Implementing system-wide risk stratification approaches: A review of critical success and failure factors.

PubMed

Huckel Schneider, Carmen; Gillespie, James A; Wilson, Andrew

2017-05-01

Risk stratification has become a widely used tool for linking people identified at risk of health deterioration to the most appropriate evidence-based care. This article systematically reviews recent literature to determine key factors that have been identified as critical enablers and/or barriers to successful implementation of risk stratification tools at a system level. A systematic search found 23 articles and four promising protocols for inclusion in the review, covering the use to 20 different risk stratification tools. These articles reported on only a small fraction of the risk stratification tools used in health systems; suggesting that while the development and statistical validation of risk stratification algorithms is widely reported, there has been little published evaluation of how they are implemented in real-world settings. Controlled studies provided some evidence that the use of risk stratification tools in combination with a care management plan offer patient benefits and that the use of a risk stratification tool to determine components of a care management plan may contribute to reductions in hospital readmissions, patient satisfaction and improved patient outcomes. Studies with the strongest focus on implementation used qualitative and case study methods. Among these, the literature converged on four key areas of implementation that were found to be critical for overcoming barriers to success: the engagement of clinicians and safeguarding equity, both of which address barriers of acceptance; the health system context to address administrative, political and system design barriers; and data management and integration to address logistical barriers.

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention.

PubMed

Bohula, Erin A; Morrow, David A; Giugliano, Robert P; Blazing, Michael A; He, Ping; Park, Jeong-Gun; Murphy, Sabina A; White, Jennifer A; Kesaniemi, Y Antero; Pedersen, Terje R; Brady, Adrian J; Mitchel, Yale; Cannon, Christopher P; Braunwald, Eugene

2017-02-28

Ezetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events. This study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy. The TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years. All 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: -0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE. Atherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Preablation 131-I scans with SPECT/CT contribute to thyroid cancer risk stratification and 131-I therapy planning.

PubMed

Avram, Anca M; Esfandiari, Nazanene H; Wong, Ka Kit

2015-05-01

The use of preablation diagnostic radioiodine scans for risk stratification and radioiodine therapy planning for differentiated thyroid cancer (DTC) remains controversial. The objective was to assess the contribution of preablation diagnostic 131-I scans with SPECT/CT (Dx 131-I scan) to (1) the risk stratification and (2) the postoperative management of DTC. The study was designed as a prospective sequential patient series. The study was conducted at a University hospital. Three hundred twenty patients (pts) with DTC (219F; 101M, mean age 47.3 ± 16.4 y, range 10-90) were studied. Using clinical and histopathology information an endocrinologist performed risk stratification and determined postoperative management with respect to radioiodine therapy (RAI) planning. The decision to withhold or to administer RAI, and the recommended low, medium or high therapeutic 131-I activity were recorded. Dx 131-I scans were performed and interpreted by two nuclear medicine physicians as showing thyroid remnant, cervical nodal, or distant metastases. The endocrinologist then reperformed risk stratification and reformulated management after consideration of Dx 131-I scans and stimulated thyroglobulin (Tg) information. Main outcome measures were changes in risk stratification and management after Dx 131-I scans. Detection of unsuspected nodal and distant metastases and elevated stimulated Tg levels resulted in a change in the estimated risk of recurrence in 15% of patients, and management in 31% of patients, as compared to initial risk stratification and management based on histopathology alone. Both imaging data and stimulated thyroglobulin levels acquired at the time of Dx 131-I scans are consequential for 131-I therapy planning, providing information that changes risk stratification in 15% of patients as compared to recurrence risk estimation based on histopathology alone. Dx 131-I scans contribute to risk stratification by defining residual nodal and distant metastatic disease, changing clinical management in 29.4% of patients.

Cardiac risk stratification in cardiac rehabilitation programs: a review of protocols

PubMed Central

da Silva, Anne Kastelianne França; Barbosa, Marianne Penachini da Costa de Rezende; Bernardo, Aline Fernanda Barbosa; Vanderlei, Franciele Marques; Pacagnelli, Francis Lopes; Vanderlei, Luiz Carlos Marques

2014-01-01

Objective Gather and describe general characteristics of different protocols of risk stratification for cardiac patients undergoing exercise. Methods We conducted searches in LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO electronic databases, using the following descriptors: Cardiovascular Disease, Rehabilitation Centers, Practice Guideline, Exercise and Risk Stratification in the past 20 years. Results Were selected eight studies addressing methods of risk stratification in patients undergoing exercise. Conclusion None of the methods described could cover every situation the patient can be subjected to; however, they are essential to exercise prescription. PMID:25140477

Indiana chronic disease management program risk stratification analysis.

PubMed

Li, Jingjin; Holmes, Ann M; Rosenman, Marc B; Katz, Barry P; Downs, Stephen M; Murray, Michael D; Ackermann, Ronald T; Inui, Thomas S

2005-10-01

The objective of this study was to compare the ability of risk stratification models derived from administrative data to classify groups of patients for enrollment in a tailored chronic disease management program. This study included 19,548 Medicaid patients with chronic heart failure or diabetes in the Indiana Medicaid data warehouse during 2001 and 2002. To predict costs (total claims paid) in FY 2002, we considered candidate predictor variables available in FY 2001, including patient characteristics, the number and type of prescription medications, laboratory tests, pharmacy charges, and utilization of primary, specialty, inpatient, emergency department, nursing home, and home health care. We built prospective models to identify patients with different levels of expenditure. Model fit was assessed using R statistics, whereas discrimination was assessed using the weighted kappa statistic, predictive ratios, and the area under the receiver operating characteristic curve. We found a simple least-squares regression model in which logged total charges in FY 2002 were regressed on the log of total charges in FY 2001, the number of prescriptions filled in FY 2001, and the FY 2001 eligibility category, performed as well as more complex models. This simple 3-parameter model had an R of 0.30 and, in terms in classification efficiency, had a sensitivity of 0.57, a specificity of 0.90, an area under the receiver operator curve of 0.80, and a weighted kappa statistic of 0.51. This simple model based on readily available administrative data stratified Medicaid members according to predicted future utilization as well as more complicated models.

A score model to predict risk of events in patients with Brugada Syndrome.

PubMed

Sieira, Juan; Conte, Giulio; Ciconte, Giuseppe; Chierchia, Gian-Battista; Casado-Arroyo, Ruben; Baltogiannis, Giannis; Di Giovanni, Giacomo; Saitoh, Yukio; Juliá, Justo; Mugnai, Giacomo; La Meir, Mark; Wellens, Francis; Czapla, Jens; Pappaert, Gudrun; de Asmundis, Carlo; Brugada, Pedro

2017-06-07

Risk stratification in Brugada Syndrome (BS) remains challenging. Arrhythmic events can occur life-long and studies with long follow-ups are sparse. The aim of our study was to investigate long-term prognosis and risk stratification of BS patients. A single centre consecutive cohort of 400 BS patients was included and analysed. Mean age was 41.1 years, 78 patients (19.5%) had a spontaneous type I electrocardiogram (ECG). Clinical presentation was aborted sudden cardiac death (SCD) in 20 patients (5.0%), syncope in 111 (27.8%) and asymptomatic in 269 (67.3%). Familial antecedents of SCD were found in 184 individuals (46.0%), in 31 (7.8%) occurred in first-degree relatives younger than 35 years. An implantable cardioverter defibrillator (ICD) was placed in 176 (44.0%). During a mean follow-up of 80.7 months, 34 arrhythmic events occurred (event rate: 1.4% year). Variables significantly associated to events were: presentation as aborted SCD (Hazard risk [HR] 20.0), syncope (HR 3.7), spontaneous type I (HR 2.7), male gender (HR 2.7), early SCD in first-degree relatives (HR 2.9), SND (HR 5.0), inducible VA (HR 4.7) and proband status (HR 2.1). A score including ECG pattern, early familial SCD antecedents, inducible electrophysiological study, presentation as syncope or as aborted SCD and SND had a predictive performance of 0.82. A score greater than 2 conferred a 5-year event probability of 9.2%. BS patients remain at risk many years after diagnosis. Early SCD in first-degree relatives and SND are risk factors for arrhythmic events. A simple risk score might help in the stratification and management of BS patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Role of Immune Microenvironmental Factors for Improving the IPI-related Risk Stratification of Aggressive B Cell Lymphoma.

PubMed

Gong, Yi; Chen, Rui; Zhang, Xi; Zou, Zhong Min; Chen, Xing Hua

2017-07-01

To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Significant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum β2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index (IPI), revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Superiority of delayed risk stratification in differentiated thyroid cancer after total thyroidectomy and radioactive iodine ablation.

PubMed

Hong, Chae Moon; Lee, Won Kee; Jeong, Shin Young; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2014-11-01

The aim of this study was to validate the effectiveness of delayed risk stratification (DRS) in predicting structural progression and compare the predictive value of American Thyroid Association (ATA) risk stratification with that of DRS in patients with differentiated thyroid cancer (DTC). A total of 398 patients with DTC who underwent surgery followed by radioactive iodine ablation were enrolled. Patients were categorized as having excellent response, acceptable response, biochemical incomplete response, or structural incomplete response at 8-15 months' evaluation after radioactive iodine ablation for DRS. Effectiveness of DRS was evaluated according to structural progression-free survival (PFS; median follow-up, 10.7 years). A total of 229 patients (57.5%) were classified as having excellent response, 78 (19.6%) as having acceptable response, 62 (15.6%) as having biochemical incomplete response, and 29 patients (7.3%) as having structural incomplete response. After DRS, 60.2% of intermediate-risk patients and 20.5% of high-risk patients were shifted to the excellent response category. Sixty-nine patients (17.3%) showed structural progression. DRS showed statistical difference in PFS (hazard ratio, 4.268; 95% confidence interval, 3.258-5.477; P<0.001). In multivariate analysis of ATA risk stratification and DRS, DRS was significantly associated with PFS (hazard ratio, 4.383; 95% confidence interval, 3.250-5.912; P<0.001), but ATA risk stratification was not. There was no significant difference in deviances between the use of DRS alone and the use of both DRS and ATA risk stratification (χ=0.103, d.f.=1, P=0.748). DRS is superior to ATA risk stratification in predicting structural disease progression for DTC patients.

Quantitative risk stratification in Markov chains with limiting conditional distributions.

PubMed

Chan, David C; Pollett, Philip K; Weinstein, Milton C

2009-01-01

Many clinical decisions require patient risk stratification. The authors introduce the concept of limiting conditional distributions, which describe the equilibrium proportion of surviving patients occupying each disease state in a Markov chain with death. Such distributions can quantitatively describe risk stratification. The authors first establish conditions for the existence of a positive limiting conditional distribution in a general Markov chain and describe a framework for risk stratification using the limiting conditional distribution. They then apply their framework to a clinical example of a treatment indicated for high-risk patients, first to infer the risk of patients selected for treatment in clinical trials and then to predict the outcomes of expanding treatment to other populations of risk. For the general chain, a positive limiting conditional distribution exists only if patients in the earliest state have the lowest combined risk of progression or death. The authors show that in their general framework, outcomes and population risk are interchangeable. For the clinical example, they estimate that previous clinical trials have selected the upper quintile of patient risk for this treatment, but they also show that expanded treatment would weakly dominate this degree of targeted treatment, and universal treatment may be cost-effective. Limiting conditional distributions exist in most Markov models of progressive diseases and are well suited to represent risk stratification quantitatively. This framework can characterize patient risk in clinical trials and predict outcomes for other populations of risk.

Self-Reported Stroke Risk Stratification: Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Howard, George; McClure, Leslie A; Moy, Claudia S; Howard, Virginia J; Judd, Suzanne E; Yuan, Ya; Long, D Leann; Muntner, Paul; Safford, Monika M; Kleindorfer, Dawn O

2017-07-01

The standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF. Participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF. Over an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores ( r Spearman =0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (c SRSRF =0.7266; 95% confidence interval, 0.7076-0.7457; c FSRF =0.7075; 95% confidence interval, 0.6877-0.7273; P =0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF. A simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk. © 2017 American Heart Association, Inc.

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

DTIC Science & Technology

2017-10-01

SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCA) is a clinically and genetically heterogeneous and the development of a molecular classification is...AWARD NUMBER: W81XWH-16-1-0739 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH

SIOP‐PODC adapted risk stratification and treatment guidelines: Recommendations for neuroblastoma in low‐ and middle‐income settings

PubMed Central

Howard, Scott C.; Chantada, Guillermo; Israels, Trijn; Khattab, Mohammed; Alcasabas, Patricia; Lam, Catherine G.; Faulkner, Lawrence; Park, Julie R.; London, Wendy B.; Matthay, Katherine K.

