflammation, as well as the effects of soy food consumption on these markers, differ between Asian and non-Asian premenopausal women in two soy intervention trials. One study randomized 220 women to a 2-yr intervention and the other one randomized 96 women in a crossover design to examine the effects of consumption of 2 daily soy servings on nipple aspirate fluid (NAF) volume; estrogens in serum, NAF, and urine; insulin-like growth factor-1 (IGF-1), IGF-binding protein 3, and inflammatory markers in serum; and mammographic densities. Mixed linear models were applied to assess ethnic differences in biomarkers and response to the soy diet. Serum C-reactive protein, serum leptin, NAF volume, and NAF estrone sulfate were lower, while urinary isoflavones were higher in Asian than in non-Asian women. A significant interaction (p interaction = 0.05) between ethnicity and soy diet was observed for IGF-1 but not for other biomarkers. The current findings suggest possible ethnic differences in levels of biomarkers for breast cancer risk but little evidence that Asian women respond differently to soy foods than non-Asian women.

  16. Snack patterns are associated with biomarkers of glucose metabolism in US men.

    Science.gov (United States)

    Shin, Dayeon; Song, SuJin; Krumhar, Kim; Song, Won O

    2015-01-01

    Few studies have made distinctions between dietary intake from meals and snacks in relating them to biomarkers. We aimed to examine if snack patterns are associated with biomarkers of glucose metabolism, specifically hemoglobin A1c and HOMA-IR in US adults. Using 24-h dietary recall data from National Health and Nutrition Examination Survey (NHANES) in 2007-2008, we derived snack patterns using factor analyses. Multivariate logistic regressions were performed to estimate adjusted odds ratios (AOR) for biomarkers of glucose metabolism by quintiles of snack pattern scores. Men in the highest quintile of dairy and sugary snack pattern had higher risk of having hemoglobin A1c ≥ 6.5% (AOR: 2.06; 95% CI: 1.20-3.51) and HOMA-IR > 3.0 (AOR: 1.73; 95% CI: 1.01-2.95) than did those in the lowest quintile. No significant association was found in women between snack patterns and biomarkers of glucose metabolism. Dairy and sugary snack patterns of US men had the greatest association with poor control of glucose metabolism.

  17. Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention

    Directory of Open Access Journals (Sweden)

    Alaa Badawi

    2010-05-01

    Full Text Available Alaa Badawi1, Amira Klip2, Pierre Haddad3, David EC Cole4, Bibiana Garcia Bailo1,5, Ahmed El-Sohemy5, Mohamed Karmali11Office for Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada; 2Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; 3Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Montreal Diabetes Research Centre, Montreal, QC, Canada; 4Department of Laboratory Medicine and Pathobiology, 5Department of Nutritional Sciences, University of Toronto, Toronto, ON, CanadaAbstract: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM, which is a significant health problem worldwide. Active disease is associated with low-grade chronic inflammation resulting in part from the activation of the innate immune system. In obesity, this activation leads to the release of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-6 that block major anabolic cascades downstream of insulin signaling and thus disrupt insulin homeostasis and action. Cytokines also trigger the production of acute-phase reactants such as C-reactive protein, plasminogen activator inhibitor-1, serum amyloid-A, and haptoglobin. The elevated synthesis of pro-inflammatory cytokines and acute-phase proteins (inflammatory network characterizes the early (or pre-clinical stages of T2DM and exhibits a graded increase with the disease progression. Current evidence suggests that understanding inflammatory networks can point to new biomarkers that may permit capturing the interaction between genetic and environmental risk factors in the pathogenesis of T2DM. Such biomarkers have a significant public health potential in the prediction of disease occurrence beyond risk factors presently monitored, such as family history, lifestyle assessment and standard clinical chemistry profiles. Furthermore, inflammatory markers may assist in the

  18. Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics

    Directory of Open Access Journals (Sweden)

    Lamiaa A. A. Barakat

    2017-11-01

    Full Text Available Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on 165 persons attending the medical outpatient clinic of Ismailia General Hospital. Their mean age was (50.69 ± 10.15 years. They were divided into three groups. The control group was composed of 55 non-obese, non-diabetic healthy volunteers, 32 males and 23 females. Two study groups were included in this study: group 2 was composed of 55 obese, non-diabetic subjects, 25 males and 30 females matched for age and gender. All patients including the control were subjected to clinical history taking, a clinical examination for the measurement of body mass index (BMI. Investigations were carried out for fasting blood glucose, fasting serum insulin, insulin resistance (IR, the lipid profile, lipoprotein band lipoprotein phospholipase A2, and non-high-density lipoprotein cholesterol (non-HDL-C. Urea, albumin and creatinine analysis and liver function tests were performed, and a complete blood count (CBC was taken. Hemoglobin A1C (HbA1C, serum high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α were tested. There were statistically significant differences among the studied groups in terms of total cholesterol, non-HDL-C, high-density lipoprotein cholesterol (HDL-C, triglycerides (TG, low-density lipoprotein cholesterol (LDL-C, lipoprotein-associated phospholipase A2 and apolipoprotein B. The inflammatory biomarkers hs-CRP, IL-6 and TNF-α were significantly statistically increased in the study groups by (1.62 ± 0.99, 2.32 ± 1.11, (1.73 ± 1.14, 2.53 ± 1.34, and (1.87 ± 1.09, 2.17 ± 0.89 respectively, where p < 0.01. Significant positive correlation was found between Homeostatic Model Assessment (HOMA-IR, hs

  19. Biomarker case-detection and prediction with potential for functional psychosis screening: development and validation of a model related to biochemistry, sensory neural timing and end organ performance.

    Directory of Open Access Journals (Sweden)

    Stephanie eFryar-Williams

    2016-04-01

    Full Text Available The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67, highly-characterized symptomatic participants were compared with results from 67 gender and age matched controls. Urine samples were analysed for catecholamines, their metabolites and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in the catecholamine synthesis and metabolism pathways. Cognitive, auditory and visual processing measures were assessed using a simple 45 minute, office-based procedure. Receiver Operating Curve (ROC and Odds Ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intra-cerebral auditory and visual processing speed and dichotic-listening performance. 15 ROC biomarker variables were divided into 5 functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥ 3 out of 5 abnormal domains achieved an AUC of 0.952 with a sensitivity of 84 per cent and a specificity of 90 percent. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94% percent. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥ 3 out of 5 abnormally scored domains predicted > 50% risk of case-ness whilst 4 abnormally-scored domains predicted 88% risk of case-ness and 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental

  20. Risk scores for diabetes and impaired glycaemia in the Middle East and North Africa

    DEFF Research Database (Denmark)

    Handlos, Line Neerup; Witte, Daniel Rinse; Almdal, Thomas Peter

    2013-01-01

    AIMS: To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk...

  1. Concordance of Motion Sensor and Clinician-Rated Fall Risk Scores in Older Adults.

    Science.gov (United States)

    Elledge, Julie

    2017-12-01

    As the older adult population in the United States continues to grow, developing reliable, valid, and practical methods for identifying fall risk is a high priority. Falls are prevalent in older adults and contribute significantly to morbidity and mortality rates and rising health costs. Identifying at-risk older adults and intervening in a timely manner can reduce falls. Conventional fall risk assessment tools require a health professional trained in the use of each tool for administration and interpretation. Motion sensor technology, which uses three-dimensional cameras to measure patient movements, is promising for assessing older adults' fall risk because it could eliminate or reduce the need for provider oversight. The purpose of this study was to assess the concordance of fall risk scores as measured by a motion sensor device, the OmniVR Virtual Rehabilitation System, with clinician-rated fall risk scores in older adult outpatients undergoing physical rehabilitation. Three standardized fall risk assessments were administered by the OmniVR and by a clinician. Validity of the OmniVR was assessed by measuring the concordance between the two assessment methods. Stability of the OmniVR fall risk ratings was assessed by measuring test-retest reliability. The OmniVR scores showed high concordance with the clinician-rated scores and high stability over time, demonstrating comparability with provider measurements.

  2. The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection.

    Science.gov (United States)

    Ritchie, Scott C; Würtz, Peter; Nath, Artika P; Abraham, Gad; Havulinna, Aki S; Fearnley, Liam G; Sarin, Antti-Pekka; Kangas, Antti J; Soininen, Pasi; Aalto, Kristiina; Seppälä, Ilkka; Raitoharju, Emma; Salmi, Marko; Maksimow, Mikael; Männistö, Satu; Kähönen, Mika; Juonala, Markus; Ripatti, Samuli; Lehtimäki, Terho; Jalkanen, Sirpa; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; Inouye, Michael

    2015-10-28

    The biomarker glycoprotein acetylation (GlycA) has been shown to predict risk of cardiovascular disease and all-cause mortality. Here, we characterize biological processes associated with GlycA by leveraging population-based omics data and health records from >10,000 individuals. Our analyses show that GlycA levels are chronic within individuals for up to a decade. In apparently healthy individuals, elevated GlycA corresponded to elevation of myriad inflammatory cytokines, as well as a gene coexpression network indicative of increased neutrophil activity, suggesting that individuals with high GlycA may be in a state of chronic inflammatory response. Accordingly, analysis of infection-related hospitalization and death records showed that increased GlycA increased long-term risk of severe non-localized and respiratory infections, particularly septicaemia and pneumonia. In total, our work demonstrates that GlycA is a biomarker for chronic inflammation, neutrophil activity, and risk of future severe infection. It also illustrates the utility of leveraging multi-layered omics data and health records to elucidate the molecular and cellular processes associated with biomarkers. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Tailoring the implementation of new biomarkers based on their added predictive value in subgroups of individuals.

    Directory of Open Access Journals (Sweden)

    A van Giessen

    Full Text Available The value of new biomarkers or imaging tests, when added to a prediction model, is currently evaluated using reclassification measures, such as the net reclassification improvement (NRI. However, these measures only provide an estimate of improved reclassification at population level. We present a straightforward approach to characterize subgroups of reclassified individuals in order to tailor implementation of a new prediction model to individuals expected to benefit from it.In a large Dutch population cohort (n = 21,992 we classified individuals to low (< 5% and high (≥ 5% fatal cardiovascular disease risk by the Framingham risk score (FRS and reclassified them based on the systematic coronary risk evaluation (SCORE. Subsequently, we characterized the reclassified individuals and, in case of heterogeneity, applied cluster analysis to identify and characterize subgroups. These characterizations were used to select individuals expected to benefit from implementation of SCORE.Reclassification after applying SCORE in all individuals resulted in an NRI of 5.00% (95% CI [-0.53%; 11.50%] within the events, 0.06% (95% CI [-0.08%; 0.22%] within the nonevents, and a total NRI of 0.051 (95% CI [-0.004; 0.116]. Among the correctly downward reclassified individuals cluster analysis identified three subgroups. Using the characterizations of the typically correctly reclassified individuals, implementing SCORE only in individuals expected to benefit (n = 2,707,12.3% improved the NRI to 5.32% (95% CI [-0.13%; 12.06%] within the events, 0.24% (95% CI [0.10%; 0.36%] within the nonevents, and a total NRI of 0.055 (95% CI [0.001; 0.123]. Overall, the risk levels for individuals reclassified by tailored implementation of SCORE were more accurate.In our empirical example the presented approach successfully characterized subgroups of reclassified individuals that could be used to improve reclassification and reduce implementation burden. In particular when newly

  4. Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Zhang, Zhiying; Pereira, Suzette L; Luo, Menghua; Matheson, Eric M

    2017-08-03

    Malnutrition is a common yet under-recognized problem in hospitalized patients. The aim of this paper was to systematically review and evaluate malnutrition biomarkers among order adults. Eligible studies were identified through Cochrane, PubMed and the ProQuest Dialog. A meta-regression was performed on concentrations of biomarkers according to malnutrition risks classified by validated nutrition assessment tools. A total of 111 studies were included, representing 52,911 participants (55% female, 72 ± 17 years old) from various clinical settings (hospital, community, care homes). The estimated BMI ( p malnutrition risk by MNA were significantly lower than those without a risk. Similar results were observed for malnutrition identified by SGA and NRS-2002. A sensitivity analysis by including patients with acute illness showed that albumin and prealbumin concentrations were dramatically reduced, indicating that they must be carefully interpreted in acute care settings. This review showed that BMI, hemoglobin, and total cholesterol are useful biomarkers of malnutrition in older adults. The reference ranges and cut-offs may need to be updated to avoid underdiagnosis of malnutrition.

  5. Liver Surface Nodularity Score Allows Prediction of Cirrhosis Decompensation and Death.

    Science.gov (United States)

    Smith, Andrew D; Zand, Kevin A; Florez, Edward; Sirous, Reza; Shlapak, Darya; Souza, Frederico; Roda, Manohar; Bryan, Jason; Vasanji, Amit; Griswold, Michael; Lirette, Seth T

    2017-06-01

    Purpose To determine whether use of the liver surface nodularity (LSN) score, a quantitative biomarker derived from routine computed tomographic (CT) images, allows prediction of cirrhosis decompensation and death. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with cirrhosis and Model for End-Stage Liver Disease (MELD) score within 3 months of initial liver CT imaging between January 3, 2006, and May 30, 2012, were identified from electronic medical records (n = 830). The LSN score was measured by using CT images and quantitative software. Competing risk regression was used to determine the association of the LSN score with hepatic decompensation and overall survival. A risk model combining LSN scores (<3 or ≥3) and MELD scores (<10 or ≥10) was created for predicting liver-related events. Results In patients with compensated cirrhosis, 40% (129 of 326) experienced decompensation during a median follow-up period of 4.22 years. After adjustment for competing risks including MELD score, LSN score (hazard ratio, 1.38; 95% confidence interval: 1.06, 1.79) was found to be independently predictive of hepatic decompensation. Median times to decompensation of patients at high (1.76 years, n = 48), intermediate (3.79 years, n = 126), and low (6.14 years, n = 152) risk of hepatic decompensation were significantly different (P < .001). Among the full cohort with compensated or decompensated cirrhosis, 61% (504 of 830) died during the median follow-up period of 2.26 years. After adjustment for competing risks, LSN score (hazard ratio, 1.22; 95% confidence interval: 1.11, 1.33) and MELD score (hazard ratio, 1.08; 95% confidence interval: 1.06, 1.11) were found to be independent predictors of death. Median times to death of patients at high (0.94 years, n = 315), intermediate (2.79 years, n = 312), and low (4.69 years, n = 203) risk were significantly different (P < .001). Conclusion The LSN score

  6. Increased serological cancer-associated biomarker levels at large bowel endoscopy and risk of subsequent primary cancer (†)

    DEFF Research Database (Denmark)

    Hvolris, Martin H; Piper, Thomas B; Hammer, Emilie

    2016-01-01

    Background: Frequently, subjects offered colonoscopy due to symptoms of colorectal neoplasia are diagnosed with diverticula. The symptoms may, however, also be related to extra-colonic neoplasia. The present retrospective study evaluated a possible association between increased levels of predefined...... biomarkers in subjects diagnosed with diverticula and risk of developing a primary malignant disease. Methods: During 2004/2005, about 4509 subjects were included in a multicenter study with collection of blood samples before bowel endoscopy. The aim was to evaluate a relation between the protein biomarkers...... was calculated. The relation with the four biomarkers was divided into three groups: 0 = none increased; 1 = one increased and 2 = two or more increased. Results: In the observation period, 148 subjects developed a primary malignant disease. Univariable analyzes of the biomarker levels showed that CEA, TIMP-1...

  7. Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

    OpenAIRE

    Muranen, Taru A.; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittom?ki, Kristiina; Blomqvist, Carl; Easton, Douglas F.; Nevanlinna, Heli

    2016-01-01

    The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breas...

  8. Blood-based biomarkers of aggressive prostate cancer.

    Directory of Open Access Journals (Sweden)

    Men Long Liong

    Full Text Available PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8 and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8 55% of G6 samples, 49% of G7(3+4, 79% of G7(4+3 and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from

  9. Identifying coronary artery disease in men with type 2 diabetes: osteoprotegerin, pulse wave velocity, and other biomarkers of cardiovascular risk.

    LENUS (Irish Health Repository)

    Davenport, Colin

    2012-02-01

    OBJECTIVES: In patients with type 2 diabetes, high serum levels of osteoprotegerin (OPG) have been associated with a greater risk of cardiovascular events. However, it remains unclear how well OPG performs when compared with traditional biomarkers of cardiovascular risk such as high-sensitivity C-reactive protein (hsCRP). Furthermore, OPG levels are also high in the presence of diabetes-related microvascular disease, and it is unclear whether OPG can distinguish microvascular disease from large-vessel atherosclerosis. The first aim of this study was to compare OPG levels against other biomarkers of cardiovascular risk in the identification of patients with documented multivessel coronary artery disease (CAD). The second aim was to compare OPG levels in patients with microvascular complications (microalbuminuria) against those with established CAD. METHODS: Three groups of male patients with type 2 diabetes were recruited: patients without microvascular complications or large-vessel atherosclerosis (n = 24), patients with microalbuminuria only (n = 23), and patients with microalbuminuria and documented multivessel CAD (n = 25). OPG, hsCRP, interleukin 6, urate, and pulse wave velocity were measured. RESULTS: Serum OPG levels were significantly higher in patients with a combination of microalbuminuria and CAD than in those with microalbuminuria alone. There were no significant differences in any of the other biomarkers between the groups. CONCLUSION: OPG was found to be superior to the other biomarkers studied in identifying patients with documented CAD. The presence of CAD was a greater determinant of serum OPG levels than microalbuminuria in our population. These findings support the use of OPG as a biomarker of cardiovascular risk.

  10. Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

    Science.gov (United States)

    Miller, Tracie L.; Borkowsky, William; DiMeglio, Linda A.; Dooley, Laurie; Geffner, Mitchell E.; Hazra, Rohan; McFarland, Elizabeth J.; Mendez, Armando J.; Patel, Kunjal; Siberry, George K.; Van Dyke, Russell B.; Worrell, Carol J.; Jacobson, Denise L.

    2011-01-01

    Objectives Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. Design Prospective cohort study Methods Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. Results The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). Conclusions HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication. PMID:22136114

  11. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

  12. Modified Mediterranean Diet Score and Cardiovascular Risk in a North American Working Population

    Science.gov (United States)

    Yang, Justin; Farioli, Andrea; Korre, Maria; Kales, Stefanos N.

    2014-01-01

    Introduction Greater adherence to a Mediterranean diet is linked to lower risk for cardiovascular morbidity/mortality in studies of Mediterranean cohorts, older subjects, and/or those with existing health conditions. No studies have examined the effects of this dietary pattern in younger working populations in the United States. We investigated the effects of Mediterranean diet adherence on cardiovascular disease (CVD) biomarkers, metabolic syndrome and body composition in an occupationally active, non-Mediterranean cohort. Methods A cross-sectional study in a cohort of 780 career male firefighters, ages 18 years or older, from the United States Midwest. No dietary intervention was performed. A modified Mediterranean diet score (mMDS) was developed for assessment of adherence to a Mediterranean dietary pattern from a previously administered life-style questionnaire that examined pre-existing dietary habits. Clinical data from fire department medical examinations were extracted and analyzed. Results Obese subjects had significantly lower mMDS, and they reported greater fast/take-out food consumption (pMediterranean-style dietary pattern had significant inverse associations with metabolic syndrome, LDL-cholesterol and reported weight gain, and was significantly and independently associated with higher HDL-cholesterol. Our results support the potential effectiveness of this diet in young, non-Mediterranean working cohorts, and justify future intervention studies. PMID:24503596

  13. Improving Blood Monitoring of Enzymes as Biomarkers of Risk from Anticholinergic Pesticides and Chemical Warfare Agents

    National Research Council Canada - National Science Library

    Wilson, Barry W

    2006-01-01

    Blood biomarkers are an important way to monitor exposure to anticholinergic pesticides and chemical warfare agents and to establish whether some personnel are at greater risk than others from exposure...

  14. Improving Blood Monitoring of Enzymes as Biomarkers of Risk from Anticholinergic Pesticides and Chemical Warfare Agents

    National Research Council Canada - National Science Library

    Wilson, Barry W

    2005-01-01

    Blood biomarkers are an important way to monitor exposure to anticholinergic pesticides and chemical warfare agents and to establish whether some personnel are at greater risk than others from exposure...

  15. [The scoring system for the risk-stratification in patients with the antiphospholipid syndrome].

    Science.gov (United States)

    Oku, Kenji

    2017-01-01

      Antiphospholipid syndrome (APS) is a clinical disorder characterized by thrombosis and/or pregnancy morbidity in the persistence of the pathogenic autoantibodies, the antiphospholipid antibodies (aPL). Recurernt thrombosis is often observed in patients with APS which requires persistent prophylaxis. However, an uniform prophylactic treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in other various diseases or elderly population. It is previously known that the multiple positivity or high titre of aPL correlate to the thrombotic events. To progress the stratification of the thrombotic risks and to quantitatively analyze them, antiphospholipid score (aPL-S) and the Global Anti-Phospholipid Syndrome Score (GAPSS) were defined as the scoring-systems. Both of these scoring-systems were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) were put into scoring system. They have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine dependent antiprothrombin antibodies (aPS/PT).

  16. BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham

    2016-07-01

    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  17. High Framingham risk score decreases quality of life in adults

    Directory of Open Access Journals (Sweden)

    Christian Yosaputra

    2010-04-01

    Full Text Available Cardiovascular disease (CVD risk factors, such as diabetes, hypertension, hypercholesterolemia, smoking, and obesity tend to occur together in the general population. Increasing prevalence of multiple CVD risk factors has been related to increased risk of death from coronary heart disease and stroke. Studies have suggested that people with several risk factors of CVD may have impaired health-related quality of life. The objective of this study was to assess the association of CVD risk factors with quality of life (QOL among adults aged 40 to 65 years. A cross-sectional study was conducted involving 220 subjects 40 - 65 years of age at a health center. The CVD risk factors were assessed using the Framingham risk score that is the standard instrument for assessment of the risk of a first cardiac event. The risk factors assessed were age, smoking, blood pressure, total cholesterol and high density lipoprotein cholesterol concentrations. QOL was assessed by means of the WHOQOL-BREF instrument that had been prevalidated. The results of the study showed that 28.2% of subjects were smokers, 56.4% had stage 1 hypertension, 42.8% high total cholesterol and 13.6% low HDL cholesterol. The high risk group amounted to 45.5% and 42.3% constitued an intermediate risk group. High CVD risk scores were significantly associated with a low QOL for all domains (physical, psychological, social and environment (p=0.000. Preventing or reducing the multiple CVD risk factors to improve QOL is necessary among adults.

  18. A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Tammaro, Leonardo; Buda, Andrea; Di Paolo, Maria Carla; Zullo, Angelo; Hassan, Cesare; Riccio, Elisabetta; Vassallo, Roberto; Caserta, Luigi; Anderloni, Andrea; Natali, Alessandro

    2014-09-01

    Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3). The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Severe Spontaneous Echo Contrast/Auricolar Thrombosis in "Nonvalvular" AF: Value of Thromboembolic Risk Scores.

    Science.gov (United States)

    Mascioli, Giosuè; Lucca, Elena; Michelotti, Federica; Alioto, Giusy; Santoro, Franco; Belli, Guido; Rota, Cristina; Ornago, Ombretta; Sirianni, Giovanni; Pulcini, Emanuela; Pennesi, Matteo; Savasta, Carlo; Russo, Rosario; Pitì, Antonino

    2017-01-01

    Patients with atrial fibrillation (AF) have an increased thromboembolic risk that can be estimated with risk scores and sometimes require oral anticoagulation therapy (OAT). Despite correct anticoagulation, some patients still develop left atrial spontaneous echo contrast (SEC) or thrombosis. The value of traditional risk scores (R 2 CHADS 2 , CHADS 2 , and CHA 2 DS 2 -VASc) in predicting such events remains controversial. The aim of our study was to explore variables linked to severe SEC or atrial thrombosis and evaluate the performance of traditional risk scores in identifying these patients. In order to do this, we retrospectively analyzed 568 patients with nonvalvular nonparoxysmal AF who underwent electrical cardioversion from January 2011 to December 2016 after OAT for a minimum of 4 weeks. A transesophageal echocardiogram was performed in 265 patients for various indications, and 24 exhibited left atrial SEC or thrombosis. Female gender, history of heart failure or left ventricular ejection fraction 1 mg/dL) of C-reactive protein (CRP) were independently associated with left atrial SEC/thrombosis. A score composed by these factors (denominated HIS [Heart Failure, Inflammation, and female Sex]) showed a sensitivity of 79% and a specificity of 60% (area under receiver operating characteristic curve 0.695, P = 0.002) in identifying patients with a positive transesophageal echo; traditional risk scores did not perform as well. In patients with persistent AF and suboptimal anticoagulation, a risk score composed by history of heart failure, high CRP, and female gender identifies patients at high risk of left atrial SEC/thrombosis when its value is >1. © 2016 Wiley Periodicals, Inc.

  20. Resilience and biomarkers of health risk in Black smokers and nonsmokers.

    Science.gov (United States)

    Berg, Carla J; Haardörfer, Regine; McBride, Colleen M; Kilaru, Varun; Ressler, Kerry J; Wingo, Aliza P; Saba, Nabil F; Payne, Jackelyn B; Smith, Alicia

    2017-11-01

    Blacks are disproportionately affected by tobacco-related illnesses as well as traumatic events associated with psychiatric conditions and smoking. We examined the potential protective nature of resilience within this context, hypothesizing resilience differentially moderates the associations of traumatic experiences to depressive symptoms and to biomarkers of health risk among Black ever versus never smokers. Measures of resilience, traumatic experiences, depressive symptoms, and biomarkers (interleukin-6 [IL-6], C-reactive protein [CRP], allostatic load) were obtained among 852 Blacks recruited from Grady Memorial Hospital in Atlanta. Ever smokers experienced more trauma (p smokers, childhood trauma was positively associated with depressive symptoms (p smokers, childhood (p smokers with higher resilience had a negative association between childhood trauma and depressive symptoms whereas those with lower resilience had a positive association between childhood trauma and depressive symptoms. Resilience was negatively associated with CRP levels (p < .001). Interventions targeting resilience may prevent smoking and adverse health outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Risk score to predict gastrointestinal bleeding after acute ischemic stroke.

    Science.gov (United States)

    Ji, Ruijun; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Singhal, Aneesh B; Wang, Yongjun

    2014-07-25

    Gastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke. The AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. A total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts

  2. Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation.

    Science.gov (United States)

    Bitan, Menachem; Ahn, Kwang Woo; Millard, Heather R; Pulsipher, Michael A; Abdel-Azim, Hisham; Auletta, Jeffery J; Brown, Valerie; Chan, Ka Wah; Diaz, Miguel Angel; Dietz, Andrew; Vincent, Marta González; Guilcher, Gregory; Hale, Gregory A; Hayashi, Robert J; Keating, Amy; Mehta, Parinda; Myers, Kasiani; Page, Kristin; Prestidge, Tim; Shah, Nirali N; Smith, Angela R; Woolfrey, Ann; Thiel, Elizabeth; Davies, Stella M; Eapen, Mary

    2017-09-01

    We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. The New York State risk score for predicting in-hospital/30-day mortality following percutaneous coronary intervention.

    Science.gov (United States)

    Hannan, Edward L; Farrell, Louise Szypulski; Walford, Gary; Jacobs, Alice K; Berger, Peter B; Holmes, David R; Stamato, Nicholas J; Sharma, Samin; King, Spencer B

    2013-06-01

    This study sought to develop a percutaneous coronary intervention (PCI) risk score for in-hospital/30-day mortality. Risk scores are simplified linear scores that provide clinicians with quick estimates of patients' short-term mortality rates for informed consent and to determine the appropriate intervention. Earlier PCI risk scores were based on in-hospital mortality. However, for PCI, a substantial percentage of patients die within 30 days of the procedure after discharge. New York's Percutaneous Coronary Interventions Reporting System was used to develop an in-hospital/30-day logistic regression model for patients undergoing PCI in 2010, and this model was converted into a simple linear risk score that estimates mortality rates. The score was validated by applying it to 2009 New York PCI data. Subsequent analyses evaluated the ability of the score to predict complications and length of stay. A total of 54,223 patients were used to develop the risk score. There are 11 risk factors that make up the score, with risk factor scores ranging from 1 to 9, and the highest total score is 34. The score was validated based on patients undergoing PCI in the previous year, and accurately predicted mortality for all patients as well as patients who recently suffered a myocardial infarction (MI). The PCI risk score developed here enables clinicians to estimate in-hospital/30-day mortality very quickly and quite accurately. It accurately predicts mortality for patients undergoing PCI in the previous year and for MI patients, and is also moderately related to perioperative complications and length of stay. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors.

    Science.gov (United States)

    Stratigou, Theodora; Dalamaga, Maria; Antonakos, Georgios; Marinou, Ioanna; Vogiatzakis, Evaggelos; Christodoulatos, Gerasimos Socrates; Karampela, Irene; Papavassiliou, Athanasios G

    2018-02-17

    Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. SH cases exhibited significantly higher circulating irisin than controls (p counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.

  5. Where to Sit? Type of Sitting Matters for the Framingham Cardiovascular Risk Score

    Directory of Open Access Journals (Sweden)

    Katja Borodulin

    2016-08-01

    Full Text Available Background: Current evidence on associations of type-specific sedentary behavior with cardiovascular disease (CVD is limited to mainly screen-time sedentary behavior (SB. We aimed to study the associations of type-specific and total time spent sitting with the Framingham 10-year cardiovascular disease risk score (Framingham score in Finnish adults. Methods: Data comprise the National FINRISK 2007 and 2012 health examination surveys with 10,185 participants aged 25-74 years, apparently free of CVD. Participants reported average daily time spent sitting in different locations: work-related sitting, at home in front of television (TV, at home in front of computer, in a vehicle, and elsewhere. Total SB time was calculated from these context-specific self-reports. Accelerometer-based sedentary time was assessed in 988 FINRISK 2012 participants. Framingham score was calculated using information on blood pressure and its medication, cholesterol levels, age, diabetes status, and smoking. Analyses were adjusted for age, study year, education, employment status, leisure time physical activity, and body mass index. Results: Out of several type-specific sitting behaviors, only TV sitting showed systematic associations with the Framingham score in both genders. The lowest Framingham risk was found for TV sitting from 6 minutes to less than 1 hour daily. Of other types of sitting, computer sitting was inversely associated with the Framingham risk in men only. Total self-reported sitting time did not show significant associations with the Framingham score, but instead higher objectively assessed sedentary time showed higher Framingham risk in men. Conclusions: TV sitting showed most systematic associations with CVD risk score. This suggests that of all types of SB, reducing TV sitting should be targeted for reducing CVD risk.

  6. Risk score prediction model for dementia in patients with type 2 diabetes.

    Science.gov (United States)

    Li, Chia-Ing; Li, Tsai-Chung; Liu, Chiu-Shong; Liao, Li-Na; Lin, Wen-Yuan; Lin, Chih-Hsueh; Yang, Sing-Yu; Chiang, Jen-Huai; Lin, Cheng-Chieh

    2018-03-30

    No study established a prediction dementia model in the Asian populations. This study aims to develop a prediction model for dementia in Chinese type 2 diabetes patients. This retrospective cohort study included 27,540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by Framingham Heart Study were used to establish a prediction model with a scoring system. The average follow-up was 8.09 years, with a total of 853 incident dementia cases in derivation set. Dementia risk score summed up the individual scores (from 0 to 20). The areas under curve of 3-, 5-, and 10-year dementia risks were 0.82, 0.79, and 0.76 in derivation set and 0.84, 0.80, and 0.75 in validation set, respectively. The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Data on coronary artery calcium score performance and cardiovascular risk reclassification across gender and ethnicities

    Directory of Open Access Journals (Sweden)

    Marat Fudim

    2016-03-01

    Full Text Available The current guidelines recommend the new risk score, Atherosclerotic Cardiovascular Disease score (ASCVD, to assess an individual׳s risk of future cardiovascular disease (CVD events. No data exist on the predictive utility of ASCVD score with the incremental value of coronary artery calcium scoring (CACS across ethnicities and gender. Multi-Ethnic Study of Atherosclerosis (MESA is a population based study (n=6814 of White (38%, Black (28%, Chinese (22% and Hispanic (12% subjects, aged 45–84 years, free from clinical cardiovascular disease. We performed a post-hoc analysis of 6742 participants (mean age 62, 53% female from the MESA cohort. We evaluated the predictive accuracy for the ASCVD score for each participant in accord with the American College of Cardiology/American Heart Association guidelines using pooled cohort equations. Similar to the publication by Fudim et al. “The Metabolic Syndrome, Coronary Artery Calcium Score and Cardiovascular Risk Reclassification” [1] the analytic properties of models incorporating the ASCVD score with and without CACS were compared for cardiovascular disease CVD prediction. Here the analysis focused on ASCVD score (with and without CACS performance across gender and ethnicities. Keywords: Risk stratification, Coronary calcium scoring, Gender, Ethnicity, MESA, {C}{C}

  8. Screening applicants for risk of poor academic performance: a novel scoring system using preadmission grade point averages and graduate record examination scores.

    Science.gov (United States)

    Luce, David

    2011-01-01

    The purpose of this study was to develop an effective screening tool for identifying physician assistant (PA) program applicants at highest risk for poor academic performance. Prior to reviewing applications for the class of 2009, a retrospective analysis of preadmission data took place for the classes of 2006, 2007, and 2008. A single composite score was calculated for each student who matriculated (number of subjects, N=228) incorporating the total undergraduate grade point average (UGPA), the science GPA (SGPA), and the three component Graduate Record Examination (GRE) scores: verbal (GRE-V), quantitative (GRE-Q), analytical (GRE-A). Individual applicant scores for each of the five parameters were ranked in descending quintiles. Each applicant's five quintile scores were then added, yielding a total quintile score ranging from 25, which indicated an excellent performance, to 5, which indicated poorer performance. Thirteen of the 228 students had academic difficulty (dismissal, suspension, or one-quarter on academic warning or probation). Twelve of the 13 students having academic difficulty had a preadmission total quintile score 12 (range, 6-14). In response to this descriptive analysis, when selecting applicants for the class of 2009, the admissions committee used the total quintile score for screening applicants for interviews. Analysis of correlations in preadmission, graduate, and postgraduate performance data for the classes of 2009-2013 will continue and may help identify those applicants at risk for academic difficulty. Establishing a threshold total quintile score of applicant GPA and GRE scores may significantly decrease the number of entering PA students at risk for poor academic performance.

  9. Biomarkers of exposure and dose: State of the art

    International Nuclear Information System (INIS)

    Brooks, A.L.

    2001-01-01

    Biomarkers provide methods to measure changes in biological systems and to relate them to environmental insults and disease processes. Biomarkers can be classified as markers of exposure and dose, markers of sensitivity, and markers of disease. It is important that the differences and applications of the various types of biomarkers be clearly understood. The military is primarily interested in early biomarkers of exposure and dose that do not require high levels of sensitivity but can be used to rapidly triage war fighters under combat or terrorist conditions and determine which, if any, require medical attention. Biomarkers of long-term radiation risk represent the second area of interest for the military. Biomarkers of risk require high sensitivity and specificity for the disease and insult but do not require rapid data turn around. Biomarkers will help provide information for quick command decisions in the field, characterise long-term troop risks and identify early stages of radiation-induced diseases. This information provides major positive reassurances about individual exposures and risk that will minimise the physical and psychological impact of wartime radiation exposures. (author)

  10. Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

    Science.gov (United States)

    Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

    2018-03-01

    While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (pbleeding scores, c-indexes were significantly higher compared to MBR factors (pbleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all pbleeding risk scores for major bleeding (all pbleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Association of a Dietary Score with Incident Type 2 Diabetes: The Dietary-Based Diabetes-Risk Score (DDS.