2015-01-01

Neuroblastoma is the most common extracranial solid tumor in childhood in high‐income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. However, in low‐ and middle‐ income countries (LMIC), suboptimal diagnosis, risk stratification, and treatment may occur due to limited resources and unavailable infrastructure. The clinical practice guidelines outlined in this manuscript are based on current published evidence and expert opinions. Standard risk stratification and treatment explicitly adapted to graduated resource settings can improve outcomes for children with neuroblastoma by reducing preventable toxic death and relapse. Pediatr Blood Cancer 2015;62:1305–1316. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc. PMID:25810263

Cardiac risk stratification: Role of the coronary calcium score

PubMed Central

Sharma, Rakesh K; Sharma, Rajiv K; Voelker, Donald J; Singh, Vibhuti N; Pahuja, Deepak; Nash, Teresa; Reddy, Hanumanth K

2010-01-01

Coronary artery calcium (CAC) is an integral part of atherosclerotic coronary heart disease (CHD). CHD is the leading cause of death in industrialized nations and there is a constant effort to develop preventative strategies. The emphasis is on risk stratification and primary risk prevention in asymptomatic patients to decrease cardiovascular mortality and morbidity. The Framingham Risk Score predicts CHD events only moderately well where family history is not included as a risk factor. There has been an exploration for new tests for better risk stratification and risk factor modification. While the Framingham Risk Score, European Systematic Coronary Risk Evaluation Project, and European Prospective Cardiovascular Munster study remain excellent tools for risk factor modification, the CAC score may have additional benefit in risk assessment. There have been several studies supporting the role of CAC score for prediction of myocardial infarction and cardiovascular mortality. It has been shown to have great scope in risk stratification of asymptomatic patients in the emergency room. Additionally, it may help in assessment of progression or regression of coronary artery disease. Furthermore, the CAC score may help differentiate ischemic from nonischemic cardiomyopathy. PMID:20730016

Early Dynamic Risk Stratification with Baseline Troponin Levels and 90-minute ST Segment Resolution to Predict 30 Day Cardiovascular Mortality in STEMI: Analysis from CLARITY TIMI-28

PubMed Central

Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Bode, Christoph; Rifai, Nader; Gerszten, Robert E.; Gibson, C. Michael; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.

2010-01-01

Background Troponin is the preferred biomarker for risk stratification in non-ST-elevation ACS. The incremental prognostic utility of the initial magnitude of troponin elevation and its value in conjunction with ST segment resolution (STRes) in STEMI is less well-defined. Methods Troponin T (TnT) was measured in 1250 patients at presentation undergoing fibrinolysis for STEMI in CLARITY-TIMI 28. STRes was measured at 90 minutes. Multivariable logistic regression was used to examine the independent association between TnT levels, STRes, and 30-day cardiovascular (CV) mortality. Results Patients were classified into undetectable TnT at baseline (n=594), detectable but below the median of 0.12 ng/ml (n=330), and above the median (n=326). Rates of 30-day CV death were 1.5%, 4.5%, and 9.5% respectively (P<0.0001). Compared with those with undetectable levels and adjusting for baseline factors, the odds ratios for 30-day CV death were 4.56 (1.72-12.08, P=0.002) and 5.81 (2.29-14.73, P=0.0002) for those below and above the median, respectively. When combined with STRes, there was a significant gradient of risk, and in a multivariable model both baseline TnT (P=0.004) and STRes (P=0.003) were significant predictors of 30-day CV death. The addition of TnT and STRes to clinical risk factors significantly improved the C-statistic (0.86 to 0.90, P=0.02) and the integrated discriminative improvement 7.1% (P=0.0009). Conclusions Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI. Use of these two simple, readily available tools can aid clinicians in early risk stratification. PMID:20569707

Natural history of Brugada syndrome in a patient with congenital heart disease.

PubMed

Silva, Doroteia; Martins, Fernando Maymone; Cavaco, Diogo; Adragão, Pedro; Silva, Margarida Matos; Anjos, Rui; Ferreira, Álvaro; Gaspar, Isabel Mendes

2015-01-01

Risk stratification of sudden death in patients with Brugada syndrome (BrS) is a controversial issue, and there is currently no consensus on the best method. Examination of data from the natural history of the disease is of fundamental importance and may help to identify relatives at risk. At the same time, study of the genetic mutations responsible for the disease may also contribute to risk stratification of the syndrome, enabling identification of asymptomatic relatives carrying mutations. This paper presents the case of a young man, aged 26, monitored as a pediatric cardiology outpatient from birth for a simple structural heart defect not requiring surgery. Analysis of the evolution of the patient's electrocardiogram revealed the appearance, at the age of 20, of a pattern compatible with type I BrS. Following an episode of syncope and induction of polymorphic ventricular tachycardia in the electrophysiological study, a cardioverter-defibrillator was implanted. One year later, a single shock terminated an episode of ventricular fibrillation. A molecular study of the SCN5A gene identified a rare mutation, c.3622G>T (p.Glu1208X), recently described and associated with more severe phenotypes in patients with BrS, as in the case presented. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Earthquake Hoax in Ghana: Exploration of the Cry Wolf Hypothesis

PubMed Central

Aikins, Moses; Binka, Fred

2012-01-01

This paper investigated the belief of the news of impending earthquake from any source in the context of the Cry Wolf hypothesis as well as the belief of the news of any other imminent disaster from any source. We were also interested in the correlation between preparedness, risk perception and antecedents. This explorative study consisted of interviews, literature and Internet reviews. Sampling was of a simple random nature. Stratification was carried out by sex and residence type. The sample size of (N=400), consisted of 195 males and 205 Females. Further stratification was based on residential classification used by the municipalities. The study revealed that a person would believe news of an impending earthquake from any source, (64.4%) and a model significance of (P=0.000). It also showed that a person would believe news of any other impending disaster from any source, (73.1%) and a significance of (P=0.003). There is association between background, risk perception and preparedness. Emergency preparedness is weak. Earthquake awareness needs to be re-enforced. There is a critical need for public education of earthquake preparedness. The authors recommend developing emergency response program for earthquakes, standard operating procedures for a national risk communication through all media including instant bulk messaging. PMID:28299086

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.« less

Using known populations of pronghorn to evaluate sampling plans and estimators

USGS Publications Warehouse

Kraft, K.M.; Johnson, D.H.; Samuelson, J.M.; Allen, S.H.

1995-01-01

Although sampling plans and estimators of abundance have good theoretical properties, their performance in real situations is rarely assessed because true population sizes are unknown. We evaluated widely used sampling plans and estimators of population size on 3 known clustered distributions of pronghorn (Antilocapra americana). Our criteria were accuracy of the estimate, coverage of 95% confidence intervals, and cost. Sampling plans were combinations of sampling intensities (16, 33, and 50%), sample selection (simple random sampling without replacement, systematic sampling, and probability proportional to size sampling with replacement), and stratification. We paired sampling plans with suitable estimators (simple, ratio, and probability proportional to size). We used area of the sampling unit as the auxiliary variable for the ratio and probability proportional to size estimators. All estimators were nearly unbiased, but precision was generally low (overall mean coefficient of variation [CV] = 29). Coverage of 95% confidence intervals was only 89% because of the highly skewed distribution of the pronghorn counts and small sample sizes, especially with stratification. Stratification combined with accurate estimates of optimal stratum sample sizes increased precision, reducing the mean CV from 33 without stratification to 25 with stratification; costs increased 23%. Precise results (mean CV = 13) but poor confidence interval coverage (83%) were obtained with simple and ratio estimators when the allocation scheme included all sampling units in the stratum containing most pronghorn. Although areas of the sampling units varied, ratio estimators and probability proportional to size sampling did not increase precision, possibly because of the clumped distribution of pronghorn. Managers should be cautious in using sampling plans and estimators to estimate abundance of aggregated populations.

Noninvasive risk stratification for sudden death in asymptomatic patients with Wolff-Parkinson-White syndrome.

PubMed

Novella, John; DeBiasi, Ralph M; Coplan, Neil L; Suri, Ranji; Keller, Seth

2014-01-01

Sudden cardiac death (SCD) as the first clinical manifestation of Wolff-Parkinson-White (WPW) syndrome is a well-documented, although rare occurrence. The incidence of SCD in patients with WPW ranges from 0% to 0.39% annually. Controversy exists regarding risk stratification for patients with preexcitation on surface electrocardiogram (ECG), particularly in those who are asymptomatic. This article focuses on the role of risk stratification using exercise and pharmacologic testing in patients with WPW pattern on ECG.

Prospective Validation of ATA and ETA Sonographic Pattern Risk of Thyroid Nodules Selected for FNAC.

PubMed

Maino, Fabio; Forleo, Raffaella; Martinelli, Martina; Fralassi, Noemi; Barbato, Filomena; Pilli, Tania; Capezzone, Marco; Brilli, Lucia; Ciuoli, Cristina; Di Cairano, Giovanni; Nigi, Laura; Pacini, Furio; Castagna, Maria Grazia

2018-06-01

Recently, the American Thyroid Association (ATA) and the European Thyroid Association (ETA) have proposed that thyroid ultrasound (US) should be used to stratify the risk of malignancy in thyroid nodules and to aid decision-making about whether fine-needle aspiration cytology (FNAC) is indicated. To validate and to compare the ATA and ETA US risk stratification systems of thyroid nodules in a prospective series of thyroid nodules submitted to FNAC. We prospectively evaluated 432 thyroid nodules selected for FNAC from 340 patients. Cytology reports were based on the five categories according to the criteria of the British Thyroid Association. The proportion of Thy2 nodules decreased significantly, whereas the proportion of Thy4/Thy5 nodules significantly increased with increasing US risk class (P < 0.0001). The ability to identify benign and malignant nodules was similar between ATA and ETA systems. According to ATA and ETA US risk stratification systems, 23.7% and 56.0% nodules did not meet the criteria for FNAC, respectively. Considering only categories at lower risk of malignancy, the cumulative malignancy rate in these nodules was 1.2% for ATA and 1.7% for ETA US risk stratification systems. ETA and ATA US risk stratification systems provide effective malignancy risk stratification for thyroid nodules. In clinical practice, using this approach, we should be able to reduce the number of unnecessary FNAC without losing clinically relevant thyroid cancer.

The Auckland Cataract Study: Assessing Preoperative Risk Stratification Systems for Phacoemulsification Surgery in a Teaching Hospital.

PubMed

Kim, Bia Z; Patel, Dipika V; Sherwin, Trevor; McGhee, Charles N J

2016-11-01

To evaluate 2 preoperative risk stratification systems for assessing the risk of complications in phacoemulsification cataract surgery, performed by residents, fellows, and attending physicians in a public teaching hospital. Cohort study. One observer assessed the clinical data of 500 consecutive cases, prior to phacoemulsification cataract surgery performed between April and June 2015 at Greenlane Clinical Centre, Auckland, New Zealand. Preoperatively 2 risk scores were calculated for each case using the Muhtaseb and Buckinghamshire risk stratification systems. Complications, intraoperative and postoperative, and visual outcomes were analyzed in relation to these risk scores. Intraoperative complication rates increased with higher risk scores using the Muhtaseb or Buckinghamshire stratification system (P = .001 and P = .003, respectively, n = 500). The odds ratios for residents and fellows were not significantly different from attending physicians after case-mix adjustment according to risk scores (P > .05). Postoperative complication rates increased with higher Buckinghamshire risk scores but not with Muhtaseb scores (P = .014 and P = .094, respectively, n = 476). Postoperative corrected-distance visual acuity was poorer with higher risk scores (P < .001 for both, n = 476). This study confirms that the risk of intraoperative complications increases with higher preoperative risk scores. Furthermore, higher risk scores correlate with poorer postoperative visual acuity and the Buckinghamshire risk score also correlates with postoperative complications. Therefore, preoperative assessment using such risk stratification systems could assist individual informed consent, preoperative surgical planning, safe allocation of cases to trainees, and more meaningful analyses of outcomes for individual surgeons and institutions. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk Stratification Methods and Provision of Care Management Services in Comprehensive Primary Care Initiative Practices.

PubMed

Reddy, Ashok; Sessums, Laura; Gupta, Reshma; Jin, Janel; Day, Tim; Finke, Bruce; Bitton, Asaf

2017-09-01

Risk-stratified care management is essential to improving population health in primary care settings, but evidence is limited on the type of risk stratification method and its association with care management services. We describe risk stratification patterns and association with care management services for primary care practices in the Comprehensive Primary Care (CPC) initiative. We undertook a qualitative approach to categorize risk stratification methods being used by CPC practices and tested whether these stratification methods were associated with delivery of care management services. CPC practices reported using 4 primary methods to stratify risk for their patient populations: a practice-developed algorithm (n = 215), the American Academy of Family Physicians' clinical algorithm (n = 155), payer claims and electronic health records (n = 62), and clinical intuition (n = 52). CPC practices using practice-developed algorithm identified the most number of high-risk patients per primary care physician (282 patients, P = .006). CPC practices using clinical intuition had the most high-risk patients in care management and a greater proportion of high-risk patients receiving care management per primary care physician (91 patients and 48%, P =.036 and P =.128, respectively). CPC practices used 4 primary methods to identify high-risk patients. Although practices that developed their own algorithm identified the greatest number of high-risk patients, practices that used clinical intuition connected the greatest proportion of patients to care management services. © 2017 Annals of Family Medicine, Inc.

Risk stratification of thyroid nodules on ultrasonography with the French TI-RADS: description and reflections

PubMed Central

2016-01-01

The widespread use of ultrasonography places it in a key position for use in the risk stratification of thyroid nodules. The French proposal is a five-tier system, our version of a thyroid imaging reporting and database system (TI-RADS), which includes a standardized vocabulary and report and a quantified risk assessment. It allows the selection of the nodules that should be referred for fine-needle aspiration biopsies. Effort should be directed towards merging the different risk stratification systems utilized around the world and testing this unified system with multi-center studies. PMID:26324117

Validation of risk stratification for children with febrile neutropenia in a pediatric oncology unit in India.

PubMed

Das, Anirban; Trehan, Amita; Oberoi, Sapna; Bansal, Deepak

2017-06-01

The study aims to validate a score predicting risk of complications in pediatric patients with chemotherapy-related febrile neutropenia (FN) and evaluate the performance of previously published models for risk stratification. Children diagnosed with cancer and presenting with FN were evaluated in a prospective single-center study. A score predicting the risk of complications, previously derived in the unit, was validated on a prospective cohort. Performance of six predictive models published from geographically distinct settings was assessed on the same cohort. Complications were observed in 109 (26.3%) of 414 episodes of FN over 15 months. A risk score based on undernutrition (two points), time from last chemotherapy (<7 days = two points), presence of a nonupper respiratory focus of infection (two points), C-reactive protein (>60 mg/l = five points), and absolute neutrophil count (<100 per μl = two points) was used to stratify patients into "low risk" (score <7, n = 208) and assessed using the following parameters: overall performance (Nagelkerke R 2 = 34.4%), calibration (calibration slope = 0.39; P = 0.25 in Hosmer-Lemeshow test), discrimination (c-statistic = 0.81), overall sensitivity (86%), negative predictive value (93%), and clinical net benefit (0.43). Six previously published rules demonstrated inferior performance in this cohort. An indigenous decision rule using five simple predefined variables was successful in identifying children at risk for complications. Prediction models derived in developed nations may not be appropriate for low-middle-income settings and need to be validated before use. © 2016 Wiley Periodicals, Inc.

Risk assessment and clinical decision making for colorectal cancer screening.

PubMed

Schroy, Paul C; Caron, Sarah E; Sherman, Bonnie J; Heeren, Timothy C; Battaglia, Tracy A

2015-10-01

Shared decision making (SDM) related to test preference has been advocated as a potentially effective strategy for increasing adherence to colorectal cancer (CRC) screening, yet primary care providers (PCPs) are often reluctant to comply with patient preferences if they differ from their own. Risk stratification advanced colorectal neoplasia (ACN) provides a rational strategy for reconciling these differences. To assess the importance of risk stratification in PCP decision making related to test preference for average-risk patients and receptivity to use of an electronic risk assessment tool for ACN to facilitate SDM. Mixed methods, including qualitative key informant interviews and a cross-sectional survey. PCPs at an urban, academic safety-net institution. Screening preferences, factors influencing patient recommendations and receptivity to use of a risk stratification tool. Nine PCPs participated in interviews and 57 completed the survey. Despite an overwhelming preference for colonoscopy by 95% of respondents, patient risk (67%) and patient preferences (63%) were more influential in their decision making than patient comorbidities (31%; P < 0.001). Age was the single most influential risk factor (excluding family history), with <20% of respondents choosing factors other than age. Most respondents reported that they would be likely to use a risk stratification tool in their practice either 'often' (43%) or sometimes (53%). Risk stratification was perceived to be important in clinical decision making, yet few providers considered risk factors other than age for average-risk patients. Providers were receptive to the use of a risk assessment tool for ACN when recommending an appropriate screening test for select patients. © 2013 John Wiley & Sons Ltd.

State of the Art: Blood Biomarkers for Risk Stratification in Patients with Stable Ischemic Heart Disease.

PubMed

Omland, Torbjørn; White, Harvey D

2017-01-01

Multiple circulating biomarkers have been associated with the incidence of cardiovascular events and proposed as potential tools for risk stratification in stable ischemic heart disease (IHD), yet current guidelines do not make any firm recommendations concerning the use of biomarkers for risk stratification in this setting. This state-of-the-art review provides an overview of biomarkers for risk stratification in stable IHD. Circulating biomarkers associated with the risk of cardiovascular events in patients with stable IHD reflect different pathophysiological processes, including myocardial injury, myocardial stress and remodeling, metabolic status, vascular inflammation, and oxidative stress. Compared to the primary prevention setting, biomarkers reflecting end-organ damage and future risk of heart failure development and cardiovascular death may play more important roles in the stable IHD setting. Accordingly, biomarkers that reflect chronic, low-grade myocardial injury, and stress, i.e., high-sensitivity cardiac troponins and natriuretic peptides, provide graded and incremental prognostic information to conventional risk markers. In contrast, in stable IHD patients the prognostic value of traditional metabolic biomarkers, including serum lipids, is limited. Among several novel biomarkers, growth-differentiation factor-15 may provide the most robust prognostic information, whereas most inflammatory markers provide limited incremental prognostic information to risk factor models that include conventional risk factors, natriuretic peptides, and high-sensitivity troponins. Circulating biomarkers hold promise as useful tools for risk stratification in stable IHD, but their future incorporation into clinically useful risk scores will depend on prospective, rigorously performed clinical trials that document enhanced risk prediction. © 2016 American Association for Clinical Chemistry.

Development and validation of the Surgical Outcome Risk Tool (SORT)

PubMed Central

Protopapa, K L; Simpson, J C; Smith, N C E; Moonesinghe, S R

2014-01-01

Background Existing risk stratification tools have limitations and clinical experience suggests they are not used routinely. The aim of this study was to develop and validate a preoperative risk stratification tool to predict 30-day mortality after non-cardiac surgery in adults by analysis of data from the observational National Confidential Enquiry into Patient Outcome and Death (NCEPOD) Knowing the Risk study. Methods The data set was split into derivation and validation cohorts. Logistic regression was used to construct a model in the derivation cohort to create the Surgical Outcome Risk Tool (SORT), which was tested in the validation cohort. Results Prospective data for 19 097 cases in 326 hospitals were obtained from the NCEPOD study. Following exclusion of 2309, details of 16 788 patients were analysed (derivation cohort 11 219, validation cohort 5569). A model of 45 risk factors was refined on repeated regression analyses to develop a model comprising six variables: American Society of Anesthesiologists Physical Status (ASA-PS) grade, urgency of surgery (expedited, urgent, immediate), high-risk surgical specialty (gastrointestinal, thoracic, vascular), surgical severity (from minor to complex major), cancer and age 65 years or over. In the validation cohort, the SORT was well calibrated and demonstrated better discrimination than the ASA-PS and Surgical Risk Scale; areas under the receiver operating characteristic (ROC) curve were 0·91 (95 per cent c.i. 0·88 to 0·94), 0·87 (0·84 to 0·91) and 0·88 (0·84 to 0·92) respectively (P < 0·001). Conclusion The SORT allows rapid and simple data entry of six preoperative variables, and provides a percentage mortality risk for individuals undergoing surgery. PMID:25388883

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

PubMed

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); p<0.001)/GBS = 0.810 (CI: 0.744-0.877; p->0.001); m-GBS = 0.802 (CI: 0.734-0.871; p<0.001)], whereas only CRS achieved significance in identifying re-bleed [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.

Stratification strategy for evaluating the influence of diabetes complication severity index on the risk of hospitalization: a record linkage data in Western Australia.

PubMed

Ha, Ninh Thi; Harris, Mark; Robinson, Suzanne; Preen, David; Moorin, Rachael

2017-07-01

This study aimed to develop a risk stratification strategy for evaluating the relationship between complications of diabetes and the risk of diabetic-related hospitalization to accurately classify diabetes severity. The study used administrative health records for 40,624 individuals with diabetes aged ≥18years in Western Australian. The adapted Diabetes Complication Severity Index (DCSI), socio-demographic and clinical characteristics were used in random effects negative binomial and threshold effect models to determine the optimal stratification strategy for diabetes severity based on the homogeneity of the risk of hospitalization in response to variation of the DCSI. The optimal stratification of people with diabetes was specified by four sub-populations. The first sub-population was no complications with an inverse association with the risk of hospitalizations (coefficient-0.247, SE 0.03). Further three sub-populations with DCSI at one (coefficient 0.289, SE 0.01), two (coefficient 0.339, SE 0.01) and three or more (coefficient 0.381, SE 0.01) were used to accurately describe the impact of DCSI on the risk of hospitalization. A stratification into four subpopulations based on the homogeneous impact of diabetes DCSI on the risk of hospitalization may be more suitable for evaluating health care interventions and planning health care provision. Copyright © 2017 Elsevier Inc. All rights reserved.

New Methods for the Analysis of Heartbeat Behavior in Risk Stratification

PubMed Central

Glass, Leon; Lerma, Claudia; Shrier, Alvin

2011-01-01

Developing better methods for risk stratification for tachyarrhythmic sudden cardiac remains a major challenge for physicians and scientists. Since the transition from sinus rhythm to ventricular tachycardia/fibrillation happens by different mechanisms in different people, it is unrealistic to think that a single measure will be adequate to provide a good index for risk stratification. We analyze the dynamical properties of ventricular premature complexes over 24 h in an effort to understand the underlying mechanisms of ventricular arrhythmias and to better understand the arrhythmias that occur in individual patients. Two dimensional density plots, called heartprints, correlate characteristic features of the dynamics of premature ventricular complexes and the sinus rate. Heartprints show distinctive characteristics in individual patients. Based on a better understanding of the natures of transitions from sinus rhythm to sudden cardiac and the mechanisms of arrhythmia prior to cardiac arrest, it should be possible to develop better methods for risk stratification. PMID:22144963

Photo stratification improves northwest timber volume estimates.

Treesearch

Colin D. MacLean

1972-01-01

Data from extensive timber inventories of 12 counties in western and central Washington were analyzed to test the relative efficiency of double sampling for stratification as a means of estimating total volume. Photo and field plots, when combined in a stratified sampling design, proved about twice as efficient as simple field sampling. Although some gains were made by...

A risk tertiles model for predicting mortality in patients with acute respiratory distress syndrome: age, plateau pressure, and P(aO(2))/F(IO(2)) at ARDS onset can predict mortality.

PubMed

Villar, Jesús; Pérez-Méndez, Lina; Basaldúa, Santiago; Blanco, Jesús; Aguilar, Gerardo; Toral, Darío; Zavala, Elizabeth; Romera, Miguel A; González-Díaz, Gumersindo; Nogal, Frutos Del; Santos-Bouza, Antonio; Ramos, Luís; Macías, Santiago; Kacmarek, Robert M

2011-04-01

Predicting mortality has become a necessary step for selecting patients for clinical trials and defining outcomes. We examined whether stratification by tertiles of respiratory and ventilatory variables at the onset of acute respiratory distress syndrome (ARDS) identifies patients with different risks of death in the intensive care unit. We performed a secondary analysis of data from 220 patients included in 2 multicenter prospective independent trials of ARDS patients mechanically ventilated with a lung-protective strategy. Using demographic, pulmonary, and ventilation data collected at ARDS onset, we derived and validated a simple prediction model based on a population-based stratification of variable values into low, middle, and high tertiles. The derivation cohort included 170 patients (all from one trial) and the validation cohort included 50 patients (all from a second trial). Tertile distribution for age, plateau airway pressure (P(plat)), and P(aO(2))/F(IO(2)) at ARDS onset identified subgroups with different mortalities, particularly for the highest-risk tertiles: age (> 62 years), P(plat) (> 29 cm H(2)O), and P(aO(2))/F(IO(2)) (< 112 mm Hg). Risk was defined by the number of coexisting high-risk tertiles: patients with no high-risk tertiles had a mortality of 12%, whereas patients with 3 high-risk tertiles had 90% mortality (P < .001). A prediction model based on tertiles of patient age, P(plat), and P(aO(2))/F(IO(2)) at the time the patient meets ARDS criteria identifies patients with the lowest and highest risk of intensive care unit death.

Thermal Stratification Analysis for Sodium Fast Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, James; Anderson, Mark; Baglietto, Emilio

The sodium fast reactor (SFR) is the most mature reactor concept of all the generation-IV nuclear systems and is a promising reactor design that is currently under development by several organizations. The majority of sodium fast reactor designs utilize a pool type arrangement which incorporates the primary coolant pumps and intermediate heat exchangers within the sodium pool. These components typically protrude into the pool thus reducing the risk and severity of a loss of coolant accidents. To further ensure safe operation under even the most severe transients a more comprehensive understanding of key thermal hydraulic phenomena in this pool ismore » desired. One of the key technology gaps identified for SFR safety is determining the extent and the effects of thermal stratification developing in the pool during postulated accident scenarios such as a protected or unprotected loss of flow incident. In an effort to address these issues, detailed flow models of transient stratification in the pool during an accident can be developed. However, to develop the calculation models, and ensure they can reproduce the underlying physics, highly spatially resolved data is needed. This data can be used in conjunction with advanced computational fluid dynamic calculations to aid in the development of simple reduced dimensional models for systems codes such as SAM and SAS4A/SASSYS-1.« less

Predictors of Post-discharge Mortality Among Patients Hospitalized for Acute Heart Failure

PubMed Central

Collins, Sean P; Greene, Stephen J; Pang, Peter S; Ambrosy, Andrew P; Antohi, Elena-Laura; Vaduganathan, Muthiah; Butler, Javed; Gheorghiade, Mihai

2017-01-01

Acute Heart Failure (AHF) is a “ multi-event disease” and hospitalisation is a critical event in the clinical course of HF. Despite relatively rapid relief of symptoms, hospitalisation for AHF is followed by an increased risk of death and re-hospitalisation. In AHF, risk stratification from clinically available data is increasingly important in evaluating long-term prognosis. From the perspective of patients, information on the risk of mortality and re-hospitalisation would be helpful in providing patients with insight into their disease. From the perspective of care providers, it may facilitate management decisions, such as who needs to be admitted and to what level of care (i.e. floor, step-down, ICU). Furthermore, risk-stratification may help identify patients who need to be evaluated for advanced HF therapies (i.e. left-ventricle assistance device or transplant or palliative care), and patients who need early a post-discharge follow-up plan. Finally, risk stratification will allow for more robust efforts to identify among risk markers the true targets for therapies that may direct treatment strategies to selected high-risk patients. Further clinical research will be needed to evaluate if appropriate risk stratification of patients could improve clinical outcome and resources allocation. PMID:29387465

Risk Stratification and Shared Decision Making for Colorectal Cancer Screening: A Randomized Controlled Trial.