    Directory of Open Access Journals (Sweden)

    Ligia J Dominguez

    Full Text Available Strong evidence supports that dietary modifications may decrease incident type 2 diabetes mellitus (T2DM. Numerous diabetes risk models/scores have been developed, but most do not rely specifically on dietary variables or do not fully capture the overall dietary pattern. We prospectively assessed the association of a dietary-based diabetes-risk score (DDS, which integrates optimal food patterns, with the risk of developing T2DM in the SUN ("Seguimiento Universidad de Navarra" longitudinal study.We assessed 17,292 participants initially free of diabetes, followed-up for a mean of 9.2 years. A validated 136-item FFQ was administered at baseline. Taking into account previous literature, the DDS positively weighted vegetables, fruit, whole cereals, nuts, coffee, low-fat dairy, fiber, PUFA, and alcohol in moderate amounts; while it negatively weighted red meat, processed meats and sugar-sweetened beverages. Energy-adjusted quintiles of each item (with exception of moderate alcohol consumption that received either 0 or 5 points were used to build the DDS (maximum: 60 points. Incident T2DM was confirmed through additional detailed questionnaires and review of medical records of participants. We used Cox proportional hazards models adjusted for socio-demographic and anthropometric parameters, health-related habits, and clinical variables to estimate hazard ratios (HR of T2DM.We observed 143 T2DM confirmed cases during follow-up. Better baseline conformity with the DDS was associated with lower incidence of T2DM (multivariable-adjusted HR for intermediate (25-39 points vs. low (11-24 category 0.43 [95% confidence interval (CI 0.21, 0.89]; and for high (40-60 vs. low category 0.32 [95% CI: 0.14, 0.69]; p for linear trend: 0.019.The DDS, a simple score exclusively based on dietary components, showed a strong inverse association with incident T2DM. This score may be applicable in clinical practice to improve dietary habits of subjects at high risk of T2DM

  12. Prognostic Value of High-Sensitivity Cardiac Troponin T Compared with Risk Scores in Stable Cardiovascular Disease.

    Science.gov (United States)

    Biener, Moritz; Giannitsis, Evangelos; Kuhner, Manuel; Zelniker, Thomas; Mueller-Hennessen, Matthias; Vafaie, Mehrshad; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald; Katus, Hugo A

    2017-05-01

    Risk stratification of patients with cardiovascular disease remains challenging despite consideration of risk scores. We aimed to evaluate the prognostic performance of high-sensitivity cardiac troponin T in a low-risk outpatient population presenting for nonsecondary and secondary prevention. All-cause mortality, a composite of all-cause mortality, acute myocardial infarction, and stroke (end point 2), and a composite of all-cause mortality, acute myocardial infarction, stroke and rehospitalization for acute coronary syndrome, and decompensated heart failure (end point 3) were defined. The prognostic performance of high-sensitivity cardiac troponin T on index visit was compared with the PROCAM score and 3 FRAMINGHAM subscores. In 693 patients with a median follow-up of 796 days, we observed 16 deaths, 32 patients with end point 2, and 83 patients with end point 3. All risk scores performed better in the prediction of all-cause mortality in nonsecondary prevention (area under the curve [AUC]: PROCAM: 0.922 vs 0.523, P = .001, consistent for all other scores). In secondary prevention, high-sensitivity cardiac troponin T outperformed all risk scores in the prediction of all-cause mortality (ΔAUC: PROCAM: 0.319, P risk scores. Our findings on the prediction of all-cause mortality compared with the FRAMINGHAM-Hard Coronary Heart Disease score were confirmed in an independent validation cohort on 2046 patients. High-sensitivity troponin T provides excellent risk stratification regarding all-cause mortality and all-cause mortality, acute myocardial infarction, and stroke in a secondary prevention cohort in whom risk scores perform poorly. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The New York risk score for in-hospital and 30-day mortality for coronary artery bypass graft surgery.

    Science.gov (United States)

    Hannan, Edward L; Farrell, Louise Szypulski; Wechsler, Andrew; Jordan, Desmond; Lahey, Stephen J; Culliford, Alfred T; Gold, Jeffrey P; Higgins, Robert S D; Smith, Craig R

    2013-01-01

    Simplified risk scores for coronary artery bypass graft surgery are frequently in lieu of more complicated statistical models and are valuable for informed consent and choice of intervention. Previous risk scores have been based on in-hospital mortality, but a substantial number of patients die within 30 days of the procedure. These deaths should also be accounted for, so we have developed a risk score based on in-hospital and 30-day mortality. New York's Cardiac Surgery Reporting System was used to develop an in-hospital and 30-day logistic regression model for patients undergoing coronary artery bypass graft surgery in 2009, and this model was converted into a simple linear risk score that provides estimated in-hospital and 30-day mortality rates for different values of the score. The accuracy of the risk score in predicting mortality was tested. This score was also validated by applying it to 2008 New York coronary artery bypass graft data. Subsequent analyses evaluated the ability of the risk score to predict complications and length of stay. The overall in-hospital and 30-day mortality rate for the 10,148 patients in the study was 1.79%. There are seven risk factors comprising the score, with risk factor scores ranging from 1 to 5, and the highest possible total score is 23. The score accurately predicted mortality in 2009 as well as in 2008, and was strongly correlated with complications and length of stay. The risk score is a simple way of estimating short-term mortality that accurately predicts mortality in the year the model was developed as well as in the previous year. Perioperative complications and length of stay are also well predicted by the risk score. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. The Surgical Site Infection Risk Score (SSIRS: A Model to Predict the Risk of Surgical Site Infections.

    Directory of Open Access Journals (Sweden)

    Carl van Walraven

    Full Text Available Surgical site infections (SSI are an important cause of peri-surgical morbidity with risks that vary extensively between patients and surgeries. Quantifying SSI risk would help identify candidates most likely to benefit from interventions to decrease the risk of SSI.We randomly divided all surgeries recorded in the National Surgical Quality Improvement Program from 2010 into a derivation and validation population. We used multivariate logistic regression to determine the independent association of patient and surgical covariates with the risk of any SSI (including superficial, deep, and organ space SSI within 30 days of surgery. To capture factors particular to specific surgeries, we developed a surgical risk score specific to all surgeries having a common first 3 numbers of their CPT code.Derivation (n = 181 894 and validation (n = 181 146 patients were similar for all demographics, past medical history, and surgical factors. Overall SSI risk was 3.9%. The SSI Risk Score (SSIRS found that risk increased with patient factors (smoking, increased body mass index, certain comorbidities (peripheral vascular disease, metastatic cancer, chronic steroid use, recent sepsis, and operative characteristics (surgical urgency; increased ASA class; longer operation duration; infected wounds; general anaesthesia; performance of more than one procedure; and CPT score. In the validation population, the SSIRS had good discrimination (c-statistic 0.800, 95% CI 0.795-0.805 and calibration.SSIRS can be calculated using patient and surgery information to estimate individual risk of SSI for a broad range of surgery types.

  15. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

    Science.gov (United States)

    Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

    2016-04-01

    The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories ( 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

  16. Unsupervised deep learning applied to breast density segmentation and mammographic risk scoring

    DEFF Research Database (Denmark)

    Kallenberg, Michiel Gijsbertus J.; Petersen, Peter Kersten; Nielsen, Mads

    2016-01-01

    Mammographic risk scoring has commonly been automated by extracting a set of handcrafted features from mammograms, and relating the responses directly or indirectly to breast cancer risk. We present a method that learns a feature hierarchy from unlabeled data. When the learned features are used...... as the input to a simple classifier, two different tasks can be addressed: i) breast density segmentation, and ii) scoring of mammographic texture. The proposed model learns features at multiple scales. To control the models capacity a novel sparsity regularizer is introduced that incorporates both lifetime...... and population sparsity. We evaluated our method on three different clinical datasets. Our state-of-the-art results show that the learned breast density scores have a very strong positive relationship with manual ones, and that the learned texture scores are predictive of breast cancer. The model is easy...

  17. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

    Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

  18. Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia[S

    Science.gov (United States)

    Medeiros, Ana Margarida; Alves, Ana Catarina; Aguiar, Pedro; Bourbon, Mafalda

    2014-01-01

    The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem≥ia. An apoB/apoA1 ratio ≥0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ≥0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients. PMID:24627126

  19. A clinically useful risk-score for chronic kidney disease in HIV infection

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Lundgren, Jens; Ross, Michael

    2014-01-01

    baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6-1.0), 5.6 (95% CI 4.5-6.7) and 37.4 (95% CI 34.......0-40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90-0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium...

  20. Risk of poor neonatal outcome at term after medically assisted reproduction: a propensity score-matched study.

    Science.gov (United States)

    Ensing, Sabine; Abu-Hanna, Ameen; Roseboom, Tessa J; Repping, Sjoerd; van der Veen, Fulco; Mol, Ben Willem J; Ravelli, Anita C J

    2015-08-01

    To study risk of birth asphyxia and related morbidity among term singletons born after medically assisted reproduction (MAR). Population cohort study. Not applicable. A total of 1,953,932 term singleton pregnancies selected from a national registry for 1999-2011. None. Primary outcome Apgar score score score matching analysis was performed with matching on multiple maternal baseline covariates (maternal age, ethnicity, socioeconomic status, parity, year of birth, and preexistent diseases). Each MAR pregnancy was matched to three SC controls. Relative to SC, the MAR singletons had an increased risk of adverse neonatal outcomes including Apgar score score matching, the risk of an Apgar score Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Global DNA hypomethylation in peripheral blood leukocytes as a biomarker for cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hae Dong Woo

    Full Text Available BACKGROUND: Good biomarkers for early detection of cancer lead to better prognosis. However, harvesting tumor tissue is invasive and cannot be routinely performed. Global DNA methylation of peripheral blood leukocyte DNA was evaluated as a biomarker for cancer risk. METHODS: We performed a meta-analysis to estimate overall cancer risk according to global DNA hypomethylation levels among studies with various cancer types and analytical methods used to measure DNA methylation. Studies were systemically searched via PubMed with no language limitation up to July 2011. Summary estimates were calculated using a fixed effects model. RESULTS: The subgroup analyses by experimental methods to determine DNA methylation level were performed due to heterogeneity within the selected studies (p<0.001, I(2: 80%. Heterogeneity was not found in the subgroup of %5-mC (p = 0.393, I(2: 0% and LINE-1 used same target sequence (p = 0.097, I(2: 49%, whereas considerable variance remained in LINE-1 (p<0.001, I(2: 80% and bladder cancer studies (p = 0.016, I(2: 76%. These results suggest that experimental methods used to quantify global DNA methylation levels are important factors in the association study between hypomethylation levels and cancer risk. Overall, cancer risks of the group with the lowest DNA methylation levels were significantly higher compared to the group with the highest methylation levels [OR (95% CI: 1.48 (1.28-1.70]. CONCLUSIONS: Global DNA hypomethylation in peripheral blood leukocytes may be a suitable biomarker for cancer risk. However, the association between global DNA methylation and cancer risk may be different based on experimental methods, and region of DNA targeted for measuring global hypomethylation levels as well as the cancer type. Therefore, it is important to select a precise and accurate surrogate marker for global DNA methylation levels in the association studies between global DNA methylation levels in peripheral

  2. Biomarker identification and effect estimation on schizophrenia –a high dimensional data analysis

    Directory of Open Access Journals (Sweden)

    Yuanzhang eLi

    2015-05-01

    Full Text Available Biomarkers have been examined in schizophrenia research for decades. Medical morbidity and mortality rates, as well as personal and societal costs, are associated with schizophrenia patients. The identification of biomarkers and alleles, which often have a small effect individually, may help to develop new diagnostic tests for early identification and treatment. Currently, there is not a commonly accepted statistical approach to identify predictive biomarkers from high dimensional data. We used space Decomposition-Gradient-Regression method (DGR to select biomarkers, which are associated with the risk of schizophrenia. Then, we used the gradient scores, generated from the selected biomarkers, as the prediction factor in regression to estimate their effects. We also used an alternative approach, classification and regression tree (CART, to compare the biomarker selected by DGR and found about 70% of the selected biomarkers were the same. However, the advantage of DGR is that it can evaluate individual effects for each biomarker from their combined effect. In DGR analysis of serum specimens of US military service members with a diagnosis of schizophrenia from 1992 to 2005 and their controls, Alpha-1-Antitrypsin (AAT, Interleukin-6 receptor (IL-6r and Connective Tissue Growth Factor (CTGF were selected to identify schizophrenia for males; and Alpha-1-Antitrypsin (AAT, Apolipoprotein B (Apo B and Sortilin were selected for females. If these findings from military subjects are replicated by other studies, they suggest the possibility of a novel biomarker panel as an adjunct to earlier diagnosis and initiation of treatment.

  3. Recurrence risk of low Apgar score among term singletons: a population-based cohort study

    NARCIS (Netherlands)

    Ensing, Sabine; Schaaf, Jelle M.; Abu-Hanna, Ameen; Mol, Ben W. J.; Ravelli, Anita C. J.

    2014-01-01

    To examine the risk of recurrence of low Apgar score in a subsequent term singleton pregnancy. Population-based cohort study. The Netherlands. A total of 190,725 women with two subsequent singleton term live births between 1999 and 2007. We calculated the recurrence risk of low Apgar score after

  4. Feasibility and reliability of a newly developed antenatal risk score card in routine care

    NARCIS (Netherlands)

    E. Birnie; E.A.P. Steegers; Drs. H.W. Torij; M.J. Veen; J. Poeran; G.J. Bonsel

    2015-01-01

    A population-based cross-sectional study (feasibility) and a cohort study (inter-rater reliability) to study in routine care the feasibility and inter-rater reliability of the Rotterdam Reproductive Risk Reduction risk score card (R4U), a new semi-quantitative score card for use during the antenatal

  5. Development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients: the VPOP score.

    Science.gov (United States)

    Bourdaud, Nathalie; Devys, Jean-Michel; Bientz, Jocelyne; Lejus, Corinne; Hebrard, Anne; Tirel, Olivier; Lecoutre, Damien; Sabourdin, Nada; Nivoche, Yves; Baujard, Catherine; Nikasinovic, Lydia; Orliaguet, Gilles A

    2014-09-01

    Few data are available in the literature on risk factors for postoperative vomiting (POV) in children. The aim of the study was to establish independent risk factors for POV and to construct a pediatric specific risk score to predict POV in children. Characteristics of 2392 children operated under general anesthesia were recorded. The dataset was randomly split into an evaluation set (n = 1761), analyzed with a multivariate analysis including logistic regression and backward stepwise procedure, and a validation set (n = 450), used to confirm the accuracy of prediction using the area under the receiver operating characteristic curve (ROCAUC ), to optimize sensitivity and specificity. The overall incidence of POV was 24.1%. Five independent risk factors were identified: stratified age (>3 and 13 years: adjusted OR 2.46 [95% CI 1.75-3.45]; ≥6 and ≤13 years: aOR 3.09 [95% CI 2.23-4.29]), duration of anesthesia (aOR 1.44 [95% IC 1.06-1.96]), surgery at risk (aOR 2.13 [95% IC 1.49-3.06]), predisposition to POV (aOR 1.81 [95% CI 1.43-2.31]), and multiple opioids doses (aOR 2.76 [95% CI 2.06-3.70], P risk score ranged from 0 to 6. The model yielded a ROCAUC of 0.73 [95% CI 0.67-0.78] when applied to the validation dataset. Independent risk factors for POV were identified and used to create a new score to predict which children are at high risk of POV. © 2014 John Wiley & Sons Ltd.

  6. Fish bioaccumulation and biomarkers in environmental risk assessment: a review.

    Science.gov (United States)

    van der Oost, Ron; Beyer, Jonny; Vermeulen, Nico P E

    2003-02-01

    In this review, a wide array of bioaccumulation markers and biomarkers, used to demonstrate exposure to and effects of environmental contaminants, has been discussed in relation to their feasibility in environmental risk assessment (ERA). Fish bioaccumulation markers may be applied in order to elucidate the aquatic behavior of environmental contaminants, as bioconcentrators to identify certain substances with low water levels and to assess exposure of aquatic organisms. Since it is virtually impossible to predict the fate of xenobiotic substances with simple partitioning models, the complexity of bioaccumulation should be considered, including toxicokinetics, metabolism, biota-sediment accumulation factors (BSAFs), organ-specific bioaccumulation and bound residues. Since it remains hard to accurately predict bioaccumulation in fish, even with highly sophisticated models, analyses of tissue levels are required. The most promising fish bioaccumulation markers are body burdens of persistent organic pollutants, like PCBs and DDTs. Since PCDD and PCDF levels in fish tissues are very low as compared with the sediment levels, their value as bioaccumulation markers remains questionable. Easily biodegradable compounds, such as PAHs and chlorinated phenols, do not tend to accumulate in fish tissues in quantities that reflect the exposure. Semipermeable membrane devices (SPMDs) have been successfully used to mimic bioaccumulation of hydrophobic organic substances in aquatic organisms. In order to assess exposure to or effects of environmental pollutants on aquatic ecosystems, the following suite of fish biomarkers may be examined: biotransformation enzymes (phase I and II), oxidative stress parameters, biotransformation products, stress proteins, metallothioneins (MTs), MXR proteins, hematological parameters, immunological parameters, reproductive and endocrine parameters, genotoxic parameters, neuromuscular parameters, physiological, histological and morphological parameters

  7. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

  8. Pre-operative risk scores for the prediction of outcome in elderly people who require emergency surgery

    Directory of Open Access Journals (Sweden)

    Bates Tom

    2007-06-01

    Full Text Available Abstract Background The decision on whether to operate on a sick elderly person with an intra-abdominal emergency is one of the most difficult in general surgery. A predictive risk-score would be of great value in this situation. Methods A Medline search was performed to identify those predictive risk-scores relevant to sick elderly patients in whom emergency surgery might be life-saving. Results Many of the risk scores for surgical patients include the operative findings or require tests which are not available in the acute situation. Most of the relevant studies include younger patients and elective surgery. The Glasgow Aneurysm Score and Hardman Index are specific to ruptured aortic aneurysm while the Boey Score and the Hacetteppe Score are specific to perforated peptic ulcer. The Reiss Index and Fitness Score can be used pre-operatively if the elements of the score can be completed in time. The ASA score, which includes a significant element of subjective clinical judgement, can be augmented with factors such as age and urgency of surgery but no test has a negative predictive value sufficient to recommend against surgical intervention without clinical input. Conclusion Risk scores may be helpful in sick elderly patients needing emergency abdominal surgery but an experienced clinical opinion is still essential.

  9. Risk-Assessment Score and Patient Optimization as Cost Predictors for Ventral Hernia Repair.

    Science.gov (United States)

    Saleh, Sherif; Plymale, Margaret A; Davenport, Daniel L; Roth, John Scott

    2018-04-01

    Ventral hernia repair (VHR) is associated with complications that significantly increase healthcare costs. This study explores the associations between hospital costs for VHR and surgical complication risk-assessment scores, need for cardiac or pulmonary evaluation, and smoking or obesity counseling. An IRB-approved retrospective study of patients having undergone open VHR over 3 years was performed. Ventral Hernia Risk Score (VHRS) for surgical site occurrence and surgical site infection, and the Ventral Hernia Working Group grade were calculated for each case. Also recorded were preoperative cardiology or pulmonary evaluations, smoking cessation and weight reduction counseling, and patient goal achievement. Hospital costs were obtained from the cost accounting system for the VHR hospitalization stratified by major clinical cost drivers. Univariate regression analyses were used to compare the predictive power of the risk scores. Multivariable analysis was performed to develop a cost prediction model. The mean cost of index VHR hospitalization was $20,700. Total and operating room costs correlated with increasing CDC wound class, VHRS surgical site infection score, VHRS surgical site occurrence score, American Society of Anesthesiologists class, and Ventral Hernia Working Group (all p variance in costs (p optimization significantly reduced direct and operating room costs (p < 0.05). Cardiac evaluation was associated with increased costs. Ventral hernia repair hospital costs are more accurately predicted by CDC wound class than VHR risk scores. A straightforward 6-factor model predicted most cost variation for VHR. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  10. 75 FR 54020 - Federal Housing Administration Risk Management Initiatives: New Loan-to-Value and Credit Score...

    Science.gov (United States)

    2010-09-03

    ... Housing Administration Risk Management Initiatives: New Loan-to-Value and Credit Score Requirements AGENCY... acceptable risks of financial loss, not unacceptable risks.\\2\\ \\2\\ While the Federal Credit Reform Act of..., specific to each applicant. Lower credit scores indicate greater risk of default on any new credit extended...

  11. Cardiovascular disease risk score prediction models for women and its applicability to Asians

    Directory of Open Access Journals (Sweden)

    Goh LGH

    2014-03-01

    Full Text Available Louise GH Goh,1 Satvinder S Dhaliwal,1 Timothy A Welborn,2 Peter L Thompson,2–4 Bruce R Maycock,1 Deborah A Kerr,1 Andy H Lee,1 Dean Bertolatti,1 Karin M Clark,1 Rakhshanda Naheed,1 Ranil Coorey,1 Phillip R Della5 1School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia; 2Sir Charles Gairdner Hospital, Nedlands, Perth, WA, Australia; 3School of Population Health, University of Western Australia, Perth, WA, Australia; 4Harry Perkins Institute for Medical Research, Perth, WA, Australia; 5School of Nursing and Midwifery, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Purpose: Although elevated cardiovascular disease (CVD risk factors are associated with a higher risk of developing heart conditions across all ethnic groups, variations exist between groups in the distribution and association of risk factors, and also risk levels. This study assessed the 10-year predicted risk in a multiethnic cohort of women and compared the differences in risk between Asian and Caucasian women. Methods: Information on demographics, medical conditions and treatment, smoking behavior, dietary behavior, and exercise patterns were collected. Physical measurements were also taken. The 10-year risk was calculated using the Framingham model, SCORE (Systematic COronary Risk Evaluation risk chart for low risk and high risk regions, the general CVD, and simplified general CVD risk score models in 4,354 females aged 20–69 years with no heart disease, diabetes, or stroke at baseline from the third Australian Risk Factor Prevalence Study. Country of birth was used as a surrogate for ethnicity. Nonparametric statistics were used to compare risk levels between ethnic groups. Results: Asian women generally had lower risk of CVD when compared to Caucasian women. The 10-year predicted risk was, however, similar between Asian and Australian women, for some models. These findings were

  12. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

    Science.gov (United States)

    Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

    2017-03-07

    Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

  13. Comparison of Risk Scores for Prediction of Complications following Aortic Valve Replacement.

    Science.gov (United States)

    Wang, Tom Kai Ming; Choi, David Hyun-Min; Haydock, David; Gamble, Greg; Stewart, Ralph; Ruygrok, Peter

    2015-06-01

    Risk models play an important role in stratification of patients for cardiac surgery, but their prognostic utilities for post-operative complications are rarely studied. We compared the EuroSCORE, EuroSCORE II, Society of Thoracic Surgeon's (STS) Score and an Australasian model (Aus-AVR Score) for predicting morbidities after aortic valve replacement (AVR), and also evaluated seven STS complications models in this context. We retrospectively calculated risk scores for 620 consecutive patients undergoing isolated AVR at Auckland City Hospital during 2005-2012, assessing their discrimination and calibration for post-operative complications. Amongst mortality scores, the EuroSCORE was the best at discriminating stroke (c-statistic 0.845); the EuroSCORE II at deep sternal wound infection (c=0.748); and the STS Score at composite morbidity or mortality (c=0.666), renal failure (c=0.634), ventilation>24 hours (c=0.732), return to theatre (c=0.577) and prolonged hospital stay >14 days post-operatively (c=0.707). The individual STS complications models had a marginally higher c-statistic (c=0.634-0.846) for all complications except mediastinitis, and had good calibration (Hosmer-Lemeshow test P-value 0.123-0.915) for all complications. The STS Score was best overall at discriminating post-operative complications and their composite for AVR. All STS complications models except for deep sternal wound infection had good discrimination and calibration for post-operative complications. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  14. The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Christine Henri

    2016-01-01

    Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

  15. A Simple Risk Score for Identifying Individuals with Impaired Fasting Glucose in the Southern Chinese Population

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2015-01-01

    Full Text Available This study aimed to develop and validate a simple risk score for detecting individuals with impaired fasting glucose (IFG among the Southern Chinese population. A sample of participants aged ≥20 years and without known diabetes from the 2006–2007 Guangzhou diabetes cross-sectional survey was used to develop separate risk scores for men and women. The participants completed a self-administered structured questionnaire and underwent simple clinical measurements. The risk scores were developed by multiple logistic regression analysis. External validation was performed based on three other studies: the 2007 Zhuhai rural population-based study, the 2008–2010 Guangzhou diabetes cross-sectional study and the 2007 Tibet population-based study. Performance of the scores was measured with the Hosmer-Lemeshow goodness-of-fit test and ROC c-statistic. Age, waist circumference, body mass index and family history of diabetes were included in the risk score for both men and women, with the additional factor of hypertension for men. The ROC c-statistic was 0.70 for both men and women in the derivation samples. Risk scores of ≥28 for men and ≥18 for women showed respective sensitivity, specificity, positive predictive value and negative predictive value of 56.6%, 71.7%, 13.0% and 96.0% for men and 68.7%, 60.2%, 11% and 96.0% for women in the derivation population. The scores performed comparably with the Zhuhai rural sample and the 2008–2010 Guangzhou urban samples but poorly in the Tibet sample. The performance of pre-existing USA, Shanghai, and Chengdu risk scores was poorer in our population than in their original study populations. The results suggest that the developed simple IFG risk scores can be generalized in Guangzhou city and nearby rural regions and may help primary health care workers to identify individuals with IFG in their practice.

  16. 'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.

    Science.gov (United States)

    Leoutsakos, J-M; Gross, A L; Jones, R N; Albert, M S; Breitner, J C S

    2016-01-01

    Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio. Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. An IRT-based APS can summarize multimodal information to provide a longitudinal measure of

  17. Abnormal temporal lobe white matter as a biomarker for genetic risk of bipolar disorder.

    Science.gov (United States)

    Mahon, Katie; Burdick, Katherine E; Ikuta, Toshikazu; Braga, Raphael J; Gruner, Patricia; Malhotra, Anil K; Szeszko, Philip R

    2013-01-15

    Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD (n=26), unaffected siblings of patients with BD (n=15), and healthy volunteers (n=27) to identify WM biomarkers of genetic risk. The FA differed significantly (punaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. A risk-scoring scheme for suicide attempts among patients with bipolar disorder in a Thai patient cohort

    Directory of Open Access Journals (Sweden)

    Patumanond J

    2012-04-01

    Full Text Available Chidchanok Ruengorn1,2, Kittipong Sanichwankul3, Wirat Niwatananun2, Suwat Mahatnirunkul3, Wanida Pumpaisalchai3, Jayanton Patumanond11Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 3Suanprung Psychiatric Hospital, Chiang Mai, ThailandBackground: In Thailand, risk factors associated with suicide attempts in bipolar disorder (BD are rarely investigated, nor has a specific risk-scoring scheme to assist in the identification of BD patients at risk for attempting suicide been proposed.Objective: To develop a simple risk-scoring scheme to identify patients with BD who may be at risk for attempting suicide.Methods: Medical files of 489 patients diagnosed with BD at Suanprung Psychiatric Hospital between October 2006 and May 2009 were reviewed. Cases included BD patients hospitalized due to attempted suicide (n = 58, and seven controls were selected (per suicide case among BD in- and out-patients who did not attempt suicide, with patients being visited the same day or within 1 week of case study (n = 431. Broad sociodemographic and clinical factors were gathered and analyzed using multivariate logistic regression, to obtain a set of risk factors. Scores for each indicator were weighted, assigned, and summed to create a total risk score, which was divided into low, moderate, and high-risk suicide attempt groups.Results: Six statistically significant indicators associated with suicide attempts were included in the risk-scoring scheme: depression, psychotic symptom(s, number of previous suicide attempts, stressful life event(s, medication adherence, and BD treatment years. A total risk score (possible range -1.5 to 11.5 explained an 88.6% probability of suicide attempts based on the receiver operating characteristic (ROC analysis. Likelihood ratios of suicide attempts with low risk scores (below 2

  19. Low amniotic fluid index in high risk pregnancy and poor apgar score at birth

    International Nuclear Information System (INIS)

    Sultana, S.; Akhtar, K.A.K.

    2008-01-01

    To determine the accuracy of antepartum Amniotic Fluid Index (AFI) of 5 cm was labeled as predictor of good outcome at birth. The subjects in both the groups were demographically matched and fulfilled the inclusion and exclusion criteria. The Apgar score was calculated at 5 minutes of birth. The newborns, with Apgar score 6 were labeled as healthy. AFI was compared with Apgar score, using Chi-square and a p-value was calculated to determine the statistical significance. Sensitivity, specificity, efficiency and the predictive values of AFI at a cut off point of < 5 cm as a predictor of adverse outcome at birth (Apgar score of < 6 at 5 minutes of birth) in high-risk pregnancy were calculated. Only 8 neonates of 50 women with low AFI had low Apgar score. Similarly, 6 neonates of 50 women with normal AFI had poor Apgar score. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and efficiency of AFI as test were 57.1%, 51.3%, 16%, 88% and 52% respectively. Low AFI is a poor predictor of adverse outcome for high-risk term patients. AFI is not a good screening test for high-risk pregnant women at term for birth of an infant with low Apgar score. (author)

  20. Application of the FOUR Score in Intracerebral Hemorrhage Risk Analysis.

    Science.gov (United States)

    Braksick, Sherri A; Hemphill, J Claude; Mandrekar, Jay; Wijdicks, Eelco F M; Fugate, Jennifer E

    2018-06-01

    The Full Outline of Unresponsiveness (FOUR) Score is a validated scale describing the essentials of a coma examination, including motor response, eye opening and eye movements, brainstem reflexes, and respiratory pattern. We incorporated the FOUR Score into the existing ICH Score and evaluated its accuracy of risk assessment in spontaneous intracerebral hemorrhage (ICH). Consecutive patients admitted to our institution from 2009 to 2012 with spontaneous ICH were reviewed. The ICH Score was calculated using patient age, hemorrhage location, hemorrhage volume, evidence of intraventricular extension, and Glasgow Coma Scale (GCS). The FOUR Score was then incorporated into the ICH Score as a substitute for the GCS (ICH Score FS ). The ability of the 2 scores to predict mortality at 1 month was then compared. In total, 274 patients met the inclusion criteria. The median age was 73 years (interquartile range 60-82) and 138 (50.4%) were male. Overall mortality at 1 month was 28.8% (n = 79). The area under the receiver operating characteristic curve was .91 for the ICH Score and .89 for the ICH Score FS . For ICH Scores of 1, 2, 3, 4, and 5, 1-month mortality was 4.2%, 29.9%, 62.5%, 95.0%, and 100%. In the ICH Score FS model, mortality was 10.7%, 26.5%, 64.5%, 88.9%, and 100% for scores of 1, 2, 3, 4, and 5, respectively. The ICH Score and the ICH Score FS predict 1-month mortality with comparable accuracy. As the FOUR Score provides additional clinical information regarding patient status, it may be a reasonable substitute for the GCS into the ICH Score. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. A Study of Correlation of Neck Circumference with Framingham Risk Score as a Predictor of Coronary Artery Disease.

    Science.gov (United States)

    Koppad, Anand K; Kaulgud, Ram S; Arun, B S

    2017-09-01

    It has been observed that metabolic syndrome is risk factor for Coronary Artery Disease (CAD) and exerts its effects through fat deposition and vascular aging. CAD has been acknowledged as a leading cause of death. In earlier studies, the metabolic risk has been estimated by Framingham risk score. Recent studies have shown that Neck Circumference (NC) has a good correlation with other traditional anthropometric measurements and can be used as marker of obesity. It also correlates with Framingham risk score, which is slightly more sophisticated measure of CAD risk. To assess the risk of CAD in a subject based on NC and to correlate the NC to Framingham risk score. The present cross-sectional study, done at Karnataka Institute of Medical Sciences, Hubli, Karnataka, India, includes 100 subjects. The study duration was of one year from 1 st January 2015 to 31 st December 2015. Anthropometric indices Body Mass Index (BMI) and NC were correlated with 10 year CAD risk as calculated by Framingham risk score. The correlation between BMI, NC, vascular age and Framingham risk score was calculated using Karl Pearson's correlation method. NC has a strong correlation with 10 year CAD risk (p≤0.001). NC was significantly greater in males as compared to females (p≤0.001). Males had greater risk of cardiovascular disease as reflected by higher 10 year Framingham risk score (p≤0.0035). NC gives simple and easy prediction of CAD risk and is more reliable than traditional risk markers like BMI. NC correlates positively with 10 year Framingham risk score.

  2. The Impact of EuroSCORE II Risk Factors on Prediction of Long-Term Mortality.

    Science.gov (United States)

    Barili, Fabio; Pacini, Davide; D'Ovidio, Mariangela; Dang, Nicholas C; Alamanni, Francesco; Di Bartolomeo, Roberto; Grossi, Claudio; Davoli, Marina; Fusco, Danilo; Parolari, Alessandro

    2016-10-01

    The European System for Cardiac Operation Risk Evaluation (EuroSCORE) II has not been tested yet for predicting long-term mortality. This study was undertaken to evaluate the relationship between EuroSCORE II and long-term mortality and to develop a new algorithm based on EuroSCORE II factors to predict long-term survival after cardiac surgery. Complete data on 10,033 patients who underwent major cardiac surgery during a 7-year period were retrieved from three prospective institutional databases and linked with the Italian Tax Register Information System. Mortality at follow-up was analyzed with time-to-event analysis. The Kaplan-Meier estimates of survival at 1 and 5 were, respectively, 95.0% ± 0.2% and 84.7% ± 0.4%. Both discrimination and calibration of EuroSCORE II decreased in the prediction of 1-year and 5-year mortality. Nonetheless, EuroSCORE II was confirmed to be an independent predictor of long-term mortality with a nonlinear trend. Several EuroSCORE II variables were independent risk factors for long-term mortality in a regression model, most of all very low ejection fraction (less than 20%), salvage operation, and dialysis. In the final model, isolated mitral valve surgery and isolated coronary artery bypass graft surgery were associated with improved long-term survival. The EuroSCORE II cannot be considered a direct estimator of long-term risk of death, as its performance fades for mortality at follow-up longer than 30 days. Nonetheless, it is nonlinearly associated with long-term mortality, and most of its variables are risk factors for long-term mortality. Hence, they can be used in a different algorithm to stratify the risk of long-term mortality after surgery. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  3. The comparison of cardiovascular risk scores using two methods of substituting missing risk factor data in patient medical records

    Directory of Open Access Journals (Sweden)

    Andrew Dalton

    2011-07-01

    Conclusions A simple method of substituting missing risk factor data can produce reliable estimates of CVD risk scores. Targeted screening for high CVD risk, using pre-existing electronic medical record data, does not require multiple imputation methods in risk estimation.

  4. Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Zhiying Zhang

    2017-08-01

    Full Text Available Malnutrition is a common yet under-recognized problem in hospitalized patients. The aim of this paper was to systematically review and evaluate malnutrition biomarkers among order adults. Eligible studies were identified through Cochrane, PubMed and the ProQuest Dialog. A meta-regression was performed on concentrations of biomarkers according to malnutrition risks classified by validated nutrition assessment tools. A total of 111 studies were included, representing 52,911 participants (55% female, 72 ± 17 years old from various clinical settings (hospital, community, care homes. The estimated BMI (p < 0.001 and concentrations of albumin (p < 0.001, hemoglobin (p < 0.001, total cholesterol (p < 0.001, prealbumin (p < 0.001 and total protein (p < 0.05 among subjects at high malnutrition risk by MNA were significantly lower than those without a risk. Similar results were observed for malnutrition identified by SGA and NRS-2002. A sensitivity analysis by including patients with acute illness showed that albumin and prealbumin concentrations were dramatically reduced, indicating that they must be carefully interpreted in acute care settings. This review showed that BMI, hemoglobin, and total cholesterol are useful biomarkers of malnutrition in older adults. The reference ranges and cut-offs may need to be updated to avoid underdiagnosis of malnutrition.

  5. Use of ABCD2 risk scoring system to determine the short-term stroke risk in patients presenting to emergency department with transient ischaemic attack

    International Nuclear Information System (INIS)

    Ozpolat, C.; Denizbasi, A.; Onur, O.; Eroglu, S.E.

    2013-01-01

    Objective: To determine the 3-day stroke risk of patients presenting to emergency department with transient ischaemic attack, and to evaluate the predictive value of ABCD2 (Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes) score for these patients. Methods: The prospective study was conducted on patients with diagnosis of transient ischaemic attack who were divided into low (0-3 points), medium (4-5 points) and high (6-7 points) risk groups according to their ABCD2 scores. The sensitivity of the scoring system on estimation of the risk of stroke in 3 days was evaluated through receiver operating characteristic curve. SPSS 15 was used for data analysis. Results: Of the 64 patients in the study, none of the low-risk group had stroke. Stroke was present in 4 of 33 (12.12%) medium-risk patients, while there were 4 in 18 (22.22%) in the high-risk group. Sensitivity and specificity of each ABCD2 score for 3rd day stroke risk was calculated. In the receiver operating curve generated by these calculations, the c statistics was determined as 0.76 (95% CI: 0.64, 0.86; p<0.01) and the most appropriate cut-off score to dichotomise the study group was determined as 4. Conclusions: In transient ischaemic attack patients with an ABCD2 score of four or higher had a markedly increased short-term stroke risk, while those with a lower score were quite safe. It is appropriate to hospitalise patients with a score of four or more and investigate for underlying cause and initiate treatment. (author)

  6. Signatures of reproductive events on blood counts and biomarkers of inflammation: Implications for chronic disease risk.

    Directory of Open Access Journals (Sweden)

    Daniel W Cramer

    Full Text Available Whether inflammation mediates how reproductive events affect chronic-disease risk is unclear. We studied inflammatory biomarkers in the context of reproductive events using National Health and Nutrition Examination Survey (NHANES data. From 15,986 eligible women from the 1999-2011 data cycles, we accessed information on reproductive events, blood counts, C-reactive protein (CRP, and total homocysteine (tHCY. We calculated blood-count ratios including: platelet-lymphocyte (PLR, lymphocyte-monocyte (LMR, platelet-monocyte (PMR, and neutrophil-monocyte (NMR. Using sampling weights per NHANES guidelines, means for counts, ratios, or biomarkers by reproductive events were compared using linear regression. We performed trend tests and calculated p-values with partial sum of squares F-tests. Higher PLR and lower LMR were associated with nulliparity. In postmenopausal women, lower PMR was associated with early age at first birth and higher NMR with later age at and shorter interval since last birth. Lower PNR and higher neutrophils and tHCY were associated with early natural menopause. In all women, the neutrophil count correlated positively with CRP; but, in premenopausal women, correlated inversely with tHCY. Reproductive events leave residual signatures on blood counts and inflammatory biomarkers that could underlie their links to chronic disease risk.