PubMed

Schroy, Paul C; Duhovic, Emir; Chen, Clara A; Heeren, Timothy C; Lopez, William; Apodaca, Danielle L; Wong, John B

2016-05-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer (CRC) screening, yet providers often fail to comply with patient preferences that differ from their own. To determine whether risk stratification for advanced colorectal neoplasia (ACN) influences provider willingness to comply with patient preferences when selecting a desired CRC screening option. Randomized controlled trial. Asymptomatic, average-risk patients due for CRC screening in an urban safety net health care setting. Patients were randomized 1:1 to a decision aid alone (n= 168) or decision aid plus risk assessment (n= 173) arm between September 2012 and September 2014. The primary outcome was concordance between patient preference and test ordered; secondary outcomes included patient satisfaction with the decision-making process, screening intentions, test completion rates, and provider satisfaction. Although providers perceived risk stratification to be useful in selecting an appropriate screening test for their average-risk patients, no significant differences in concordance were observed between the decision aid alone and decision aid plus risk assessment groups (88.1% v. 85.0%,P= 0.40) or high- and low-risk groups (84.5% v. 87.1%,P= 0.51). Concordance was highest for colonoscopy and relatively low for tests other than colonoscopy, regardless of study arm or risk group. Failure to comply with patient preferences was negatively associated with satisfaction with the decision-making process, screening intentions, and test completion rates. Single-institution setting; lack of provider education about the utility of risk stratification into their decision making. Providers perceived risk stratification to be useful in their decision making but often failed to comply with patient preferences for tests other than colonoscopy, even among those deemed to be at low risk of ACN. © The Author(s) 2016.

Segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

PubMed

Voss, A; Fischer, C; Schroeder, R; Figulla, H R; Goernig, M

2010-01-01

The prognostic value of heart rate variability in patients with dilated cardiomyopathy (DCM) is limited and does not contribute to risk stratification although the dynamics of ventricular repolarization differs considerably between DCM patients and healthy subjects. Neither linear nor nonlinear methods of heart rate variability analysis could discriminate between patients at high and low risk for sudden cardiac death. The aim of this study was to analyze the suitability of the new developed segmented Poincaré plot analysis (SPPA) to enhance risk stratification in DCM. In contrast to the usual applied Poincaré plot analysis the SPPA retains nonlinear features from investigated beat-to-beat interval time series. Main features of SPPA are the rotation of cloud of points and their succeeded variability depended segmentation. Significant row and column probabilities were calculated from the segments and led to discrimination (up to p<0.005) between low and high risk in DCM patients. For the first time an index from Poincaré plot analysis of heart rate variability was able to contribute to risk stratification in patients suffering from DCM.

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Evidence-based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons learned from the US Armed Forces: Consensus and Future Directions

PubMed Central

Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander

2013-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409

Neuroticism Combined With Slower and More Variable Reaction Time: Synergistic Risk Factors for 7-Year Cognitive Decline in Females

PubMed Central

Shickle, Darren A.; Roberts, Beverly A.; Deary, Ian J.

2012-01-01

Objective. Among adults, slower and more variable reaction times are associated with worse cognitive function and increased mortality risk. Therefore, it is important to elucidate risk factors for reaction time change over the life course. Method. Data from the Health and Lifestyle Survey (HALS) were used to examine predictors of 7-year decline in reaction time (N = 4,260). Regression-derived factor scores were used to summarize general change across 4 reaction time variables: simple mean, 4-choice mean, simple variability, and 4-choice variability (53.52% of variance). Results. Age (B = .02, p < .001) and HALS1 baseline reaction time (B = −.10, p = .001) were significant risk factors for males (N = 1,899). In addition to these variables, in females (N = 2,361), neuroticism was significant and interacted synergistically with baseline reaction time (B = .06, p = .04). Adjustment for physiological variables explained the interaction with neuroticism, suggesting that candidate mechanisms had been identified. Discussion. A priority for future research is to replicate interactions between personality and reaction time in other samples and find specific mechanisms. Stratification of population data on cognitive health by personality and reaction time could improve strategies for identifying those at greater risk of cognitive decline. PMID:22367712

Risk stratification using SpO2/FiO2 and PEEP at initial ARDS diagnosis and after 24 h in patients with moderate or severe ARDS.

PubMed

Pisani, Luigi; Roozeman, Jan-Paul; Simonis, Fabienne D; Giangregorio, Antonio; van der Hoeven, Sophia M; Schouten, Laura R; Horn, Janneke; Neto, Ary Serpa; Festic, Emir; Dondorp, Arjen M; Grasso, Salvatore; Bos, Lieuwe D; Schultz, Marcus J

2017-10-25

We assessed the potential of risk stratification of ARDS patients using SpO 2 /FiO 2 and positive end-expiratory pressure (PEEP) at ARDS onset and after 24 h. We used data from a prospective observational study in patients admitted to a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Risk stratification was by cutoffs for SpO 2 /FiO 2 and PEEP. The primary outcome was in-hospital mortality. Patients with moderate or severe ARDS with a length of stay of > 24 h were included in this study. Patients were assigned to four predefined risk groups: group I (SpO 2 /FiO 2  ≥ 190 and PEEP < 10 cm H 2 O), group II (SpO 2 /FiO 2  ≥ 190 and PEEP ≥ 10 cm), group III (SpO 2 /FiO 2  < 190 and PEEP < 10 cm H 2 O) and group IV (SpO 2 /FiO 2  < 190 and PEEP ≥ 10 cm H 2 O). The analysis included 456 patients. SpO 2 /FiO 2 and PaO 2 /FiO 2 had a strong relationship (P < 0.001, R 2  = 0.676) that could be described in a linear regression equation (SpO 2 /FiO 2  = 42.6 + 1.0 * PaO 2 /FiO 2 ). Risk stratification at initial ARDS diagnosis resulted in groups that had no differences in in-hospital mortality. Risk stratification at 24 h resulted in groups with increasing mortality rates. The association between group assignment at 24 h and outcome was confounded by several factors, including APACHE IV scores, arterial pH and plasma lactate levels, and vasopressor therapy. In this cohort of patients with moderate or severe ARDS, SpO 2 /FiO 2 and PaO 2 /FiO 2 have a strong linear relationship. In contrast to risk stratification at initial ARDS diagnosis, risk stratification using SpO 2 /FiO 2 and PEEP after 24 h resulted in groups with worsening outcomes. Risk stratification using SpO 2 /FiO 2 and PEEP could be practical, especially in resource-limited settings.

A clinical risk stratification tool for predicting treatment resistance in major depressive disorder.

PubMed

Perlis, Roy H

2013-07-01

Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches--a naïve Bayes classifier and a support vector machine, and a random forest model--was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions.

PubMed

Otani, Iris M; Lax, Timothy; Long, Aidan A; Slawski, Benjamin R; Camargo, Carlos A; Banerji, Aleena

2017-10-03

Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel-induced HSR are needed. The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel-induced HSRs. The study population (n = 35) had a mean age of 56.1 ± 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Brachial-Ankle PWV: Current Status and Future Directions as a Useful Marker in the Management of Cardiovascular Disease and/or Cardiovascular Risk Factors.

PubMed

Tomiyama, Hirofumi; Matsumoto, Chisa; Shiina, Kazuki; Yamashina, Akira

2016-01-01

Since 2001, brachial-ankle pulse wave velocity (brachial-ankle PWV) measurement has been applied for risk stratification of patients with atherosclerotic cardiovascular disease and/or its risk factors in Japan. Measurement of the brachial-ankle PWV is simple and well standardized, and its reproducibility and accuracy are acceptable. Several cross-sectional studies have demonstrated a significant correlation between the brachial-ankle PWV and known risk factors for cardiovascular disease; the correlation is stronger in subjects with cardiovascular disease than in those without cardiovascular disease. We conducted a meta-analysis, which demonstrated that the brachial-ankle PWV is an independent predictor of future cardiovascular events. Furthermore, the treatment of cardiovascular risk factors and lifestyle modifications have been shown to improve the brachial-ankle PWV. Thus, at present, brachial-ankle PWV is close to being considered as a useful marker in the management of atherosclerotic cardiovascular disease and/or its risk factors.

Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification.

PubMed

Voss, Andreas; Schroeder, Rico; Vallverdú, Montserrat; Schulz, Steffen; Cygankiewicz, Iwona; Vázquez, Rafael; Bayés de Luna, Antoni; Caminal, Pere

2013-01-01

In industrialized countries with aging populations, heart failure affects 0.3-2% of the general population. The investigation of 24 h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive, and delay the initial diagnosis. The objective of this study was to investigate whether 30 min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24 h-HRV analysis. From 256 IHF patients [221 at low risk (IHFLR) and 35 at high risk (IHFHR)] (a) 24 h beat-to-beat time series (b) the first 30 min segment (c) the 30 min most stationary day segment and (d) the 30 min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 h and for each 30 min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p < 0.01) discriminating between IHFLR and IHFHR. For multivariate risk stratification, optimal mixed parameter sets consisting of 5 indices (clinical and nonlinear) achieved 80.4% AUC (area under the curve of receiver operating characteristics) from 24 h HRV analysis, 84.3% AUC from first 30 min, 82.2 % AUC from daytime 30 min and 81.7% AUC from nighttime 30 min. The optimal parameter set obtained from the first 30 min showed nearly the same classification power when compared to the optimal 24 h-parameter set. As results from stationary daytime and nighttime, 30 min segments indicate that short-term analyses of 30 min may provide at least a comparable risk stratification power in IHF in comparison to a 24 h analysis period.

The introduction of an acute physiological support service for surgical patients is an effective error reduction strategy.

PubMed

Clarke, D L; Kong, V Y; Naidoo, L C; Furlong, H; Aldous, C

2013-01-01

Acute surgical patients are particularly vulnerable to human error. The Acute Physiological Support Team (APST) was created with the twin objectives of identifying high-risk acute surgical patients in the general wards and reducing both the incidence of error and impact of error on these patients. A number of error taxonomies were used to understand the causes of human error and a simple risk stratification system was adopted to identify patients who are particularly at risk of error. During the period November 2012-January 2013 a total of 101 surgical patients were cared for by the APST at Edendale Hospital. The average age was forty years. There were 36 females and 65 males. There were 66 general surgical patients and 35 trauma patients. Fifty-six patients were referred on the day of their admission. The average length of stay in the APST was four days. Eleven patients were haemo-dynamically unstable on presentation and twelve were clinically septic. The reasons for referral were sepsis,(4) respiratory distress,(3) acute kidney injury AKI (38), post-operative monitoring (39), pancreatitis,(3) ICU down-referral,(7) hypoxia,(5) low GCS,(1) coagulopathy.(1) The mortality rate was 13%. A total of thirty-six patients experienced 56 errors. A total of 143 interventions were initiated by the APST. These included institution or adjustment of intravenous fluids (101), blood transfusion,(12) antibiotics,(9) the management of neutropenic sepsis,(1) central line insertion,(3) optimization of oxygen therapy,(7) correction of electrolyte abnormality,(8) correction of coagulopathy.(2) CONCLUSION: Our intervention combined current taxonomies of error with a simple risk stratification system and is a variant of the defence in depth strategy of error reduction. We effectively identified and corrected a significant number of human errors in high-risk acute surgical patients. This audit has helped understand the common sources of error in the general surgical wards and will inform on-going error reduction initiatives. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Suboptimal identification of patient-specific risk factors for poor wound healing can be improved by simple interventions.