  7. A risk score for predicting mortality in patients with asymptomatic mild to moderate aortic stenosis

    DEFF Research Database (Denmark)

    Holme, Ingar; Pedersen, Terje R; Boman, Kurt

    2012-01-01

    BackgroundPrognostic information for asymptomatic patients with aortic stenosis (AS) from prospective studies is scarce and there is no risk score available to assess mortality.ObjectivesTo develop an easily calculable score, from which clinicians could stratify patients into high and lower risk...

  8. CRISP: Catheterization RISk score for Pediatrics: A Report from the Congenital Cardiac Interventional Study Consortium (CCISC).

    Science.gov (United States)

    Nykanen, David G; Forbes, Thomas J; Du, Wei; Divekar, Abhay A; Reeves, Jaxk H; Hagler, Donald J; Fagan, Thomas E; Pedra, Carlos A C; Fleming, Gregory A; Khan, Danyal M; Javois, Alexander J; Gruenstein, Daniel H; Qureshi, Shakeel A; Moore, Phillip M; Wax, David H

    2016-02-01

    We sought to develop a scoring system that predicts the risk of serious adverse events (SAE's) for individual pediatric patients undergoing cardiac catheterization procedures. Systematic assessment of risk of SAE in pediatric catheterization can be challenging in view of a wide variation in procedure and patient complexity as well as rapidly evolving technology. A 10 component scoring system was originally developed based on expert consensus and review of the existing literature. Data from an international multi-institutional catheterization registry (CCISC) between 2008 and 2013 were used to validate this scoring system. In addition we used multivariate methods to further refine the original risk score to improve its predictive power of SAE's. Univariate analysis confirmed the strong correlation of each of the 10 components of the original risk score with SAE attributed to a pediatric cardiac catheterization (P pediatric cardiac catheterization procedures. © 2015 Wiley Periodicals, Inc.

  9. Prognostic value of liver fibrosis and steatosis biomarkers in type-2 diabetes and dyslipidaemia.

    Science.gov (United States)

    Perazzo, H; Munteanu, M; Ngo, Y; Lebray, P; Seurat, N; Rutka, F; Couteau, M; Jacqueminet, S; Giral, P; Monneret, D; Imbert-Bismut, F; Ratziu, V; Hartemann-Huertier, A; Housset, C; Poynard, T

    2014-11-01

    In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5-15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [HR (95% CI)] [2.98 (95% CI 1.78-4.99); P < 0.0001] or severe steatosis [1.86 (1.34-2.58); P = 0.0002] was associated with an increased risk of mortality. In a multivariate Cox model adjusted for confounders: the presence of advanced fibrosis was associated with overall mortality [1.95 (1.12-3.41); P = 0.02]; advanced fibrosis at baseline [n = 50/677; 1.92 (1.04-3.55); P = 0.04] and progression to advanced fibrosis during follow-up [n = 16/127; 4.8 (1.5-14.9); P = 0.007] were predictors of cardiovascular events in patients with type-2 diabetes. In patients with a Framingham-risk score ≥20%, the presence of advanced fibrosis was predictive of cardiovascular events [2.24 (1.16-4.33); P < 0.05]. Liver biomarkers, such as FibroTest and SteatoTest, have prognostic values in patients with metabolic disorders. FibroTest has prognostic value for predicting overall survival in patients with type-2 diabetes and/or dyslipidaemia. In type-2 diabetes, FibroTest predicted cardiovascular events and improved the Framingham-risk score. © 2014 John Wiley & Sons Ltd.

  10. Calcium scores in the risk assessment of an asymptomatic population: implications for airline pilots.

    Science.gov (United States)

    Wirawan, I Made Ady; Wu, Rodney; Abernethy, Malcolm; Aldington, Sarah; Larsen, Peter D

    2014-08-01

    This study evaluated whether coronary artery calcium score (CACS) improved cardiovascular disease risk prediction when compared to the New Zealand Cardiovascular Risk Charts (NZ-CRC), and describes the potential utilization of CACS in cardiovascular disease (CVD) risk assessment of pilots. A cross-sectional study was performed among asymptomatic patients who underwent coronary computed tomography angiography at Pacific Radiology Wellington, New Zealand, between August 2007 and July 2012 and had their CACS and CVD risk score calculated. Receiver-operating characteristics (ROC) analyses were used to measure the accuracy of the NZ-CRC and CACS. Reclassification analyses were performed to examine the net reclassification improvement (NRI) of CACS when compared to NZ-CRC. Over a 5-yr study period, 237 male asymptomatic patients with ages ranging from 30 to 69 yr with a mean (SD) of 53.24 (8.18) yr, were included. The area under the ROC curves (AUC) (95% CI) for CACS and NZ-CRC were 0.88 (0.83-0.93) and 0.66 (0.59-0.73), respectively. The NRI (95% CI) of the calcium scores was 0.39 (0.17-0.62). CACS should be assessed in pilots with 5-yr CVD risk scores of 5-10% and 10-15%. CACS has a better accuracy than the NZ-CRC and reclassified a considerable proportion of asymptomatic patients into correct cardiovascular risk categories. An approach on how the CACS should be employed in the cardiovascular risk assessment of airline pilots is noted in this paper.

  11. Circulating biomarkers for predicting cardiovascular disease risk : a systematic review and comprehensive overview of meta-analyses

    NARCIS (Netherlands)

    Holten, van T.C.; Waanders, L.F.; Groot, de P.G.; Vissers, J.; Hoefer, I.E.; Pasterkamp, G.; Prins, M.W.J.; Roest, M.

    2013-01-01

    Background : Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming

  12. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease

    Science.gov (United States)

    Our aim was to investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) a...

  13. The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Jaja, Blessing N R; Schweizer, Tom A; Claassen, Jan; Le Roux, Peter; Mayer, Stephan A; Macdonald, R Loch

    2018-06-01

    Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at-risk patients. To develop and validate a risk score for convulsive seizure during acute admission for SAH. A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in-hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness-of-fit test. The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had AUC = 0.77, 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH.

  14. Possible biomarkers modulating haloperidol efficacy and/or tolerability.

    Science.gov (United States)

    Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

    2016-04-01

    Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

  15. Novel biomarkers for prediabetes, diabetes, and associated complications

    Science.gov (United States)

    Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

    2017-01-01

    The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

  16. Hemostasis biomarkers and incident cognitive impairment: the REGARDS study.

    Science.gov (United States)

    Gillett, S R; McClure, L A; Callas, P W; Thacker, E L; Unverzagt, F W; Wadley, V G; Letter, A J; Cushman, M

    2018-05-07

    Vascular risk factors are associated with cognitive impairment, a condition with substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with risk of incident cognitive impairment. We performed a nested case control study including 1,082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30,239 black and white Americans ≥45 years old. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII, and protein C were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on ≥2 of 3 cognitive tests) and 587 controls. Unadjusted ORs for incident cognitive impairment were 1.32 (95% CI 1.02, 1.70) for D-dimer >0.50 μg/mL, 1.83 (CI 1.24, 2.71) for fibrinogen >90 th percentile, 1.63 (CI 1.11, 2.38) for factor VIII >90 th percentile and 1.10 (CI 0.73, 1.65) for protein C impairment, with an adjusted OR 1.73 (CI 1.10, 2.69). Elevated D-dimer, fibrinogen, and factor VIII were not associated with occurrence of cognitive impairment after multivariable adjustment; however, having at least 2 abnormal biomarkers was associated, suggesting the burden of these biomarkers is relevant. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke : Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals

    NARCIS (Netherlands)

    Khan, Tauseef A.; Shah, Tina; Prieto, David; Zhang, Weili; Price, Jackie; Fowkes, Gerald R.; Cooper, Jackie; Talmud, Philippa J.; Humphries, Steve E.; Sundstrom, Johan; Hubacek, Jaroslav A.; Ebrahim, Shah; Lawlor, Debbie A.; Ben-Shlomo, Yoav; Abdollahi, Mohammad R.; Slooter, Arjen J. C.; Szolnoki, Zoltan; Sandhu, Manjinder; Wareham, Nicholas; Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Fillenbaum, Gerda; Heijmans, Bastiaan T.; Katsuya, Tomohiro; Gromadzka, Grazyna; Singleton, Andrew; Ferrucci, Luigi; Hardy, John; Worrall, Bradford; Rich, Stephen S.; Matarin, Mar; Whittaker, John; Gaunt, Tom R.; Whincup, Peter; Morris, Richard; Deanfield, John; Donald, Ann; Smith, George Davey; Kivimaki, Mika; Kumari, Meena; Smeeth, Liam; Khaw, Kay-Tee; Nalls, Michael; Meschia, James; Sun, Kai; Hui, Rutai; Day, Ian; Hingorani, Aroon D.; Casas, Juan P.

    Background At the APOE gene, encoding apolipoprotein E, genotypes of the epsilon 2/epsilon 3/epsilon 4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk

  18. Development and validation of a postpartum depression risk score in delivered women, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad R Maracy

    2012-01-01

    Full Text Available Background: Investigators describe a dramatic increase in the incidence of mood disorder after childbirth, with the largest risk in the 90 days after delivery. This study is designed to develop a relatively simple screening tool and validate it from the significant variables associated with postpartum depression (PPD to detect delivered women at high risk of having PPD. Materials and Methods: In the cross-sectional study, 6,627 from a total of 7,300 delivered women, 2-12 months after delivery were recruited and screened for PPD. Split-half validation was used to develop the risk score. The training data set was used to develop the model, and the validation data set was used to validate the developed the risk factors of postpartum depression risk score using multiple logistic regression analysis to compute the β coefficients and odds ratio (OR for the dependent variables associated with possible PPD in this study. Calibration was checked using the Hosmer and Lemeshow test. A score for independent variables contributing to PPD was calculated. Cutoff points using a trade-off between the sensitivity and specificity of risk scores derived from PPD model using the Receiver Operating Characteristic (ROC curve. Results: The predicted and observed PPD were not different (P value = 0.885. The aROC with area under the curve (S.E. of 0.611 (0.008 for predicting PPD using the suggested cut-off point of -0.702, the proportion of participants screening positive for PPD was 70.9% (sensitivity (CI 95%; 69.5, 72.3 while the proportion screening negative was 60.1% (specificity (CI 95%; 58.2, 62.1. Conclusion: Despite of the relatively low sensitivity and specificity in this study, it could be a simple, practical and useful screening tool to identify individual at high risk for PPD in the target population.

  19. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  20. Assessment of Diabetes Risk in an Adult Population Using Indian Diabetes Risk Score in an Urban Resettlement Colony of Delhi.

    Science.gov (United States)

    Acharya, Anita Shankar; Singh, Anshu; Dhiman, Balraj

    2017-03-01

    Diabetes mellitus is one of the non-communicable diseases which has become a major global health problem whose prevalence is increasing worldwide and is expected to reach 4.4% by 2030. The risk of diabetes escalates with increase in the number of risk factors and their duration as well. The Indian Diabetic Risk Score (IDRS) is a simple, low cost, feasible tool for mass screening programme at the community level. To assess the risk score of diabetes among the study subjects using IDRS. A cross sectional survey was conducted on adults >30 years (n=580) on both gender in an urban resettlement colony of Delhi during December 2013 to March 2015. A Semi-structured interview schedule consisting of Socio-demographic characteristics, risk factor profile and Indian Diabetes Risk Score was used. Data was entered and analyzed in SPSS. Out of 580 subjects, 31 (5.3%) study subjects were not at risk of having diabetes, rest 94.5% were at moderate or high risk of diabetes.A statistically significant association of diabetes risk with marital status(p=0.0001), education(0.005),body mass index(0.049) and systolic blood pressure was seen.(p=0.006). More than 90% of the study subjects were at risk of having diabetes, hence screening is of utmost importance so that interventions can be initiated at an early stage.

  1. Venous Thrombosis Risk after Cast Immobilization of the Lower Extremity: Derivation and Validation of a Clinical Prediction Score, L-TRiP(cast), in Three Population-Based Case-Control Studies.

    Science.gov (United States)

    Nemeth, Banne; van Adrichem, Raymond A; van Hylckama Vlieg, Astrid; Bucciarelli, Paolo; Martinelli, Ida; Baglin, Trevor; Rosendaal, Frits R; le Cessie, Saskia; Cannegieter, Suzanne C

    2015-11-01

    included between March 2003 and December 2008 and (2) the Milan study, a population-based case-control study with 2,117 cases and 2,088 controls selected between December 1993 and December 2010 at the Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. The full model consisted of 32 predictors, including three genetic factors and six biomarkers. For this model, an AUC of 0.85 (95% CI 0.77-0.92) was found in individuals with plaster cast immobilization of the lower extremity. The AUC for the restricted model (containing 11 predictors, including two genetic factors and one biomarker) was 0.84 (95% CI 0.77-0.92). The clinical model (consisting of 14 environmental predictors) resulted in an AUC of 0.77 (95% CI 0.66-0.87). The clinical model was converted into a risk score, the L-TRiP(cast) score (Leiden-Thrombosis Risk Prediction for patients with cast immobilization score), which showed an AUC of 0.76 (95% CI 0.66-0.86). Validation in the THE-VTE study data resulted in an AUC of 0.77 (95% CI 0.58-0.96) for the L-TRiP(cast) score. Validation in the Milan study resulted in an AUC of 0.93 (95% CI 0.86-1.00) for the full model, an AUC of 0.92 (95% CI 0.76-0.87) for the restricted model, and an AUC of 0.96 (95% CI 0.92-0.99) for the clinical model. The L-TRiP(cast) score resulted in an AUC of 0.95 (95% CI 0.91-0.99). Major limitations of this study were that information on thromboprophylaxis was not available for patients who had plaster cast immobilization of the lower extremity and that blood was drawn 3 mo after the thrombotic event. These results show that information on environmental risk factors, coagulation factors, and genetic determinants in patients with plaster casts leads to high accuracy in the prediction of VTE risk. In daily practice, the clinical model may be the preferred model as its factors are most easy to determine, while the model still has good predictive performance. These results may provide guidance for

  2. Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes

    DEFF Research Database (Denmark)

    Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald

    2015-01-01

    biomarkers address the predictive performance of novel biomarker panels in addition to the classical panel in type 2 diabetes. However, the prospective studies conducted so far have small sample sizes, are insufficiently powered and lack external validation. Adequately sized validation studies of multiple......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification...... and metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

  3. "Score the Core" Web-based pathologist training tool improves the accuracy of breast cancer IHC4 scoring.

    Science.gov (United States)

    Engelberg, Jesse A; Retallack, Hanna; Balassanian, Ronald; Dowsett, Mitchell; Zabaglo, Lila; Ram, Arishneel A; Apple, Sophia K; Bishop, John W; Borowsky, Alexander D; Carpenter, Philip M; Chen, Yunn-Yi; Datnow, Brian; Elson, Sarah; Hasteh, Farnaz; Lin, Fritz; Moatamed, Neda A; Zhang, Yanhong; Cardiff, Robert D

    2015-11-01

    Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called "Score the Core" (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Genetic risk scores link body fat distribution with specific cardiometabolic profiles

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Sandholt, Camilla H; Andersson Galijatovic, Ehm Astrid

    2016-01-01

    , including fasting serum triglyceride (β = 0.98% mmol/L, P = 3.33 × 10(-) (8) ) and Matsuda index (β = -0.74%, P = 1.29 × 10(-) (4) ). No similar associations for Clusters 2 and 3 were found. The three clusters showed different patterns of association with waist circumference, hip circumference, and height......OBJECTIVE: Forty-nine known single nucleotide polymorphisms (SNPs) associating with body mass index (BMI)-adjusted waist-hip-ratio (WHR) (WHRadjBMI) were recently suggested to cluster into three groups with different associations to cardiometabolic traits. Genetic risk scores of the clusters...... risk scores and anthropometry and blood samples at fasting and during an oral glucose tolerance test were tested. Analyses were adjusted for age, sex, and BMI. RESULTS: Cluster 1 associated with an increased risk of diabetes (HR = 1.05, P = 2.74 × 10(-) (4) ) and with a poor metabolic profile...

  5. Use and Customization of Risk Scores for Predicting Cardiovascular Events Using Electronic Health Record Data.

    Science.gov (United States)

    Wolfson, Julian; Vock, David M; Bandyopadhyay, Sunayan; Kottke, Thomas; Vazquez-Benitez, Gabriela; Johnson, Paul; Adomavicius, Gediminas; O'Connor, Patrick J

    2017-04-24

    Clinicians who are using the Framingham Risk Score (FRS) or the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) to estimate risk for their patients based on electronic health data (EHD) face 4 questions. (1) Do published risk scores applied to EHD yield accurate estimates of cardiovascular risk? (2) Are FRS risk estimates, which are based on data that are up to 45 years old, valid for a contemporary patient population seeking routine care? (3) Do the PCE make the FRS obsolete? (4) Does refitting the risk score using EHD improve the accuracy of risk estimates? Data were extracted from the EHD of 84 116 adults aged 40 to 79 years who received care at a large healthcare delivery and insurance organization between 2001 and 2011. We assessed calibration and discrimination for 4 risk scores: published versions of FRS and PCE and versions obtained by refitting models using a subset of the available EHD. The published FRS was well calibrated (calibration statistic K=9.1, miscalibration ranging from 0% to 17% across risk groups), but the PCE displayed modest evidence of miscalibration (calibration statistic K=43.7, miscalibration from 9% to 31%). Discrimination was similar in both models (C-index=0.740 for FRS, 0.747 for PCE). Refitting the published models using EHD did not substantially improve calibration or discrimination. We conclude that published cardiovascular risk models can be successfully applied to EHD to estimate cardiovascular risk; the FRS remains valid and is not obsolete; and model refitting does not meaningfully improve the accuracy of risk estimates. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. The role of novel biomarkers in predicting diabetic nephropathy: a review

    Directory of Open Access Journals (Sweden)

    Uwaezuoke SN

    2017-08-01

    Full Text Available Samuel N Uwaezuoke Pediatric Nephrology Firm, Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Diabetic nephropathy (DN is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM, and occasionally from type 2 diabetes mellitus (T2DM. Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN. Keywords: type 1 diabetes mellitus, renal microvascular complication, microalbuminuria, end-stage kidney disease, biomarker panel

  7. Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

    Science.gov (United States)

    Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

    2017-09-01

    The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

  8. Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.

    Science.gov (United States)

    Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2016-01-01

    Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

  10. Scope Complexity Options Risks Excursions (SCORE) Factor Mathematical Description.

    Energy Technology Data Exchange (ETDEWEB)

    Gearhart, Jared Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Samberson, Jonell Nicole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Shettigar, Subhasini [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jungels, John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Welch, Kimberly M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jones, Dean A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-03-01

    The purpose of the Scope, Complexity, Options, Risks, Excursions (SCORE) model is to estimate the relative complexity of design variants of future warhead options, resulting in scores. SCORE factors extend this capability by providing estimates of complexity relative to a base system (i.e., all design options are normalized to one weapon system). First, a clearly defined set of scope elements for a warhead option is established. The complexity of each scope element is estimated by Subject Matter Experts (SMEs), including a level of uncertainty, relative to a specific reference system. When determining factors, complexity estimates for a scope element can be directly tied to the base system or chained together via comparable scope elements in a string of reference systems that ends with the base system. The SCORE analysis process is a growing multi-organizational Nuclear Security Enterprise (NSE) effort, under the management of the NA-12 led Enterprise Modeling and Analysis Consortium (EMAC). Historically, it has provided the data elicitation, integration, and computation needed to support the out-year Life Extension Program (LEP) cost estimates included in the Stockpile Stewardship Management Plan (SSMP).

  11. Recurrent epistaxis: predicting risk of 30-day readmission, derivation and validation of RHINO-ooze score.

    Science.gov (United States)

    Addison, A; Paul, C; Kuo, R; Lamyman, A; Martinez-Devesa, P; Hettige, R

    2017-06-01

    To derive and validate a predictive scoring tool (RHINO-ooze score) with good sensitivity and specificity in identifying patients with epistaxis at high risk of 30 day readmission and to enable risk stratification for possible definitive intervention. Using medical databases, we searched for factors influencing recurrent epistaxis. The information ascertained together with our analysis of retrospective data on patients admitted with epistaxis between October 2013 and September 2014, was used as the derivation cohort to develop the predictive scoring model (RHINO-ooze score). The tool was validated by performing statistical analysis on the validation cohort of patients admitted with epistaxis between October 2014 and October 2015. Multiple linear regressions with backwards elimination was used to derive the predictive model. The area under the curve (AUC), sensitivity and specificity were calculated. 834 admissions were encountered within the study period. Using the derivative cohort (n= 302) the RHINO-ooze score with a maximum score of 8 from five variables (Recent admission, Haemorrhage point unidentified, Increasing age over 70, posterior Nasal packing, Oral anticoagulant) was developed. The RHINO-ooze score had a chi-square value of 99.72 with a significance level of smaller than 0.0001 and hence an overall good model fit. Comparison between the derivative and validation groups revealed similar rates of 30-day readmission between the cohorts. The sensitivity and specificity of predicting 30-day readmission in high risk patients with recurrent epistaxis (RHINO-ooze score equal/larger than 6) was 81% and 84%, respectively. The RHINO-ooze scoring tool demonstrates good specificity and sensitivity in predicting the risk of 30 day readmission in patients with epistaxis and can be used as an adjunct to clinical decision making with regards to timing of operative intervention in order to reduce readmission rates.

  12. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians.

    Science.gov (United States)

    Arends, Pauline; Sonneveld, Milan J; Zoutendijk, Roeland; Carey, Ivana; Brown, Ashley; Fasano, Massimo; Mutimer, David; Deterding, Katja; Reijnders, Jurriën G P; Oo, Ye; Petersen, Jörg; van Bömmel, Florian; de Knegt, Robert J; Santantonio, Teresa; Berg, Thomas; Welzel, Tania M; Wedemeyer, Heiner; Buti, Maria; Pradat, Pierre; Zoulim, Fabien; Hansen, Bettina; Janssen, Harry L A

    2015-08-01

    Hepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population. We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network. A total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82-212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (peliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Dietary score and the risk of oral cancer: a case-control study in southeast China.

    Science.gov (United States)

    Chen, Fa; Yan, Lingjun; Lin, Lisong; Liu, Fengqiong; Qiu, Yu; Wang, Jing; Wu, Junfeng; Liu, Fangping; Huang, Jiangfeng; Cai, Lin; He, Baochang

    2017-05-23

    This study aims to develop a simple dietary score to comprehensively evaluate the role of diet in the risk of oral cancer. A case-control study including 930 oral cancer cases and 2667 frequency-matched controls was performed in Fujian, China. Unconditional logistic regression model was used to estimate the effects of dietary factors on oral cancer. After adjustment for potential confounders, less intake of domestic meat (oral cancer. Then these variables were incorporated to establish dietary risk score. Assessed by the receiver operating characteristic curve, the score showed a satisfactory discriminatory capacity, with an area under the curve of 0.682 (95% CI: 0.662-0.702). Moreover, the score was positively associated with the risk of oral cancer as quartiles, and the association was apparently stronger in tobacco smokers or alcohol drinkers. Additionally, there were significant multiplicative interactions between the score and tobacco smoking or alcohol drinking for oral cancer. In the present study, a convenient dietary score with satisfactory discriminatory capacity was developed to assess the collected effect of dietary factors on oral cancer, which could provide a new strategy for the prevention of oral cancer through changing in dietary habits.

  14. Screening for Behavioral Risk: Identification of High Risk Cut Scores within the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS)

    Science.gov (United States)

    Kilgus, Stephen P.; Taylor, Crystal N.; von der Embse, Nathaniel P.

    2018-01-01

    The purpose of this study was to support the identification of Social, Academic, and Emotional Behavior Risk Screener (SAEBRS) cut scores that could be used to detect high-risk students. Teachers rated students across two time points (Time 1 n = 1,242 students; Time 2 n = 704) using the SAEBRS and the Behavioral and Emotional Screening System…

  15. Improved predictive value of GRACE risk score combined with platelet reactivity for 1-year cardiovascular risk in patients with acute coronary syndrome who underwent coronary stent implantation.

    Science.gov (United States)

    Li, Shan; Liu, Hongbin; Liu, Jianfeng; Wang, Haijun

    2016-11-01

    Both high platelet reactivity (HPR) and Global Registry of Acute Coronary Events (GRACE) risk score have moderate predictive value for major adverse cardiovascular disease (CVD) events in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI), whereas the prognostic significance of GRACE risk score combined with platelet function testing remains unclear. A total of 596 patients with non-ST elevation ACS who underwent PCI were enrolled. The P2Y 12 reaction unit (PRU) value was measured by VerifyNow P2Y 12 assay and GRACE score was calculated by GRACE risk 2.0 calculator. Patients were stratified by a pre-specified cutoff value of PRU 230 and GRACE score 140 to assess 1-year risk of cardiovascular death, non-fatal myocardial infarction (MI), and stent thrombosis. Seventy-two (12.1%) patients developed CVD events during 1-year follow-up. Patients with CVD events had a higher PRU value (244.6 ± 50.9 vs. 203.7 ± 52.0, p risk independently. Compared to patients with normal platelet reactivity (NPR) and GRACE score risk (HR: 5.048; 95% CI: 2.268-11.237; p risk score yielded superior risk predictive capacity beyond GRACE score alone, which is shown by improved c-statistic value (0.871, p = 0.002) as well as net reclassification improvement (NRI 0.263, p risk of adverse CVD events. The combination of platelet function testing and GRACE score predicted 1-year CVD risk better.

  16. A Score for Risk of Thrombolysis-Associated Hemorrhage Including Pretreatment with Statins

    Directory of Open Access Journals (Sweden)

    Hebun Erdur

    2018-02-01

    Full Text Available BackgroundSymptomatic intracranial hemorrhage (sICH after intravenous thrombolysis with recombinant tissue-plasminogen activator (rt-PA for acute ischemic stroke is associated with a poor functional outcome. We aimed to develop a score assessing risk of sICH including novel putative predictors—namely, pretreatment with statins and severe renal impairment.MethodsWe analyzed our local cohort (Berlin of patients receiving rt-PA for acute ischemic stroke between 2006 and 2016. Outcome was sICH according to ECASS-III criteria. A multiple regression model identified variables associated with sICH and receiver operating characteristics were calculated for the best discriminatory model for sICH. The model was validated in an independent thrombolysis cohort (Basel.ResultssICH occurred in 53 (4.0% of 1,336 patients in the derivation cohort. Age, baseline National Institutes of Health Stroke Scale, systolic blood pressure on admission, blood glucose on admission, and prior medication with medium- or high-dose statins were associated with sICH and included into the risk of intracranial hemorrhage score. The validation cohort included 983 patients of whom 33 (3.4% had a sICH. c-Statistics for sICH was 0.72 (95% CI 0.66–0.79 in the derivation cohort and 0.69 (95% CI 0.60–0.77 in the independent validation cohort. Inclusion of severe renal impairment did not improve the score.ConclusionWe developed a simple score with fair discriminating capability to predict rt-PA-related sICH by adding prior statin use to known prognostic factors of sICH. This score may help clinicians to identify patients with higher risk of sICH requiring intensive monitoring.

  17. Biomarkers in cancer screening: a public health perspective.

    Science.gov (United States)

    Srivastava, Sudhir; Gopal-Srivastava, Rashmi

    2002-08-01

    The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of

  18. Relation of the aortic stiffness with the GRACE risk score in patients with the non ST-segment elevation myocardial infarction.

    Science.gov (United States)

    Omer, Gedikli; Gokhan, Aksan; Adem, Uzun; Sabri, Demircan; Korhan, Soylu

    2014-01-01

    Current guidelines recommend clinical risk scoring systems for the patients diagnosed and determinated treatment strategy with in Non-ST-elevation elevation myocardial infarction (NSTEMI). Previous studies demonstrated association between aortic elasticity properties, stiffness and severity CAD. However, the associations between Aortic stiffness, elasticity properties and clinical risk scores have not been investigated. In the present study we have evaluated the relation between the Global Registry of Acute Coronary Events (GRACE) risk score and aortic stiffness in patients with NSTEMI. We prospectively analyzed 87 consecutive patients with NSTEMI. Aortic elastic parameter and stiffness parameter were calculated from the echocardiographically derived thoracic aortic diameters (mm/m(2)), and the measurement of pulse pressure obtained by cuff sphygmomanometry. We have categorized the patients in to two groups as low ((n = 45) (GRACE risk score ≤ 140)) and high ((n = 42) (GRACE risk score > 140)) risk group according to GRACE risk score and compare the both groups. Table 1 shows baseline characteristics of patients. Our study showed that Aortic strain was significantly low (3.5 ± 1.4, 7.9 ± 2.3 respectively, p < 0.001) and aortic stiffness index was significantly high (3.9 ± 0.38; 3 ± 0.35, respectively, p < 0.001) in the high risk group values compared to those with low risk group. The aortic stiffness index was the only independent predictor of GRACE risk score (OR: 119.390; 95% CI: 2.925-4872.8; p = 0.011) in multivariate analysis. We found a significant correlation between aortic stiffness, impaired elasticity and GRACE risk score. Aortic stiffness index was the only independent variable of the high GRACE risk score. The inclusion of aortic stiffness into the GRACE risk score could allow improved risk classification of patients with ACS at admission and this may be important in the diagnosis, follow up and treatment of the patients.

  19. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  20. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  1. Risk prediction is improved by adding markers of subclinical organ damage to SCORE

    DEFF Research Database (Denmark)

    Sehestedt, Thomas; Jeppesen, Jørgen; Hansen, Tine W

    2010-01-01

    cardiovascular, anti-diabetic, or lipid-lowering treatment, aged 41, 51, 61, or 71 years, we measured traditional cardiovascular risk factors, left ventricular (LV) mass index, atherosclerotic plaques in the carotid arteries, carotid/femoral pulse wave velocity (PWV), and urine albumin/creatinine ratio (UACR......) and followed them for a median of 12.8 years. Eighty-one subjects died because of cardiovascular causes. Risk of cardiovascular death was independently of SCORE associated with LV hypertrophy [hazard ratio (HR) 2.2 (95% CI 1.2-4.0)], plaques [HR 2.5 (1.6-4.0)], UACR > or = 90th percentile [HR 3.3 (1.......07). CONCLUSION: Subclinical organ damage predicted cardiovascular death independently of SCORE and the combination may improve risk prediction....

  2. Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population.

    Science.gov (United States)

    Isma'eel, Hussain A; Almedawar, Mohamad M; Harbieh, Bernard; Alajaji, Wissam; Al-Shaar, Laila; Hourani, Mukbil; El-Merhi, Fadi; Alam, Samir; Abchee, Antoine

    2015-10-01

    The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.

  3. Risk behavior score: a practical approach for assessing risk among men who have sex with men in Brazil

    Directory of Open Access Journals (Sweden)

    Gustavo Machado Rocha

    2018-03-01

    Full Text Available HIV/AIDS epidemic is not well controlled, and multiple sexual behavior factors help explain high rates of HIV infection among men who have sex with men (MSM. This article proposes to exam the use of a potential risk behavior score for HIV infection, based on the type and number of sexual partners, and condom use, and their associated factors in a sample of MSM in Brazil. A cross sectional RDS (Respondent Driven Sampling study was performed among 3738 MSM aged 18+ years old from ten Brazilian cities. The risk behavior score was composed by the number of male partners and anal condom use in the last year with steady, casual, and commercial partners. Most participants were 25+ years old (58.1%, non-white (83.1%, and single (84.9%. Final weighted ordinal logistic model showed that age ≤ 25 years old (p = 0.037, homosexual or bisexual identity (p < 0.001, sexual initiation before 15-year-old (p < 0.001, having sex with men only in the last 12 months (p < 0.001, frequent alcohol and illicit drug use (p < 0.001, and use of local sites to meet sexual partners in the last month were independently associated with higher scores of risky behavior. Specific strategies should be developed aimed at the MSM population. Additionally, pre-exposed prophylaxis (Prep should be considered for those at higher score as a strategy for reducing risk for HIV infection in this population. Keywords: Homosexuals, High-risk sex, Unsafe sex, HIV, AIDS

  4. The predictive value of CHADS₂ risk score in post myocardial infarction arrhythmias - a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine Huth; Gang, Uffe; Thomsen, Poul Erik Bloch

    2014-01-01

    BACKGROUND: Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose...... of this study was to investigate if CHADS₂ score (congestive heart failure, hypertension, age ≥75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI. METHODS: The study included 297 post-MI patients from the CARISMA study with left....... Patients were stratified according to CHADS₂ score at enrollment. Congestive heart failure was defined as LVEF ≤40% and NYHA class II, III or IV. RESULTS: We found significantly increased risk of an arrhythmic event with increasing CHADS₂ score (CHADS₂ score=1-2: HR=2.1 [1.1-3.9], p=0.021, CHADS₂ score ≥ 3...

  5. Hearing loss is associated with increased CHD risk and unfavorable CHD-related biomarkers in the Dongfeng-Tongji cohort.

    Science.gov (United States)

    Fang, Qin; Wang, Zhichao; Zhan, Yue; Li, Dan; Zhang, Kun; Zhou, Tao; Yang, Handong; Zhang, Ce; Li, Xiulou; Min, Xinwen; Chen, Weihong; Guo, Huan; He, Mei-An; Kong, Weijia; Wu, Tangchun; Zhang, Xiaomin

    2018-04-01

    The association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population. We included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers. The adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild- and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels. There may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Analysis of Plasma Albumin, Vitamin D, and Apolipoproteins A and B as Predictive Coronary Risk Biomarkers in the REGICOR Study.

    Science.gov (United States)

    Vázquez-Oliva, Gabriel; Zamora, Alberto; Ramos, Rafel; Subirana, Isaac; Grau, María; Dégano, Irene R; Muñoz, Daniel; Fitó, Montserrat; Elosua, Roberto; Marrugat, Jaume

    2018-05-12

    New biomarkers could improve the predictive capacity of classic risk functions. The aims of this study were to determine the association between circulating levels of apolipoprotein A1 (apoA1), apolipoprotein B (apoB), albumin, and 25-OH-vitamin D and coronary events and to analyze whether these biomarkers improve the predictive capacity of the Framingham-REGICOR risk function. A case-cohort study was designed. From an initial cohort of 5404 individuals aged 35 to 74 years with a 5-year follow-up, all the participants who had a coronary event (n = 117) and a random group of the cohort (subcohort; n = 667) were selected. Finally, 105 cases and 651 individuals representative of the cohort with an available biological sample were included. The events of interest were angina, fatal and nonfatal myocardial infarction and coronary deaths. Case participants were older, had a higher proportion of men and cardiovascular risk factors, and showed higher levels of apoB and lower levels of apoA1, apoA1/apoB ratio, 25-OH-vitamin D and albumin than the subcohort. In multivariate analyses, plasma albumin concentration was the only biomarker independently associated with coronary events (HR, 0.73; P = .002). The inclusion of albumin in the risk function properly reclassified a significant proportion of individuals, especially in the intermediate risk group (net reclassification improvement, 32.3; P = .048). Plasma albumin levels are inversely associated with coronary risk and improve the predictive capacity of classic risk functions. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Predicting asthma in preschool children with asthma-like symptoms : Validating and updating the PIAMA risk score

    NARCIS (Netherlands)

    Hafkamp-de Groen, Esther; Lingsma, Hester F.; Caudri, Daan; Levie, Deborah; Wijga, Alet; Koppelman, Gerard H.; Duijts, Liesbeth; Jaddoe, Vincent W. V.; Smit, Henriette A.; Kerkhof, Marjan; Moll, Henriette A.; Hofman, Albert; Steyerberg, Ewout W.; de Jongste, Johan C.; Raat, Hein

    2013-01-01

    Background: The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) risk score predicts the probability of having asthma at school age among preschool children with suggestive symptoms. Objective: We sought to externally validate the PIAMA risk score at different ages and in ethnic and

  8. The Patient- And Nutrition-Derived Outcome Risk Assessment Score (PANDORA: Development of a Simple Predictive Risk Score for 30-Day In-Hospital Mortality Based on Demographics, Clinical Observation, and Nutrition.

    Directory of Open Access Journals (Sweden)

    Michael Hiesmayr

    Full Text Available To develop a simple scoring system to predict 30 day in-hospital mortality of in-patients excluding those from intensive care units based on easily obtainable demographic, disease and nutrition related patient data.Score development with general estimation equation methodology and model selection by P-value thresholding based on a cross-sectional sample of 52 risk indicators with 123 item classes collected with questionnaires and stored in an multilingual online database.Worldwide prospective cross-sectional cohort with 30 day in-hospital mortality from the nutritionDay 2006-2009 and an external validation sample from 2012.We included 43894 patients from 2480 units in 32 countries. 1631(3.72% patients died within 30 days in hospital. The Patient- And Nutrition-Derived Outcome Risk Assessment (PANDORA score predicts 30-day hospital mortality based on 7 indicators with 31 item classes on a scale from 0 to 75 points. The indicators are age (0 to 17 points, nutrient intake on nutritionDay (0 to 12 points, mobility (0 to 11 points, fluid status (0 to 10 points, BMI (0 to 9 points, cancer (9 points and main patient group (0 to 7 points. An appropriate model fit has been achieved. The area under the receiver operating characteristic curve for mortality prediction was 0.82 in the development sample and 0.79 in the external validation sample.The PANDORA score is a simple, robust scoring system for a general population of hospitalised patients to be used for risk stratification and benchmarking.

  9. Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups.