PubMed

Harris, Lauren S; Luck, Joshua E; Atherton, Rachel R

2017-02-01

Poor wound healing is an important surgical complication. At-risk wounds must be identified early and monitored appropriately. Wound surveillance is frequently inadequate, leading to increased rates of surgical site infections (SSIs). Although the literature demonstrates that risk factor identification reduces SSI rates, no studies have focused on wound management at a junior level. Our study assesses documentation rates of patient-specific risk factors for poor wound healing at a large district general hospital in the UK. It critically evaluates the efficacy of interventions designed to promote surveillance of high-risk wounds. We conducted a full-cycle clinical audit examining medical records of patients undergoing elective surgery over 5 days. Interventions included education of the multidisciplinary team and addition of a Wound Healing Risk Assessment (WHRA) checklist to surgical admissions booklets. This checklist provided a simple stratification tool for at-risk wounds and recommendations for escalation. Prior to interventions, the documentation of patient-specific risk factors ranged from 0·0% to 91·7% (mean 42·6%). Following interventions, this increased to 86·4-95·5% (mean 92·5%), a statistically significant increase of 117·1% (P < 0·01). This study demonstrates that documentation of patient-specific risk factors for poor wound healing is inadequate. We have shown the benefit of introducing interventions to increase risk factor awareness. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Prediction of Breast Cancer Risk by Aberrant Methylation in Mammary Duct Lavage

DTIC Science & Technology

2006-07-01

Assessment of breast epithelial cells obtained by nipple duct lavage (NDL) may have value for breast cancer risk stratification. NDL was performed in 150...contribute to risk stratification. 15. SUBJECT TERMS breast cancer, DNA methylation, Methylation Specific PCR, Nipple Duct Lavage, Risk assessment 16...carcinogenesis. Nipple duct lavage (NDL) is a minimally invasive approach for obtaining breast epithelial cells. Cytological atypia identified in nipple

Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

PubMed Central

Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

2015-01-01

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

The HARM score for gastrointestinal surgery: Application and validation of a novel, reliable and simple tool to measure surgical quality and outcomes.

PubMed

Crawshaw, Benjamin P; Keller, Deborah S; Brady, Justin T; Augestad, Knut M; Schiltz, Nicholas K; Koroukian, Siran M; Navale, Suparna M; Steele, Scott R; Delaney, Conor P

2017-03-01

The HospitAl length of stay, Readmissions and Mortality (HARM) score is a simple, inexpensive quality tool, linked directly to patient outcomes. We assess the HARM score for measuring surgical quality across multiple surgical populations. Upper gastrointestinal, hepatobiliary, and colorectal surgery cases between 2005 and 2009 were identified from the Healthcare Cost and Utilization Project California State Inpatient Database. Composite and individual HARM scores were calculated from length of stay, 30-day readmission and mortality, correlated to complication rates for each hospital and stratified by operative type. 71,419 admissions were analyzed. Higher HARM scores correlated with higher complication rates for all cases after risk adjustment and stratification by operation type, elective or emergent status. The HARM score is a simple and valid quality measurement for upper gastrointestinal, hepatobiliary and colorectal surgery. The HARM score could facilitate benchmarking to improve patient outcomes and resource utilization, and may facilitate outcome improvement. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk stratification and staging in prostate cancer with prostatic specific membrane antigen PET/CTObjective: A one-stop-shop.

PubMed

Gupta, Manoj; Choudhury, Partha Sarathi; Rawal, Sudhir; Goel, Harish Chandra; Singh, Amitabh; Talwar, Vineet; Sahoo, Saroj Kumar

2017-01-01

Current imaging modalities for prostate cancer (PC) had limitations for risk stratification and staging. Magnetic resonance imaging (MRI) frequently underestimated lymphatic metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and staging. We hypothesized it can become one-stop-shop for initial risk stratification and staging. Ninety seven PSMA PET-CT studies were re analysed for tumor node metastases (TNM) staging and risk stratification of lymphatic and distant metastases proportion. The histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), over-estimation, under-estimation and correct-estimation of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for inter-rater agreement. Lymphic or distant metastases detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE), seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%, 36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively. Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymphic metastases (κ 0.734) however, it was just in fair agreement (κ 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, 86.96% cases, respectively. We found that PSMA PET/CT has potential for initial risk stratifications with reasonable correct estimation for N stage. However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should be used for staging and initial risk stratification of PC as one-stop-shop with regional MRI in surgically resectable cases.

Deep simple epicotyl morphophysiological dormancy in seeds of two Viburnum species, with special reference to shoot growth and development inside the seed.

PubMed

Chien, Ching-Te; Chen, Shun-Ying; Tsai, Ching-Chu; Baskin, Jerry M; Baskin, Carol C; Kuo-Huang, Ling-Long

2011-07-01

In seeds with deep simple epicotyl morphophysiological dormancy, warm and cold stratification are required to break dormancy of the radicle and shoot, respectively. Although the shoot remains inside the seed all winter, little is known about its growth and morphological development prior to emergence in spring. The aims of the present study were to determine the temperature requirements for radicle and shoot emergence in seeds of Viburnum betulifolium and V. parvifolium and to monitor growth of the epicotyl, plumule and cotyledons in root-emerged seeds. Fresh and pre-treated seeds of V. betulifolium and V. parvifolium were incubated under various temperature regimes and monitored for radicle and shoot emergence. Growth of the epicotyl and cotyledons at different stages was observed with dissecting and scanning electron microscopes. The optimum temperature for radicle emergence of seeds of both species, either kept continuously at a single regime or exposed to a sequence of regimes, was 20/10 °C. GA(3) had no effect on radicle emergence. Cold stratification (5 °C) was required for shoot emergence. The shoot apical meristem in fresh seeds did not form a bulge until the embryo had grown to the critical length for radicle emergence. After radicle emergence, the epicotyl--plumule and cotyledons grew slowly at 5 and 20/10 °C, and the first pair of true leaves was initiated. However, the shoot emerged only from seeds that received cold stratification. Seeds of V. betulifolium and V. parvifolium have deep simple epicotyl morphophysiological dormancy, C(1b)B (root)-C(3) (epicotyl). Warm stratification was required to break the first part of physiological dormancy (PD), thereby allowing embryo growth and subsequently radicle emergence. Although cold stratification was not required for differentiation of the epicotyl--plumule, it was required to break the second part of PD, thereby allowing the shoot to emerge in spring.

Deep simple epicotyl morphophysiological dormancy in seeds of two Viburnum species, with special reference to shoot growth and development inside the seed

PubMed Central

Chien, Ching-Te; Chen, Shun-Ying; Tsai, Ching-Chu; Baskin, Jerry M.; Baskin, Carol C.; Kuo-Huang, Ling-Long

2011-01-01

Background and Aims In seeds with deep simple epicotyl morphophysiological dormancy, warm and cold stratification are required to break dormancy of the radicle and shoot, respectively. Although the shoot remains inside the seed all winter, little is known about its growth and morphological development prior to emergence in spring. The aims of the present study were to determine the temperature requirements for radicle and shoot emergence in seeds of Viburnum betulifolium and V. parvifolium and to monitor growth of the epicotyl, plumule and cotyledons in root-emerged seeds. Methods Fresh and pre-treated seeds of V. betulifolium and V. parvifolium were incubated under various temperature regimes and monitored for radicle and shoot emergence. Growth of the epicotyl and cotyledons at different stages was observed with dissecting and scanning electron microscopes. Key Results The optimum temperature for radicle emergence of seeds of both species, either kept continuously at a single regime or exposed to a sequence of regimes, was 20/10 °C. GA3 had no effect on radicle emergence. Cold stratification (5 °C) was required for shoot emergence. The shoot apical meristem in fresh seeds did not form a bulge until the embryo had grown to the critical length for radicle emergence. After radicle emergence, the epicotyl–plumule and cotyledons grew slowly at 5 and 20/10 °C, and the first pair of true leaves was initiated. However, the shoot emerged only from seeds that received cold stratification. Conclusions Seeds of V. betulifolium and V. parvifolium have deep simple epicotyl morphophysiological dormancy, C1bB (root)–C3 (epicotyl). Warm stratification was required to break the first part of physiological dormancy (PD), thereby allowing embryo growth and subsequently radicle emergence. Although cold stratification was not required for differentiation of the epicotyl–plumule, it was required to break the second part of PD, thereby allowing the shoot to emerge in spring. PMID:21562028

[Comparison of the present and previously used protocol of risk stratification in children with acute lymphoblastic leukemia].

PubMed

Glodkowska, Eliza; Bialas, Agnieszka; Jackowska, Teresa

2007-01-01

Acute lymphoblastic leukaemia (ALL) is one of the most common cancers in children. In Poland, since November 2002 a new protocol of risk stratification has been recommended for assessment of risk factors and for choosing therapy regimens. assessment of accuracy of protocol ALL-IC 2002 in comparison to previously used risk stratification protocols. ALL was diagnosed in 100 children (44 girls, 56 boys; 1-18 years of age) in the Department of Pediatric Hematology and Oncology, Warsaw Medical University, over the period from November 2002 to November 2006. According to the ALL-IC 2002 protocol the patients were divided into three risk groups: SR-standard, IR-intermediate and HR-high. The stratification was by age, leukocyte count, cytogenetic changes, early response to prednisone therapy and bone marrow remission. In the previously used risk stratification protocols-BFM-90, only hepatosplenomegaly and the number of blasts in peripheral blood (PB) were considered, and the patients were divided into three risk groups: low (LRG<0.8), medium (MRG) and high (HRG>1.2). out of the 100 patients qualified for treatment regimens according to the ALL-IC 2002 protocol, 97 entered remission, 11 died and 3 had a relapse. Under the ALL-IC 2002 protocol these children were stratified into the following groups: SR-31%, IR-44% and HR-25%. In the previously used stratification, there would be 26% children in low, 46% in the medium and 28% in the high risk group. According to the BFM-90 protocol 18/31 (58%) and 16/44 (36%) patients from the SR and IR groups respectively would be given more intensive treatment. On the other hand 11/44 (25%) and 14/25 (56%) patients from the IR and HR groups respectively would be given less intensive treatment. 1. ALL-IC 2002 protocol in comparison with the previously used protocol BFM-90, changes the qualification of children with ALL for the SR, IR and HR risk groups. This is linked to basic change of treatment protocol, adequate to severity of disease. 2. Children with ALL qualified according to protocol BFM-90 for moderate risk group (IR) constitute a mixed group in the ALL-IC 2002 classification. Part of the children was moved to the standard risk group (SR), part to high risk group (HR), and the rest remains in the intermediate risk category (IR). 3. Further studies are needed on stratification validity according to ALL-IL 2002 and on the need of further modification (eg assessment of additional factors) in order to decide on the best treatment, adequate to severity of disease.

Deep circulations under simple classes of stratification

NASA Technical Reports Server (NTRS)

Salby, Murry L.

1989-01-01

Deep circulations where the motion field is vertically aligned over one or more scale heights are studied under barotropic and equivalent barotropic stratifications. The study uses two-dimensional equations reduced from the three-dimensional primitive equations in spherical geometry. A mapping is established between the full primitive equations and general shallow water behavior and the correspondence between variables describing deep atmospheric motion and those of shallow water behavior is established.

Prostate cancer: predicting high-risk prostate cancer-a novel stratification tool.

PubMed

Buck, Jessica; Chughtai, Bilal

2014-05-01

Currently, numerous systems exist for the identification of high-risk prostate cancer, but few of these systems can guide treatment strategies. A new stratification tool that uses common diagnostic factors can help to predict outcomes after radical prostatectomy. The tool aids physicians in the identification of appropriate candidates for aggressive, local treatment.

Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

PubMed

Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

2017-11-01

To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Urothelial cancer of the upper urinary tract: emerging biomarkers and integrative models for risk stratification.

PubMed

Mathieu, Romain; Vartolomei, Mihai D; Mbeutcha, Aurélie; Karakiewicz, Pierre I; Briganti, Alberto; Roupret, Morgan; Shariat, Shahrokh F

2016-08-01

The aim of this review was to provide an overview of current biomarkers and risk stratification models in urothelial cancer of the upper urinary tract (UTUC). A non-systematic Medline/PubMed literature search was performed using the terms "biomarkers", "preoperative models", "postoperative models", "risk stratification", together with "upper tract urothelial carcinoma". Original articles published between January 2003 and August 2015 were included based on their clinical relevance. Additional references were collected by cross referencing the bibliography of the selected articles. Various promising predictive and prognostic biomarkers have been identified in UTUC thanks to the increasing knowledge of the different biological pathways involved in UTUC tumorigenesis. These biomarkers may help identify tumors with aggressive biology and worse outcomes. Current tools aim at predicting muscle invasive or non-organ confined disease, renal failure after radical nephroureterectomy and survival outcomes. These models are still mainly based on imaging and clinicopathological feature and none has integrated biomarkers. Risk stratification in UTUC is still suboptimal, especially in the preoperative setting due to current limitations in staging and grading. Identification of novel biomarkers and external validation of current prognostic models may help improve risk stratification to allow evidence-based counselling for kidney-sparing approaches, perioperative chemotherapy and/or risk-based surveillance. Despite growing understanding of the biology underlying UTUC, management of this disease remains difficult due to the lack of validated biomarkers and the limitations of current predictive and prognostic tools. Further efforts and collaborations are necessaryry to allow their integration in daily practice.

Predicting the risk of sudden cardiac death.

PubMed

Lerma, Claudia; Glass, Leon

2016-05-01

Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this article we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT or VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modelling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy.

PubMed

Cadrin-Tourigny, Julia; Tadros, Rafik; Talajic, Mario; Rivard, Lena; Abadir, Sylvia; Khairy, Paul

2015-06-01

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) is an uncommon but increasingly recognized inherited cardiomyopathy that is associated with malignant ventricular arrhythmias and sudden cardiac death, particularly in young individuals. The implantable cardioverter-defibrillator (ICD) is widely regarded as the only treatment modality with evidence to support improved survival in patients with ARVC and secondary prevention indications. In contrast, there is no universally accepted risk stratification scheme to guide ICD therapy for primary prevention against sudden cardiac death. Potential benefits must be weighed against the considerable risks of complications and inappropriate shocks in this young patient population. This article tackles the challenges of risk stratification for sudden cardiac death in ARVC and critically appraises available evidence for various proposed risk factors. The authors' over-arching objective is to provide the clinician with evidence-based guidance to inform decisions regarding the selection of appropriate candidates with ARVC for ICD therapy.