    Science.gov (United States)

    Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih

    2015-07-01

    Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values. Eighty-five patients with AD underwent neurobehavioral assessments including the minimental state examination (MMSE) and 12-item neuropsychiatric inventory twice with a 1.5-year interval to represent major outcome factors. In the cross-sectional data, total cholesterol, low-density lipoprotein, vitamin B12, and homocysteine levels correlated variably with WM FA values. After entering the biomarkers and WM FA into a regression model to predict neurobehavioral outcomes, only fiber tract FA or homocysteine level predicted the MMSE score, and fiber tract FA or age predicted the neuropsychiatric inventory total scores and subdomains of apathy, disinhibition, and aberrant motor behavior. In the follow-up neurobehavioral data, the mean global FA value predicted the MMSE and aberrant motor behavior subdomain, while age predicted the anxiety and elation subdomains. Cerebrovascular risk biomarkers may modify WM microstructural organization, while the association with fiber integrity showed greater clinical significance to the prediction of neurobehavioral outcomes both cross-sectionally and longitudinally.

  10. Complete blood count risk score and its components, including RDW, are associated with mortality in the JUPITER trial.

    Science.gov (United States)

    Horne, Benjamin D; Anderson, Jeffrey L; Muhlestein, Joseph B; Ridker, Paul M; Paynter, Nina P

    2015-04-01

    Previously, we showed that sex-specific complete blood count (CBC) risk scores strongly predicted risk of all-cause mortality in multiple sets of general medical patients. This study evaluated the CBC risk score in an independent, well-studied international primary risk population of lower-risk individuals initially free from cardiovascular (CV) disease. Observational secondary analysis of a randomized trial population. The previously derived and validated CBC score was evaluated for association with all-cause mortality among CV disease-free females (n = 6568) and males (n = 10,629) enrolled for up to 5 years in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Associations of the CBC score with CV mortality and with major CV disease were also tested. The CBC score predicted all-cause mortality, with univariable hazard ratio (HR) 4.83 (95% CI 3.70-6.31) for the third CBC score tertile vs. the first tertile, and HR 2.31 (CI 1.75-3.05) for the second tertile (p trend JUPITER endpoint (p trend = 0.015). c-statistics for mortality were 0.729 among all, and 0.722 and 0.750 for females and males, respectively. The CBC risk score was strongly associated with all-cause mortality among JUPITER trial participants and had good discrimination. It also predicted CV-specific outcomes. This CBC score may be useful in identifying cardiac disease-free individuals at increased risk of mortality. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. A simple score for estimating the long-term risk of fracture in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Bazelier, M. T.; van Staa, T. P.; Uitdehaag, B. M. J.

    2012-01-01

    was converted into integer risk scores. Results: In comparison with the FRAX calculator, our risk score contains several new risk factors that have been linked with fracture, which include MS, use of antidepressants, use of anticonvulsants, history of falling, and history of fatigue. We estimated the 5- and 10......Objective: To derive a simple score for estimating the long-term risk of osteoporotic and hip fracture in individual patients with MS. Methods: Using the UK General Practice Research Database linked to the National Hospital Registry (1997-2008), we identified patients with incident MS (n = 5......,494). They were matched 1:6 by year of birth, sex, and practice with patients without MS (control subjects). Cox proportional hazards models were used to calculate the long-term risk of osteoporotic and hip fracture. We fitted the regression model with general and specific risk factors, and the final Cox model...

  12. Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis.

    Science.gov (United States)

    Agerbo, Esben; Sullivan, Patrick F; Vilhjálmsson, Bjarni J; Pedersen, Carsten B; Mors, Ole; Børglum, Anders D; Hougaard, David M; Hollegaard, Mads V; Meier, Sandra; Mattheisen, Manuel; Ripke, Stephan; Wray, Naomi R; Mortensen, Preben B

    2015-07-01

    Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult. To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual's genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband's genetic makeup mediates the risk associated with familial background. We conducted a nested case-control study based on Danish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34,600 cases and 45,968 control individuals) were applied to calculate polygenic risk scores. Polygenic risk scores, parental socioeconomic status, and family psychiatric history. Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated. Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95% CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95% CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95% CI, 2.57-6.79). The R2 values were 3.4% (95% CI, 2.1-4.6) for the polygenic risk score, 3.1% (95% CI, 1.9-4.3) for parental socioeconomic status, and 3.4% (95% CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95% CI, 36.1-55.5) and 25.8% (95% CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history

  13. Fall Risk Score at the Time of Discharge Predicts Readmission Following Total Joint Arthroplasty.

    Science.gov (United States)

    Ravi, Bheeshma; Nan, Zhang; Schwartz, Adam J; Clarke, Henry D

    2017-07-01

    Readmission among Medicare recipients is a leading driver of healthcare expenditure. To date, most predictive tools are too coarse for direct clinical application. Our objective in this study is to determine if a pre-existing tool to identify patients at increased risk for inpatient falls, the Hendrich Fall Risk Score, could be used to accurately identify Medicare patients at increased risk for readmission following arthroplasty, regardless of whether the readmission was due to a fall. This study is a retrospective cohort study. We identified 2437 Medicare patients who underwent a primary elective total joint arthroplasty (TJA) of the hip or knee for osteoarthritis between 2011 and 2014. The Hendrich Fall Risk score was recorded for each patient preoperatively and postoperatively. Our main outcome measure was hospital readmission within 30 days of discharge. Of 2437 eligible TJA recipients, there were 226 (9.3%) patients who had a score ≥6. These patients were more likely to have an unplanned readmission (unadjusted odds ratio 2.84, 95% confidence interval 1.70-4.76, P 3 days (49.6% vs 36.6%, P = .0001), and were less likely to be sent home after discharge (20.8% vs 35.8%, P fall risk score after TJA is strongly associated with unplanned readmission. Application of this tool will allow hospitals to identify these patients and plan their discharge. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

    2016-01-01

    Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32...

  15. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries

    DEFF Research Database (Denmark)

    Ueda, Peter; Woodward, Mark; Lu, Yuan

    2017-01-01

    BACKGROUND: Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and ...

  16. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

    2008-05-01

    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  17. Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women

    OpenAIRE

    Beulens, Joline W.J.; Hendriks, Henk F.J.; Rimm, Eric B.; Hu, Frank B.; Mukamal, Ken J.

    2008-01-01

    OBJECTIVE?The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes. RESEARCH DESIGN AND METHODS?In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for mark...

  18. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

    Science.gov (United States)

    Filella, Xavier; Foj, Laura

    2016-10-26

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

  19. Differentiation among prostate cancer patients with Gleason score of 7 using histopathology whole-slide image and genomic data

    Science.gov (United States)

    Ren, Jian; Karagoz, Kubra; Gatza, Michael; Foran, David J.; Qi, Xin

    2018-03-01

    Prostate cancer is the most common non-skin related cancer affecting 1 in 7 men in the United States. Treatment of patients with prostate cancer still remains a difficult decision-making process that requires physicians to balance clinical benefits, life expectancy, comorbidities, and treatment-related side effects. Gleason score (a sum of the primary and secondary Gleason patterns) solely based on morphological prostate glandular architecture has shown as one of the best predictors of prostate cancer outcome. Significant progress has been made on molecular subtyping prostate cancer delineated through the increasing use of gene sequencing. Prostate cancer patients with Gleason score of 7 show heterogeneity in recurrence and survival outcomes. Therefore, we propose to assess the correlation between histopathology images and genomic data with disease recurrence in prostate tumors with a Gleason 7 score to identify prognostic markers. In the study, we identify image biomarkers within tissue WSIs by modeling the spatial relationship from automatically created patches as a sequence within WSI by adopting a recurrence network model, namely long short-term memory (LSTM). Our preliminary results demonstrate that integrating image biomarkers from CNN with LSTM and genomic pathway scores, is more strongly correlated with patients recurrence of disease compared to standard clinical markers and engineered image texture features. The study further demonstrates that prostate cancer patients with Gleason score of 4+3 have a higher risk of disease progression and recurrence compared to prostate cancer patients with Gleason score of 3+4.

  20. Predictive value of updating Framingham risk scores with novel risk markers in the U.S. general population.

    Directory of Open Access Journals (Sweden)

    Bart S Ferket

    Full Text Available BACKGROUND: According to population-based cohort studies CT coronary calcium score (CTCS, carotid intima-media thickness (cIMT, high-sensitivity C- reactive protein (CRP, and ankle-brachial index (ABI are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. METHODS AND FINDINGS: Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES 2003-2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male, 70% (80% were at low (<10%, 19% (14% at intermediate (≥10-<20%, and 11% (6% at high (≥20% 10-year CVD (CHD risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02-0.19. The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01-0.03 with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38% moved to low and 22% (30% to high CVD (CHD risk. Improvements with other novel risk markers were limited. CONCLUSIONS: Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies.

  1. Predictive Value of Updating Framingham Risk Scores with Novel Risk Markers in the U.S. General Population

    Science.gov (United States)

    Hunink, M. G. Myriam; Agarwal, Isha; Kavousi, Maryam; Franco, Oscar H.; Steyerberg, Ewout W.; Max, Wendy; Fleischmann, Kirsten E.

    2014-01-01

    Background According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. Methods and Findings Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02–0.19). The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01–0.03) with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38%) moved to low and 22% (30%) to high CVD (CHD) risk. Improvements with other novel risk markers were limited. Conclusions Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies. PMID:24558385

  2. The clinical performance of an office-based risk scoring system for fatal cardiovascular diseases in North-East of Iran.

    Directory of Open Access Journals (Sweden)

    Sadaf G Sepanlou

    Full Text Available Cardiovascular diseases (CVD are becoming major causes of death in developing countries. Risk scoring systems for CVD are needed to prioritize allocation of limited resources. Most of these risk score algorithms have been based on a long array of risk factors including blood markers of lipids. However, risk scoring systems that solely use office-based data, not including laboratory markers, may be advantageous. In the current analysis, we validated the office-based Framingham risk scoring system in Iran.The study used data from the Golestan Cohort in North-East of Iran. The following risk factors were used in the development of the risk scoring method: sex, age, body mass index, systolic blood pressure, hypertension treatment, current smoking, and diabetes. Cardiovascular risk functions for prediction of 10-year risk of fatal CVDs were developed.A total of 46,674 participants free of CVD at baseline were included. Predictive value of estimated risks was examined. The resulting Area Under the ROC Curve (AUC was 0.774 (95% CI: 0.762-0.787 in all participants, 0.772 (95% CI: 0.753-0.791 in women, and 0.763 (95% CI: 0.747-0.779 in men. AUC was higher in urban areas (0.790, 95% CI: 0.766-0.815. The predicted and observed risks of fatal CVD were similar in women. However, in men, predicted probabilities were higher than observed.The AUC in the current study is comparable to results of previous studies while lipid profile was replaced by body mass index to develop an office-based scoring system. This scoring algorithm is capable of discriminating individuals at high risk versus low risk of fatal CVD.

  3. The Zhongshan Score

    Science.gov (United States)

    Zhou, Lin; Guo, Jianming; Wang, Hang; Wang, Guomin

    2015-01-01

    Abstract In the zero ischemia era of nephron-sparing surgery (NSS), a new anatomic classification system (ACS) is needed to adjust to these new surgical techniques. We devised a novel and simple ACS, and compared it with the RENAL and PADUA scores to predict the risk of NSS outcomes. We retrospectively evaluated 789 patients who underwent NSS with available imaging between January 2007 and July 2014. Demographic and clinical data were assessed. The Zhongshan (ZS) score consisted of three parameters. RENAL, PADUA, and ZS scores are divided into three groups, that is, high, moderate, and low scores. For operative time (OT), significant differences were seen between any two groups of ZS score and PADUA score (all P RENAL showed no significant difference between moderate and high complexity in OT, WIT, estimated blood loss, and increase in SCr. Compared with patients with a low score of ZS, those with a high or moderate score had 8.1-fold or 3.3-fold higher risk of surgical complications, respectively (all P RENAL score, patients with a high or moderate score had 5.7-fold or 1.9-fold higher risk of surgical complications, respectively (all P RENAL and PADUA scores. ZS score could be used to reflect the surgical complexity and predict the risk of surgical complications in patients undergoing NSS. PMID:25654399

  4. Heart valve surgery: EuroSCORE vs. EuroSCORE II vs. Society of Thoracic Surgeons score

    Directory of Open Access Journals (Sweden)

    Muhammad Sharoz Rabbani

    2014-12-01

    Full Text Available Background This is a validation study comparing the European System for Cardiac Operative Risk Evaluation (EuroSCORE II with the previous additive (AES and logistic EuroSCORE (LES and the Society of Thoracic Surgeons’ (STS risk prediction algorithm, for patients undergoing valve replacement with or without bypass in Pakistan. Patients and Methods Clinical data of 576 patients undergoing valve replacement surgery between 2006 and 2013 were retrospectively collected and individual expected risks of death were calculated by all four risk prediction algorithms. Performance of these risk algorithms was evaluated in terms of discrimination and calibration. Results There were 28 deaths (4.8% among 576 patients, which was lower than the predicted mortality of 5.16%, 6.96% and 4.94% by AES, LES and EuroSCORE II but was higher than 2.13% predicted by STS scoring system. For single and double valve replacement procedures, EuroSCORE II was the best predictor of mortality with highest Hosmer and Lemmeshow test (H-L p value (0.346 to 0.689 and area under the receiver operating characteristic (ROC curve (0.637 to 0.898. For valve plus concomitant coronary artery bypass grafting (CABG patients actual mortality was 1.88%. STS calculator came out to be the best predictor of mortality for this subgroup with H-L p value (0.480 to 0.884 and ROC (0.657 to 0.775. Conclusions For Pakistani population EuroSCORE II is an accurate predictor for individual operative risk in patients undergoing isolated valve surgery, whereas STS performs better in the valve plus CABG group.

  5. Therapeutic implications of selecting the SCORE (European versus the D'AGOSTINO (American risk charts for cardiovascular risk assessment in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Giné-Garriga Maria

    2009-05-01

    Full Text Available Abstract Background No comparisons have been made of scales estimating cardiovascular mortality and overall cardiovascular morbidity and mortality. The study objectives were to assess the agreement between the Framingham-D'Agostino cardiovascular risk (CVR scale and the chart currently recommended in Europe (SCORE with regard to identification of patients with high CVR, and to describe the discrepancies between them and the attendant implications for the treatment of hypertension and hyperlipidaemia. Methods A total of 474 hypertensive patients aged 40–65 years monitored in primary care were enrolled into the study. CVR was assessed using the Framingham-D'Agostino scale, which estimates the overall cardiovascular morbidity and mortality risk, and the SCORE chart, which estimates the cardiovascular mortality risk. Cardiovascular risk was considered to be high for values ≥ 20% and ≥ 5% according to the Framingham-D'Agostino and SCORE charts respectively. Kappa statistics was estimated for agreement in classification of patients with high CVR. The therapeutic recommendations in the 2007 European Guidelines on Cardiovascular Disease Prevention were followed. Results Mean patient age was 54.1 (SD 7.3, and 58.4% were males. A high CVR was found in 17.5% using the SCORE chart (25.3% males, 6.6% females and in 32.7% using the D'Agostino method (56.9% males, 12,7% females. Kappa coefficient was 0.52, and increased to 0.68 when the high CVR threshold was established at 29% according to D'Agostino. Hypertensive patients with high SCORE and non-high D'Agostino (1.7% were characterized by an older age, diabetes, and a lower atherogenic index, while the opposite situation (16.9% was associated to males, hyperlipidaemia, and a higher atherogenic index. Variables with a greater weight in discrepancies were sex and smoking. A 32.0% according to SCORE and 33.5% according to D'Agostino would be candidates to receive antihypertensive treatment, and 15.8% and

  6. Micronuclei in breast aspirates. Is scoring them helpful?

    Directory of Open Access Journals (Sweden)

    A Hemalatha

    2014-01-01

    Conclusion: An increase in micronuclei values was seen from fibroadenoma to infiltrating ductal carcinoma. Micronuclei scoring can be used as a biomarker on fine needle aspiration cytology smears of breast carcinoma.

  7. Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia

    Directory of Open Access Journals (Sweden)

    Julia Kuligowski

    2017-08-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6 h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia. The metabolite score's performance as a biomarker for perinatal hypoxia and its usefulness for clinical grading and decision making have been assessed and compared to the performance of lactate which is currently considered the gold standard. For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate. However, it provided an enhanced predictive capacity at 2 h after resuscitation. The present study evidences the usefulness of the metabolite score for improving the early assessment of the severity of the hypoxic insult based on serial determinations in a minimally invasive biofluid. The applicability of the metabolite score for clinical diagnosis and patient stratification for hypothermia treatment has to be confirmed in multicenter trials involving newborns suffering from HIE. Keywords: Hypoxia, Perinatal asphyxia, Newborn, Metabolic biomarker, Neonatal piglet model, Liquid Chromatography – Time-of-Flight Mass Spectrometry (LC-TOF-MS

  8. A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

    Science.gov (United States)

    VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

    2017-12-01

    Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver

  9. Society of Thoracic Surgeons Risk Score Predicts Hospital Charges and Resource Utilization After Aortic Valve Replacement

    Science.gov (United States)

    Arnaoutakis, George J.; George, Timothy J.; Alejo, Diane E.; Merlo, Christian A.; Baumgartner, William A.; Cameron, Duke E.; Shah, Ashish S.

    2011-01-01

    Context The impact of Society of Thoracic Surgeons (STS) predicted mortality risk score on resource utilization after aortic valve replacement (AVR) has not been previously studied. Objective We hypothesize that increasing STS risk scores in patients having AVR are associated with greater hospital charges. Design, Setting, and Patients Clinical and financial data for patients undergoing AVR at a tertiary care, university hospital over a ten-year period (1/2000–12/2009) were retrospectively reviewed. The current STS formula (v2.61) for in-hospital mortality was used for all patients. After stratification into risk quartiles (Q), index admission hospital charges were compared across risk strata with Rank-Sum tests. Linear regression and Spearman’s coefficient assessed correlation and goodness of fit. Multivariable analysis assessed relative contributions of individual variables on overall charges. Main Outcome Measures Inflation-adjusted index hospitalization total charges Results 553 patients had AVR during the study period. Average predicted mortality was 2.9% (±3.4) and actual mortality was 3.4% for AVR. Median charges were greater in the upper Q of AVR patients [Q1–3,$39,949 (IQR32,708–51,323) vs Q4,$62,301 (IQR45,952–97,103), p=<0.01]. On univariate linear regression, there was a positive correlation between STS risk score and log-transformed charges (coefficient: 0.06, 95%CI 0.05–0.07, p<0.01). Spearman’s correlation R-value was 0.51. This positive correlation persisted in risk-adjusted multivariable linear regression. Each 1% increase in STS risk score was associated with an added $3,000 in hospital charges. Conclusions This study showed increasing STS risk score predicts greater charges after AVR. As competing therapies such as percutaneous valve replacement emerge to treat high risk patients, these results serve as a benchmark to compare resource utilization. PMID:21497834

  10. Latent class models for joint analysis of disease prevalence and high-dimensional semicontinuous biomarker data.

    Science.gov (United States)

    Zhang, Bo; Chen, Zhen; Albert, Paul S

    2012-01-01

    High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exposure data, including a large number of biomarkers, numerous zero values, and complex mean-variance relationship in the biomarkers levels. A Monte Carlo EM (MCEM) algorithm is proposed for parameter estimation. Both the MCEM algorithm and model selection procedures are shown to work well in simulations and applications. In applying the proposed approach to an epidemiological study that examined the relationship between environmental polychlorinated biphenyl (PCB) exposure and the risk of endometriosis, we identified a highly significant overall effect of PCB concentrations on the risk of endometriosis.

  11. A score combining baseline neutrophilia and primary tumor SUV{sub peak} measured from FDG PET is associated with outcome in locally advanced cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schernberg, Antoine; Sun, Roger; Chargari, Cyrus [Gustave Roussy Cancer Campus, Radiation Oncology Department, Villejuif (France); INSERM, U1030, Villejuif (France); Reuze, Sylvain [Gustave Roussy Cancer Campus, Radiation Oncology Department, Villejuif (France); INSERM, U1030, Villejuif (France); Universite Paris-Saclay, Univ Paris Sud, Le Kremlin-Bicetre (France); Gustave Roussy, Universite Paris-Saclay, Department of Medical Physics, Villejuif (France); Orlhac, Fanny [INSERM, U1030, Villejuif (France); Universite Paris-Saclay, CEA-SHFJ, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Orsay (France); Buvat, Irene [Universite Paris-Saclay, CEA-SHFJ, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Orsay (France); Dercle, Laurent [Gustave Roussy, Universite Paris-Saclay, Department of Nuclear Medicine and Endocrine Oncology, Villejuif (France); INSERM, U1015, Villejuif (France); Limkin, Elaine [INSERM, U1030, Villejuif (France); Universite Paris-Saclay, Univ Paris Sud, Le Kremlin-Bicetre (France); Escande, Alexandre; Haie-Meder, Christine [Gustave Roussy Cancer Campus, Radiation Oncology Department, Villejuif (France); Deutsch, Eric [Gustave Roussy Cancer Campus, Radiation Oncology Department, Villejuif (France); INSERM, U1030, Villejuif (France); Universite Paris-Saclay, Univ Paris Sud, Le Kremlin-Bicetre (France); Robert, Charlotte [Gustave Roussy Cancer Campus, Radiation Oncology Department, Villejuif (France); INSERM, U1030, Villejuif (France); Universite Paris-Saclay, Univ Paris Sud, Le Kremlin-Bicetre (France); Gustave Roussy, Universite Paris-Saclay, Department of Medical Physics, Villejuif (France)

    2018-02-15

    We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC). Patients homogeneously treated with definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT) between 2006 and 2013 were analyzed retrospectively. We divided patients into two groups depending on the PET device used: a training set (TS) and a validation set (VS). Primary tumors were semi-automatically delineated on PET images, and 11 radiomics features were calculated (LIFEx software). A PET radiomic index was selected using the time-dependent area under the curve (td-AUC) for 3-year local control (LC). We defined the neutrophil SUV grade (NSG = 0, 1 or 2) score as the number of risk factors among (i) neutrophilia (neutrophil count >7 G/L) and (ii) high risk defined from the PET radiomic index. The NSG prognostic value was evaluated for LC and overall survival (OS). Data from 108 patients were analyzed. Estimated 3-year LC was 72% in the TS (n = 69) and 65% in the VS (n = 39). In the TS, SUV{sub peak} was selected as the most LC-predictive biomarker (td-AUC = 0.75), and was independent from neutrophilia (p = 0.119). Neutrophilia (HR = 2.6), high-risk SUV{sub peak} (SUV{sub peak} > 10, HR = 4.4) and NSG = 2 (HR = 9.2) were associated with low probability of LC in TS. In multivariate analysis, NSG = 2 was independently associated with low probability of LC (HR = 7.5, p < 0.001) and OS (HR = 5.8, p = 0.001) in the TS. Results obtained in the VS (HR = 5.2 for OS and 3.5 for LC, p < 0.02) were promising. This innovative scoring approach combining baseline neutrophilia and a PET biomarker provides an independent prognostic factor to consider for further clinical investigations. (orig.)

  12. How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores.

    Science.gov (United States)

    Oku, Kenji; Amengual, Olga; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-08-01

    Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population. It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). Additionally, clinicians may need to be aware of the patient's medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.

  13. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie-Louise

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...

  14. Clinical audit in gynecological cancer surgery: development of a risk scoring system to predict adverse events.

    Science.gov (United States)

    Kondalsamy-Chennakesavan, Srinivas; Bouman, Chantal; De Jong, Suzanne; Sanday, Karen; Nicklin, Jim; Land, Russell; Obermair, Andreas

    2009-12-01

    Advanced gynecological surgery undertaken in a specialized gynecologic oncology unit may be associated with significant perioperative morbidity. Validated risk prediction models are available for general surgical specialties but currently not for gynecological cancer surgery. The objective of this study was to evaluate risk factors for adverse events (AEs) of patients treated for suspected or proven gynecological cancer and to develop a clinical risk score (RS) to predict such AEs. AEs were prospectively recorded and matched with demographical, clinical and histopathological data on 369 patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center. Stepwise multiple logistic regression was used to determine the best predictors of AEs. For the risk score (RS), the coefficients from the model were scaled using a factor of 2 and rounded to the nearest integer to derive the risk points. Sum of all the risk points form the RS. Ninety-five patients (25.8%) had at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra- and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The independent predictors for any AE were complexity of the surgical procedure, elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher ASA scores and overweight. The risk score can vary from 0 to 14. The risk for developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))). RS allows for quantification of the risk for AEs. Risk factors are generally not modifiable with the possible exception of obesity.

  15. A Healthy Lifestyle Score Is Associated with Cardiometabolic and Neuroendocrine Risk Factors among Puerto Rican Adults.

    Science.gov (United States)

    Sotos-Prieto, Mercedes; Bhupathiraju, Shilpa N; Falcón, Luis M; Gao, Xiang; Tucker, Katherine L; Mattei, Josiemer

    2015-07-01

    Although individual healthy lifestyle behaviors may reduce cardiovascular disease risk, few studies have analyzed the combined effect of multiple lifestyle components as one all-inclusive measure on such outcomes, much less in minority populations. We aimed to develop a Healthy Lifestyle Score (HLS) that included several lifestyle recommendations and to test its association with metabolic syndrome (MetS) and allostatic load (AL) and their cardiometabolic and neuroendocrine factors in Puerto Ricans. In a cross-sectional study in 787 Puerto Ricans living in Boston (aged 45-75 y), we developed an HLS that ranged from 0 to 190 (higher score indicative of healthier lifestyle) and included 5 components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep). Multivariable-adjusted models were used to test associations between the HLS and biomarkers of dysregulation and odds of MetS and high AL (≥4 out of 10 components). The HLS showed adequate internal consistency (ρ = 0.31-0.69) and was inversely associated with urinary cortisol (β ± SE = -0.22 ± 0.11; P = 0.042), epinephrine (-0.20 ± 0.09; P = 0.017), and norepinephrine (-0.26 ± 0.11; P = 0.016); waist circumference (-0.014 ± 0.004; P = 0.003); and serum insulin (-0.30 ± 0.13; P = 0.028) and positively associated with plasma HDL cholesterol (0.007 ± 0.003; P = 0.021) after adjustment for potential confounders. For each 20-unit increase in HLS, participants had 19% (95% CI: 2%, 33%) and 25% (11%, 36%) lower odds of MetS or AL, respectively. Healthier scores for social support and network and smoking components were associated with lower odds of high AL (P lifestyle components. Following an overall healthy lifestyle that comprises a combination of multiple behaviors may provide stronger protection against MetS and AL in Puerto Rican adults than individual components. The HLS may be a useful tool for examining health-related outcomes. This trial was registered at

  16. Physical activity, stress, and metabolic risk score in 8- to 18-year-old boys.

    Science.gov (United States)

    Holmes, Megan E; Eisenmann, Joey C; Ekkekakis, Panteleimon; Gentile, Douglas

    2008-03-01

    We examined whether physical activity modifies the relationship between stress and the metabolic risk score in 8- to 18-year-old males (n = 37). Physical activity (PA) and television (TV)/videogame (VG) use were assessed via accelerometer and questionnaire, respectively. Stress was determined from self-report measures. A metabolic risk score (MRS) was created by summing age-standardized residuals for waist circumference, mean arterial pressure, glycosylated hemoglobin, and high-density lipoprotein cholesterol. Correlations between PA and MRS were low (r adolescents.

  17. A user-friendly risk-score for predicting in-hospital cardiac arrest among patients admitted with suspected non ST-elevation acute coronary syndrome - The SAFER-score.

    Science.gov (United States)

    Faxén, Jonas; Hall, Marlous; Gale, Chris P; Sundström, Johan; Lindahl, Bertil; Jernberg, Tomas; Szummer, Karolina

    2017-12-01

    To develop a simple risk-score model for predicting in-hospital cardiac arrest (CA) among patients hospitalized with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART), we identified patients (n=242 303) admitted with suspected NSTE-ACS between 2008 and 2014. Logistic regression was used to assess the association between 26 candidate variables and in-hospital CA. A risk-score model was developed and validated using a temporal cohort (n=126 073) comprising patients from SWEDEHEART between 2005 and 2007 and an external cohort (n=276 109) comprising patients from the Myocardial Ischaemia National Audit Project (MINAP) between 2008 and 2013. The incidence of in-hospital CA for NSTE-ACS and non-ACS was lower in the SWEDEHEART-derivation cohort than in MINAP (1.3% and 0.5% vs. 2.3% and 2.3%). A seven point, five variable risk score (age ≥60 years (1 point), ST-T abnormalities (2 points), Killip Class >1 (1 point), heart rate Model discrimination was good in the derivation cohort (c-statistic 0.72) and temporal validation cohort (c-statistic 0.74), and calibration was reasonable with a tendency towards overestimation of risk with a higher sum of score points. External validation showed moderate discrimination (c-statistic 0.65) and calibration showed a general underestimation of predicted risk. A simple points score containing five variables readily available on admission predicts in-hospital CA for patients with suspected NSTE-ACS. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

    Science.gov (United States)

    Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

    2017-04-01

    Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.

  19. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    Science.gov (United States)

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  20. Assessment of different biomarkers provides valuable diagnostic standards in the evaluation of the risk of acute rejection.

    Science.gov (United States)

    Zheng, Jin; Ding, Xiaoming; Tian, Xiaohui; Jin, Zhankui; Pan, Xiaoming; Yan, Hang; Feng, Xinshun; Hou, Jun; Xiang, Heli; Ren, Li; Tian, Puxun; Xue, Wujun

    2012-09-01

    Acute rejection (AR) is a strong risk factor for chronic rejection in renal transplant recipients. Accurate and timely diagnosis of AR episodes is very important for disease control and prognosis. Therefore, objectively evaluated the immune status of patients is essential in the field of post-transplantation treatment. This longitudinal study investigated the usefulness of five biomarkers, human leukocyte antigen (HLA)-G5 and sCD30 level in sera, intracellular adenosine triphosphate (iATP) release level of CD4(+) T cells, and granzyme B/perforin expression in peripheral blood mononuclear cells (PBMCs) and biopsies, to detect AR and the resolution of biomarkers in a total of 84 cases of renal transplantation. The data demonstrated that recipients with clinical or biopsy proven rejection significantly increased iATP release level of CD4(+) T cells, and elevated sCD30 but lowered HLA-G5 level in sera compared with individuals with stable graft function. Expression levels of granzyme B and perforin were also elevated in PBMCs and graft biopsies of AR patients. Taken together, we identified that upregulation of sCD30, iATP, granzyme B, perforin, and downregulation of HLA-G5 could provide valuable diagnostic standards to identify those recipients in the risk of AR. And iATP may be a better biomarker than others for predicting the graft rejection episode.

  1. Evaluation of mass spectrometry of urinary proteins and peptides as biomarkers for cats at risk of developing azotemia.

    Science.gov (United States)

    Jepson, Rosanne E; Coulton, Gary R; Cowan, Matthew L; Markwell, Peter; Syme, Harriet M; Elliott, Jonathan

    2013-02-01

    To evaluate proteomic delineation of feline urine by mass spectrometry as a method for identifying biomarkers in cats at risk of developing azotemia. Urine samples from geriatric cats (> 9 years old) with chronic kidney disease and nonazotemic cats that either remained nonazotemic (n = 10) or developed azotemia (10) within 1 year. Optimization studies with pooled urine were performed to facilitate the use of surface enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for analysis of the urinary proteome of cats. Urine samples from nonazotemic cats at entry to the study were analyzed via SELDI-TOF-MS with weak cation exchange and strong anion exchange arrays. Spectral data were compared to identify biomarkers for development of azotemia. Low protein concentration in feline urine precluded direct application to array surfaces, and a buffer exchange and concentration step was required prior to SELDI-TOF-MS analysis. Three preparation conditions by use of weak cation and strong anion exchange arrays were selected on the basis of optimization studies for detection of biomarkers. Eight potential biomarkers with an m/z of 2,822, 9,886, 10,033, 10,151, 10,234, 11,653, 4,421, and 9,505 were delineated. SELDI-TOF-MS can be used to detect urinary low-molecular weight peptides and proteins that may represent biomarkers for early detection of renal damage. Further study is required to purify and identify potential biomarkers before their use in a clinical setting.

  2. Biomarkers of PTSD: military applications and considerations

    OpenAIRE

    Amy Lehrner; Rachel Yehuda

    2014-01-01

    Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

  3. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  4. Limitations of the Parsonnet score for measuring risk stratified mortality in the north west of England

    Science.gov (United States)

    Wynne-Jones, K; Jackson, M; Grotte, G; Bridgewater, B; North, W

    2000-01-01

    OBJECTIVE—To study the use of the Parsonnet score to predict mortality following adult cardiac surgery.
DESIGN—Prospective study.
SETTING—All centres performing adult cardiac surgery in the north west of England.
SUBJECTS—8210 patients undergoing surgery between April 1997 and March 1999.
MAIN OUTCOME MEASURES—Risk factors and in-hospital mortality were recorded according to agreed definitions. Ten per cent of cases from each centre were selected at random for validation. A Parsonnet score was derived for each patient and its predictive ability was studied.
RESULTS—Data collection was complete. The operative mortality was 3.5% (95% confidence interval 3.1% to 3.9%), ranging from 2.7% to 3.8% across the centres. On validation, the incidence of discrepancies ranged from 0% to 13% for the different risk factors. The predictive ability of the Parsonnet score measured by area under the receiver operating characteristic curve was 0.74. The mean Parsonnet score for the region was 7.0, giving an observed to expected mortality ratio of 0.51 (range 0.4 to 0.64 across the centres). A new predictive model was derived from the data by multivariate analysis which includes nine objective risk factors, all with a significant association with mortality, which highlights some of the deficits of the Parsonnet score.
CONCLUSIONS—Risk stratified mortality data were collected on 100% of patients undergoing adult cardiac surgery in two years within a defined geographical region and were used to set an audit standard. Problems with the Parsonnet score of subjectivity, inclusion of many items not associated with mortality, and the overprediction of mortality have been highlighted.


Keywords: risk stratification; cardiac surgery; Parsonnet score; audit PMID:10862595

  5. Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

    Science.gov (United States)

    Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

    2018-06-01

    Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

  6. Role of Biomarkers in the Diagnosis, Risk Assessment, and Management of Pulmonary Hypertension.

    Science.gov (United States)

    Rameh, Vanessa; Kossaify, Antoine

    2016-01-01

    Pulmonary hypertension is a severe and debilitating disease with no definite cure, and the domain of targeted therapies is a promising field for better management of this severe condition. The disease comprises pulmonary arterial remodeling, hypoxia, endothelial dysfunction, and inflammation, with subsequent organ damage including right heart and liver dysfunction. Biomarkers have a valuable role at different levels of the disease, from diagnosis to risk assessment and management, in order to decrease the burden of the disease in terms of both morbidity and mortality.

  7. Predictive Accuracy of Violence Risk Scale-Sexual Offender Version Risk and Change Scores in Treated Canadian Aboriginal and Non-Aboriginal Sexual Offenders.

    Science.gov (United States)

    Olver, Mark E; Sowden, Justina N; Kingston, Drew A; Nicholaichuk, Terry P; Gordon, Audrey; Beggs Christofferson, Sarah M; Wong, Stephen C P

    2018-04-01

    The present study examined the predictive properties of Violence Risk Scale-Sexual Offender version (VRS-SO) risk and change scores among Aboriginal and non-Aboriginal sexual offenders in a combined sample of 1,063 Canadian federally incarcerated men. All men participated in sexual offender treatment programming through the Correctional Service of Canada (CSC) at sites across its five regions. The Static-99R was also examined for comparison purposes. In total, 393 of the men were identified as Aboriginal (i.e., First Nations, Métis, Circumpolar) while 670 were non-Aboriginal and primarily White. Aboriginal men scored significantly higher on the Static-99R and VRS-SO and had higher rates of sexual and violent recidivism; however, there were no significant differences between Aboriginal and non-Aboriginal groups on treatment change with both groups demonstrating close to a half-standard deviation of change pre and post treatment. VRS-SO risk and change scores significantly predicted sexual and violent recidivism over fixed 5- and 10-year follow-ups for both racial/ancestral groups. Cox regression survival analyses also demonstrated positive treatment changes to be significantly associated with reductions in sexual and violent recidivism among Aboriginal and non-Aboriginal men after controlling baseline risk. A series of follow-up Cox regression analyses demonstrated that risk and change score information accounted for much of the observed differences between Aboriginal and non-Aboriginal men in rates of sexual recidivism; however, marked group differences persisted in rates of general violent recidivism even after controlling for these covariates. The results support the predictive properties of VRS-SO risk and change scores with treated Canadian Aboriginal sexual offenders.

  8. Predicting dementia risk in primary care: development and validation of the Dementia Risk Score using routinely collected data.