Direct thrombin and factor Xa inhibition for stroke prevention in patients with atrial fibrillation.

PubMed

Galanis, Taki; Merli, Geno J

2013-02-01

Nonvalvular atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia occurring in patients in the United States. The primary clinical consequence of AF is an increase in the risk and severity of strokes. Treatment guidelines recommend anticoagulation therapy for most patients with AF. One risk-stratification scheme, the CHADS2 index, is simple and widely used to determine the management of patients with AF in regard to stroke prevention. However, new schemes, such as CHA2DS2-VASc, further refine risk stratification to identify patients who would obtain a net clinical benefit from a particular management strategy, thus improving the quality of management. For patients with AF for whom oral anticoagulation (OAC) is advisable, vitamin K antagonist (VKA) therapy is well established and effective. However, OAC with VKAs presents challenges to prescribers and patients in maintaining therapeutic efficacy. Novel OACs may offer alternatives to VKAs. Dabigatran etexilate, a direct thrombin inhibitor, was approved by the US Food and Drug Administration (FDA) in 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. The activated factor X (factor Xa) inhibitor rivaroxaban was recently approved by the FDA both for prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip arthroplasty, and for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. Apixaban, another factor Xa inhibitor, was recently shown to be effective for stroke prevention in patients with nonvalvular AF. This article reviews clinical considerations regarding new agents that may offer alternatives to VKA therapy for the prevention of stroke in patients with AF.

Role of imaging in evaluation of sudden cardiac death risk in hypertrophic cardiomyopathy.

PubMed

Geske, Jeffrey B; Ommen, Steve R

2015-09-01

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is associated with sudden cardiac death (SCD) - an uncommon but devastating clinical outcome. This review is designed to assess the role of imaging in established risk factor assessment and its role in emerging SCD risk stratification. Recent publications have highlighted the crucial role of imaging in HCM SCD risk stratification. Left ventricular hypertrophy assessment remains the key imaging determinant of risk. Data continue to emerge on the role of systolic dysfunction, apical aneurysms, left atrial enlargement and left ventricular outflow tract obstruction as markers of risk. Quantitative assessment of delayed myocardial enhancement and T1 mapping on cardiac MRI continue to evolve. Recent multicenter trials have allowed multivariate SCD risk assessment in large HCM cohorts. Given aggregate risk with presence of multiple risk factors, a single parameter should not be used in isolation to determine implantable cardiac defibrillator candidacy. Use of all available imaging data, including cardiac magnetic resonance tissue characterization, allows a comprehensive approach to SCD stratification and implantable cardiac defibrillator decision-making.

The role of non-invasive cardiovascular imaging in the assessment of cardiovascular risk in rheumatoid arthritis: where we are and where we need to be.

PubMed

Fent, Graham J; Greenwood, John P; Plein, Sven; Buch, Maya H

2017-07-01

This review assesses the risk assessment of cardiovascular disease (CVD) in rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve risk stratification in future. RA is common and patients are at greater risk of CVD than the general population. Cardiovascular (CV) risk stratification is recommended in European guidelines for patients at high and very high CV risk in order to commence preventative therapy. Ideally, such an assessment should be carried out immediately after diagnosis and as part of ongoing long-term patient care in order to improve patient outcomes. The risk profile in RA is different from the general population and is not well estimated using conventional clinical CVD risk algorithms, particularly in patients estimated as intermediate CVD risk. Non-invasive imaging techniques may therefore play an important role in improving risk assessment. However, there are currently very limited prognostic data specific to patients with RA to guide clinicians in risk stratification using these imaging techniques. RA is associated with increased risk of CV mortality, mainly attributable to atherosclerotic disease, though in addition, RA is associated with many other disease processes which further contribute to increased CV mortality. There is reasonable evidence for using carotid ultrasound in patients estimated to be at intermediate risk of CV mortality using clinical CVD risk algorithms. Newer imaging techniques such as cardiovascular magnetic resonance and CT offer the potential to improve risk stratification further; however, longitudinal data with hard CVD outcomes are currently lacking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Perioperative Management of Patients with Inflammatory Rheumatic Diseases Undergoing Major Orthopaedic Surgery: A Practical Overview.

PubMed

Gualtierotti, Roberta; Parisi, Marco; Ingegnoli, Francesca

2018-04-01

Patients with inflammatory rheumatic diseases often need orthopaedic surgery due to joint involvement. Total hip replacement and total knee replacement are frequent surgical procedures in these patients. Due to the complexity of the inflammatory rheumatic diseases, the perioperative management of these patients must envisage a multidisciplinary approach. The frequent association with extraarticular comorbidities must be considered when evaluating perioperative risk of the patient and should guide the clinician in the decision-making process. However, guidelines of different medical societies may vary and are sometimes contradictory. Orthopaedics should collaborate with rheumatologists, anaesthesiologists and, when needed, cardiologists and haematologists with the common aim of minimising perioperative risk in patients with inflammatory rheumatic diseases. The aim of this review is to provide the reader with simple practical recommendations regarding perioperative management of drugs such as disease-modifying anti-rheumatic drugs, corticosteroids, non-steroidal anti-inflammatory drugs and tools for a risk stratification for cardiovascular and thromboembolic risk based on current evidence for patients with inflammatory rheumatic diseases.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

PubMed

Castagna, Maria Grazia; Maino, Fabio; Cipri, Claudia; Belardini, Valentina; Theodoropoulou, Alexandra; Cevenini, Gabriele; Pacini, Furio

2011-09-01

After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging.

PubMed

Pu, Yonglin; Zhang, James X; Liu, Haiyan; Appelbaum, Daniel; Meng, Jianfeng; Penney, Bill C

2018-06-07

We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient's MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller's concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort. This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.

Utility of the exercise electrocardiogram testing in sudden cardiac death risk stratification.

PubMed

Refaat, Marwan M; Hotait, Mostafa; Tseng, Zian H

2014-07-01

Sudden cardiac death (SCD) remains a major public health problem. Current established criteria identifying those at risk of sudden arrhythmic death, and likely to benefit from implantable cardioverter defibrillators (ICDs), are neither sensitive nor specific. Exercise electrocardiogram (ECG) testing was traditionally used for information concerning patients' symptoms, exercise capacity, cardiovascular function, myocardial ischemia detection, and hemodynamic responses during activity in patients with hypertrophic cardiomyopathy. We conducted a systematic review of MEDLINE on the utility of exercise ECG testing in SCD risk stratification. Exercise testing can unmask suspected primary electrical diseases in certain patients (catecholaminergic polymorphic ventricular tachycardia or concealed long QT syndrome) and can be effectively utilized to risk stratify patients at an increased (such as early repolarization syndrome and Brugada syndrome) or decreased risk of SCD, such as the loss of preexcitation on exercise testing in asymptomatic Wolff-Parkinson-White syndrome. Exercise ECG testing helps in SCD risk stratification in patients with and without arrhythmogenic hereditary syndromes. © 2014 Wiley Periodicals, Inc.

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

Wall-based measurement features provides an improved IVUS coronary artery risk assessment when fused with plaque texture-based features during machine learning paradigm.

PubMed

Banchhor, Sumit K; Londhe, Narendra D; Araki, Tadashi; Saba, Luca; Radeva, Petia; Laird, John R; Suri, Jasjit S

2017-12-01

Planning of percutaneous interventional procedures involves a pre-screening and risk stratification of the coronary artery disease. Current screening tools use stand-alone plaque texture-based features and therefore lack the ability to stratify the risk. This IRB approved study presents a novel strategy for coronary artery disease risk stratification using an amalgamation of IVUS plaque texture-based and wall-based measurement features. Due to common genetic plaque makeup, carotid plaque burden was chosen as a gold standard for risk labels during training-phase of machine learning (ML) paradigm. Cross-validation protocol was adopted to compute the accuracy of the ML framework. A set of 59 plaque texture-based features was padded with six wall-based measurement features to show the improvement in stratification accuracy. The ML system was executed using principle component analysis-based framework for dimensionality reduction and uses support vector machine classifier for training and testing-phases. The ML system produced a stratification accuracy of 91.28%, demonstrating an improvement of 5.69% when wall-based measurement features were combined with plaque texture-based features. The fused system showed an improvement in mean sensitivity, specificity, positive predictive value, and area under the curve by: 6.39%, 4.59%, 3.31% and 5.48%, respectively when compared to the stand-alone system. While meeting the stability criteria of 5%, the ML system also showed a high average feature retaining power and mean reliability of 89.32% and 98.24%, respectively. The ML system showed an improvement in risk stratification accuracy when the wall-based measurement features were fused with the plaque texture-based features. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computational cardiology and risk stratification for sudden cardiac death: one of the grand challenges for cardiology in the 21st century

PubMed Central

Perry, Matthew D.; Abi‐Gerges, Najah; Couderc, Jean‐Philippe; Fermini, Bernard; Hancox, Jules C.; Knollmann, Bjorn C.; Mirams, Gary R.; Skinner, Jon; Zareba, Wojciech; Vandenberg, Jamie I.

2016-01-01

Abstract Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ‐level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well‐developed case of acquired or drug‐induced long QT syndrome as an exemplar case. PMID:27060987

Analysis of agreement between cardiac risk stratification protocols applied to participants of a center for cardiac rehabilitation

PubMed Central

Santos, Ana A. S.; Silva, Anne K. F.; Vanderlei, Franciele M.; Christofaro, Diego G. D.; Gonçalves, Aline F. L.; Vanderlei, Luiz C. M.

2016-01-01

ABSTRACT Background Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. Objective To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. Method The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Société Française de Cardiologie, and the Sociedad Española de Cardiología. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. Results Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. Conclusion The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID:27556385

The first Latin-American risk stratification system for cardiac surgery: can be used as a graphic pocket-card score.

PubMed

Carosella, Victorio C; Navia, Jose L; Al-Ruzzeh, Sharif; Grancelli, Hugo; Rodriguez, Walter; Cardenas, Cesar; Bilbao, Jorge; Nojek, Carlos

2009-08-01

This study aims to develop the first Latin-American risk model that can be used as a simple, pocket-card graphic score at bedside. The risk model was developed on 2903 patients who underwent cardiac surgery at the Spanish Hospital of Buenos Aires, Argentina, between June 1994 and December 1999. Internal validation was performed on 708 patients between January 2000 and June 2001 at the same center. External validation was performed on 1087 patients between February 2000 and January 2007 at three other centers in Argentina. In the development dataset the area under receiver operating characteristics (ROC) curve was 0.73 and the Hosmer-Lemeshow (HL) test was P=0.88. In the internal validation ROC curve was 0.77. In the external validation ROC curve was 0.81, but imperfect calibration was detected because the observed in-hospital mortality (3.96%) was significantly lower than the development dataset (8.20%) (P<0.0001). Recalibration was done in 2007, showing excellent level of agreement between the observed and predicted mortality rates on all patients (P=0.92). This is the first risk model for cardiac surgery developed in a population of Latin-America with both internal and external validation. A simple graphic pocket-card score allows an easy bedside application with acceptable statistic precision.

A Practical Risk Stratification Approach for Implementing a Primary Care Chronic Disease Management Program in an Underserved Community.

PubMed

Xu, Junjun; Williams-Livingston, Arletha; Gaglioti, Anne; McAllister, Calvin; Rust, George

2018-01-01

The use of value metrics is often dependent on payer-initiated health care management incentives. There is a need for practices to define and manage their own patient panels regardless of payer to participate effectively in population health management. A key step is to define a panel of primary care patients with high comorbidity profiles. Our sample included all patients seen in an urban academic family medicine clinic over a two-year period. The simplified risk stratification was built using internal electronic health record and billing system data based on ICD-9 codes. There were 347 patients classified as high-risk out of the 5,364 patient panel. Average age was 59 years (SD 15). Hypertension (90%), hyperlipidemia (62%), and depression (55%) were the most common conditions among high-risk patients. Simplified risk stratification provides a feasible option for our team to understand and respond to the nuances of population health in our underserved community.

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

PubMed

Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

2016-03-01

Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A clinical study of ischaemic strokes with micro-albuminuria for risk stratification, short-term predictive value and outcome.

PubMed

Das, Sukdeb; Yadav, Ujjal; Ghosh, Kartik Chandra; Panchadhyayee, Sujoy; Kundu, Shib Shankar; Ganguly, Prasanta Kumar

2012-12-01

Stroke results more than 4.3 million deaths worldwide per annum and 85% of all strokes are ischaemic in nature. Besides numerous modifiable and non-modifiable known risk factors, microalbuminuria is thought to be an important marker of global endothelial dysfunction and associated with cardiovascular disease including stroke. Fifty ischaemic stroke cases and 50 (age, sex matched) control subjects were subjected to study to compare and evaluate risk stratification of micro-albuminuria, its predictive value and outcome on day 1 and day 7 among admitted ischaemic stroke cases.The result was found that micro-albuminuria was present in 66% of ischaemic stroke cases compared to only 8% of control group (p < 0.001). Most validated National Institute of Health Stroke Scale (NIHSS) score was used for evaluation and calculation of predictive value and outcome of micro-albuminuria positive patient where higher value indicates poor prognosis, and the result was mean NIHSS score 29.12 versus 18.88 between two groups of strokes ie, with and without micro-albuminuria. Out of 50 ischaemic stroke patients 33 (66%) had micro-albuminuria. Among 11 patients who died, 10 (90.9%) had micro-albuminuria and NIHSS score was 33.64 and 25.0 on day 1 and day 7. Among 39 patients who were discharged, 23 patients (58.97%) were MA positive and NIHSS score was much less than death group ie, 23.38 and 16.38 on day 1 and day 7 respectively. So this study reveals micro-albuminuria itself results higher risk for ischaemic stroke compared to control group and it shows good predictive value for early assessment of clinical severity and subsequent fatal outcome. This is also simple, cost effective and affordable.