    Science.gov (United States)

    Walters, K; Hardoon, S; Petersen, I; Iliffe, S; Omar, R Z; Nazareth, I; Rait, G

    2016-01-21

    Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data. We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60-95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60-79 and 80-95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables. Dementia incidence was 1.88 (95% CI, 1.83-1.93) and 16.53 (95% CI, 16.15-16.92) per 1000 PYAR for those aged 60-79 (n = 6017) and 80-95 years (n = 7104), respectively. Predictors for those aged 60-79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60-79 years model; D statistic 2.03 (95% CI, 1.95-2.11), C index 0.84 (95% CI, 0.81-0.87), and calibration slope 0.98 (95% CI, 0.93-1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80-95 years model. Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60-79, but not those aged 80+. This

  9. Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

    Science.gov (United States)

    Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

    2017-10-11

    Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

  10. Portsmouth physiological and operative severity score for the Enumeration of Mortality and morbidity scoring system in general surgical practice and identifying risk factors for poor outcome

    Science.gov (United States)

    Tyagi, Ashish; Nagpal, Nitin; Sidhu, D. S.; Singh, Amandeep; Tyagi, Anjali

    2017-01-01

    Background: Estimation of the outcome is paramount in disease stratification and subsequent management in severely ill surgical patients. Risk scoring helps us quantify the prospects of adverse outcome in a patient. Portsmouth-Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (P-POSSUM) the world over has proved itself as a worthy scoring system and the present study was done to evaluate the feasibility of P-POSSUM as a risk scoring system as a tool in efficacious prediction of mortality and morbidity in our demographic profile. Materials and Methods: Validity of P-POSSUM was assessed prospectively in fifty major general surgeries performed at our hospital from May 2011 to October 2012. Data were collected to obtain P-POSSUM score, and statistical analysis was performed. Results: Majority (72%) of patients was male and mean age was 40.24 ± 18.6 years. Seventy-eight percentage procedures were emergency laparotomies commonly performed for perforation peritonitis. Mean physiological score was 17.56 ± 7.6, and operative score was 17.76 ± 4.5 (total score = 35.3 ± 10.4). The ratio of observed to expected mortality rate was 0.86 and morbidity rate was 0.78. Discussion: P-POSSUM accurately predicted both mortality and morbidity in patients who underwent major surgical procedures in our setup. Thus, it helped us in identifying patients who required preferential attention and aggressive management. Widespread application of this tool can result in better distribution of care among high-risk surgical patients. PMID:28250670

  11. Influence of bone mineral density measurement on fracture risk assessment tool® scores in postmenopausal Indian women.

    Science.gov (United States)

    Daswani, Bhavna; Desai, Meena; Mitra, Sumegha; Gavali, Shubhangi; Patil, Anushree; Kukreja, Subhash; Khatkhatay, M Ikram

    2016-03-01

    Fracture risk assessment tool® calculations can be performed with or without addition of bone mineral density; however, the impact of this addition on fracture risk assessment tool® scores has not been studied in Indian women. Given the limited availability and high cost of bone mineral density testing in India, it is important to know the influence of bone mineral density on fracture risk assessment tool® scores in Indian women. Therefore, our aim was to assess the contribution of bone mineral density in fracture risk assessment tool® outcome in Indian women. Apparently healthy postmenopausal Indian women (n = 506), aged 40-72 years, without clinical risk factors for bone disease, were retrospectively selected, and their fracture risk assessment tool® scores calculated with and without bone mineral density were compared. Based on WHO criteria, 30% women were osteoporotic, 42.9% were osteopenic and 27.1% had normal bone mineral density. Fracture risk assessment tool® scores for risk of both major osteoporotic fracture and hip fracture significantly increased on including bone mineral density (P women eligible without bone mineral density was 0 and with bone mineral density was 1, P > 0.05, whereas, for hip fracture risk number of women eligible without bone mineral density was 2 and with bone mineral density was 17, P Indian women. © The Author(s) 2016.

  12. Association of malnutrition-inflammation score, dialysis-malnutrition score and serum albumin with novel risk factors for cardiovascular diseases in hemodialysis patients.

    Science.gov (United States)

    As'habi, Atefeh; Tabibi, Hadi; Hedayati, Mehdi; Mahdavi-Mazdeh, Mitra; Nozary-Heshmati, Behnaz

    2015-02-01

    This study was designed to investigate the associations between malnutrition-inflammation score (MIS), dialysis-malnutrition score (DMS) and serum albumin with novel risk factors for cardiovascular diseases (CVD) in hemodialysis (HD) patients. In this cross-sectional study, 291 HD patients were randomly selected from among 2302 adult HD patients in Tehran HD centers. The MIS and DMS were determined during one of the dialysis sessions in these patients. In addition, 4 mL blood was obtained before dialysis and analyzed for serum albumin and novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)]. MIS and DMS were significantly positively correlated with serum CRP (p protein-energy wasting indicators in HD patients are associated with serum CRP and sICAM-1, as two CVD risk factors.

  13. Can the integration of multiple biomarkers and sediment geochemistry aid solving the complexity of sediment risk assessment? A case study with a benthic fish

    International Nuclear Information System (INIS)

    Costa, Pedro M.; Caeiro, Sandra; Vale, Carlos; DelValls, T. Àngel; Costa, Maria H.

    2012-01-01

    Surveying toxicity of complex geochemical media as aquatic sediments often yields results that are either difficult to interpret or even contradictory to acknowledged theory. Multi-level biomarkers were investigated in a benthic fish exposed to estuarine sediments through laboratory and in situ bioassays, to evaluate their employment either in ecological risk assessment or in more mechanistic approaches to assess sediment-bound toxicity. Biomarkers reflecting lesions (such as genotoxicity or histopathology), regardless of their low or absent specificity to contaminants, are efficient in segregating exposure to contaminated from uncontaminated sediments even when classical biomarkers like CYP1A and metallothionein induction are inconclusive. Conversely, proteomics and gene transcription analyses provided information on the mechanics of toxicity and aided explaining response variation as a function of metabolic imbalance and impairment of defences against insult. In situ bioassays, although less expedite and more affected by confounding factors, produced data better correlated to overall sediment contamination. Highlights: ► Sediment-bound contaminant mixtures can yield unexpected biomarker responses in fish. ► Biomarkers reflecting lesions are sturdier predictors of pollution by mixed xenobiotics. ► Proteomics and gene transcription analyses disclosed the existence of complex patterns of response to toxicity. ► Laboratory bioassays are less impacted by noise variables but tend to lose ecological relevance. - Evaluation of multi-level biomarker responses in fish for ecological risk assessment

  14. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    International Nuclear Information System (INIS)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-01-01

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases

  15. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo, E-mail: anamariafeoli@hotmail.com [Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS (Brazil)

    2014-04-15

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

  16. Biomarkers in Diabetic Retinopathy.

    Science.gov (United States)

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  17. Validation of the Brazilian Healthy Eating Index-Revised Using Biomarkers in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Roseli B. D. Toffano

    2018-01-01

    Full Text Available The Brazilian Healthy Eating Index-Revised (BHEI-R can be used to determine overall dietary patterns. We assessed the BHEI-R scores in children and adolescents, aged from 9 to 13 years old, and associated its component scores with biomarkers of health and dietary exposure. Three 24-h recalls were used to generate BHEI-R. Biomarkers were analyzed in plasma and red blood cells. Correlation tests, agreement, and covariance analyses were used to associate BHEI-R components with biomarkers. Data from 167 subjects were used. The strongest correlations were between fruits, vegetables and legumes with omega-6 and omega-3 fatty acids, and β-carotene intakes. Milk and dairy correlated with plasma retinol and pyridoxine. All components rich in vegetable and animal protein sources correlated with plasma creatine. Total BHEI-R scores were positively associated with intakes of omega-6, omega-3, fiber and vitamin C, and inversely associated with energy and saturated fat intakes of individuals. Plasma β-carotene and riboflavin biomarkers were positively associated with total BHEI-R. An inadequate food consumption pattern was captured by both biomarkers of health and dietary exposure. BHEI-R was validated for the above dietary components and can be associated with metabolomics and nutritional epidemiological data in future pediatric studies.

  18. Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis.

    Science.gov (United States)

    Scott, A J; Mason, S E; Arunakirinathan, M; Reissis, Y; Kinross, J M; Smith, J J

    2015-04-01

    Current management of suspected appendicitis is hampered by the overadmission of patients with non-specific abdominal pain and a significant negative exploration rate. The potential benefits of risk stratification by the Appendicitis Inflammatory Response (AIR) score to guide clinical decision-making were assessed. During this 50-week prospective observational study at one institution, the AIR score was calculated for all patients admitted with suspected appendicitis. Appendicitis was diagnosed by histological examination, and patients were classified as having non-appendicitis pain if histological findings were negative or surgery was not performed. The diagnostic performance of the AIR score and the potential for risk stratification to reduce admissions, optimize imaging and prevent unnecessary explorations were quantified. A total of 464 patients were included, of whom 210 (63·3 per cent) with non-appendicitis pain were correctly classified as low risk. However, 13 low-risk patients had appendicitis. Low-risk patients accounted for 48·1 per cent of admissions (223 of 464), 57 per cent of negative explorations (48 of 84) and 50·7 per cent of imaging requests (149 of 294). An AIR score of 5 or more (intermediate and high risk) had high sensitivity for all severities of appendicitis (90 per cent) and also for advanced appendicitis (98 per cent). An AIR score of 9 or more (high risk) was very specific (97 per cent) for appendicitis, and the majority of patients with appendicitis in the high-risk group (21 of 30, 70 per cent) had perforation or gangrene. Ultrasound imaging could not exclude appendicitis in low-risk patients (negative likelihood ratio (LR) 1·0) but could rule-in the diagnosis in intermediate-risk patients (positive LR 10·2). CT could exclude appendicitis in low-risk patients (negative LR 0·0) and rule-in appendicitis in the intermediate group (positive LR 10·9). Risk stratification of patients with suspected appendicitis by the AIR score could

  19. Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

    Directory of Open Access Journals (Sweden)

    Straand Jørund

    2011-03-01

    Full Text Available Abstract Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK, 4.4% (SCORE and 14.5% (Framingham had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females.

  20. Histological scoring and associated risk factors of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Majid, N; Ali, Z; Rahman, M R; Akhter, A; Rajib, R C; Ahmad, F; Sharmin, S; Akond, A K; Huq, N

    2013-10-01

    Non alcoholic steatohepatitis is a hepatic disorder with histological features of alcohol induced liver disease that occurs in individual who do not consume significant alcohol. Liver biopsy is an important part of the evaluation in term of both grade & stage. A cross sectional study was carried out in the department of Pathology, Dhaka Medical College, Dhaka & department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2007 to June 2009. Total 55 adult subjects of both sex were included on the basis of predefined inclusion & exclusion criteria in this study to evaluate the histological pattern of non alcoholic fatty liver disease (NAFLD) and its correlation with risk factors. Liver biopsy was done and H & E and Masson's Trichrome stain slides were examined to evaluate the grade and stage of NAFLD. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). The results of Pearson correlation showed only BMI and triglyceride level significantly correlated with NAS score. The results of Spearman's rank correlation showed that BMI, central obesity, triglyceridaemia and age significantly correlated with staging of fibrosis. The results of multiple regression analysis showed that variation of NAS depend on BMI and triglyceride level. The study also revealed that risk factors contributed about 29% risk for the occurrence of non alcoholic steatohepatitis.

  1. Score-driven exponentially weighted moving averages and Value-at-Risk forecasting

    NARCIS (Netherlands)

    Lucas, A.; Zhang, X.

    2016-01-01

    We present a simple methodology for modeling the time variation in volatilities and other higher-order moments using a recursive updating scheme that is similar to the familiar RiskMetrics approach. The parameters are updated using the score of the forecasting distribution, which allows the

  2. Thrombogenicity and central pulse pressure to enhance prediction of ischemic event occurrence in patients with established coronary artery disease: The MAGMA-ischemia score.

    Science.gov (United States)

    Bliden, Kevin P; Chaudhary, Rahul; Navarese, Eliano P; Sharma, Tushar; Kaza, Himabindu; Tantry, Udaya S; Gurbel, Paul A

    2018-01-01

    Conventional cardiovascular risk estimators based on clinical demographics have limited prediction of coronary events. Markers for thrombogenicity and vascular function have not been explored in risk estimation of high-risk patients with coronary artery disease. We aimed to develop a clinical and biomarker score to predict 3-year adverse cardiovascular events. Four hundred eleven patients, with ejection fraction ≥40% undergoing coronary angiography, and found to have a luminal diameter stenosis ≥50%, were included in the analysis. Thrombelastography indices and central pulse pressure (CPP) were determined at the time of catheterization. We identified predictors of death, myocardial infarction (MI) or stroke and developed a numerical ischemia risk score. The primary endpoint of cardiovascular death, MI or stroke occurred in 22 patients (5.4%). The factors associated with events were age, prior PCI or CABG, diabetes, CPP, and thrombin-induced platelet-fibrin clot strength, and were included in the MAGMA-ischemia score. The MAGMA-ischemia score showed a c-statistic of 0.85 (95% Confidence Interval [CI] 0.80-0.87; pMAGMA-ischemia score greater than 5 had highest risk to develop clinical events, hazard ratio for the primary endpoint: 13.9 (95% CI 5.8-33.1, pMAGMA-ischemia score yielded a higher discrimination. Inclusion of CPP and assessment of thrombogenicity in a novel score for patients with documented CAD enhanced the prediction of events. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. New risk markers may change the HeartScore risk classification significantly in one-fifth of the population

    DEFF Research Database (Denmark)

    Olsen, M H; Hansen, T W; Christensen, M K

    2008-01-01

    subjects with estimated risk below 5%. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (CEP) occurred in 204 subjects. CEP was predicted in all three groups by UACR (HRs: 2.1, 2.1 and 2.3 per 10-fold increase, all P...CRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population....

  4. Adiposity, mediating biomarkers and risk of colon cancer in the european prospective investigation into cancer and nutrition study

    NARCIS (Netherlands)

    Aleksandrova, K.; Drogan, D.; Boeing, H.; Jenab, M.; Bueno de Mesquita, H.B.; Duijnhoven, van F.J.B.

    2014-01-01

    Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer

  5. Society of Thoracic Surgeons Risk Score predicts hospital charges and resource use after aortic valve replacement.

    Science.gov (United States)

    Arnaoutakis, George J; George, Timothy J; Alejo, Diane E; Merlo, Christian A; Baumgartner, William A; Cameron, Duke E; Shah, Ashish S

    2011-09-01

    The impact of Society of Thoracic Surgeons predicted mortality risk score on resource use has not been previously studied. We hypothesize that increasing Society of Thoracic Surgeons risk scores in patients undergoing aortic valve replacement are associated with greater hospital charges. Clinical and financial data for patients undergoing aortic valve replacement at The Johns Hopkins Hospital over a 10-year period (January 2000 to December 2009) were reviewed. The current Society of Thoracic Surgeons formula (v2.61) for in-hospital mortality was used for all patients. After stratification into risk quartiles, index admission hospital charges were compared across risk strata with rank-sum and Kruskal-Wallis tests. Linear regression and Spearman's coefficient assessed correlation and goodness of fit. Multivariable analysis assessed relative contributions of individual variables on overall charges. A total of 553 patients underwent aortic valve replacement during the study period. Average predicted mortality was 2.9% (±3.4) and actual mortality was 3.4% for aortic valve replacement. Median charges were greater in the upper quartile of patients undergoing aortic valve replacement (quartiles 1-3, $39,949 [interquartile range, 32,708-51,323] vs quartile 4, $62,301 [interquartile range, 45,952-97,103], P < .01]. On univariate linear regression, there was a positive correlation between Society of Thoracic Surgeons risk score and log-transformed charges (coefficient, 0.06; 95% confidence interval, 0.05-0.07; P < .01). Spearman's correlation R-value was 0.51. This positive correlation persisted in risk-adjusted multivariable linear regression. Each 1% increase in Society of Thoracic Surgeons risk score was associated with an added $3000 in hospital charges. This is the first study to show that increasing Society of Thoracic Surgeons risk score predicts greater charges after aortic valve replacement. As competing therapies, such as percutaneous valve replacement, emerge to

  6. The development of a risk score for unplanned removal of peripherally inserted central catheter in newborns

    Directory of Open Access Journals (Sweden)

    Priscila Costa

    2015-06-01

    Full Text Available OBJECTIVE: to develop a risk score for unplanned removal of peripherally inserted central catheter in newborns.METHOD: prospective cohort study conducted in a neonatal intensive care unit with newborn babies who underwent 524 catheter insertions. The clinical characteristics of the newborn, catheter insertion and intravenous therapy were tested as risk factors for the unplanned removal of catheters using bivariate analysis. The risk score was developed using logistic regression. Accuracy was internally validated based on the area under the Receiver Operating Characteristic curve.RESULTS: the risk score was made up of the following risk factors: transient metabolic disorders; previous insertion of catheter; use of a polyurethane double-lumen catheter; infusion of multiple intravenous solutions through a single-lumen catheter; and tip in a noncentral position. Newborns were classified into three categories of risk of unplanned removal: low (0 to 3 points, moderate (4 to 8 points, and high (≥ 9 points. Accuracy was 0.76.CONCLUSION: the adoption of evidence-based preventative strategies based on the classification and risk factors faced by the newborn is recommended to minimize the occurrence of unplanned removals.

  7. Fall risk assessment: retrospective analysis of Morse Fall Scale scores in Portuguese hospitalized adult patients.

    Science.gov (United States)

    Sardo, Pedro Miguel Garcez; Simões, Cláudia Sofia Oliveira; Alvarelhão, José Joaquim Marques; Simões, João Filipe Fernandes Lindo; Melo, Elsa Maria de Oliveira Pinheiro de

    2016-08-01

    The Morse Fall Scale is used in several care settings for fall risk assessment and supports the implementation of preventive nursing interventions. Our work aims to analyze the Morse Fall Scale scores of Portuguese hospitalized adult patients in association with their characteristics, diagnoses and length of stay. Retrospective cohort analysis of Morse Fall Scale scores of 8356 patients hospitalized during 2012. Data were associated to age, gender, type of admission, specialty units, length of stay, patient discharge, and ICD-9 diagnosis. Elderly patients, female, with emergency service admission, at medical units and/or with longer length of stays were more frequently included in the risk group for falls. ICD-9 diagnosis may also be an important risk factor. More than a half of hospitalized patients had "medium" to "high" risk of falling during the length of stay, which determines the implementation and maintenance of protocoled preventive nursing interventions throughout hospitalization. There are several fall risk factors not assessed by Morse Fall Scale. There were no statistical differences in Morse Fall Scale score between the first and the last assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Biomarkers and Genetics in Peripheral Artery Disease.

    Science.gov (United States)

    Hazarika, Surovi; Annex, Brian H

    2017-01-01

    Peripheral artery disease (PAD) is highly prevalent and there is considerable diversity in the initial clinical manifestation and disease progression among individuals. Currently, there is no ideal biomarker to screen for PAD, to risk stratify patients with PAD, or to monitor therapeutic response to revascularization procedures. Advances in human genetics have markedly enhanced the ability to develop novel diagnostic and therapeutic approaches across a host of human diseases, but such developments in the field of PAD are lagging. In this article, we will discuss the epidemiology, traditional risk factors for, and clinical presentations of PAD. We will discuss the possible role of genetic factors and gene-environment interactions in the development and/or progression of PAD. We will further explore future avenues through which genetic advances can be used to better our understanding of the pathophysiology of PAD and potentially find newer therapeutic targets. We will discuss the potential role of biomarkers in identifying patients at risk for PAD and for risk stratifying patients with PAD, and novel approaches to identification of reliable biomarkers in PAD. The exponential growth of genetic tools and newer technologies provides opportunities to investigate and identify newer pathways in the development and progression of PAD, and thereby in the identification of newer biomarkers and therapies. © 2016 American Association for Clinical Chemistry.

  9. Proteomic candidate biomarkers of drug-induced nephrotoxicity in the rat.

    Directory of Open Access Journals (Sweden)

    Rodney Rouse

    Full Text Available Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10-20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity.

  10. Recalibration of the Global Registry of Acute Coronary Events risk score in a multiethnic Asian population.

    Science.gov (United States)

    Chan, Mark Y; Shah, Bimal R; Gao, Fei; Sim, Ling Ling; Chua, Terrance; Tan, Huay Cheem; Yeo, Tiong Cheng; Ong, Hean Yee; Foo, David; Goh, Ping Ping; Surrun, Soondal K; Pieper, Karen S; Granger, Christopher B; Koh, Tian Hai; Salim, Agus; Tai, E Shyong

    2011-08-01

    Acute myocardial infarction (AMI) is a leading cause of mortality in Asia. However, quantitative risk scores to predict mortality after AMI were developed without the participation of Asian countries. We evaluated the performance of the Global Registry of Acute Coronary Events (GRACE) in-hospital mortality risk score, directly and after recalibration, in a large Singaporean cohort representing 3 major Asian ethnicities. The GRACE cohort included 11,389 patients, predominantly of European descent, hospitalized for AMI or unstable angina from 2002 to 2003. The Singapore cohort included 10,100 Chinese, 3,005 Malay, and 2,046 Indian patients hospitalized for AMI from 2002 to 2005.Using the original GRACE score, predicted in-hospital mortality was 2.4% (Chinese), 2.0% (Malay), and 1.6% (Indian). However, observed in-hospital mortality was much greater at 9.8% (Chinese), 7.6% (Malay), and 6.4% (Indian). The c statistic for Chinese, Malays, and Indians was 0.86, 0.86, and 0.84, respectively, and the Hosmer-Lemeshow statistic was 250, 56, and 41, respectively. Recalibration of the GRACE score, using the mean-centered constants derived from the Singapore cohort, did not change the c statistic but substantially improved the Hosmer-Lemeshow statistic to 90, 24, and 18, respectively. The recalibrated GRACE score predicted in-hospital mortality as follows: 7.7% (Chinese), 6.0% (Malay), and 5.2% (Indian). In this large cohort of 3 major Asian ethnicities, the original GRACE score, derived from populations outside Asia, underestimated in-hospital mortality after AMI. Recalibration improved risk estimation substantially and may help adapt externally developed risk scores for local practice. Copyright © 2011 Mosby, Inc. All rights reserved.

  11. Volumetry based biomarker speed of growth: Quantifying the change of total tumor volume in whole-body magnetic resonance imaging over time improves risk stratification of smoldering multiple myeloma patients.

    Science.gov (United States)

    Wennmann, Markus; Kintzelé, Laurent; Piraud, Marie; Menze, Bjoern H; Hielscher, Thomas; Hofmanninger, Johannes; Wagner, Barbara; Kauczor, Hans-Ulrich; Merz, Maximilian; Hillengass, Jens; Langs, Georg; Weber, Marc-André

    2018-05-18

    The purpose of this study was to improve risk stratification of smoldering multiple myeloma patients, introducing new 3D-volumetry based imaging biomarkers derived from whole-body MRI. Two-hundred twenty whole-body MRIs from 63 patients with smoldering multiple myeloma were retrospectively analyzed and all focal lesions >5mm were manually segmented for volume quantification. The imaging biomarkers total tumor volume, speed of growth (development of the total tumor volume over time), number of focal lesions, development of the number of focal lesions over time and the recent imaging biomarker '>1 focal lesion' of the International Myeloma Working Group were compared, taking 2-year progression rate, sensitivity and false positive rate into account. Speed of growth, using a cutoff of 114mm 3 /month, was able to isolate a high-risk group with a 2-year progression rate of 82.5%. Additionally, it showed by far the highest sensitivity in this study and in comparison to other biomarkers in the literature, detecting 63.2% of patients who progress within 2 years. Furthermore, its false positive rate (8.7%) was much lower compared to the recent imaging biomarker '>1 focal lesion' of the International Myeloma Working Group. Therefore, speed of growth is the preferable imaging biomarker for risk stratification of smoldering multiple myeloma patients.

  12. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers.

    Science.gov (United States)

    Reitz, Christiane; Mayeux, Richard

    2014-04-15

    The global prevalence of dementia is as high as 24 million, and has been predicted to quadruple by the year 2050. In the US alone, Alzheimer disease (AD) - the most frequent cause of dementia characterized by a progressive decline in cognitive function in particular the memory domain - causes estimated health-care costs of $ 172 billion per year. Key neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques - often surrounded by dystrophic neurites - and intracellular neurofibrillary tangles. These pathological changes are frequently accompanied by reactive microgliosis and loss of neurons, white matter and synapses. The etiological mechanisms underlying these neuropathological changes remain unclear, but are probably caused by both environmental and genetic factors. In this review article, we provide an overview of the epidemiology of AD, review the biomarkers that may be used for risk assessment and in diagnosis, and give suggestions for future research. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Easy calculations of lod scores and genetic risks on small computers.

    Science.gov (United States)

    Lathrop, G M; Lalouel, J M

    1984-01-01

    A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139

  14. Biomarkers to Stratify Risk Groups among Children with Malnutrition in Resource-Limited Settings and to Monitor Response to Intervention.

    Science.gov (United States)

    McGrath, Christine J; Arndt, Michael B; Walson, Judd L

    2017-01-01

    Despite global efforts to reduce childhood undernutrition, current interventions have had little impact on stunting and wasting, and the mechanisms underlying growth faltering are poorly understood. There is a clear need to distinguish populations of children most likely to benefit from any given intervention and to develop tools to monitor response to therapy prior to the development of morbid sequelae. In resource-limited settings, environmental enteric dysfunction (EED) is common among children, contributing to malnutrition and increasing childhood morbidity and mortality risk. In addition to EED, early alterations in the gut microbiota can adversely affect growth through nutrient malabsorption, altered metabolism, gut inflammation, and dysregulation of the growth hormone axis. We examined the evidence linking EED and the gut microbiome to growth faltering and explored novel biomarkers to identify subgroups of children at risk of malnutrition due to underlying pathology. These and other biomarkers could be used to identify specific groups of children at risk of malnutrition and monitor response to targeted interventions. © 2017 S. Karger AG, Basel.

  15. DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.

    Science.gov (United States)

    Di Cello, Annalisa; Di Sanzo, Maddalena; Perrone, Francesca Marta; Santamaria, Gianluca; Rania, Erika; Angotti, Elvira; Venturella, Roberta; Mancuso, Serafina; Zullo, Fulvio; Cuda, Giovanni; Costanzo, Francesco

    2017-06-01

    New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

  16. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  17. Serotonin Metabolites in the Cerebrospinal Fluid in the Sudden Infant Death Syndrome: In Search of a Biomarker of Risk

    Science.gov (United States)

    Rognum, Ingvar J.; Tran, Hoa; Haas, Elisabeth A.; Hyland, Keith; Paterson, David S.; Haynes, Robin L.; Broadbelt, Kevin G.; Harty, Brian J.; Mena, Othon; Krous, Henry F.; Kinney, Hannah C.

    2015-01-01

    Clinical biomarkers are urgently needed in the sudden infant death syndrome (SIDS) to identify living infants at risk because it because it occurs without occurs without clinical warning. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. Here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared to autopsy controls, as a first step towards their assessment as diagnostic biomarkers of medullary pathology. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high performance liquid chromatography in 57 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude use of 5-HIAA, HVA, Trp or Tyr measurements as CSF biomarkers of 5-HT medullary pathology in infants at risk. They provide, however, important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

  18. Clinical, functional, behavioural and epigenomic biomarkers of obesity.

    Science.gov (United States)

    Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

    2017-06-01

    Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

  19. Coronary artery calcification scores improve contrast-induced nephropathy risk assessment in chronic kidney disease patients.

    Science.gov (United States)

    Osugi, Naohiro; Suzuki, Susumu; Shibata, Yohei; Tatami, Yosuke; Harata, Shingo; Ota, Tomoyuki; Hayashi, Mutsuharu; Yasuda, Yoshinari; Ishii, Hideki; Shimizu, Atsuya; Murohara, Toyoaki

    2017-06-01

    Coronary artery calcification (CAC) is an independent predictor of cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. The aim of the present study was to evaluate the predictive value of CAC scores for the incidence of contrast-induced nephropathy (CIN) after cardiac catheterization in non-dialyzed CKD patients. The present study evaluated a total of 140 CKD patients who underwent cardiac catheterization. Patients were stratified into two groups based on the optimal cut-off value of the CAC score, which was graded by a non-triggered, routine diagnostic chest computed tomography scan: CAC score ≥8 (high CAC group); and CAC score 10 % in the baseline serum cystatin C level at 24 h after contrast administration. The mean estimated glomerular filtration rate levels were 41.1 mL/min/1.73 m 2 , and the mean contrast dose administered was 37.5 mL. Patients with high CAC scores exhibited a higher incidence of CIN than patients with low CAC scores (25.5 vs. 3.2 %, p < 0.001). After multivariate adjustment for confounders, the CAC score predicted CIN (odds ratio 1.68, 95 % confidence interval 1.28-2.21, p < 0.001). Moreover, the C-index for CIN prediction significantly increased when the CAC scores were added to the Mehran risk score (0.855 vs. 0.760, p = 0.023). CAC scores, as evaluated using semi-quantitative methods, are a simple and powerful predictor of CIN. Incorporating the CAC score in the Mehran risk score significantly improved the predictive ability to predict CIN incidence.

  20. A genetic risk score combining ten psoriasis risk loci improves disease prediction.

    Directory of Open Access Journals (Sweden)

    Haoyan Chen

    2011-04-01

    Full Text Available Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS and a weighted (wGRS approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7 versus 12.09 (SD 1.8, p = 4.577×10(-40. The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57, p = 2.010×10(-65. To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC. The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p = 2.13×10(-8. Additionally, the AUC for HLA-C alone (rs10484554 was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p = 0.18, highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p = 4.91×10(-6 and family history (p = 0.020. Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.

  1. Ten years cardiovascular risk estimation according to Framingham score and non HDL-cholesterol in blood donors.

    Science.gov (United States)

    Graffigna, Mabel Nora; Berg, Gabriela; Migliano, Marta; Salgado, Pablo; Soutelo, Jimena; Musso, Carla

    2015-01-01

    Cardiovascular disease (CVD) is currently the primary cause of morbidity and mortality. (1) Assess the 10 years risk for CVD in Argentinean blood donors, according to Framingham score (updated by ATP III), (2) evaluate the prevalence of the MS, (3) evaluate non HDL-cholesterol level in this population as other risk for CVD. A prospective, epidemiological, transversal study was performed to evaluate 585 volunteer blood donors for two years. Non HDL-C was calculated as total cholesterol minus HDL-C and we evaluated the 10 years risk for CVD according to Framingham score (updated by ATP III). Metabolic syndrome prevalence was estimated according to ATP III and IDF criteria. Non HDL-C was (media±SD) 178.3±48.0 mg/dl in participants with MS and 143.7±39.3 mg/dl without MS (ATPIII) and 160.1±43.6 mg/dl in participants with MS and 139.8±43.1 mg/dl without MS (IDF). Participants with MS presented an OR of 3.1; IC 95% (2-5) of CVD according to de Framingham score. Individuals with MS and elevated non HDL-C are at a higher estimated risk for cardiovascular events in the next 10 years according to the Framingham risk score. Copyright © 2014. Published by Elsevier Ltd.

  2. Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

    Science.gov (United States)

    Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

    2017-03-01

    Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

  3. Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort.

    NARCIS (Netherlands)

    Aleksandrova, Krasimira; Jenab, Mazda; Leitzmann, Michael; Bueno-de-Mesquita, Bas; Kaaks, Rudolf; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Rinaldi, Sabina; Freisling, Heinz; Carayol, Marion; Pischon, Tobias; Drogan, Dagmar; Weiderpass, Elisabete; Jakszyn, Paula; Overvad, Kim; Dahm, Christina C; Tjønneland, Anne; Bouton-Ruault, Marie-Christine; Kühn, Tilman; Peppa, Eleni; Valanou, Elissavet; La Vecchia, Carlo; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Agnoli, Claudia; Tumino, Rosario; May, Anne; van Vulpen, Jonna; Benjaminsen Borch, Kristin; Oluwafemi Oyeyemi, Sunday; Quirós, J Ramón; Bonet, Catalina; Sánchez, María-José; Dorronsoro, Miren; Navarro, Carmen; Barricarte, Aurelio; van Guelpen, Bethany; Wennberg, Patrik; Key, Timothy J; Khaw, Kay-Tee; Wareham, Nicholas; Assi, Nada; Ward, Heather A; Aune, Dagfinn; Riboli, Elio; Boeing, Heiner

    2017-01-01

    There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association

  4. Risk of low Apgar score and socioeconomic position: a study of Swedish male births.

    Science.gov (United States)

    Odd, David E; Doyle, Pat; Gunnell, David; Lewis, Glyn; Whitelaw, Andrew; Rasmussen, Finn

    2008-09-01

    The aim of this study was to investigate the association between maternal socioeconomic position and a persistent low Apgar score (a score of manual (Odds ratio (OR) 0.83 (0.72-0.97)) and self-employed (OR 0.64 (0.44-0.93)) occupations were less likely to have an infant with a low Apgar score, compared to manual workers. There was evidence that the risk of a low Apgar score decreased as the mother's level of education increased, if the infant was born by instrumental (OR 0.86 (0.74-0.99)) or caesarean section (OR 0.80 (0.68-0.93)) delivery, but not by unassisted vaginal delivery (OR 1.01 (0.92-1.10)). There was a lower risk of poor birth condition in male infants born to more educated and non-manual/self-employed mothers. These differences may contribute to our understanding of socioeconomic differences in infant health and development although the results may not be applicable due to changes over the last 30 years.

  5. Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

    Science.gov (United States)

    Terry, Mary Beth; McDonald, Jasmine A; Wu, Hui Chen; Eng, Sybil; Santella, Regina M

    2016-01-01

    Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

  6. A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Gislason, Gunnar H; Hlatky, Mark A

    2014-01-01

    BACKGROUND: Heart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. METHODS AND RESULTS: All individuals...... with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n = 16 827). In total, 1787 (10.6%) died within 30 days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute...... by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P heart failure, this simple...

  7. Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Parker, Alexander S.; Heckman, Michael G.; Wu, Kevin J.; Crook, Julia E.; Hilton, Tracy W.; Pisansky, Thomas M.; Bernard, Johnny R.; Schild, Steven E.; Khor, Li Yan; Hammond, Elizabeth H.; Pollack, Alan; Buskirk, Steven J.

    2009-01-01

    Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

  8. Emerging biomarkers in the diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Filella X

    2018-05-01

    Full Text Available Xavier Filella, Esther Fernández-Galan, Rosa Fernández Bonifacio, Laura Foj Department of Biochemistry and Molecular Genetics (CDB, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain Abstract: Prostate cancer (PCa is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients’ life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI, and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis. Keywords: prostate cancer, PSA, PHI, four-kallikrein panel, PCA3, miRNAs

  9. Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Masayuki Yamanouchi

    Full Text Available There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD.We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD: the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification. They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR of incident ESRD were reported with 95% confidence interval (CI of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI, and integrated discrimination improvement (IDI.During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90 and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83. Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%.We found that the predict values of the KFRE and the D-score

  10. Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

    Science.gov (United States)

    Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

    2018-01-01

    There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were

  11. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  12. Novel biomarkers for prediabetes, diabetes, and associated complications

    Directory of Open Access Journals (Sweden)

    Dorcely B

    2017-08-01

    Full Text Available Brenda Dorcely,1 Karin Katz,1 Ram Jagannathan,2 Stephanie S Chiang,1 Babajide Oluwadare,1 Ira J Goldberg,1 Michael Bergman1 1New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, 2Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA Abstract: The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c, fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recogni­zing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. Keywords: prediabetes, biomarkers, inflammatory markers, diabetes, diabetes complications

  13. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study.

    Science.gov (United States)

    Stanley, Adrian J; Laine, Loren; Dalton, Harry R; Ngu, Jing H; Schultz, Michael; Abazi, Roseta; Zakko, Liam; Thornton, Susan; Wilkinson, Kelly; Khor, Cristopher J L; Murray, Iain A; Laursen, Stig B

    2017-01-04

     To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding.  International multicentre prospective study.  Six large hospitals in Europe, North America, Asia, and Oceania.  3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding.  Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined.  The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length

  14. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  15. Can the Obesity Surgery Mortality Risk Score predict postoperative complications other than mortality?

    Science.gov (United States)

    Major, Piotr; Wysocki, Michał; Pędziwiatr, Michał; Małczak, Piotr; Pisarska, Magdalena; Migaczewski, Marcin; Winiarski, Marek; Budzyński, Andrzej

    2016-01-01

    Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are bariatric procedures with acceptable risk of postoperative morbidities and mortalities, but identification of high-risk patients is an ongoing issue. DeMaria et al. introduced the Obesity Surgery Mortality Risk Score (OS-MRS), which was designed for mortality risk assessment but not perioperative morbidity risk. To assess the possibility to use the OS-MRS to predict the risk of perioperative complications related to LSG and LRYGB. Retrospective analysis of patients operated on for morbid obesity was performed. Patients were evaluated before and after surgery. We included 408 patients (233 LSG, 175 LRYGB). Perioperative complications were defined as adverse effects in the 30-day period. The Clavien-Dindo scale was used for description of complications. Patients were assigned to five grades and three classes according to the OS-MRS results, then risk of morbidity was analyzed. Complications were observed in 30 (7.35%) patients. Similar morbidity was related to both procedures (OR = 1.14, 95% CI: 0.53-2.44, p = 0.744). The reoperation and mortality rates were 1.23% and 0.49% respectively. There were no significant differences in median OS-MRS value between the group without and the group with perioperative complications. There were no significant differences in OS-MRS between groups (p = 0.091). Obesity Surgery Mortality Risk Score was not related to Clavien-Dindo grades (p = 0.800). It appears that OS-MRS is not useful in predicting risk of perioperative morbidity after bariatric procedures.

  16. Prediction of individual genetic risk to prostate cancer using a polygenic score

    DEFF Research Database (Denmark)

    Szulkin, Robert; Whitington, Thomas; Eklund, Martin

    2015-01-01

    BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate ca...

  17. Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

    Science.gov (United States)

    Tu, Hung-Pin; Chung, Chia-Min; Min-Shan Ko, Albert; Lee, Su-Shin; Lai, Han-Ming; Lee, Chien-Hung; Huang, Chung-Ming; Liu, Chiu-Shong; Ko, Ying-Chin

    2016-09-01

    The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (Pgout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

  18. Cardiovascular risk assessment in elderly adults using SCORE OP model in a Latin American population: The experience from Ecuador.

    Science.gov (United States)

    Sisa, Ivan

    2018-02-09

    Cardiovascular disease (CVD) mortality is predicted to increase in Latin America countries due to their rapidly aging population. However, there is very little information about CVD risk assessment as a primary preventive measure in this high-risk population. We predicted the national risk of developing CVD in Ecuadorian elderly population using the Systematic COronary Risk Evaluation in Older Persons (SCORE OP) High and Low models by risk categories/CVD risk region in 2009. Data on national cardiovascular risk factors were obtained from the Encuesta sobre Salud, Bienestar y Envejecimiento. We computed the predicted 5-year risk of CVD risk and compared the extent of agreement and reclassification in stratifying high-risk individuals between SCORE OP High and Low models. Analyses were done by risk categories, CVD risk region, and sex. In 2009, based on SCORE OP Low model almost 42% of elderly adults living in Ecuador were at high risk of suffering CVD over a 5-year period. The extent of agreement between SCORE OP High and Low risk prediction models was moderate (Cohen's kappa test of 0.5), 34% of individuals approximately were reclassified into different risk categories and a third of the population would benefit from a pharmacologic intervention to reduce the CVD risk. Forty-two percent of elderly Ecuadorians were at high risk of suffering CVD over a 5-year period, indicating an urgent need to tailor primary preventive measures for this vulnerable and high-risk population. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Physical activity attenuates age-related biomarker alterations in preclinical AD.

    Science.gov (United States)

    Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L; Dowling, N M; Carlsson, Cynthia M; Bendlin, Barbara B; LaRue, Asenath; Rowley, Howard A; Christian, Brad T; Asthana, Sanjay; Hermann, Bruce P; Johnson, Sterling C; Sager, Mark A

    2014-11-04

    To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. © 2014 American Academy of Neurology.

  20. Oxidative stress biomarkers in Oreochromis niloticus as early ...

    African Journals Online (AJOL)

    2018-04-10

    Apr 10, 2018 ... warning signals in assessing pollution from acid mine drainage and ... fish species Oreochromis niloticus as a bio-indicator organism in active ... Key water quality parameters, including ... Biomarkers can provide early warning of potential higher- ...... CT (2001) The use of biomarkers in Ecological Risk.

  1. Risk of future trauma based on alcohol screening scores: A two-year prospective cohort study among US veterans

    Science.gov (United States)

    2012-01-01

    Background Severe alcohol misuse as measured by the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) is associated with increased risk of future fractures and trauma-related hospitalizations. This study examined the association between AUDIT-C scores and two-year risk of any type of trauma among US Veterans Health Administration (VHA) patients and assessed whether risk varied by age or gender. Methods Outpatients (215, 924 male and 9168 female) who returned mailed AUDIT-C questionnaires were followed for 24 months in the medical record for any International Statistical Classification of Diseases and Related Health Problems (ICD-9) code related to trauma. The two-year prevalence of trauma was examined as a function of AUDIT-C scores, with low-level drinking (AUDIT-C 1–4) as the reference group. Men and women were examined separately, and age-stratified analyses were performed. Results Having an AUDIT-C score of 9–12 (indicating severe alcohol misuse) was associated with increased risk for trauma. Mean (SD) ages for men and women were 68.2 (11.5) and 57.2 (15.8), respectively. Age-stratified analyses showed that, for men ≤50 years, those with AUDIT-C scores ≥9 had an increased risk for trauma compared with those with AUDIT-C scores in the 1–4 range (adjusted prevalence, 25.7% versus 20.8%, respectively; OR = 1.24; 95% confidence interval [CI], 1.03–1.50). For men ≥65 years with average comorbidity and education, those with AUDIT-C scores of 5–8 (adjusted prevalence, 7.9% versus 7.4%; OR = 1.16; 95% CI, 1.02–1.31) and 9–12 (adjusted prevalence 11.1% versus 7.4%; OR = 1.68; 95% CI, 1.30–2.17) were at significantly increased risk for trauma compared with men ≥65 years in the reference group. Higher AUDIT-C scores were not associated with increased risk of trauma among women. Conclusions Men with severe alcohol misuse (AUDIT-C 9–12) demonstrate an increased risk of trauma. Men ≥65 showed an increased risk

  2. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  3. Potential biomarkers for bipolar disorder: Where do we stand?

    Directory of Open Access Journals (Sweden)

    Rajesh Sagar

    2017-01-01

    Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

  4. Development of a Simple Clinical Risk Score for Early Prediction of Severe Dengue in Adult Patients.

    Directory of Open Access Journals (Sweden)

    Ing-Kit Lee

    Full Text Available We aimed to develop and validate a risk score to aid in the early identification of laboratory-confirmed dengue patients at high risk of severe dengue (SD (i.e. severe plasma leakage with shock or respiratory distress, or severe bleeding or organ impairment. We retrospectively analyzed data of 1184 non-SD patients at hospital presentation and 69 SD patients before SD onset. We fit a logistic regression model using 85% of the population and converted the model coefficients to a numeric risk score. Subsequently, we validated the score using the remaining 15% of patients. Using the derivation cohort, two scoring algorithms for predicting SD were developed: models 1 (dengue illness ≤4 days and 2 (dengue illness >4 days. In model 1, we identified four variables: age ≥65 years, minor gastrointestinal bleeding, leukocytosis, and platelet count ≥100×109 cells/L. Model 1 (ranging from -2 to +6 points showed good discrimination between SD and non-SD, with an area under the receiver operating characteristic curve (AUC of 0.848 (95% confidence interval [CI], 0.771-0.924. The optimal cutoff value for model 1 was 1 point, with a sensitivity and specificity for predicting SD of 70.3% and 90.6%, respectively. In model 2 (ranging from 0 to +3 points, significant predictors were age ≥65 years and leukocytosis. Model 2 showed an AUC of 0.859 (95% CI, 0.756-0.963, with an optimal cutoff value of 1 point (sensitivity, 80.3%; specificity, 85.8%. The median interval from hospital presentation to SD was 1 day. This finding underscores the importance of close monitoring, timely resuscitation of shock including intravenous fluid adjustment and early correction of dengue-related complications to prevent the progressive dengue severity. In the validation data, AUCs of 0.904 (95% CI, 0.825-0.983 and 0.917 (95% CI, 0.833-1.0 in models 1 and 2, respectively, were achieved. The observed SD rates (in both cohorts were 50% for those with a score of ≥2 points

  5. Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

    Science.gov (United States)

    Mino-Kenudson, Mari

    2017-10-01

    In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

  6. Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers

    Directory of Open Access Journals (Sweden)

    Daniel M Spagnolo

    2016-01-01

    Full Text Available Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME are key contributors to heterogeneity. Methods: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI and visually represent heterogeneity with a two-dimensional map. Results: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score. Conclusions: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI, which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different

  7. SCORING ASSESSMENT AND FORECASTING MODELS BANKRUPTCY RISK OF COMPANIES

    Directory of Open Access Journals (Sweden)

    SUSU Stefanita

    2014-07-01

    Full Text Available Bankruptcy risk made the subject of many research studies that aim at identifying the time of the bankruptcy, the factors that compete to achieve this state, the indicators that best express this orientation (the bankruptcy. The threats to enterprises require the managers knowledge of continually economic and financial situations, and vulnerable areas with development potential. Managers need to identify and properly manage the threats that would prevent achieving the targets. In terms of methods known in the literature of assessment and evaluation of bankruptcy risk they are static, functional, strategic, and scoring nonfinancial models. This article addresses Altman and Conan-Holder-known internationally as the model developed at national level by two teachers from prestigious universities in our country-the Robu-Mironiuc model. Those models are applied to data released by the profit and loss account and balance sheet Turism Covasna company over which bankruptcy risk analysis is performed. The results of the analysis are interpreted while trying to formulate solutions to the economic and financial viability of the entity.

  8. Validation of the EBMT risk score in chronic myeloid leukemia in Brazil and allogeneic transplant outcome.

    Science.gov (United States)

    De Souza, Carmino Antonio; Vigorito, Afonso Celso; Ruiz, Milton Artur; Nucci, Márcio; Dulley, Frederico Luiz; Funcke, Vaneusa; Tabak, Daniel; Azevedo, Alexandre Mello; Byington, Rita; Macedo, Maria Cristina; Saboya, Rosaura; Penteado Aranha, Francisco José; Oliveira, Gislaine Barbosa; Zulli, Roberto; Martins Miranda, Eliana Cristina; Azevedo, Wellington Moraes; Lodi, Fernanda Maria; Voltarelli, Júlio Cesar; Simões, Belinda Pinto; Colturato, Vergílio; De Souza, Mair Pedro; Silla, Lúcia; Bittencourt, Henrique; Piron-Ruiz, Lilian; Maiolino, Angelo; Gratwohl, Alois; Pasquini, Ricardo

    2005-02-01

    The management of chronic myeloid leukemia (CML) has changed radically since the introduction of imatinib therapy. The decision of whether to offer a patient a hematopoietic stem cell transplant (HSCT) must be based on the probability of success of the procedure. The aim of this retrospective analysis of 1,084 CML patients who received an allogeneic HSCT in 10 Brazilian Centers between February 1983 and March 2003 was to validate the EBMT risk score. The study population comprised 647 (60%) males and 437 (40%) females, with a median age of 32 years old (range 1 - 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1,025 (94%) received an HLA fully matched sibling transplant and only 59 (6%) received an unrelated transplant. In 283 cases (26%) a male recipient received a graft from a female donor. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The overall survival, disease-free survival, transplant-related mortality and relapse incidence were 49%, 50%, 45% and 25%, respectively. Of the 1084 patients, 179 (17%) had a risk score of 0 or 1, 397 (37%) had a score of 2, 345 (32%) had a score of 3, 135 (12%) had a score of 4 and 28 (2%) a score of 5 or 6. The overall survival (OS) rate in patients with risk scores 0-1 and 2 was similar (58% and 55%, respectively) but significantly better than that in patients with scores 3 or more (score 3 - 44%, 4 - 36 % and 5-6 - 27%, respectively) pp<0.001). Disease-free survival (DFS) and transplant related mortality (TRM) in a patients with a score of 3 or more were 46% and 49%, respectively and the relapse rate beyond score 5-6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). The OS rate for male recipients of a graft from a female donor was 40% compared to 52

  9. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T.; Olsen, Inge C.; Andreassen, Bettina K.; Viken, Marte K.; Jiang, Xia; Alfredsson, Lars; Kallberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I. W.; Martin, Javier; Teruel, Maria; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K.; Lie, Benedicte A.

    Objective Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  10. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T; Olsen, Inge C; Andreassen, Bettina K; Viken, Marte K; Jiang, Xia; Alfredsson, Lars; Källberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I W; Martin, Javier; Teruel, María; Gonzalez-Gay, Miguel A; Rodríguez-Rodríguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K; Lie, Benedicte A

    OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  11. Effect of Antihypertensive Therapy on SCORE-Estimated Total Cardiovascular Risk: Results from an Open-Label, Multinational Investigation—The POWER Survey

    Directory of Open Access Journals (Sweden)

    Guy De Backer

    2013-01-01

    Full Text Available Background. High blood pressure is a substantial risk factor for cardiovascular disease. Design & Methods. The Physicians' Observational Work on patient Education according to their vascular Risk (POWER survey was an open-label investigation of eprosartan-based therapy (EBT for control of high blood pressure in primary care centers in 16 countries. A prespecified element of this research was appraisal of the impact of EBT on estimated 10-year risk of a fatal cardiovascular event as determined by the Systematic Coronary Risk Evaluation (SCORE model. Results. SCORE estimates of CVD risk were obtained at baseline from 12,718 patients in 15 countries (6504 men and from 9577 patients at 6 months. During EBT mean (±SD systolic/diastolic blood pressures declined from 160.2 ± 13.7/94.1 ± 9.1 mmHg to 134.5 ± 11.2/81.4 ± 7.4 mmHg. This was accompanied by a 38% reduction in mean SCORE-estimated CVD risk and an improvement in SCORE risk classification of one category or more in 3506 patients (36.6%. Conclusion. Experience in POWER affirms that (a effective pharmacological control of blood pressure is feasible in the primary care setting and is accompanied by a reduction in total CVD risk and (b the SCORE instrument is effective in this setting for the monitoring of total CVD risk.

  12. Effect of Antihypertensive Therapy on SCORE-Estimated Total Cardiovascular Risk: Results from an Open-Label, Multinational Investigation—The POWER Survey

    Science.gov (United States)

    De Backer, Guy; Petrella, Robert J.; Goudev, Assen R.; Radaideh, Ghazi Ahmad; Rynkiewicz, Andrzej; Pathak, Atul

    2013-01-01

    Background. High blood pressure is a substantial risk factor for cardiovascular disease. Design & Methods. The Physicians' Observational Work on patient Education according to their vascular Risk (POWER) survey was an open-label investigation of eprosartan-based therapy (EBT) for control of high blood pressure in primary care centers in 16 countries. A prespecified element of this research was appraisal of the impact of EBT on estimated 10-year risk of a fatal cardiovascular event as determined by the Systematic Coronary Risk Evaluation (SCORE) model. Results. SCORE estimates of CVD risk were obtained at baseline from 12,718 patients in 15 countries (6504 men) and from 9577 patients at 6 months. During EBT mean (±SD) systolic/diastolic blood pressures declined from 160.2 ± 13.7/94.1 ± 9.1 mmHg to 134.5 ± 11.2/81.4 ± 7.4 mmHg. This was accompanied by a 38% reduction in mean SCORE-estimated CVD risk and an improvement in SCORE risk classification of one category or more in 3506 patients (36.6%). Conclusion. Experience in POWER affirms that (a) effective pharmacological control of blood pressure is feasible in the primary care setting and is accompanied by a reduction in total CVD risk and (b) the SCORE instrument is effective in this setting for the monitoring of total CVD risk. PMID:23997946

  13. Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States

    Directory of Open Access Journals (Sweden)

    Yang eJiang

    2016-02-01

    Full Text Available ß-amyloid (Aß plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD. The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF, in predicting future AD risk and cognitive decline is still being refined. Here we explored potential relationships between functional connectivity patterns within the default-mode network (DMN, age, CSF biomarkers (Aß42 and pTau181 and cognitive status in older adults. Multiple measures of functional connectivity were explored including a novel time series based measure (Total Interdependence; TI. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aß42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of functional connectivity in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk. Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults.

  14. Myocardium at risk assessed by electrocardiographic scores and cardiovascular magnetic resonance - a MITOCARE substudy

    DEFF Research Database (Denmark)

    Sejersten, Maria; Fakhri, Yama; Pape, Marianne

    2017-01-01

    Introduction The myocardium at risk (MaR) represents the quantitative ischemic area destined to myocardial infarction (MI) if no reperfusion therapy is initiated. Different ECG scores for MaR have been developed, but there is no consensus as to which should be preferred. Objective Comparisons...... of ECG scores and Cardiac Magnetic Resonance (CMR) for determining MaR. Methods MaR was determined by 3 different ECG scores, and by CMR in ST-segment elevation MI (STEMI) patients from the MITOCARE cardioprotection trial. The Aldrich score (AL) is based on the number of leads with ST-elevation...... for anterior MI and the sum of ST-segment elevation for inferior MI on the admission ECG. The van Hellemond score (VH) considers both the ischemic and infarcted component of the MaR by adding the AL and the QRS score, which is an estimate of final infarct size. The Hasche score is based on the maximal possible...

  15. Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

    Science.gov (United States)

    Higashikawa, Toshihiro; Okuro, Masashi; Ishigami, Keiichirou; Mae, Kunihiro; Sangen, Ryusho; Mizuno, Takurou; Usuda, Daisuke; Saito, Atushi; Kasamaki, Yuji; Fukuda, Akihiro; Saito, Hitoshi; Morimoto, Shigeto; Kanda, Tsugiyasu

    2018-01-01

    Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

  16. Identification of novel biomarkers to monitor β-cell function and enable early detection of type 2 diabetes risk.

    Directory of Open Access Journals (Sweden)

    Kirstine J Belongie

    Full Text Available A decline in β-cell function is a prerequisite for the development of type 2 diabetes, yet the level of β-cell function in individuals at risk of the condition is rarely measured. This is due, in part, to the fact that current methods for assessing β-cell function are inaccurate, prone to error, labor-intensive, or affected by glucose-lowering therapy. The aim of the current study was to identify novel circulating biomarkers to monitor β-cell function and to identify individuals at high risk of developing β-cell dysfunction. In a nested case-control study from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC cohort (n = 1157, proteomics and miRNA profiling were performed on fasting plasma samples from 43 individuals who progressed to impaired glucose tolerance (IGT and 43 controls who maintained normal glucose tolerance (NGT over three years. Groups were matched at baseline for age, gender, body mass index (BMI, insulin sensitivity (euglycemic clamp and β-cell glucose sensitivity (mathematical modeling. Proteomic profiling was performed using the SomaLogic platform (Colorado, USA; miRNA expression was performed using a modified RT-PCR protocol (Regulus Therapeutics, California, USA. Results showed differentially expressed proteins and miRNAs including some with known links to type 2 diabetes, such as adiponectin, but also novel biomarkers and pathways. In cross sectional analysis at year 3, the top differentially expressed biomarkers in people with IGT/ reduced β-cell glucose sensitivity were adiponectin, alpha1-antitrypsin (known to regulate adiponectin levels, endocan, miR-181a, miR-342, and miR-323. At baseline, adiponectin, cathepsin D and NCAM.L1 (proteins expressed by pancreatic β-cells were significantly lower in those that progressed to IGT. Many of the novel prognostic biomarker candidates were within the epithelial-mesenchymal transition (EMT pathway: for example, Noggin, DLL4 and miR-181a. Further

  17. Alcohol and Mortality: Combining Self-Reported (AUDIT-C) and Biomarker Detected (PEth) Alcohol Measures Among HIV Infected and Uninfected.

    Science.gov (United States)

    Eyawo, Oghenowede; McGinnis, Kathleen A; Justice, Amy C; Fiellin, David A; Hahn, Judith A; Williams, Emily C; Gordon, Adam J; Marshall, Brandon D L; Kraemer, Kevin L; Crystal, Stephen; Gaither, Julie R; Edelman, E Jennifer; Bryant, Kendall J; Tate, Janet P

    2018-02-01

    Unhealthy alcohol use may be particularly detrimental among individuals living with HIV and/or hepatitis C virus (HCV), and is often under-reported. Direct biomarkers of alcohol exposure may facilitate improved detection of alcohol use. We evaluated the association of alcohol exposure determined by both self-report [Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and a direct biomarker [phosphatidylethanol (PEth)], with mortality among HIV-infected and HIV-uninfected in the Veterans Aging Cohort Study-Biomarker Cohort. We considered PEth AUDIT-C scores [0, 1-3/1-2 (men/women), 4-7/3-7 (men/women), 8-12] and PEth (AUDIT-C = 0 (abstinence). Of these, 15% (149/1015) had PEth ≥8 suggesting recent alcohol exposure. Among those with AUDIT-C = 0, HCV+ individuals were more likely to have PEth ≥8. After controlling for age, sex, race, HIV, HCV, and HIV viral suppression, those with AUDIT-C = 0 but PEth ≥8 had the highest risk of mortality (adjusted hazard ratio 2.15, 95% confidence interval: 1.40 to 3.29). PEth in addition to self-report may improve detection of alcohol use in clinical settings, particularly among those at increased risk of harm from alcohol use. Individuals infected with HCV were more likely to under-report alcohol use.

  18. Exposure assessment of process-related contaminants in food by biomarker monitoring.

    Science.gov (United States)

    Rietjens, Ivonne M C M; Dussort, P; Günther, Helmut; Hanlon, Paul; Honda, Hiroshi; Mally, Angela; O'Hagan, Sue; Scholz, Gabriele; Seidel, Albrecht; Swenberg, James; Teeguarden, Justin; Eisenbrand, Gerhard

    2018-01-01

    Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario's and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.

  19. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    A number of different types of biomarkers have been used to understand the etiology and progression of hepatocellular cancer (HCC. Perhaps the most well known are the serum/ plasma markers of HBV or HCV infection. These markers include analysis of viral DNA or proteins or antibodies produced against the viral proteins. HBV surface antigen (HBsAg is most frequently used to determine chronic infection with high or low viral replication, while HBeAg is a measure of chronic infection with high viral replication. Analysis of antibodies includes measurement of anti-HBV core antigen, anti-HBV e antigen and anti-HBsAg. The response to immunization can be monitored by analysis of anti-HBsAg. The other major classes of biomarkers used in studies of HCC are biomarkers of exposure to environmental, lifestyle or dietary carcinogens, biomarkers of oxidative stress and early biologic response. In addition, studies of genetic susceptibility have studied polymorphisms in a number of pathways and their role in HCC risk. The biomarkers of exposure include the measurement of carcinogens in urine and carcinogen-DNA and protein adducts. Examples are measurement of aflatoxin and polycyclic aromatic hydrocarbon metabolites, and DNA and protein adducts.

    Biomarkers of oxidative stress include urinary isoprostanes and 8-oxodeoxyguanosine and oxidized plasma proteins. Most of these assays are immunologic although the use of high performance liquid chromatograph (HPLC as well as gas chromatography/mass spectroscopy (GC/MS have been utilized. In nested case-control studies, many of these markers are associated with elevated risk. For example, elevated aflatoxin and polycyclic aromatic hydrocarbon-albumin adducts, aflatoxin metabolites in urine and urinary isoprostanes were observed in baseline samples from

  20. Comparison of the HEART and TIMI Risk Scores for Suspected Acute Coronary Syndrome in the Emergency Department.

    Science.gov (United States)

    Sun, Benjamin C; Laurie, Amber; Fu, Rongwei; Ferencik, Maros; Shapiro, Michael; Lindsell, Christopher J; Diercks, Deborah; Hoekstra, James W; Hollander, Judd E; Kirk, J Douglas; Peacock, W Frank; Anantharaman, Venkataraman; Pollack, Charles V

    2016-03-01

    The emergency department evaluation for suspected acute coronary syndrome (ACS) is common, costly, and challenging. Risk scores may help standardize clinical care and screening for research studies. The Thrombolysis in Myocardial Infarction (TIMI) and HEART are two commonly cited risk scores. We tested the null hypothesis that the TIMI and HEART risk scores have equivalent test characteristics. We analyzed data from the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS) from 9 EDs on patients with suspected ACS, 1999-2001. We excluded patients with an emergency department diagnosis consistent with ACS, or without sufficient data to calculate TIMI and HEART scores. The primary outcome was 30-day major adverse cardiovascular events, including all-cause death, acute myocardial infarction, and urgent revascularization. We describe test characteristics of the TIMI and HEART risk scores. The study cohort included 8255 patients with 508 (6.2%) 30-day major adverse cardiovascular events. Receiver operating curve and reclassification analyses favored HEART [c statistic: 0.753, 95% confidence interval (CI): 0.733-0.773; continuous net reclassification improvement: 0.608, 95% CI: 0.527-0.689] over TIMI (c statistic: 0.678, 95% CI: 0.655-0.702). A HEART score 0-3 [negative predictive value (NPV) 0.982, 95% CI: 0.978-0.986; positive predictive value (PPV) 0.103, 95% CI: 0.094-0.113; likelihood ratio (LR) positive 1.76; LR negative 0.28] demonstrates similar or superior NPV/PPV/LR compared with TIMI = 0 (NPV 0.978, 95% CI: 0.971-0.983; PPV 0.077, 95% CI: 0.071-0.084; LR positive 1.28; LR negative 0.35) and TIMI = 0-1 (NPV 0.963, 95% CI: 0.958-0.968; PPV 0.102, 95% CI: 0.092-0.113; LR positive 1.73; LR negative 0.58). The HEART score has better discrimination than TIMI and outperforms TIMI within previously published "low-risk" categories.

  1. A score to predict short-term risk of COPD exacerbations (SCOPEX

    Directory of Open Access Journals (Sweden)

    Make BJ

    2015-01-01

    Full Text Available Barry J Make,1 Göran Eriksson,2 Peter M Calverley,3 Christine R Jenkins,4 Dirkje S Postma,5 Stefan Peterson,6 Ollie Östlund,7 Antonio Anzueto8 1Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado Denver School of Medicine, Denver, CO, USA; 2Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 3Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK; 4George Institute for Global Health, The University of Sydney and Concord Clinical School, Woolcock Institute of Medical Research, Sydney, NSW, Australia; 5Department of Pulmonology, University of Groningen and GRIAC Research Institute, University Medical Center Groningen, Groningen, The Netherlands; 6StatMind AB, Lund, Sweden; 7Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; 8Department of Pulmonary/Critical Care, University of Texas Health Sciences Center and South Texas Veterans Healthcare System, San Antonio, TX, USA Background: There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Methods: Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC curves and the corresponding C-index were used to investigate the discriminatory

  2. Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing primary PCI: results from the Belgian STEMI registry.

    Science.gov (United States)

    Gevaert, Sofie A; De Bacquer, Dirk; Evrard, Patrick; Convens, Carl; Dubois, Philippe; Boland, Jean; Renard, Marc; Beauloye, Christophe; Coussement, Patrick; De Raedt, Herbert; de Meester, Antoine; Vandecasteele, Els; Vranckx, Pascal; Sinnaeve, Peter R; Claeys, Marc J

    2014-01-22

    The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI). Here, we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI. In-hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%] male patients) consecutive pPCI-treated STEMI patients, included in the prospective, observational Belgian STEMI registry (January 2007 to February 2011). A multivariable logistic regression model, including TIMI risk score variables and gender, evaluated differences in in-hospital mortality between men and women. The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration. Mortality rates for TIMI scores in women and men were compared. Female patients were older, had more comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1% in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, pdiscrimination and calibration in women as well as in men (c-statistic=0.84 [95% CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873-0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI scores was better in men (p=0.02 for TIMI score x gender interaction). In the Belgian STEMI registry, pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables. The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men. The database was registered with clinicaltrials.gov (NCT00727623).

  3. Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

    Science.gov (United States)

    Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

    2015-01-01

    Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Physical activity, the Framingham risk score and risk of coronary heart disease in men and women of the EPIC-Norfolk study

    NARCIS (Netherlands)

    Arsenault, Benoit J.; Rana, Jamal S.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J. P.; Boekholdt, S. Matthijs; Khaw, Kay-Tee

    2010-01-01

    Objective: Test the hypothesis that considering leisure-time and work-related physical activity habits in addition to the Framingham risk score (FRS) would result into better classification of coronary heart disease (CHD) risk than FRS alone. Methods: Prospective, population-based study of 9564 men

  5. Development of a risk score for geographic atrophy in complications of the age-related macular degeneration prevention trial.

    Science.gov (United States)

    Ying, Gui-Shuang; Maguire, Maureen G

    2011-02-01

    To develop a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen. Cohort study within a multicenter randomized clinical trial. We included 1052 participants with ≥ 10 large (>125 μm) drusen and visual acuity ≥ 20/40 in each eye. In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 μm] > 1 disc area), GA (>175 μm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk. Development of end point GA, CGA, and any GA. Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for prevention of GA and for clinical assessment of GA risk in early AMD patients. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  6. The future of blood-based biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Henriksen, Kim; O'Bryant, Sid E; Hampel, Harald

    2014-01-01

    Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease...

  7. Quantifying prognosis with risk predictions.

    Science.gov (United States)

    Pace, Nathan L; Eberhart, Leopold H J; Kranke, Peter R

    2012-01-01

    Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes.

  8. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  9. Biomarkers in prostate cancer - Current clinical utility and future perspectives.

    Science.gov (United States)

    Kretschmer, Alexander; Tilki, Derya

    2017-12-01

    Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI ® , 4K score, SelectMDx ® , ConfirmMDx ® , PCA3, MiPS, ExoDX ® , mpMRI) and prognostic (OncotypeDX GPS ® , Prolaris ® , ProMark ® , DNA-ploidy, Decipher ® ) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumor cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Risk score for predicting long-term mortality after coronary artery bypass graft surgery.

    Science.gov (United States)

    Wu, Chuntao; Camacho, Fabian T; Wechsler, Andrew S; Lahey, Stephen; Culliford, Alfred T; Jordan, Desmond; Gold, Jeffrey P; Higgins, Robert S D; Smith, Craig R; Hannan, Edward L

    2012-05-22

    No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. The New York State Cardiac Surgery Reporting System was used to identify 8597 patients who underwent isolated coronary artery bypass graft surgery in July through December 2000. The National Death Index was used to ascertain patients' vital statuses through December 31, 2007. A Cox proportional hazards model was fit to predict death after CABG surgery using preprocedural risk factors. Then, points were assigned to significant predictors of death on the basis of the values of their regression coefficients. For each possible point total, the predicted risks of death at years 1, 3, 5, and 7 were calculated. It was found that the 7-year mortality rate was 24.2 in the study population. Significant predictors of death included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and history of open heart surgery. The points assigned to these risk factors ranged from 1 to 7; possible point totals for each patient ranged from 0 to 28. The observed and predicted risks of death at years 1, 3, 5, and 7 across patient groups stratified by point totals were highly correlated. The simplified risk score accurately predicted the risk of mortality after coronary artery bypass graft surgery and can be used for informed consent and as an aid in determining treatment choice.

  11. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

    Science.gov (United States)

    Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

    2009-01-01

    One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

  12. Simple Scoring System and Artificial Neural Network for Knee Osteoarthritis Risk Prediction: A Cross-Sectional Study

    Science.gov (United States)

    Yoo, Tae Keun; Kim, Deok Won; Choi, Soo Beom; Oh, Ein; Park, Jee Soo

    2016-01-01

    Background Knee osteoarthritis (OA) is the most common joint disease of adults worldwide. Since the treatments for advanced radiographic knee OA are limited, clinicians face a significant challenge of identifying patients who are at high risk of OA in a timely and appropriate way. Therefore, we developed a simple self-assessment scoring system and an improved artificial neural network (ANN) model for knee OA. Methods The Fifth Korea National Health and Nutrition Examination Surveys (KNHANES V-1) data were used to develop a scoring system and ANN for radiographic knee OA. A logistic regression analysis was used to determine the predictors of the scoring system. The ANN was constructed using 1777 participants and validated internally on 888 participants in the KNHANES V-1. The predictors of the scoring system were selected as the inputs of the ANN. External validation was performed using 4731 participants in the Osteoarthritis Initiative (OAI). Area under the curve (AUC) of the receiver operating characteristic was calculated to compare the prediction models. Results The scoring system and ANN were built using the independent predictors including sex, age, body mass index, educational status, hypertension, moderate physical activity, and knee pain. In the internal validation, both scoring system and ANN predicted radiographic knee OA (AUC 0.73 versus 0.81, p<0.001) and symptomatic knee OA (AUC 0.88 versus 0.94, p<0.001) with good discriminative ability. In the external validation, both scoring system and ANN showed lower discriminative ability in predicting radiographic knee OA (AUC 0.62 versus 0.67, p<0.001) and symptomatic knee OA (AUC 0.70 versus 0.76, p<0.001). Conclusions The self-assessment scoring system may be useful for identifying the adults at high risk for knee OA. The performance of the scoring system is improved significantly by the ANN. We provided an ANN calculator to simply predict the knee OA risk. PMID:26859664

  13. The cost-effectiveness of using chronic kidney disease risk scores to screen for early-stage chronic kidney disease.

    Science.gov (United States)

    Yarnoff, Benjamin O; Hoerger, Thomas J; Simpson, Siobhan K; Leib, Alyssa; Burrows, Nilka R; Shrestha, Sundar S; Pavkov, Meda E

    2017-03-13

    Better treatment during early stages of chronic kidney disease (CKD) may slow progression to end-stage renal disease and decrease associated complications and medical costs. Achieving early treatment of CKD is challenging, however, because a large fraction of persons with CKD are unaware of having this disease. Screening for CKD is one important method for increasing awareness. We examined the cost-effectiveness of identifying persons for early-stage CKD screening (i.e., screening for moderate albuminuria) using published CKD risk scores. We used the CKD Health Policy Model, a micro-simulation model, to simulate the cost-effectiveness of using CKD two published risk scores by Bang et al. and Kshirsagar et al. to identify persons in the US for CKD screening with testing for albuminuria. Alternative risk score thresholds were tested (0.20, 0.15, 0.10, 0.05, and 0.02) above which persons were assigned to receive screening at alternative intervals (1-, 2-, and 5-year) for follow-up screening if the first screening was negative. We examined incremental cost-effectiveness ratios (ICERs), incremental lifetime costs divided by incremental lifetime QALYs, relative to the next higher screening threshold to assess cost-effectiveness. Cost-effective scenarios were determined as those with ICERs less than $50,000 per QALY. Among the cost-effective scenarios, the optimal scenario was determined as the one that resulted in the highest lifetime QALYs. ICERs ranged from $8,823 per QALY to $124,626 per QALY for the Bang et al. risk score and $6,342 per QALY to $405,861 per QALY for the Kshirsagar et al. risk score. The Bang et al. risk score with a threshold of 0.02 and 2-year follow-up screening was found to be optimal because it had an ICER less than $50,000 per QALY and resulted in the highest lifetime QALYs. This study indicates that using these CKD risk scores may allow clinicians to cost-effectively identify a broader population for CKD screening with testing for albuminuria

  14. Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

    Science.gov (United States)

    Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

    2016-11-15

    In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

  15. CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

    DEFF Research Database (Denmark)

    Diederichsen, Søren Zöga; Grønhøj, Mette Hjortdal; Mickley, Hans

    2017-01-01

    , but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. Methods At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate...... of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate.......47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11). Conclusions In this prospective study, a large part of participants had incident CAC or progression...

  16. A modified risk assessment scoring system for post laser in situ keratomileusis ectasia in topographically normal patients

    Directory of Open Access Journals (Sweden)

    Mohammad Miraftab

    2014-01-01

    Conclusion: Our modified ectasia risk scoring system for patients with normal corneal topography can predict post LASIK ectasia risk with acceptable sensitivity and specificity. However, there are still unidentified risk factors for which further studies are required.

  17. The East London glaucoma prediction score: web-based validation of glaucoma risk screening tool

    Science.gov (United States)

    Stephen, Cook; Benjamin, Longo-Mbenza

    2013-01-01

    AIM It is difficult for Optometrists and General Practitioners to know which patients are at risk. The East London glaucoma prediction score (ELGPS) is a web based risk calculator that has been developed to determine Glaucoma risk at the time of screening. Multiple risk factors that are available in a low tech environment are assessed to provide a risk assessment. This is extremely useful in settings where access to specialist care is difficult. Use of the calculator is educational. It is a free web based service. Data capture is user specific. METHOD The scoring system is a web based questionnaire that captures and subsequently calculates the relative risk for the presence of Glaucoma at the time of screening. Three categories of patient are described: Unlikely to have Glaucoma; Glaucoma Suspect and Glaucoma. A case review methodology of patients with known diagnosis is employed to validate the calculator risk assessment. RESULTS Data from the patient records of 400 patients with an established diagnosis has been captured and used to validate the screening tool. The website reports that the calculated diagnosis correlates with the actual diagnosis 82% of the time. Biostatistics analysis showed: Sensitivity = 88%; Positive predictive value = 97%; Specificity = 75%. CONCLUSION Analysis of the first 400 patients validates the web based screening tool as being a good method of screening for the at risk population. The validation is ongoing. The web based format will allow a more widespread recruitment for different geographic, population and personnel variables. PMID:23550097

  18. Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause

    NARCIS (Netherlands)

    Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C.; Khoury, Nabil; Hadi, Christiane M.; van der Ende, Arie; Wootton, Susan H.; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

    2013-01-01

    We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193)

  19. Use of biomarkers to evaluate the ecological risk of xenobiotics associated with agriculture.

    Science.gov (United States)

    Lima, Liana Bezerra Dias de; Morais, Paula Benevides de; Andrade, Ricardo Lopes Tortorela de; Mattos, Luciana Vieira; Moron, Sandro Estevan

    2018-06-01

    This research aimed to evaluate the ecological risk of xenobiotics associated with agricultural activities by determining metal contents and biomarker responses using tucunaré (Cichla sp.) as a bioindicator. The work was conducted in the southwest region of the state of Tocantins, in the cities of Lagoa da Confusão and Pium. Water samples and specimens of Cichla sp. were collected in the Javaés and Formoso Rivers at three collection points (A, B and C). The concentrations of Cd, Pb, Cu, Cr, Mn, Ni and Zn in water and fish were analyzed. In fish, genotoxic, biochemical (glucose serum levels, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) and histological (gills and liver) biomarkers were assessed. In the water, the Cr and Mn concentrations at the three collection points exceeded the values for Class 1 rivers. In the muscle, Cr was above the maximum limit allowed for human consumption at the three collection points, although the values at Points B and C were not significantly different from that at Point A (p > 0.05). At the three collection points, the micronucleus test revealed a low frequency of micronuclei. Significant hyperglycemia and a decrease in the AST activity of the fish collected at Point C was observed. In the gills, the most frequent alterations were at Stages I and II, which indicated mild to moderate damage, and epithelial detachment was the most frequent variation. In the liver tissue, the most frequently observed histological changes were at Stages I and II and included cytoplasmic vacuolization, nuclear hypertrophy, dilated sinusoids and bile stagnation. The integrated evaluation of these biomarkers indicated that fish collected from areas with intense agricultural activities presented adaptive responses that were likely caused by the availability and bioaccumulation of certain xenobiotics in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Evaluating biomarkers for prognostic enrichment of clinical trials.