Surgery for left ventricular aneurysm: early and late survival after simple linear repair and endoventricular patch plasty.

PubMed

Lundblad, Runar; Abdelnoor, Michel; Svennevig, Jan Ludvig

2004-09-01

Simple linear resection and endoventricular patch plasty are alternative techniques to repair postinfarction left ventricular aneurysm. The aim of the study was to compare these 2 methods with regard to early mortality and long-term survival. We retrospectively reviewed 159 patients undergoing operations between 1989 and 2003. The epidemiologic design was of an exposed (simple linear repair, n = 74) versus nonexposed (endoventricular patch plasty, n = 85) cohort with 2 endpoints: early mortality and long-term survival. The crude effect of aneurysm repair technique versus endpoint was estimated by odds ratio, rate ratio, or relative risk and their 95% confidence intervals. Stratification analysis by using the Mantel-Haenszel method was done to quantify confounders and pinpoint effect modifiers. Adjustment for multiconfounders was performed by using logistic regression and Cox regression analysis. Survival curves were analyzed with the Breslow test and the log-rank test. Early mortality was 8.2% for all patients, 13.5% after linear repair and 3.5% after endoventricular patch plasty. When adjusted for multiconfounders, the risk of early mortality was significantly higher after simple linear repair than after endoventricular patch plasty (odds ratio, 4.4; 95% confidence interval, 1.1-17.8). Mean follow-up was 5.8 +/- 3.8 years (range, 0-14.0 years). Overall 5-year cumulative survival was 78%, 70.1% after linear repair and 91.4% after endoventricular patch plasty. The risk of total mortality was significantly higher after linear repair than after endoventricular patch plasty when controlled for multiconfounders (relative risk, 4.5; 95% confidence interval, 2.0-9.7). Linear repair dominated early in the series and patch plasty dominated later, giving a possible learning-curve bias in favor of patch plasty that could not be adjusted for in the regression analysis. Postinfarction left ventricular aneurysm can be repaired with satisfactory early and late results. Surgical risk was lower and long-term survival was higher after endoventricular patch plasty than simple linear repair. Differences in outcome should be interpreted with care because of the retrospective study design and the chronology of the 2 repair methods.

Mortality risk stratification in severely anaemic Jehovah's Witness patients.

PubMed

Beliaev, A M; Marshall, R J; Smith, W; Windsor, J A

2012-03-01

The aim of this retrospective cohort study was to identify early risk factors of mortality and develop a mortality risk stratification instrument for severely anaemic Jehovah's Witness patients. It has been shown that Jehovah's Witness patients with the Auckland Anaemia Mortality Risk Score (Auckland AMRS) of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5 32%, Auckland AMRS 6 to 7 50% and Auckland AMRS 8 and above 83%. It is concluded that the Auckland AMRS predicts mortality of severely anaemic Jehovah's Witness patients. © 2012 The Authors. Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

PubMed Central

2018-01-01

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction. PMID:29581968

The Heinz Nixdorf Recall study and its potential impact on the adoption of atherosclerosis imaging in European primary prevention guidelines.

PubMed

Mahabadi, Amir A; Möhlenkamp, Stefan; Moebus, Susanne; Dragano, Nico; Kälsch, Hagen; Bauer, Marcus; Jöckel, Karl-Heinz; Erbel, Raimund

2011-10-01

Non-contrast-enhanced computed tomography (CT) imaging of the heart enables noninvasive quantification of coronary artery calcification (CAC), a surrogate marker of the atherosclerotic burden in the coronary artery tree. Multiple studies have underlined the ability of CAC score for individual risk stratification and, accordingly, the American Heart Association recommended cardiac CT for risk assessment in individuals with an intermediate risk of cardiovascular events as measured by Framingham Risk Score. However, limitations in transcribing risk stratification algorithms based on American cohort studies into European populations have been acknowledged in the past. Moreover, data on implications for reclassification into higher- or lower-risk groups based on CAC scores were lacking. The Heinz Nixdorf Recall (HNR) study is a population-based cohort study that investigated the ability of CAC scoring in risk prediction for major cardiovascular events above and beyond traditional cardiovascular risk factors. According to Heinz Nixdorf Recall findings, CAC can be used for reclassification, especially in those in the intermediate-risk group, to advise on lifestyle changes for the reclassified low-risk category, or to implement intensive treatments for the reclassified high-risk individuals. This article discusses the present findings of the Heinz Nixdorf Recall Study with respect to the current literature, risk stratification algorithms, and current European guidelines for risk prediction.

Raynaud’s phenomenon and digital ischemia: a practical approach to risk stratification, diagnosis and management

PubMed Central

McMahan, Zsuzsanna H.; Wigley, Fredrick M.

2015-01-01

Digital ischemia is a painful and often disfiguring event. Such an ischemic event often leads to tissue loss and can significantly affect the patient’s quality of life. Digital ischemia can be secondary to a vasculopathy, vasculitis, embolic disease, trauma, or extrinsic vascular compression. It is an especially serious complication in patients with scleroderma. Risk stratification of patients with scleroderma at risk for digital ischemia is now possible with clinical assessment and autoantibody profiles. Because there are a variety of conditions that lead to digital ischemia, it is important to understand the pathophysiology underlying each ischemic presentation in order to target therapy appropriately. Significant progress has been made in the last two decades in defining the pathophysiological processes leading to digital ischemia in rheumatic diseases. In this article we review the risk stratification, diagnosis, and management of patients with digital ischemia and provide a practical approach to therapy, particularly in scleroderma. PMID:26523153

Computational cardiology and risk stratification for sudden cardiac death: one of the grand challenges for cardiology in the 21st century.

PubMed

Hill, Adam P; Perry, Matthew D; Abi-Gerges, Najah; Couderc, Jean-Philippe; Fermini, Bernard; Hancox, Jules C; Knollmann, Bjorn C; Mirams, Gary R; Skinner, Jon; Zareba, Wojciech; Vandenberg, Jamie I

2016-12-01

Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ-level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well-developed case of acquired or drug-induced long QT syndrome as an exemplar case. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Predicting the need for muscle flap salvage after open groin vascular procedures: a clinical assessment tool.

PubMed

Fischer, John P; Nelson, Jonas A; Shang, Eric K; Wink, Jason D; Wingate, Nicholas A; Woo, Edward Y; Jackson, Benjamin M; Kovach, Stephen J; Kanchwala, Suhail

2014-12-01

Groin wound complications after open vascular surgery procedures are common, morbid, and costly. The purpose of this study was to generate a simple, validated, clinically usable risk assessment tool for predicting groin wound morbidity after infra-inguinal vascular surgery. A retrospective review of consecutive patients undergoing groin cutdowns for femoral access between 2005-2011 was performed. Patients necessitating salvage flaps were compared to those who did not, and a stepwise logistic regression was performed and validated using a bootstrap technique. Utilising this analysis, a simplified risk score was developed to predict the risk of developing a wound which would necessitate salvage. A total of 925 patients were included in the study. The salvage flap rate was 11.2% (n = 104). Predictors determined by logistic regression included prior groin surgery (OR = 4.0, p < 0.001), prosthetic graft (OR = 2.7, p < 0.001), coronary artery disease (OR = 1.8, p = 0.019), peripheral arterial disease (OR = 5.0, p < 0.001), and obesity (OR = 1.7, p = 0.039). Based upon the respective logistic coefficients, a simplified scoring system was developed to enable the preoperative risk stratification regarding the likelihood of a significant complication which would require a salvage muscle flap. The c-statistic for the regression demonstrated excellent discrimination at 0.89. This study presents a simple, internally validated risk assessment tool that accurately predicts wound morbidity requiring flap salvage in open groin vascular surgery patients. The preoperatively high-risk patient can be identified and selectively targeted as a candidate for a prophylactic muscle flap.

Domain and nanoridge growth kinetics in stratifying foam films

NASA Astrophysics Data System (ADS)

Zhang, Yiran; Sharma, Vivek

Ultrathin films exhibit stratification due to confinement-induced structuring and layering of small molecules in simple fluids, and of supramolecular structures like micelles, lipid layers and nanoparticles in complex fluids. Stratification proceeds by the formation and growth of thinner domains at the expense of surrounding thicker film, and results in formation of nanoscopic terraces and mesas within a film. The detailed mechanisms underlying stratification are still under debate, and are resolved in this contribution by addressing long-standing experimental and theoretical challenges. Thickness variations in stratifying films are visualized and analyzed using interferometry, digital imaging and optical microscopy (IDIOM) protocols, with unprecedented high spatial (thickness <100 nm, lateral 500 nm) and temporal resolution (<1 ms). Using IDIOM protocols we developed recently, we characterize the shape and the growth dynamics of nanoridges that flank the expanding domains in micellar thin films. We show that topographical changes including nanoridge growth, and the overall stratification dynamics, can be described quantitatively by nonlinear thin film equation, amended with supramolecular oscillatory surface forces.

Cardiovascular risk assessment: addition of CKD and race to the Framingham equation

PubMed Central

Drawz, Paul E.; Baraniuk, Sarah; Davis, Barry R.; Brown, Clinton D.; Colon, Pedro J.; Cujyet, Aloysius B.; Dart, Richard A.; Graumlich, James F.; Henriquez, Mario A.; Moloo, Jamaluddin; Sakalayen, Mohammed G.; Simmons, Debra L.; Stanford, Carol; Sweeney, Mary Ellen; Wong, Nathan D.; Rahman, Mahboob

2012-01-01

Background/Aims The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. Methods Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were studied. Those randomized to doxazosin, age greater than 74 years, and those with a history of coronary heart disease (CHD) were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by eGFR categories, and stratification by race (Black vs. Non-Black). The primary outcome was a composite of fatal CHD, nonfatal MI, coronary revascularization, and hospitalized angina. Results There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and gender and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P=0.02). Additionally, net reclassification improvement was not significant for any subgroup based on race and gender, ranging from −5.5% to 4.4%. Conclusion The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients. PMID:23194494

Value of Exercise Stress Electrocardiography for Risk Stratification in Patients With Suspected or Known Coronary Artery Disease in the Era of Advanced Imaging Technologies

PubMed Central

Bourque, Jamieson M.; Beller, George A.

2015-01-01

Exercise stress electrocardiography (ExECG) is underutilized as the initial test modality in patients with interpretable electrocardiograms able to exercise. Although, stress myocardial imaging techniques provide valuable diagnostic and prognostic information, variables derived from ExECG can yield substantial data for risk stratification, either supplementary to imaging variables, or without concurrent imaging. In addition to exercise-induced ischemic ST depression, such markers as ST segment elevation in lead AVR, abnormal heart rate recovery post-exercise, failure to achieve target heart rate, and poor exercise capacity improve risk stratification of ExECG. For example, patients achieving ≥10 METS on ExECG have a very low prevalence of inducible ischemia and an excellent prognosis. In contrast, cardiac imaging techniques add diagnostic and prognostic value in higher risk populations (e.g. poor functional capacity, diabetes, chronic kidney disease). Optimal test selection for symptomatic patients with suspected coronary artery disease requires a patient-centered approach factoring in the risk/benefit ratio and cost-effectiveness. PMID:26563861

Penetrative cellular convection in a stratified atmosphere. [of stars

NASA Technical Reports Server (NTRS)

Massaguer, J. M.; Latour, J.; Toomre, J.; Zahn, J.-P.

1984-01-01

In the present investigation of penetrative convection within a simple compressible model, the middle one of the three layers of differing stratification prior to the onset of convection is a convectively unstable polytrope bounded above and below by two stably stratified polytropes. One- and two-mode steady solutions with hexagonal planforms have been studied for Rayleigh numbers up to aobut 1000 times critical, and for a range of Prandtl numbers, horizontal wavenumbers, and stratifications. These indicate that the penetration into the lower stable layer by downward plumes is substantially larger in a stratified medium than in a Boussinesq fluid, and produces an extended region of adiabatic stratification. The strong asymmetry between upward and downward penetration in compressible media has major implications for the mixing of stable regions above and below stellar convection zones.

Vertical Stratification of Soil Phosphorus as a Concern for Dissolved Phosphorus Runoff in the Lake Erie Basin.