    Science.gov (United States)

    Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

    2017-12-01

    A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

  1. TV time but not computer time is associated with cardiometabolic risk in Dutch young adults.

    Science.gov (United States)

    Altenburg, Teatske M; de Kroon, Marlou L A; Renders, Carry M; Hirasing, Remy; Chinapaw, Mai J M

    2013-01-01

    TV time and total sedentary time have been positively related to biomarkers of cardiometabolic risk in adults. We aim to examine the association of TV time and computer time separately with cardiometabolic biomarkers in young adults. Additionally, the mediating role of waist circumference (WC) is studied. Data of 634 Dutch young adults (18-28 years; 39% male) were used. Cardiometabolic biomarkers included indicators of overweight, blood pressure, blood levels of fasting plasma insulin, cholesterol, glucose, triglycerides and a clustered cardiometabolic risk score. Linear regression analyses were used to assess the cross-sectional association of self-reported TV and computer time with cardiometabolic biomarkers, adjusting for demographic and lifestyle factors. Mediation by WC was checked using the product-of-coefficient method. TV time was significantly associated with triglycerides (B = 0.004; CI = [0.001;0.05]) and insulin (B = 0.10; CI = [0.01;0.20]). Computer time was not significantly associated with any of the cardiometabolic biomarkers. We found no evidence for WC to mediate the association of TV time or computer time with cardiometabolic biomarkers. We found a significantly positive association of TV time with cardiometabolic biomarkers. In addition, we found no evidence for WC as a mediator of this association. Our findings suggest a need to distinguish between TV time and computer time within future guidelines for screen time.

  2. Risk Pricing in Emerging Economies: Credit Scoring and Private Banking in Iran

    Directory of Open Access Journals (Sweden)

    Yiannis Anagnostopoulos

    2016-01-01

    Full Text Available Iran’s banking industry as a developing country is comparatively very new to risk management practices. An inevitable predictive implication of this rapid growth is the growing concerns with regard to credit risk management which is the motivation of conducting this research. The paper focuses on the credit scoring aspect of credit risk management using both logit and probit regression approaches. Real data on corporate customers are available for conducting this research which is also a contribution to this area for all other developing countries. Our questions focus on how future customers can be classified in terms of credibility, which models and methods are more effective in better capturing risks. Findings suggest that probit approaches are more effective in capturing the significance of variables and goodness-of-fitness tests. Seven variables of the Ohlson O-Score model are used: CL_CA, INTWO, OENEG, TA_TL, SIZE, WCAP_TA, and ROA; two were found to be statistically significant in logit (ROA, TL_TA and three were statistically significant in probit (ROA, TL_TA, SIZE. Also, CL_CA, ROA, and WCAP_TA were the three variables with an unexpected correlation to the probability of default. The prediction power with the cut-off point is set equal to 26% and 56.91% for defaulted customers in both logit and probit models. However, logit achieved 54.85% correct estimation of defaulted assets, 0.37% more than what probit estimated.

  3. How much does HDL cholesterol add to risk estimation? A report from the SCORE Investigators.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2009-06-01

    Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC\\/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation.

  4. Identifying patients with less potential to benefit from implantable cardioverter-defibrillator therapy: comparison of the performance of four risk scoring systems.

    Science.gov (United States)

    Kaura, Amit; Sunderland, Nicholas; Kamdar, Ravi; Petzer, Edward; McDonagh, Theresa; Murgatroyd, Francis; Dhillon, Para; Scott, Paul

    2017-08-01

    Patients at high non-sudden cardiac death risk may gain no significant benefit from implantable cardioverter-defibrillator (ICD) therapy. A number of approaches have been proposed to identify these patients, including single clinical markers and more complex scoring systems. The aims of this study were to use the proposed scoring systems to (1) establish how many current ICD recipients may be too high risk to derive significant benefit from ICD therapy and (2) evaluate how well the scoring systems predict short-term mortality in an unselected ICD cohort. We performed a single-centre retrospective observational study of all new ICD implants over 5 years (2009-2013). We used four published scoring systems (Bilchick, Goldenberg, Kramer and Parkash) and serum urea to identify new ICD recipients whose short-term predicted mortality risk was high. We evaluated how well the scoring systems predicted death. Over 5 years, there were 406 new implants (79% male, mean age 70 (60-76), 58% primary prevention). During a follow-up of 936 ± 560 days, 96 patients died. Using the scoring systems, the proportion of ICD recipients predicted to be at high short-term mortality risk were 5.9% (Bilchick), 34.7% (Goldenberg), 7.4% (Kramer), 21.4% (Parkash) and 25% (urea, cut-off of >9.28 mM). All four risk scores predicted mortality (P systems, a significant proportion of current ICD recipients are at high short-term mortality risk. Although all four scoring systems predicted mortality during follow-up, none significantly outperformed serum urea.

  5. [Clinical scores for the risk of recurrent VTED and for the relationship cancer-VTED].

    Science.gov (United States)

    Junod, Alain

    2016-02-17

    Clinical scores related to the risk of recurrent venous thromboembolic disease (VTED), to the relationship between cancer and VTED (risk of development of VTED, risk of recurrent VTED, prognosis of pulmonary embolism) and to the risk of cancer following VTED are analysed and commented upon. Although they most often rely on appropriate methodology and are often based on a large number of subjects, they unfortunately provide information that is not necessarily useful for the care of patients. Their use should be considered only when positive impact studies are published.

  6. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  7. Metabolic syndrome and Framingham risk score in obese young adults

    Directory of Open Access Journals (Sweden)

    Felix F. Widjaja

    2013-05-01

    Full Text Available Background: The increase number of the metabolic syndrome (MetS among young adults was mostly caused by obesity. MetS increases the risk of coronary heart disease (CHD which can be estimated by Framingham risk score (FRS. The study was aimed to know the prevalence of MetS and FRS in obese young adults and to associate them with the components of MetS. Methods: A total of 70 male and female students aged 18 to 25 years with BMI ≥ 25 kg/m2 in Faculty of Medicine Universitas Indonesia were selected consecutively. The blood samples used to test fasting blood glucose, total cholesterol, high-density lipoprotein, and triglyceride were examined in Department of Clinical Pathology, Cipto Mangunkusumo Hospital after fasting for 14 to 16 hours. International Diabetes Federation (IDF definition was used to diagnose MetS. Univariate and bivariate analysis were done. Results: The prevalence of MetS based on IDF definition was 18.6% among obese young adults. The most associated MetS components was hypertriglyceridemia (OR 12.13; 95% CI 2.92-50.46; p = 0.001, followed with high blood pressure (OR 9.33; 95% CI 2.26-38.56; p = 0.001, low-HDL (OR 8.33; 95% CI 2.17-32.05; p = 0.003, and impaired fasting glucose (p = 0.03. Four subjects had FRS ≥ 1% and 66 subjects had risk < 1%. Increased FRS was not associated with MetS (p = 0.154. There was no component of MetS associated with increased FRS. Conclusion: Prevalence of MetS in obese young adults was similar with obese children and adolescents. Although no association of MetS and FRS was found, they are significant predictors for CHD which should not be used separately. (Med J Indones. 2013;22:100-6Keywords: Abdominal obesity, Framingham risk score, metabolic syndrome, young adults

  8. The association between creatinine versus cystatin C-based eGFR and cardiovascular risk in children with chronic kidney disease using a modified PDAY risk score.

    Science.gov (United States)

    Sharma, Sheena; Denburg, Michelle R; Furth, Susan L

    2017-08-01

    Children with chronic kidney disease (CKD) have a high prevalence of cardiovascular disease (CVD) risk factors which may contribute to the development of cardiovascular events in adulthood. Among adults with CKD, cystatin C-based estimates of glomerular filtration rate (eGFR) demonstrate a stronger predictive value for cardiovascular events than creatinine-based eGFR. The PDAY (Pathobiological Determinants of Atherosclerosis in Youth) risk score is a validated tool used to estimate the probability of advanced coronary atherosclerotic lesions in young adults. To assess the association between cystatin C-based versus creatinine-based eGFR (eGFR cystatin C and eGFR creatinine, respectively) and cardiovascular risk using a modified PDAY risk score as a proxy for CVD in children and young adults. We performed a cross-sectional study of 71 participants with CKD [median age 15.5 years; inter-quartile range (IQR) 13, 17], and 33 healthy controls (median age 15.1 years; IQR 13, 17). eGFR was calculated using age-appropriate creatinine- and cystatin C-based formulas. Median eGFR creatinine and eGFR cystatin C for CKD participants were 50 (IQR 30, 75) and 53 (32, 74) mL/min/1.73 m 2 , respectively. For the healthy controls, median eGFR creatinine and eGFR cystatin were 112 (IQR 85, 128) and 106 mL/min/1.73m 2 (95, 123) mL/min/1.73 m 2 , respectively. A modified PDAY risk score was calculated based on sex, age, serum lipoprotein concentrations, obesity, smoking status, hypertension, and hyperglycemia. Modified PDAY scores ranged from -2 to 20. The Spearman's correlations of eGFR creatinine and eGFR cystatin C with coronary artery PDAY scores were -0.23 (p = 0.02) and -0.28 (p = 0.004), respectively. Ordinal logistic regression also showed a similar association of higher eGFR creatinine and higher eGFR cystatin C with lower PDAY scores. When stratified by age creatinine and eGFR cystatin C with PDAY score were modest and similar in children [-0.29 (p = 0.008) vs. -0.32 (p = 0

  9. Scope Complexity Options Risks Excursions (SCORE) Version 3.0 Mathematical Description.

    Energy Technology Data Exchange (ETDEWEB)

    Gearhart, Jared Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Samberson, Jonell Nicole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Shettigar, Subhasini [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jungels, John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Welch, Kimberly M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jones, Dean A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-03-01

    The purpose of the Scope, Complexity, Options, Risks, Excursions (SCORE) model is to estimate the relative complexity of design variants of future warhead options. The results of this model allow those considering these options to understand the complexity tradeoffs between proposed warhead options. The core idea of SCORE is to divide a warhead option into a well- defined set of scope elements and then estimate the complexity of each scope element against a well understood reference system. The uncertainty associated with estimates can also be captured. A weighted summation of the relative complexity of each scope element is used to determine the total complexity of the proposed warhead option or portions of the warhead option (i.e., a National Work Breakdown Structure code). The SCORE analysis process is a growing multi-organizational Nuclear Security Enterprise (NSE) effort, under the management of the NA- 12 led Enterprise Modeling and Analysis Consortium (EMAC), that has provided the data elicitation, integration and computation needed to support the out-year Life Extension Program (LEP) cost estimates included in the Stockpile Stewardship Management Plan (SSMP).

  10. Predicting PTSD using the New York Risk Score with genotype data: potential clinical and research opportunities

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2013-04-01

    Full Text Available Joseph A Boscarino,1,2 H Lester Kirchner,3,4 Stuart N Hoffman,5 Porat M Erlich1,4 1Center for Health Research, Geisinger Clinic, Danville, 2Department of Psychiatry, Temple University School of Medicine, Philadelphia, 3Division of Medicine, Geisinger Clinic, Danville, 4Department of Medicine, Temple University School of Medicine, Philadelphia, 5Department of Neurology, Geisinger Clinic, Danville, PA, USA Background: We previously developed a post-traumatic stress disorder (PTSD screening instrument, ie, the New York PTSD Risk Score (NYPRS, that was effective in predicting PTSD. In the present study, we assessed a version of this risk score that also included genetic information. Methods: Utilizing diagnostic testing methods, we hierarchically examined different prediction variables identified in previous NYPRS research, including genetic risk-allele information, to assess lifetime and current PTSD status among a population of trauma-exposed adults. Results: We found that, in predicting lifetime PTSD, the area under the receiver operating characteristic curve (AUC for the Primary Care PTSD Screen alone was 0.865. When we added psychosocial predictors from the original NYPRS to the model, including depression, sleep disturbance, and a measure of health care access, the AUC increased to 0.902, which was a significant improvement (P = 0.0021. When genetic information was added in the form of a count of PTSD risk alleles located within FKBP, COMT, CHRNA5, and CRHR1 genetic loci (coded 0–6, the AUC increased to 0.920, which was also a significant improvement (P = 0.0178. The results for current PTSD were similar. In the final model for current PTSD with the psychosocial risk factors included, genotype resulted in a prediction weight of 17 for each risk allele present, indicating that a person with six risk alleles or more would receive a PTSD risk score of 17 × 6 = 102, the highest risk score for any of the predictors studied. Conclusion: Genetic

  11. Obesity phenotype and coronary heart disease risk as estimated by the Framingham risk score.

    Science.gov (United States)

    Park, Yong Soon; Kim, Jun-Su

    2012-03-01

    There are conflicting data as to whether general or abdominal obesity is a better predictor of cardiovascular risk. This cross-sectional study involved 4,573 subjects aged 30 to 74 yr who participated in the Fourth Korea National Health and Nutrition Examination Survey conducted in 2008. Obesity phenotype was classified by means of body mass index (BMI) and waist circumference (WC), and participants were categorized into 4 groups. Individuals' 10-yr risk of coronary heart diseases (CHD) was determined from the Framingham risk score. Subjects with obese WC had a higher proportion of high risk for CHD compared to the normal WC group, irrespective of BMI level. Relative to subjects with normal BMI/normal WC, the adjusted odds ratios (ORs) of normal BMI/obese WC group (OR 2.93 [1.70, 5.04] and OR 3.10 [1.49, 6.46]) for CHD risk in male were higher than obese BMI/obese WC group (OR 1.91 [1.40, 2.61] and OR 1.70 [1.16, 2.47]), whereas the adjusted ORs of obese BMI/obese WC group (OR 1.94 [1.24, 3.04] and OR 3.92 [1.75, 8.78]) were higher than the others in female. Subjects with obese BMI/normal WC were not significantly associated with 10-yr CHD risk in men (P = 0.449 and P = 0.067) and women (P = 0.702 and P = 0.658). WC is associated with increased CHD risk regardless of the level of BMI. Men with normal BMI and obese WC tend to be associated with CHD risk than those with obese BMI and obese WC.

  12. Blood eosinophil levels as a biomarker in COPD.

    Science.gov (United States)

    Brusselle, Guy; Pavord, Ian D; Landis, Sarah; Pascoe, Steven; Lettis, Sally; Morjaria, Nikhil; Barnes, Neil; Hilton, Emma

    2018-05-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017). Overall, clinical data suggest that in patients with a history of COPD exacerbations, a higher blood eosinophil count predicts an increased risk of future exacerbations and is associated with improved response to treatment with inhaled corticosteroids (in combination with long-acting bronchodilator[s]). Blood eosinophils are therefore a promising biomarker for phenotyping patients with COPD, although prospective studies are needed to assess blood eosinophils as a biomarker of corticosteroid response for this. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. The role of self-esteem and gender in pen scores and risk-taking ...

    African Journals Online (AJOL)

    The role of self-esteem and gender in pen scores and risk-taking behaviour of learners in a South African school. ... RTB to some extent but not on the moderation effects of self-esteem (SE) and gender on RTB ... AJOL African Journals Online.

  14. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease: results from the Framingham Heart Study.

    Science.gov (United States)

    van Himbergen, Thomas M; Beiser, Alexa S; Ai, Masumi; Seshadri, Sudha; Otokozawa, Seiko; Au, Rhoda; Thongtang, Nuntakorn; Wolf, Philip A; Schaefer, Ernst J

    2012-05-01

    To investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia. Prospective cohort study. Dementia-free Framingham Heart Study participants had sera measured for these biomarkers at the 19th biennial examination (1985-1988) and were followed up prospectively for the development of AD and all-cause dementia. Eight hundred forty (541 women, median age of 76 years) subjects participated in the study. We used sex-pooled and sex-specific multivariable Cox proportional hazards models adjusted for age, education, body mass index, recent change in weight, APOE ε4 allele status, and plasma docosahexaenoic acid levels to determine association of these biomarkers with the development of all-cause dementia and AD. Over a mean follow-up period of 13 years, 159 persons developed dementia (including 125 with AD). After adjustment for other risk factors, only adiponectin in women was associated with an increased risk of all-cause dementia (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.00-1.66; P=.054) and AD (HR, 1.33; 95% CI, 1.00-1.76; P=.050) per 1-SD increase in adiponectin level. Women with baseline adiponectin values more than the median had a higher risk of all-cause dementia (HR, 1.63; 95% CI, 1.03-2.56; P=.04) and AD (HR, 1.87; 95% CI, 1.13-3.10; P=.01) as compared with those with values less than the median. In women, increased plasma adiponectin levels are an independent risk factor for the development of both all-cause dementia and AD.

  15. Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

    Science.gov (United States)

    van Vollenhoven, Ronald F; Bolce, Rebecca; Hambardzumyan, Karen; Saevarsdottir, Saedis; Forslind, Kristina; Petersson, Ingemar F; Sasso, Eric H; Hwang, C C; Segurado, Oscar G; Geborek, Pierre

    2015-11-01

    Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44." © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  16. Subclinical cardiovascular disease assessment and its relationship with cardiovascular risk SCORE in a healthy adult population: A cross-sectional community-based study.

    Science.gov (United States)

    Mitu, Ovidiu; Roca, Mihai; Floria, Mariana; Petris, Antoniu Octavian; Graur, Mariana; Mitu, Florin

    The aim of this study is to evaluate the relationship and the accuracy of SCORE (Systematic Coronary Risk Evaluation Project) risk correlated to multiple methods for determining subclinical cardiovascular disease (CVD) in a healthy population. This cross-sectional study included 120 completely asymptomatic subjects, with an age range 35-75 years, and randomly selected from the general population. The individuals were evaluated clinically and biochemical, and the SCORE risk was computed. Subclinical atherosclerosis was assessed by various methods: carotid ultrasound for intima-media thickness (cIMT) and plaque detection; aortic pulse wave velocity (aPWV); echocardiography - left ventricular mass index (LVMI) and aortic atheromatosis (AA); ankle-brachial index (ABI). SCORE mean value was 2.95±2.71, with 76% of subjects having SCORE <5. Sixty-four percent of all subjects have had increased subclinical CVD changes, and SCORE risk score was correlated positively with all markers, except for ABI. In the multivariate analysis, increased cIMT and aPWV were significantly associated with high value of SCORE risk (OR 4.14, 95% CI: 1.42-12.15, p=0.009; respectively OR 1.41, 95% CI: 1.01-1.96, p=0.039). A positive linear relationship was observed between 3 territories of subclinical CVD (cIMT, LVMI, aPWV) and SCORE risk (p<0.0001). There was evidence of subclinical CVD in 60% of subjects with a SCORE value <5. As most subjects with a SCORE value <5 have subclinical CVD abnormalities, a more tailored subclinical CVD primary prevention program should be encouraged. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

    Science.gov (United States)

    Cooper, Christine A; Chahine, Lama M

    2016-11-01

    Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

  18. Genetic Biomarkers of Barrett's Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Findlay, John M; Middleton, Mark R; Tomlinson, Ian

    2016-01-01

    Barrett's esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II-III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some-in particular, those identified by genome-wide association studies, and chromosomal instability for progression-appear plausible, although robust validation is required.

  19. Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

    Science.gov (United States)

    Gonçalves, Samuel M.; Lagrou, Katrien; Rodrigues, Cláudia S.; Campos, Cláudia F.; Bernal-Martínez, Leticia; Rodrigues, Fernando; Silvestre, Ricardo; Alcazar-Fuoli, Laura; Maertens, Johan A.; Cunha, Cristina; Carvalho, Agostinho

    2017-01-01

    Background: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution. Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk. Results: Among the 32 analytes tested, IL-1β, IL-6, IL-8, IL-17A, IL-23, and TNFα were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels ≥904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%). Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, which might be useful in supporting current diagnostic approaches for IPA. PMID:29238334

  20. Heterogeneity of PTEN and ERG expression in prostate cancer on core needle biopsies: implications for cancer risk stratification and biomarker sampling.

    Science.gov (United States)

    Shah, Rajal B; Bentley, James; Jeffery, Zach; DeMarzo, Angelo M

    2015-05-01

    ERG and PTEN biomarkers are increasingly being analyzed on prostate core biopsies (NBXs); ERG as a marker of clonality and number of separately arising tumor foci and PTEN for prognostic information. Yet, in patients with multiple biopsy cores positive for cancer (PCa), there is no standardized approach for interrogation of these biomarkers in terms of the number of positive cores to evaluate. A total of 194 NBX cases containing more than one positive core with cancer were evaluated for ERG overexpression and PTEN loss by immunostaining (immunohistochemistry) of all positive cores. ERG overexpression or PTEN loss in at least one cancer core was present in 111 (57%) and 69 (36%) cases respectively. ERG overexpression was significantly associated with PTEN loss (P < .0001), and PTEN loss was associated with a high Gleason score (P < .0001). Inter- and intra-tumor core staining heterogeneity for ERG overexpression occurred in 42% and 5% cases and for PTEN loss both intra- and inter-tumor core heterogeneity was 68%. PTEN staining was highly discordant between PCa sites regardless of laterality. When the Gleason score was non-uniform across PCa sites, the combination of cores showing the highest Gleason score and largest tumor volume provided the best representation of ERG overexpression (92%) and PTEN loss (98%). When grades were uniform across cancer sites, the highest tumor volume core was generally representative of ERG overexpression (90%) but was less representative for PTEN loss (76%). Our results suggest that knowledge of this heterogeneity is critical for developing optimal yet cost-effective strategies to identify these underlying molecular abnormalities. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Development of a novel scoring system for identifying emerging chemical risks in the food chain.

    Science.gov (United States)

    Oltmanns, J; Licht, O; Bitsch, A; Bohlen, M-L; Escher, S E; Silano, V; MacLeod, M; Serafimova, R; Kass, G E N; Merten, C

    2018-02-21

    The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

  2. DUAL-ENERGY X-RAY ABSORPTIOMETRY AND CALCULATED FRAX RISK SCORES MAY UNDERESTIMATE OSTEOPOROTIC FRACTURE RISK IN VITAMIN D-DEFICIENT VETERANS WITH HIV INFECTION.

    Science.gov (United States)

    Stephens, Kelly I; Rubinsztain, Leon; Payan, John; Rentsch, Chris; Rimland, David; Tangpricha, Vin

    2016-04-01

    We evaluated the utility of the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency. This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the WHO FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures. We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant. We found a high prevalence of subclinical vertebral fractures among vitamin D-deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.

  3. Antithrombotic drugs and non-variceal bleeding outcomes and risk scoring systems: comparison of Glasgow Blatchford, Rockall and Charlson scores

    Science.gov (United States)

    Taha, Ali S; McCloskey, Caroline; Craigen, Theresa; Angerson, Wilson J

    2016-01-01

    Objectives Antithrombotic drugs (ATDs) cause non-variceal upper gastrointestinal bleeding (NVUGIB). Risk scoring systems have not been validated in ATD users. We compared Blatchford, Rockall and Charlson scores in predicting outcomes of NVUGIB in ATD users and controls. Methods A total of 2071 patients with NVUGIB were grouped into ATD users (n=851) and controls (n=1220) in a single-centre retrospective analysis. Outcomes included duration of hospital admission, the need for blood transfusion, rebleeding requiring surgery and 30-day mortality. Results Duration of admission correlated with all scores in controls, but correlations were significantly weaker in ATD users. Rank correlation coefficients in control versus ATD: 0.45 vs 0.20 for Blatchford; 0.48 vs 0.32 for Rockall and 0.42 vs 0.26 for Charlson (all p<0.001). The need for transfusion was best predicted by Blatchford (p<0.001 vs Rockall and Charlson in both ATD users and controls), but all scores performed less well in ATD users. Area under the receiver operation characteristic curve (AUC) in control versus ATD: 0.90 vs 0.85 for Blatchford; 0.77 vs 0.61 for Rockall and 0.69 vs 0.56 for Charlson (all p<0.005). In predicting surgery, Rockall performed best; while mortality was best predicted by Charlson with lower AUCs in ATD patients than controls (p<0.05). Stratification showed the scores' performance to be age-dependent. Conclusions Blatchford score was the strongest predictor of transfusion, Rockall's had the strongest correlation with duration of admission and with rebleeding requiring surgery and Charlson was best in predicting 30-day mortality. Modifications of these systems should be explored to improve their efficiency in ATD users. PMID:28839866

  4. Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Skye Hung-Chun Cheng

    Full Text Available We validated an 18-gene classifier (GC initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP. Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7% and high-risk (n = 537, 78.6% were 96.2% (95% CI, 91.1%-98.8% and 80.9% (74.6%-81.9%, respectively (median follow-up interval, 71.8 months. The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%, stage II (n = 66, 20.1%, and stage III (n = 18, 10.3% were 100%, 94.2% (78.5%-98.5%, and 90.9% (50.8%-98.7%, respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017 for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100% and 80.3% (70.7%-89.9%, p = 0.06 in a Singapore dataset, and 89.5% (81.9%-94.1% and 73.6% (67.2%-79.0%, p = 0.0039 in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

  5. Do Subjective Alcohol Screening Tools Correlate with Biomarkers Among High-Risk Transgender Women and Men Who Have Sex with Men in Lima, Peru?

    Science.gov (United States)

    Herrera, M C; Konda, K A; Leon, S R; Brown, B; Calvo, G M; Salvatierra, H J; Caceres, C F; Klausner, J D; Deiss, R

    2017-11-01

    Alcohol abuse can influence sexual risk behavior; however, its measurement is not straightforward. This study compared self-reported alcohol use, via the AUDIT and CAGE, with levels of phosphatidylethanol (Peth), a phospholipid biomarker that forms with chronic, heavy drinking, among high-risk MSM and TW in Lima, Peru. Chi square, Fisher's exact, Wilcoxon ranksum tests compared the instruments. Receiver operating curves determined sensitivity and specificity of the self-reported measures. Among 69 MSM and 17 TW, PEth was positive for 86% (95% CI 77-93%) of participants, while 67% reported binge-drinking in the last 2 weeks. The AUDIT classified 25% as hazardous drinkers while CAGE identified 6% as problem drinkers. Self-reported binge drinking was more sensitive than the AUDIT for PEth positivity (71% vs. 27%, p = 0.022). Among high-risk MSM and TW in Lima, validated, self-report measures of alcohol abuse underestimated biological measures. Further research correlating bio-markers and self-reported alcohol abuse measures is needed.

  6. WHipple-ABACUS, a simple, validated risk score for 30-day mortality after pancreaticoduodenectomy developed using the ACS-NSQIP database.

    Science.gov (United States)

    Gleeson, Elizabeth M; Shaikh, Mohammad F; Shewokis, Patricia A; Clarke, John R; Meyers, William C; Pitt, Henry A; Bowne, Wilbur B

    2016-11-01

    Pancreaticoduodenectomy needs simple, validated risk models to better identify 30-day mortality. The goal of this study is to develop a simple risk score to predict 30-day mortality after pancreaticoduodenectomy. We reviewed cases of pancreaticoduodenectomy from 2005-2012 in the American College of Surgeons-National Surgical Quality Improvement Program databases. Logistic regression was used to identify preoperative risk factors for morbidity and mortality from a development cohort. Scores were created using weighted beta coefficients, and predictive accuracy was assessed on the validation cohort using receiver operator characteristic curves and measuring area under the curve. The 30-day mortality rate was 2.7% for patients who underwent pancreaticoduodenectomy (n = 14,993). We identified 8 independent risk factors. The score created from weighted beta coefficients had an area under the curve of 0.71 (95% confidence interval, 0.66-0.77) on the validation cohort. Using the score WHipple-ABACUS (hypertension With medication + History of cardiac surgery + Age >62 + 2 × Bleeding disorder + Albumin procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 'Mechanical restraint-confounders, risk, alliance score': testing the clinical validity of a new risk assessment instrument.

    Science.gov (United States)

    Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise; Alkier Gildberg, Frederik

    2017-08-01

    Unstructured risk assessment, as well as confounders (underlying reasons for the patient's risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients. To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical restraint. The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. The three sub-scales (Confounders, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. MR-CRAS contains 18 clinically valid items, and the instrument can be used to support the clinical decision-making regarding the possibility of releasing the patient from mechanical restraint. The present three studies have clinically validated a short MR-CRAS scale that is currently being psychometrically tested in a larger study.

  8. Prediction of Outcome After Emergency High-Risk Intra-abdominal Surgery Using the Surgical Apgar Score

    DEFF Research Database (Denmark)

    Cihoric, Mirjana; Toft Tengberg, Line; Bay-Nielsen, Morten

    2016-01-01

    BACKGROUND: With current literature quoting mortality rates up to 45%, emergency high-risk abdominal surgery has, compared with elective surgery, a significantly greater risk of death and major complications. The Surgical Apgar Score (SAS) is predictive of outcome in elective surgery, but has nev...... emergency high-risk abdominal surgery. Despite its predictive value, the SAS cannot in its current version be recommended as a standalone prognostic tool in an emergency setting....

  9. Analysis of Surgical Site Infection after Musculoskeletal Tumor Surgery: Risk Assessment Using a New Scoring System

    Directory of Open Access Journals (Sweden)

    Satoshi Nagano

    2014-01-01

    Full Text Available Surgical site infection (SSI has not been extensively studied in musculoskeletal tumors (MST owing to the rarity of the disease. We analyzed incidence and risk factors of SSI in MST. SSI incidence was evaluated in consecutive 457 MST cases (benign, 310 cases and malignant, 147 cases treated at our institution. A detailed analysis of the clinical background of the patients, pre- and postoperative hematological data, and other factors that might be associated with SSI incidence was performed for malignant MST cases. SSI occurred in 0.32% and 12.2% of benign and malignant MST cases, respectively. The duration of the surgery (P=0.0002 and intraoperative blood loss (P=0.0005 was significantly more in the SSI group than in the non-SSI group. We established the musculoskeletal oncological surgery invasiveness (MOSI index by combining 4 risk factors (blood loss, operation duration, preoperative chemotherapy, and the use of artificial materials. The MOSI index (0–4 points score significantly correlated with the risk of SSI, as demonstrated by an SSI incidence of 38.5% in the group with a high score (3-4 points. The MOSI index score and laboratory data at 1 week after surgery could facilitate risk evaluation and prompt diagnosis of SSI.

  10. Development of Risk Score for Predicting 3-Year Incidence of Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

    Directory of Open Access Journals (Sweden)

    Akiko Nanri

    Full Text Available Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population.Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008-2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG ≥ 126 mg/dl, random plasma glucose ≥ 200 mg/dl, glycated hemoglobin (HbA1c ≥ 6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort.The area under the curve (AUC for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703-0.731. In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883-0.902. When the risk scores were applied to the validation cohort, AUCs (95% CI for the non-invasive and invasive model were 0.734 (0.715-0.753 and 0.882 (0.868-0.895, respectively. Participants with a non-invasive score of ≥ 15 and invasive score of ≥ 19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years.The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c.

  11. Prospective comparison of three risk scoring systems in non-variceal and variceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Thanapirom, Kessarin; Ridtitid, Wiriyaporn; Rerknimitr, Rungsun; Thungsuk, Rattikorn; Noophun, Phadet; Wongjitrat, Chatchawan; Luangjaru, Somchai; Vedkijkul, Padet; Lertkupinit, Comson; Poonsab, Swangphong; Ratanachu-ek, Thawee; Hansomburana, Piyathida; Pornthisarn, Bubpha; Thongbai, Thirada; Mahachai, Varocha; Treeprasertsuk, Sombat

    2016-04-01

    Data regarding the efficacy of the Glasgow Blatchford score (GBS), full Rockall score (FRS) and pre-endoscopic Rockall scores (PRS) in comparing non-variceal and variceal upper gastrointestinal bleeding (UGIB) are limited. Our aim was to determine the performance of these three risk scores in predicting the need for treatment, mortality, and re-bleeding among patients with non-variceal and variceal UGIB. During January, 2010 and September, 2011, patients with UGIB from 11 hospitals were prospectively enrolled. The GBS, FRS, and PRS were calculated. Discriminative ability for each score was assessed using the receiver operated characteristics curve (ROC) analysis. A total of 981 patients presented with acute UGIB, 225 patients (22.9%) had variceal UGIB. The areas under the ROC (AUC) of the GBS, FRS, and PRS for predicting the need for treatment were 0.77, 0.69, and 0.61 in non-variceal versus 0.66, 0.66, and 0.59 in variceal UGIB. The AUC for predicting mortality and re-bleeding during admission were 0.66, 0.80, and 0.76 in non-variceal versus 0.63, 0.57, and 0.63 in variceal UGIB. AUC score was not statistically significant for predicting need for therapy and clinical outcome in variceal UGIB. The GBS ≤ 2 and FRS ≤ 1 identified low-risk non-variceal UGIB patients for death and re-bleeding during hospitalization. In contrast to non-variceal UGIB, the GBS, FRS, and PRS were not precise scores for assessing the need for therapy, mortality, and re-bleeding during admission in variceal UGIB. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  12. Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

  13. Genetic risk score predicting risk of rheumatoid arthritis phenotypes and age of symptom onset.

    Directory of Open Access Journals (Sweden)

    Lori B Chibnik

    Full Text Available Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the impact of 39 validated genetic risk alleles on the risk of RA phenotypes characterized by serologic and erosive status.We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human Leukocyte Antigen alleles among 542 Caucasian RA cases and 551 Caucasian controls from Nurses' Health Study and Nurses' Health Study II. We created a weighted genetic risk score (GRS and evaluated it as 7 ordinal groups using logistic regression (adjusting for age and smoking to assess the relationship between GRS group and odds of developing seronegative (RF- and CCP-, seropositive (RF+ or CCP+, erosive, and seropositive, erosive RA phenotypes. In separate case only analyses, we assessed the relationships between GRS and age of symptom onset. In 542 RA cases, 317 (58% were seropositive, 163 (30% had erosions and 105 (19% were seropositive with erosions. Comparing the highest GRS risk group to the median group, we found an OR of 1.2 (95% CI = 0.8-2.1 for seronegative RA, 3.0 (95% CI = 1.9-4.7 for seropositive RA, 3.2 (95% CI = 1.8-5.6 for erosive RA, and 7.6 (95% CI = 3.6-16.3 for seropositive, erosive RA. No significant relationship was seen between GRS and age of onset.Results suggest that seronegative and seropositive/erosive RA have different genetic architecture and support the importance of considering RA phenotypes in RA genetic studies.

  14. Urinary trans-trans muconic acid (exposure biomarker to benzene) and hippuric acid (exposure biomarker to toluene) concentrations in Mexican women living in high-risk scenarios of air pollution.

    Science.gov (United States)

    Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Maldonado, Iván N

    2017-11-02

    This study aimed to determine t,t-muconic acid (t,t-MA; exposure biomarker for benzene) and hippuric acid (HA; exposure biomarker for toluene) concentrations in the urine of women living in Mexico. In a cross-sectional study, apparently healthy women (n = 104) were voluntarily recruited from localities with a high risk of air pollution; t,t-MA and HA in urine were quantified using a high-performance liquid chromatography (HPLC) technique. Mean urinary levels of t,t-MA ranged from 680 to 1,310 μg/g creatinine. Mean values of HA ranged from 0.38 to 0.87 g/g creatinine. In conclusion, compared to data recently reported in literature, we found high urinary levels of t,t-MA and HA in assessed women participating in this study. We therefore deem the implementation of a strategy aimed at the reduction of exposure as a necessary measure for the evaluated communities.

  15. Inclusion of Highest Glasgow Coma Scale Motor Component Score in Mortality Risk Adjustment for Benchmarking of Trauma Center Performance.

    Science.gov (United States)

    Gomez, David; Byrne, James P; Alali, Aziz S; Xiong, Wei; Hoeft, Chris; Neal, Melanie; Subacius, Harris; Nathens, Avery B

    2017-12-01

    The Glasgow Coma Scale (GCS) is the most widely used measure of traumatic brain injury (TBI) severity. Currently, the arrival GCS motor component (mGCS) score is used in risk-adjustment models for external benchmarking of mortality. However, there is evidence that the highest mGCS score in the first 24 hours after injury might be a better predictor of death. Our objective was to evaluate the impact of including the highest mGCS score on the performance of risk-adjustment models and subsequent external benchmarking results. Data were derived from the Trauma Quality Improvement Program analytic dataset (January 2014 through March 2015) and were limited to the severe TBI cohort (16 years or older, isolated head injury, GCS ≤8). Risk-adjustment models were created that varied in the mGCS covariates only (initial score, highest score, or both initial and highest mGCS scores). Model performance and fit, as well as external benchmarking results, were compared. There were 6,553 patients with severe TBI across 231 trauma centers included. Initial and highest mGCS scores were different in 47% of patients (n = 3,097). Model performance and fit improved when both initial and highest mGCS scores were included, as evidenced by improved C-statistic, Akaike Information Criterion, and adjusted R-squared values. Three-quarters of centers changed their adjusted odds ratio decile, 2.6% of centers changed outlier status, and 45% of centers exhibited a ≥0.5-SD change in the odds ratio of death after including highest mGCS score in the model. This study supports the concept that additional clinical information has the potential to not only improve the performance of current risk-adjustment models, but can also have a meaningful impact on external benchmarking strategies. Highest mGCS score is a good potential candidate for inclusion in additional models. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Recent developments in biomarkers in Parkinson disease

    Science.gov (United States)

    Schapira, Anthony H.V.

    2013-01-01

    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

  17. Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker.

    Science.gov (United States)

    Iasonos, Alexia; Chapman, Paul B; Satagopan, Jaya M

    2016-05-01

    An increased interest has been expressed in finding predictive biomarkers that can guide treatment options for both mutation carriers and noncarriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time-to-event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a proportional hazards regression model is commonly used as a measure of variation in TB. Although this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus noncarriers. We illustrate the use and interpretation of the proposed measures with data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. Clin Cancer Res; 22(9); 2114-20. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Modelo predictivo de "score" de calcio alto en pacientes con factores de riesgo cardiovascular Predictive model of high calcium score in patients with cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Gloria Franco

    2007-12-01

    prueba del score de calcio coronario a un paciente con factores de riesgo cardiovascular. Se puede observar que muchos de los factores de riesgo que se correlacionan con un valor elevado de "score" de calcio coronario pueden ser modificables: cesar el hábito de fumar o realizar ejercicio.Introduction: it has been found through multiple studies that coronary calcium score is a good predictor of coronary disease in asymptomatic individuals with one or more cardiovascular risk factors; therefore it would be ideal to perform this test in order to stratify its risk, but due to economic factors this is not possible in most cases. The model presented allows predicting the probability that a patient may have a high coronary calcium score by means of his cardiovascular risk factors. The originality of the model is that it also comprises "protector" factors that diminish such probability. Methods: study of cases and controls in asymptomatic patients with cardiovascular risk factors to whom a PCC had been performed. The cases are patients with coronary calcium score greater than percentile 75 for his age and gender; the control case relationship is 2:1. Results: ages ranged between 35 and 75 years; 14.4% were female; 44.4% had family history of CHD; 34.4% were hypertensive; 38.9% had high total cholesterol; 24.4% had HDL cholesterol under 40 mg/dl; 33.3% had LDL cholesterol greater than 160 mg/dl; 25.6% were cigarette smokers; 23.3% were sedentary; 13.3% were periodical alcohol consumers; 15.6% were obese (BMI > 30; 18.9% exercised periodically and 34.4% received statins. Cardiovascular risk factors correlated with high coronary calcium score are recorded in table 1. In the logistic regression model, factors having a p table 2 are obtained. Expression for the model would be: The values of ci values are 1, if the factor is present and 0 if it is not. Conclusions: this model does not pretend to replace stratification through Framinghan model; on the contrary, it is a complement that

  19. Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps.

    Science.gov (United States)

    Castiella, Agustin; Múgica, Fernando; Zapata, Eva; Zubiaurre, Leire; Iribarren, Arantxa; de Juan, M Dolores; Alzate, Luis; Gil, Ines; Urdapilleta, Gregorio; Otazua, Pedro; Emparanza, José Ignacio

    2015-09-01

    A cohort study of patients included in the Basque Country colorectal cancer (CRC) screening programme was carried out to assess the risk of adenomatous polyps and CRC (P-CRC) associated with HFE gene mutations, with gender and with iron biomarkers (serum ferritin (SF), iron (Fe) and transferrin saturation index (TSI)). Among 432 included patients (mean age 59.8 years), 263 were men (60.9 %) and 169 women (39.1 %). P-CRC were identified in 221 patients (51.2 %) and no polyps (NP) in 211 patients (48.8 %). HFE mutations were identified in 43.8 % of the patients. C282Y/wt genotypic frequency was 6.8 % in the P-CRC group and 1.4 % in the NP group (p < 0.05). The allelic frequency was 3.8 versus 1.2 % (p < 0.05). For laboratory, all three iron biomarkers showed a statistically significant difference: mean Fe, 91.29 ± 34 for P-CRC and 80.81 ± 30.59 for NP group. Mean TSI for P-CRC was 24.95 ± 8.90 and 22.74 ± 8.79 for NP group. Mean SF 308.09 ± 536.32 for P-CRC and 177.55 ± 159.95 for NP group. In a multivariate logistic regression analysis, only male gender (odds ratio (OR) = 2.04, 1.29-3.22), SF (OR = 1.001, 1.0004-1.003) and Fe (OR = 1.01, 1.004-1.02) were related with the presence of CRC and adenoma. Men gender and raised serum iron biomarkers increase the risk of P-CRC.

  20. Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk.

    Science.gov (United States)

    Kim, Jihye; Kraft, Peter; Hagan, Kaitlin A; Harrington, Laura B; Lindstroem, Sara; Kabrhel, Christopher

    2018-06-01

    Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk. © 2018 WILEY PERIODICALS, INC.

  1. Inflammatory biomarkers and academic performance in youth. The UP & DOWN Study.

    Science.gov (United States)

    Esteban-Cornejo, Irene; Martinez-Gomez, David; Gómez-Martínez, Sonia; Del Campo-Vecino, Juan; Fernández-Santos, Jorge; Castro-Piñero, Jose; Marcos, Ascensión; Veiga, Oscar L

    2016-05-01

    Inflammation influences cognitive development in infants and older adults, however, how inflammation may affect academic development during childhood and adolescence remains to be elucidated. This study aimed to examine the association between inflammatory biomarkers and academic performance in children and adolescents. A total of 494 youth (238 girls) aged 10.6 ± 3.4 years participated in the study. Four inflammatory biomarkers were selected: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and white blood cell (WBC) count. An inflammatory index was created using the above mentioned biomarkers. Academic performance was assessed through schools records. Results showed that three of the four inflammatory biomarkers (CRP, IL-6 and WBC) and the inflammatory index were negatively associated with all academic indicators (β values ranging from -0.094 to -0.217, all Pacademic indicators compared with youth in the middle tertile (scores ranging from -0.578 to -0.344) and in the lowest tertile (scores ranging from -0.678 to -0.381). In conclusion, inflammation may impair academic performance independently of body fat levels in youth. Our results are of importance because the consequences of childhood and adolescence inflammation tend to continue into adulthood. Lifestyle interventions in youth may be promising in reducing levels of inflammation beyond the reduction in body fat in order to achieve cognitive benefits. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Prediction value of deceleration capacity of rate and GRACE risk score on major adverse cardiac events in patients with acute myocardial infarction].

    Science.gov (United States)

    Gao, L; Chen, Y D; Shi, Y J; Xue, H; Wang, J L

    2016-07-24

    To investigate the prediction value of deceleration capacity of rate (DC) and GRACE risk score for cardiovascular events in AMI patients. Consecutive AMI patients with sinus rhythm hospitalized in our department during August 2012 to August 2013 were included in this prospective study. 24-hour ECG Holter monitoring was performed within 1 week, and the DC value was analyzed, GRACE risk score was acquired with the application of GRACE risk score calculator. Patients were followed up for more than 1 year and major adverse cardiac events (MACE) were obtained. Analysised the Kaplan Meier survival according to DC and GRACE score risk stratification respectively. A total of 157 patients were enrolled in the study (average age: (58.9±12.7)years old). The average follow-up was (20.54±2.85) months. Mortality during follow-up was significantly higher in patients with DC>2.5 compared to patients with DC≤2.5 (Prisk stratification was 0.898 (95%CI 0.840-0.940, Prisk stratification was 0.786 (95%CI 0.714-0.847, Prisk stratification was 0.708 (95%CI 0.652-0.769, Prisk patients than those with intermediate and low risk patients according to DC risk stratification in intermediate and low risk patients by GRACE risk stratification (Prisk stratification is superior to GRACE risk score on outcome assessment in this AMI patient cohort.

  3. Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction

    Directory of Open Access Journals (Sweden)

    Dai Hongying

    2013-01-01

    Full Text Available Abstract Background Multifactor Dimensionality Reduction (MDR has been widely applied to detect gene-gene (GxG interactions associated with complex diseases. Existing MDR methods summarize disease risk by a dichotomous predisposing model (high-risk/low-risk from one optimal GxG interaction, which does not take the accumulated effects from multiple GxG interactions into account. Results We propose an Aggregated-Multifactor Dimensionality Reduction (A-MDR method that exhaustively searches for and detects significant GxG interactions to generate an epistasis enriched gene network. An aggregated epistasis enriched risk score, which takes into account multiple GxG interactions simultaneously, replaces the dichotomous predisposing risk variable and provides higher resolution in the quantification of disease susceptibility. We evaluate this new A-MDR approach in a broad range of simulations. Also, we present the results of an application of the A-MDR method to a data set derived from Juvenile Idiopathic Arthritis patients treated with methotrexate (MTX that revealed several GxG interactions in the folate pathway that were associated with treatment response. The epistasis enriched risk score that pooled information from 82 significant GxG interactions distinguished MTX responders from non-responders with 82% accuracy. Conclusions The proposed A-MDR is innovative in the MDR framework to investigate aggregated effects among GxG interactions. New measures (pOR, pRR and pChi are proposed to detect multiple GxG interactions.

  4. The Usefulness of the MEESSI Score for Risk Stratification of Patients With Acute Heart Failure at the Emergency Department.

    Science.gov (United States)

    Miró, Òscar; Rosselló, Xavier; Gil, Víctor; Martín-Sánchez, Francisco Javier; Llorens, Pere; Herrero, Pablo; Jacob, Javier; López-Grima, María Luisa; Gil, Cristina; Lucas Imbernón, Francisco Javier; Garrido, José Manuel; Pérez-Durá, María José; López-Díez, María Pilar; Richard, Fernando; Bueno, Héctor; Pocock, Stuart J

    2018-06-11

    The MEESSI scale stratifies acute heart failure (AHF) patients at the emergency department (ED) according to the 30-day mortality risk. We validated the MEESSI risk score in a new cohort of Spanish patients to assess its accuracy in stratifying patients by risk and to compare its performance in different settings. We included consecutive patients diagnosed with AHF in 30 EDs during January and February 2016. The MEESSI score was calculated for each patient. The c-statistic measured the discriminatory capacity to predict 30-day mortality of the full MEESSI model and secondary models. Further comparisons were made among subgroups of patients from university and community hospitals, EDs with high-, medium- or low-activity and EDs that recruited or not patients in the original MEESSI derivation cohort. We analyzed 4711 patients (university/community hospitals: 3811/900; high-/medium-/low-activity EDs: 2695/1479/537; EDs participating/not participating in the previous MEESSI derivation study: 3892/819). The distribution of patients according to the MEESSI risk categories was: 1673 (35.5%) low risk, 2023 (42.9%) intermediate risk, 530 (11.3%) high risk and 485 (10.3%) very high risk, with 30-day mortality of 2.0%, 7.8%, 17.9%, and 41.4%, respectively. The c-statistic for the full model was 0.810 (95%CI, 0.790-0.830), ranging from 0.731 to 0.785 for the subsequent secondary models. The discriminatory capacity of the MEESSI risk score was similar among subgroups of hospital type, ED activity, and original recruiter EDs. The MEESSI risk score successfully stratifies AHF patients at the ED according to the 30-day mortality risk, potentially helping clinicians in the decision-making process for hospitalizing patients. Copyright © 2018. Published by Elsevier España, S.L.U.

  5. Population-based metabolic syndrome risk score and its determinants: The Isfahan Healthy Heart Program

    Directory of Open Access Journals (Sweden)

    Mohsen Hosseini

    2014-01-01

    Full Text Available Background: Metabolic syndrome (MetSy, an important predisposing factor for the most of noncommunicable diseases, has become a global pandemic. Given different definitions used for the MetSy, recently using a score termed "continuous MetSy risk score (CMetSyS" is recommended. The aim of this study was to provide a CMetSyS in a population-based sample of Iranian adults and to assess its determinants. Materials and Methods: We used the data of the baseline survey of a community trial entitled "the Isfahan health heart program." The MetSy was defined according to the Revised National Cholesterol Education Program Third Adult Treatment Panel. All probable predictive models and their predictive performance were provided using leave-one-out cross-validated logistic regression and the receiver operation characteristic curve methods. Multiple linear regression was performed to assess factors associated with the CMetSyS. Results: The study population consisted of 8313 persons (49.9% male, mean age 38.54 ± 15.86 years. The MetSy was documented in 1539 persons (21.86%. Triglycerides and waist circumference were the best predictive components, and fasting plasma glucose had the lowest area under curve (AUC. The AUC for our best model was 95.36 (94.83-95.83%. The best predictive cutoff for this risk score was −1.151 with 89% sensitivity and 87.93% specificity. Conclusion: We provided four population-based leave-one-out cross-validated risk score models, with moderate to perfect predictive performance to identify the MetSy in Iranian adults. The CMetSyS had significant associations with high sensitive C-reactive protein, body mass index, leisure time, and workplace physical activity as well as age and gender.

  6. An international study to increase concordance in Ki67 scoring

    DEFF Research Database (Denmark)

    Polley, Mei-Yin C; Leung, Samuel C Y; Gao, Dongxia

    2015-01-01

    these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies...

  7. Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Garofallo, Silvia Bueno; Machado, Daniel Pinheiro; Rodrigues, Clarissa Garcia; Bordim, Odemir Jr.; Kalil, Renato A. K.; Portal, Vera Lúcia, E-mail: veraportal.pesquisa@gmail.com [Post-Graduation Program in Health Sciences: Cardiology, Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS (Brazil)

    2014-06-15

    The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe. To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP). Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP. Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus. Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery.

  8. Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in Brazil

    International Nuclear Information System (INIS)

    Garofallo, Silvia Bueno; Machado, Daniel Pinheiro; Rodrigues, Clarissa Garcia; Bordim, Odemir Jr.; Kalil, Renato A. K.; Portal, Vera Lúcia

    2014-01-01

    The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe. To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP). Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP. Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus. Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery

  9. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

    Directory of Open Access Journals (Sweden)

    Bas C T van Bussel

    Full Text Available BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574, by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD and single-biomarker techniques (ELISA or immunoturbidimetric assay, the following biomarkers of low-grade inflammation: C-reactive protein (CRP, serum amyloid A (SAA, soluble intercellular adhesion molecule 1 (sICAM-1 and soluble vascular cell adhesion molecule 1 (sVCAM-1. These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755 absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP, 0.711 (SAA, 0.895 (sICAM-1 and 0.858 (sVCAM-1. Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

  10. Biomarkers in Sports and Exercise: Tracking Health, Performance, and Recovery in Athletes.

    Science.gov (United States)

    Lee, Elaine C; Fragala, Maren S; Kavouras, Stavros A; Queen, Robin M; Pryor, John Luke; Casa, Douglas J

    2017-10-01

    Biomarker discovery and validation is a critical aim of the medical and scientific community. Research into exercise and diet-related biomarkers aims to improve health, performance, and recovery in military personnel, athletes, and lay persons. Exercise physiology research has identified individual biomarkers for assessing health, performance, and recovery during exercise training. However, there are few recommendations for biomarker panels for tracking changes in individuals participating in physical activity and exercise training programs. Our approach was to review the current literature and recommend a collection of validated biomarkers in key categories of health, performance, and recovery that could be used for this purpose. We determined that a comprehensive performance set of biomarkers should include key markers of (a) nutrition and metabolic health, (b) hydration status, (c) muscle status, (d) endurance performance, (e) injury status and risk, and (f) inflammation. Our review will help coaches, clinical sport professionals, researchers, and athletes better understand how to comprehensively monitor physiologic changes, as they design training cycles that elicit maximal improvements in performance while minimizing overtraining and injury risk.

  11. The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research.

    Science.gov (United States)

    Iyegbe, Conrad; Campbell, Desmond; Butler, Amy; Ajnakina, Olesya; Sham, Pak

    2014-02-01

    Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.

  12. Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

    Institute of Scientific and Technical Information of China (English)

    Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

    2017-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

  13. Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers.

    Directory of Open Access Journals (Sweden)

    Lesley M E McCowan

    Full Text Available Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks' with ultrasound parameters at 20±1 weeks' gestation.Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE cohort study were divided into Training (n = 3735 and Validation datasets (n = 1871. The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile, Normotensive-SGA (small for gestational age with a normotensive mother and Hypertensive-SGA (small for gestational age with an hypertensive mother. The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve.633 (11.2% infants were All-SGA, 465(8.2% Normotensive-SGA and 168 (3% Hypertensive-SGA. Area under the curve (95% Confidence Intervals for All-SGA using 15±1 weeks' clinical variables, 15±1 weeks' clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks' were: 0.63 (0.59-0.67, 0.64 (0.60-0.68 and 0.69 (0.66-0.73 respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57-0.66, 0.61 (0.56-0.66 and 0.68 (0.64-0.73 with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals for Hypertensive-SGA were: 0.76 (0.70-0.82, 0.80 (0.75-0.86 and 0.84 (0.78-0.89 with minimal change in the Training datasets.Models for prediction of small for gestational age, which combine biomarkers, clinical and

  14. Cardiovascular biomarkers and sex: the case for women.

    Science.gov (United States)

    Daniels, Lori B; Maisel, Alan S

    2015-10-01

    Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

  15. siMS Score: Simple Method for Quantifying Metabolic Syndrome.

    Science.gov (United States)

    Soldatovic, Ivan; Vukovic, Rade; Culafic, Djordje; Gajic, Milan; Dimitrijevic-Sreckovic, Vesna

    2016-01-01

    To evaluate siMS score and siMS risk score, novel continuous metabolic syndrome scores as methods for quantification of metabolic status and risk. Developed siMS score was calculated using formula: siMS score = 2*Waist/Height + Gly/5.6 + Tg/1.7 + TAsystolic/130-HDL/1.02 or 1.28 (for male or female subjects, respectively). siMS risk score was calculated using formula: siMS risk score = siMS score * age/45 or 50 (for male or female subjects, respectively) * family history of cardio/cerebro-vascular events (event = 1.2, no event = 1). A sample of 528 obese and non-obese participants was used to validate siMS score and siMS risk score. Scores calculated as sum of z-scores (each component of metabolic syndrome regressed with age and gender) and sum of scores derived from principal component analysis (PCA) were used for evaluation of siMS score. Variants were made by replacing glucose with HOMA in calculations. Framingham score was used for evaluation of siMS risk score. Correlation between siMS score with sum of z-scores and weighted sum of factors of PCA was high (r = 0.866 and r = 0.822, respectively). Correlation between siMS risk score and log transformed Framingham score was medium to high for age groups 18+,30+ and 35+ (0.835, 0.707 and 0.667, respectively). siMS score and siMS risk score showed high correlation with more complex scores. Demonstrated accuracy together with superior simplicity and the ability to evaluate and follow-up individual patients makes siMS and siMS risk scores very convenient for use in clinical practice and research as well.

  16. Crowdsourcing Disease Biomarker Discovery Research: The IP4IC Study.

    Science.gov (United States)

    Chancellor, Michael B; Bartolone, Sarah N; Veerecke, Andrew; Lamb, Laura E

    2018-05-01

    Biomarker discovery is limited by readily assessable, cost efficient human samples available in large numbers that represent the entire heterogeneity of the disease. We developed a novel, active participation crowdsourcing method to determine BP-RS (Bladder Permeability Defect Risk Score). It is based on noninvasive urinary cytokines to discriminate patients with interstitial cystitis/bladder pain syndrome who had Hunner lesions from controls and patients with interstitial cystitis/bladder pain syndrome but without Hunner lesions. We performed a national crowdsourcing study in cooperation with the Interstitial Cystitis Association. Patients answered demographic, symptom severity and urinary frequency questionnaires on a HIPAA (Health Insurance Portability and Accountability Act) compliant website. Urine samples were collected at home, stabilized with a preservative and sent to Beaumont Hospital for analysis. The expression of 3 urinary cytokines was used in a machine learning algorithm to develop BP-RS. The IP4IC study collected a total of 448 urine samples, representing 153 patients (147 females and 6 males) with interstitial cystitis/bladder pain syndrome, of whom 54 (50 females and 4 males) had Hunner lesions. A total of 159 female and 136 male controls also participated, who were age matched. A defined BP-RS was calculated to predict interstitial cystitis/bladder pain syndrome with Hunner lesions or a bladder permeability defect etiology with 89% validity. In this novel participation crowdsourcing study we obtained a large number of urine samples from 46 states, which were collected at home, shipped and stored at room temperature. Using a machine learning algorithm we developed BP-RS to quantify the risk of interstitial cystitis/bladder pain syndrome with Hunner lesions, which is indicative of a bladder permeability defect etiology. To our knowledge BP-RS is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome and one of the

  17. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  18. Development of a Korean Fracture Risk Score (KFRS for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service.

    Directory of Open Access Journals (Sweden)

    Ha Young Kim

    Full Text Available Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model.A total of 718,306 Korean men and women aged 50-90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS.During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk.We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr.

  19. Risk factors affecting injury severity determined by the MAIS score.

    Science.gov (United States)

    Ferreira, Sara; Amorim, Marco; Couto, Antonio

    2017-07-04

    . This study showed the impact of variables, such as the presence of blood alcohol, the use of protection devices, the type of crash, and the site characteristics, on the injury severity classified according to the MAIS score. Additionally, the sex and age of the victims were analyzed as risk factors, showing that elderly and male road users are highly associated with MAIS 3+ injuries. The comparison between the marginal effects of the variables estimated by the MAIS and LHS models showed significant differences. In addition to the differences in the magnitude of impact of each variable, we found that the impact of the road environment variable was dependent on the injury severity classification. The differences in the effects of risk factors between the classifications highlight the importance of using a reliable classification of injury severity. Additionally, the relationship between LHS and MAIS levels is quite different among countries, supporting the previous conclusion that bias is expected in the assessment of risk factors if an injury severity classification other than MAIS is used.

  20. Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

    Science.gov (United States)

    Bista, Rajan K.; Uttam, Shikhar; Hartman, Douglas J.; Qiu, Wei; Yu, Jian; Zhang, Lin; Brand, Randall E.; Liu, Yang

    2012-06-01

    The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and

  1. N-alkylvaline levels in globin as a new type of biomarker in risk assessment of alkylating agents.

    Science.gov (United States)

    Lewalter, J

    1996-01-01

    Adducts with the N-terminal valine of erythrocyte globin can serve as individual biomarkers of systemic and cellular exposure to endogenous and exogenous alkylating agents. In contrast to "detoxification markers" of this kind of mecapturic acids derived from alkylation of glutathione, individual N-alkylations of valine in globin reflect the formally "toxifying" part of the stress due to alkylating agents transformed into the ultimate toxicant. Thus, in contrast to the traditional methods of biological monitoring this approach enables a better evaluation of systemic exposure to reactive agents, adapted more sensibly to the exposure situation over the whole life span of erythrocytes, and it can serve as a specific biomarker of exposure for the purpose of health surveillance in occupational medicine. An individual evaluation of exposures in comparison with the range of corresponding background levels is discussed from the point of view of supplementary risk assessment in medical surveillance of occupationally exposed persons.

  2. More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers

    Directory of Open Access Journals (Sweden)

    James Michael Menke

    2017-10-01

    Full Text Available Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC. Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs, sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs and Bayes factors (BFs estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV. As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.

  3. Development and Validation of a Risk Score Predicting Substantial Weight Gain over 5 Years in Middle-Aged European Men and Women

    DEFF Research Database (Denmark)

    Steffen, Annika; Sørensen, Thorkild I.A.; Knüppel, Sven

    2013-01-01

    Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population.......Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population....

  4. Development of risk-based trading farm scoring system to assist with the control of bovine tuberculosis in cattle in England and Wales.

    Science.gov (United States)

    Adkin, A; Brouwer, A; Simons, R R L; Smith, R P; Arnold, M E; Broughan, J; Kosmider, R; Downs, S H

    2016-01-01

    Identifying and ranking cattle herds with a higher risk of being or becoming infected on known risk factors can help target farm biosecurity, surveillance schemes and reduce spread through animal trading. This paper describes a quantitative approach to develop risk scores, based on the probability of infection in a herd with bovine tuberculosis (bTB), to be used in a risk-based trading (RBT) scheme in England and Wales. To produce a practical scoring system the risk factors included need to be simple and quick to understand, sufficiently informative and derived from centralised national databases to enable verification and assess compliance. A logistic regression identified herd history of bTB, local bTB prevalence, herd size and movements of animals onto farms in batches from high risk areas as being significantly associated with the probability of bTB infection on farm. Risk factors were assigned points using the estimated odds ratios to weight them. The farm risk score was defined as the sum of these individual points yielding a range from 1 to 5 and was calculated for each cattle farm that was trading animals in England and Wales at the start of a year. Within 12 months, of those farms tested, 30.3% of score 5 farms had a breakdown (sensitivity). Of farms scoring 1-4 only 5.4% incurred a breakdown (1-specificity). The use of this risk scoring system within RBT has the potential to reduce infected cattle movements; however, there are cost implications in ensuring that the information underpinning any system is accurate and up to date. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  5. Development and validation of a risk score to assist screening for acute HIV-1 infection among men who have sex with men

    Directory of Open Access Journals (Sweden)

    Maartje Dijkstra

    2017-06-01

    Full Text Available Abstract Background Early treatment of acute HIV-1 infection (AHI is beneficial for patients and could reduce onward transmission. However, guidelines on whom to test for AHI with HIV-1 RNA testing are lacking. Methods A risk score for possible AHI based on literature and expert opinion – including symptoms associated with AHI and early HIV-1 – was evaluated using data from the Amsterdam Cohort Studies among men who have sex with men (MSM. Subsequently, we optimized the risk score by constructing two multivariable logistic regression models: one including only symptoms and one combining symptoms with known risk factors for HIV-1 seroconversion, using generalized estimating equations. Several risk scores were generated from these models and the optimal risk score was validated using data from the Multicenter AIDS Cohort Study. Results Using data from 1562 MSM with 175 HIV-1 seroconversion visits and 17,271 seronegative visits in the Amsterdam Cohort Studies, the optimal risk score included four symptoms (oral thrush, fever, lymphadenopathy, weight loss and three risk factors (self-reported gonorrhea, receptive condomless anal intercourse, more than five sexual partners, all in the preceding six months and yielded an AUC of 0.82. Sensitivity was 76.3% and specificity 76.3%. Validation in the Multicenter AIDS Cohort Study resulted in an AUC of 0.78, sensitivity of 56.2% and specificity of 88.8%. Conclusions The optimal risk score had good overall performance in the Amsterdam Cohort Studies and performed comparable (but showed lower sensitivity in the validation study. Screening for AHI with four symptoms and three risk factors would increase the efficiency of AHI testing and potentially enhance early diagnosis and immediate treatment.

  6. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter

    2015-01-01

    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...... and mortality in patients with NSTI and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS: This is a prospective, observational study being conducted in a tertiary referral centre. Biomarkers will be measured in 114 patients who have been operatively diagnosed with NSTI. On admission, baseline...

  7. Framingham coronary heart disease risk score can be predicted from structural brain images in elderly subjects.

    Directory of Open Access Journals (Sweden)

    Jane Maryam Rondina

    2014-12-01

    Full Text Available Recent literature has presented evidence that cardiovascular risk factors (CVRF play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer’s disease (AD and vascular dementia in the presence of a high degree of cardiovascular risk. In the present paper, we explore the association between CVRF and brain changes using pattern recognition techniques applied to structural MRI and the Framingham score (a composite measure of cardiovascular risk largely used in epidemiological studies in a sample of healthy elderly individuals. We aim to answer the following questions: Is it possible to decode (i.e., to learn information regarding cardiovascular risk from structural brain images enabling individual predictions? Among clinical measures comprising the Framingham score, are there particular risk factors that stand as more predictable from patterns of brain changes? Our main findings are threefold: i we verified that structural changes in spatially distributed patterns in the brain enable statistically significant prediction of Framingham scores. This result is still significant when controlling for the presence of the APOE 4 allele (an important genetic risk factor for both AD and cardiovascular disease. ii When considering each risk factor singly, we found different levels of correlation between real and predicted factors; however, single factors were not significantly predictable from brain images when considering APOE4 allele presence as covariate. iii We found important gender differences, and the possible causes of that finding are discussed.

  8. Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF.

    Science.gov (United States)

    Simpson, Joanne; Jhund, Pardeep S; Silva Cardoso, Jose; Martinez, Felipe; Mosterd, Arend; Ramires, Felix; Rizkala, Adel R; Senni, Michele; Squire, Iain; Gong, Jianjian; Lefkowitz, Martin P; Shi, Victor C; Desai, Akshay S; Rouleau, Jean L; Swedberg, Karl; Zile, Michael R; McMurray, John J V; Packer, Milton; Solomon, Scott D

    2015-11-10

    Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. The effect of increasing body mass index on cardio-metabolic risk and biomarkers of oxidative stress and inflammation in nascent metabolic syndrome.

    Science.gov (United States)

    Pahwa, Roma; Adams-Huet, Beverley; Jialal, Ishwarlal

    2017-05-01

    The effect of BMI defined obesity on cardio-metabolic features and biomarkers of oxidative stress and inflammation in patients with nascent metabolic Syndrome (MetS) is poorly defined. Hence the aim of this study was to examine the effect of increasing obesity on the cardio metabolic risk profile, pro-oxidant state and pro-inflammatory features in nascent MetS patients without Diabetes or CVD. MetS was diagnosed by ATPIII criteria using waist circumference (WC) as the measure of adiposity. Patients (n=58) were stratified into overweight, obese and extreme obesity groups using BMI cut offs of 25-29.9, 30-39.9kg/m 2 and ≥40kg/m 2 and cardio-metabolic features, circulating and cellular biomarkers of oxidative stress and inflammation were determined and correlated with BMI. None of the main cardio-metabolic features including blood pressure, blood glucose, HDL-cholesterol, triglycerides, HOMA-IR, free fatty acids were increased with increasing BMI. Also none of the biomarkers of oxidative stress (ox-LDL, nitrotyrosine and monocyte superoxide anion release) were increased with increasing BMI. However, significant increase in hsCRP, the soluble TNFR1 and sTNFR2 and leptin, were observed with increasing adiposity. Other inflammatory bio-mediators (IL-1β, IL-6, IL-8, MCP-1, Toll-like receptors 2-4), endotoxin, LBP, sCD14 and HMGB1, adiponectin, and chemerin did not show significant increases with increasing BMI. Leptin, hsCRP, sTNFR1, and sTNFR2 correlated significantly with BMI. In conclusion, capturing the cardio-metabolic cluster of MetS that predisposed to both increased risk of diabetes and CVD, using waist circumference, as one of the 5 diagnostic criteria is sufficient and BMI does not appear to afford any major incremental benefit on the cardio-metabolic risk factors, increased oxidative stress and the majority of both cellular and circulating biomarkers of inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Screening for type 2 diabetes mellitus in patients with mental illness: application of a self-assessment score for diabetes mellitus risk.

    Science.gov (United States)

    Shin, Jinah K; Shortridge-Baggett, Lillie M; Sachmechi, Issac; Barron, Charles; Chiu, Ya-Lin; Bajracharya, Bhavana; Bang, Heejung

    2014-12-30

    Various methods for diabetes risk assessment have been developed over a decade, but they were not evaluated in patients with mental illness. This study examined the feasibility and utility of a self-assessment score for type 2 diabetes mellitus (DM2) risk among patients with mental illness. DM2 risk was assessed by patients with mental illness as well as clinicians via a self-assessment questionnaire, and the resulting scores were compared to each other as well as with actual diagnosis. Of 100 patients, nine patients were newly revealed to have DM2 and 34 patients have pre-DM2. Patients tended to underreport risk factors - obesity and physical activity - so perceived to have lower risk. Sensitivity of the self-assessment score was different when used by patients and by clinicians despite correlation coefficient of 0.82. Based on positive predictive values, we may expect one out of two patients who have high scores actually have DM2 or pre-DM2. Also, the discrimination capability was reasonably high (AUC=0.79), comparable to its performance observed in general populations. The self-assessment score has potential as a simple and adjunct tool to identify a high risk group of DM2/pre-DM2 among persons with mental illness, especially, when used together with health care providers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  12. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-02-07

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

  13. Derivation and validation of a novel risk score for safe discharge after acute lower gastrointestinal bleeding: a modelling study.

    Science.gov (United States)

    Oakland, Kathryn; Jairath, Vipul; Uberoi, Raman; Guy, Richard; Ayaru, Lakshmana; Mortensen, Neil; Murphy, Mike F; Collins, Gary S

    2017-09-01

    Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission. We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015. Multivariable logistic regression modelling was used to identify predictors of safe discharge, defined as the absence of rebleeding, blood transfusion, therapeutic intervention, 28 day readmission, or death. The model was converted into a simplified risk scoring system and was externally validated in 288 patients admitted with lower gastrointestinal bleeding (184 safely discharged) from two UK hospitals (Charing Cross Hospital, London, and Hammersmith Hospital, London) that had not contributed data to the development cohort. We calculated C statistics for the new model and did a comparative assessment with six previously developed risk scores. Of 2336 prospectively identified admissions in the development cohort, 1599 (68%) were safely discharged. Age, sex, previous admission for lower gastrointestinal bleeding, rectal examination findings, heart rate, systolic blood pressure, and haemoglobin concentration strongly discriminated safe discharge in the development cohort (C statistic 0·84, 95% CI 0·82-0·86) and in the validation cohort (0·79, 0·73-0·84). Calibration plots showed the new risk score to have good calibration in the validation cohort. The score was better than the Rockall, Blatchford, Strate, BLEED, AIMS65, and NOBLADS scores in predicting safe discharge. A score of 8 or less predicts a 95% probability of safe discharge. We developed and validated a novel clinical prediction model with good discriminative

  14. Framingham risk score for estimation of 10-years of cardiovascular diseases risk in patients with metabolic syndrome.

    Science.gov (United States)

    Jahangiry, Leila; Farhangi, Mahdieh Abbasalizad; Rezaei, Fatemeh

    2017-11-13

    There are a few studies evaluating the predictive value of Framingham risk score (FRS) for cardiovascular disease (CVD) risk assessment in patients with metabolic syndrome in Iran. Because of the emerging high prevalence of CVD among Iranian population, it is important to predict its risk among populations with potential predictive tools. Therefore, the aim of the current study is to evaluate the FRS and its determinants in patients with metabolic syndrome. In the current cross-sectional study, 160 patients with metabolic syndrome diagnosed according to the National Cholesterol Education Adult Treatment Panel (ATP) III criteria were enrolled. The FRS was calculated using a computer program by a previously suggested algorithm. Totally, 77.5, 16.3, and 6.3% of patients with metabolic syndrome were at low, intermediate, and high risk of CVD according to FRS categorization. The highest prevalence of all of metabolic syndrome components were in low CVD risk according to the FRS grouping (P metabolic syndrome and different FRS categorization among patients with metabolic syndrome were identified. High SBP and FSG were associated with meaningfully increased risk of CVD compared with other parameters. The study is not a trial; the registration number is not applicable.

  15. Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.

    Science.gov (United States)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-04-01

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

  16. Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids

    Science.gov (United States)

    2014-01-01

    Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer

  17. A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.

    Science.gov (United States)

    Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee H

    2013-01-28

    We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; Pmortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.

  18. [Inflammatory biomarkers in ischemic acute coronary syndrome].

    Science.gov (United States)

    Domínguez-Rodríguez, Alberto; Abreu-González, Pedro

    2015-10-01

    Diagnosing acute coronary syndrome (ACS) in the emergency department is often a complex process. Inflammatory markers might be useful for the rapid assessment of a patient's overall risk and might also help predict future episodes. The clinical use of these biomarkers could potentially lower the number of emergency visits and help in the prevention of future adverse events. The aim of this review was to evaluate the clinical utility of markers of cardiovascular inflammation in emergency patients with ACS. Based on a critical analysis of a selection of the literature, we concluded that none of the biomarkers of cardiovascular inflammation would at present be useful for stratifying risk in emergency situations, aiding prognosis, or guiding therapy for patients with ACS.

  19. A Risk Prediction Score for Kidney Failure or Mortality in Rhabdomyolysis

    Science.gov (United States)

    McMahon, Gearoid M.; Zeng, Xiaoxi; Waikar, Sushrut S.

    2016-01-01

    IMPORTANCE Rhabdomyolysis ranges in severity from asymptomatic elevations in creatine phosphokinase levels to a life-threatening disorder characterized by severe acute kidney injury requiring hemodialysis or continuous renal replacement therapy (RRT). OBJECTIVE To develop a risk prediction tool to identify patients at greatest risk of RRT or in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 2371 patients admitted between January 1, 2000, and March 31, 2011, to 2 large teaching hospitals in Boston, Massachusetts, with creatine phosphokinase levels in excess of 5000 U/L within 3 days of admission. The derivation cohort consisted of 1397 patients from Massachusetts General Hospital, and the validation cohort comprised 974 patients from Brigham and Women’s Hospital. MAIN OUTCOMES AND MEASURES The composite of RRT or in-hospital mortality. RESULTS The causes and outcomes of rhabdomyolysis were similar between the derivation and validation cohorts. In total, the composite outcome occurred in 19.0% of patients (8.0% required RRT and 14.1% died during hospitalization). The highest rates of the composite outcome were from compartment syndrome (41.2%), sepsis (39.3%), and following cardiac arrest (58.5%). The lowest rates were from myositis (1.7%), exercise (3.2%), and seizures (6.0%). The independent predictors of the composite outcome were age, female sex, cause of rhabdomyolysis, and values of initial creatinine, creatine phosphokinase, phosphate, calcium, and bicarbonate. We developed a risk-prediction score from these variables in the derivation cohort and subsequently applied it in the validation cohort. The C statistic for the prediction model was 0.82 (95% CI, 0.80–0.85) in the derivation cohort and 0.83 (0.80–0.86) in the validation cohort. The Hosmer-Lemeshow P values were .14 and .28, respectively. In the validation cohort, among the patients with the lowest risk score (10), 61.2% died or needed RRT. CONCLUSIONS AND

  20. Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

    Science.gov (United States)

    Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

    2015-05-01

    The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.