PubMed

Baker, David B; Johnson, Laura T; Confesor, Remegio B; Crumrine, John P

2017-11-01

During the re-eutrophication of Lake Erie, dissolved reactive phosphorus (DRP) loading and concentrations to the lake have nearly doubled, while particulate phosphorus (PP) has remained relatively constant. One potential cause of increased DRP concentrations is P stratification, or the buildup of soil-test P (STP) in the upper soil layer (<5 cm). Stratification often accompanies no-till and mulch-till practices that reduce erosion and PP loading, practices that have been widely implemented throughout the Lake Erie Basin. To evaluate the extent of P stratification in the Sandusky Watershed, certified crop advisors were enlisted to collect stratified soil samples (0-5 or 0-2.5 cm) alongside their normal agronomic samples (0-20 cm) ( = 1758 fields). The mean STP level in the upper 2.5 cm was 55% higher than the mean of agronomic samples used for fertilizer recommendations. The amounts of stratification were highly variable and did not correlate with agronomic STPs (Spearman's = 0.039, = 0.178). Agronomic STP in 70% of the fields was within the buildup or maintenance ranges for corn ( L.) and soybeans [ (L.) Merr.] (0-46 mg kg Mehlich-3 P). The cumulative risks for DRP runoff from the large number of fields in the buildup and maintenance ranges exceeded the risks from fields above those ranges. Reducing stratification by a one-time soil inversion has the potential for larger and quicker reductions in DRP runoff risk than practices related to drawing down agronomic STP levels. Periodic soil inversion and mixing, targeted by stratified STP data, should be considered a viable practice to reduce DRP loading to Lake Erie. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Cytoplasmic expression of C-MYC protein is associated with risk stratification of mantle cell lymphoma.

PubMed

Gong, Yi; Zhang, Xi; Chen, Rui; Wei, Yan; Zou, Zhongmin; Chen, Xinghua

2017-01-01

To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman's Rank correlation coefficient analysis. Immunohistochemical staining in our study indicated that SOX11, Ki-67 and p53 presented nuclear positivity of tumor cells, CD8 showed membrane positivity in infiltrating T lymphocytes while PD-L1 showed membrane and cytoplasmic positivity mainly in macrophage cells and little in tumor cells. We observed positive staining of C-MYC either in the nucleus or cytoplasm or in both subcellular locations. There were significant differences in cytoplasmic C-MYC expression, Ki-67 proliferative index of tumor cells, and CD8 positive tumor infiltrating lymphocytes (CD8+TIL) among three risk groups ( P  = 0.000, P  = 0.037 and P =0.020, respectively). However, no significant differences existed in the expression of nuclear C-MYC, SOX11, p53, and PD-L1 in MCL patients with low-, intermediate-, and high risks. In addition, patient age and serum LDH level were also significantly different among 3 groups of patients ( P  = 0.006 and P  = 0.000, respectively). Spearman's rank correlation coefficient analysis indicated that cytoplasmic C-MYC expression, Ki-67 index, age, WBC, as well as LDH level had significantly positive correlations with risk stratification ( P  = 0.000, 0.015, 0.000, 0.029 and 0.000, respectively), while CD8+TIL in tumor microenvironment negatively correlated with risk stratification of patients ( P  = 0.006). Patients with increased positive cytoplasmic expression of C-MYC protein and decreased CD8+TIL appeared to be associated with a poor response to chemotherapy, but the correlation was not statistically significant. Our study suggested that assessment of cytoplasmic C-MYC overexpression and cytotoxic T lymphocytes (CTLs) by immunohistochemical staining might be helpful for MCL risk stratification and outcome prediction. However, large cohort studies of MCL patients with complete follow up are needed to validate our speculation.

Stratification in anterior teeth using one dentine shade and a predefined thickness of enamel: a new concept in composite layering--Part I.

PubMed

Manauta, J; Salat, A; Putignano, A; Devoto, W; Paolone, G; Hardan, L S

2014-06-01

Restoring an anterior tooth has always been a challenge, regarding the shade matching, the choice of colors, opacities, translucencies of our composites and the final anatomical outcome. This article proposes a new method for color matching and a clinical stratification using a simple and reproducible procedure for anterior restorations. The physical and optical characteristics of enamel and dentine will be studied and applied to our dental materials that we are using to restore anterior teeth.

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype

PubMed Central

Seegers, Joachim; Vos, Marc A.; Flevari, Panagiota; Willems, Rik; Sohns, Christian; Vollmann, Dirk; Lüthje, Lars; Kremastinos, Dimitrios T.; Floré, Vincent; Meine, Mathias; Tuinenburg, Anton; Myles, Rachel C.; Simon, Dirk; Brockmöller, Jürgen; Friede, Tim; Hasenfuß, Gerd; Lehnart, Stephan E.; Zabel, Markus

2012-01-01

Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. PMID:22117037

A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.

PubMed

Baum, Christian L; Wright, Adam C; Martinez, Juan-Carlos; Arpey, Christopher J; Brewer, Jerry D; Roenigk, Randall K; Otley, Clark C

2018-01-01

Most primary cutaneous squamous cell carcinomas are cured with surgery. A subset, however, may develop local and nodal metastasis that may eventuate in disease-specific; death. This subset has been variably termed high risk. Herein, we review; an emerging body of data on the risks of these outcomes and propose an evidence-based; risk stratification for low-, intermediate-, and high-risk tumors that takes into; account both tumor and patient characteristics. Finally, we discuss a framework for; management of these tumors on the basis of data, when available, and our; recommendations when data are sparse. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Recent advances in the management of chronic stable angina I: Approach to the patient, diagnosis, pathophysiology, risk stratification, and gender disparities

PubMed Central

Kones, Richard

2010-01-01

The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization. PMID:20730020

Recent advances in the management of chronic stable angina I: approach to the patient, diagnosis, pathophysiology, risk stratification, and gender disparities.

PubMed

Kones, Richard

2010-08-09

The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

PubMed

Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

2018-03-01

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE. © 2017 International Society on Thrombosis and Haemostasis.

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

PubMed Central

Shafizadeh, Tracy B.; Moler, Edward J.; Kolberg, Janice A.; Nguyen, Uyen Thao; Hansen, Torben; Jorgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

2011-01-01

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. PMID:21829540

Incorporating Stroke and Bleeding Risk Stratification Tools into Atrial Fibrillation Management Making Sense of the Alphabet Soup.

PubMed

Deering, Thomas F

2017-01-01

Atrial fibrillation (AF) is a common arrhythmia managed by many physicians in a variety of clinical settings. One of the most important clinical decisions related to effective AF management centers upon the need to perform accurate thromboembolic risk stratification followed by effective management decisions that align with established guidelines. This manuscript will review the present state of the art and provide guidance to physicians to enhance patient outcomes.

Benefit-risk perception of natalizumab therapy in neurologists and a large cohort of multiple sclerosis patients.

PubMed

Heesen, Christoph; Kleiter, Ingo; Meuth, Sven G; Krämer, Julia; Kasper, Jürgen; Köpke, Sascha; Gaissmaier, Wolfgang

2017-05-15

Natalizumab (NAT) is associated with the risk of progressive multifocal leukoencephalopathy (PML). Risk stratification algorithms have been developed, however, without detectable reduction of PML incidence. To evaluate to which extent patients and physicians understand and accept risks associated with NAT treatment. Prospective observational cohort study in German MS centers (n=73) among NAT-treated MS patients (n=801) and their neurologists (n=99). Patients included in this study had mean disease duration of 10.2years and a mean NAT treatment duration of 24months. More than 90% of patients and physicians voted for shared decision making or an informed choice decision making approach. Patients and physicians perceived a similar threat from MS as serious disease and both overestimated treatment benefits from NAT based on trial data. Men perceived MS more severe than women and perception of seriousness increased with age in both groups and in patients as well with increasing disability. Although patients evaluated their PML risk higher, their risk acceptance was significantly higher than of their neurologists. Risk stratification knowledge was good among neurologists and significantly lower among patients. While patients and physicians seem to have realistic risk perception of PML and knowledge of risk stratification concepts, the threat of MS and the perception of treatment benefits may explain the ongoing high acceptance of PML risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

PubMed Central

Huebner, Thomas; Goernig, Matthias; Schuepbach, Michael; Sanz, Ernst; Pilgram, Roland; Seeck, Andrea; Voss, Andreas

2010-01-01

Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient-assisted living support the electrocardiological monitoring of at-risk patients. Conclusions: There are many promising methods for the exercise-free, non-invasive detection of CAD and myocardial ischemia in the stable and acute phases. In the coming years, these new methods will help enhance state-of-the-art procedures in routine diagnostics. The future can expect that equally novel methods for risk stratification and telemedicine will transition into clinical routine. PMID:21063467

Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators

PubMed Central

Brun, Francesca; Groeneweg, Judith A.; Gear, Kathleen; Sinagra, Gianfranco; van der Heijden, Jeroen; Mestroni, Luisa; Hauer, Richard N.; Borgstrom, Mark; Marcus, Frank I.; Hughes, Trina

2016-01-01

Objectives The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). Background There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. Methods This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. Results Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. Conclusion These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death. PMID:27790640

Accurate Diabetes Risk Stratification Using Machine Learning: Role of Missing Value and Outliers.

PubMed

Maniruzzaman, Md; Rahman, Md Jahanur; Al-MehediHasan, Md; Suri, Harman S; Abedin, Md Menhazul; El-Baz, Ayman; Suri, Jasjit S

2018-04-10

Diabetes mellitus is a group of metabolic diseases in which blood sugar levels are too high. About 8.8% of the world was diabetic in 2017. It is projected that this will reach nearly 10% by 2045. The major challenge is that when machine learning-based classifiers are applied to such data sets for risk stratification, leads to lower performance. Thus, our objective is to develop an optimized and robust machine learning (ML) system under the assumption that missing values or outliers if replaced by a median configuration will yield higher risk stratification accuracy. This ML-based risk stratification is designed, optimized and evaluated, where: (i) the features are extracted and optimized from the six feature selection techniques (random forest, logistic regression, mutual information, principal component analysis, analysis of variance, and Fisher discriminant ratio) and combined with ten different types of classifiers (linear discriminant analysis, quadratic discriminant analysis, naïve Bayes, Gaussian process classification, support vector machine, artificial neural network, Adaboost, logistic regression, decision tree, and random forest) under the hypothesis that both missing values and outliers when replaced by computed medians will improve the risk stratification accuracy. Pima Indian diabetic dataset (768 patients: 268 diabetic and 500 controls) was used. Our results demonstrate that on replacing the missing values and outliers by group median and median values, respectively and further using the combination of random forest feature selection and random forest classification technique yields an accuracy, sensitivity, specificity, positive predictive value, negative predictive value and area under the curve as: 92.26%, 95.96%, 79.72%, 91.14%, 91.20%, and 0.93, respectively. This is an improvement of 10% over previously developed techniques published in literature. The system was validated for its stability and reliability. RF-based model showed the best performance when outliers are replaced by median values.

A risk score for predicting near-term incidence of hypertension: the Framingham Heart Study.

PubMed

Parikh, Nisha I; Pencina, Michael J; Wang, Thomas J; Benjamin, Emelia J; Lanier, Katherine J; Levy, Daniel; D'Agostino, Ralph B; Kannel, William B; Vasan, Ramachandran S

2008-01-15

Studies suggest that targeting high-risk, nonhypertensive individuals for treatment may delay hypertension onset, thereby possibly mitigating vascular complications. Risk stratification may facilitate cost-effective approaches to management. To develop a simple risk score for predicting hypertension incidence by using measures readily obtained in the physician's office. Longitudinal cohort study. Framingham Heart Study, Framingham, Massachusetts. 1717 nonhypertensive white individuals 20 to 69 years of age (mean age, 42 years; 54% women), without diabetes and with both parents in the original cohort of the Framingham Heart Study, contributed 5814 person-examinations. Scores were developed for predicting the 1-, 2-, and 4-year risk for new-onset hypertension, and performance characteristics of the prediction algorithm were assessed by using calibration and discrimination measures. Parental hypertension was ascertained from examinations of the original cohort of the Framingham Heart Study. During follow-up (median time over all person-examinations, 3.8 years), 796 persons (52% women) developed new-onset hypertension. In multivariable analyses, age, sex, systolic and diastolic blood pressure, body mass index, parental hypertension, and cigarette smoking were significant predictors of hypertension. According to the risk score based on these factors, the 4-year risk for incident hypertension was classified as low (<5%) in 34% of participants, medium (5% to 10%) in 19%, and high (>10%) in 47%. The c-statistic for the prediction model was 0.788, and calibration was very good. The risk score findings may not be generalizable to persons of nonwhite race or ethnicity or to persons with diabetes. The risk score algorithm has not been validated in an independent cohort and is based on single measurements of risk factors and blood pressure. The hypertension risk prediction score can be used to estimate an individual's absolute risk for hypertension on short-term follow-up, and it represents a simple, office-based tool that may facilitate management of high-risk individuals with prehypertension.

Development of a Bayesian Classifier for Breast Cancer Risk Stratification: A Feasibility Study

DTIC Science & Technology

2010-03-29

IV 0 2 10 23 BIRADS V 0 1 2 1 No mammogram 116 94 55 45 Breast biopsy category .4076 Benign, no atypia 19 12 27 34 Premalignant 1 0 2 4 Infiltrating... breast EIS result∗ Estimated outcome, % Known evidence Biopsy category EIS Gail Benign, no Infiltrating cancer Case frequency, % result cutoff‘ atypia or...Development of a Bayesian Classifier for Breast Cancer Risk Stratification: A Feasibility Study Alexander Stojadinovic, MD,a,b Christina Eberhardt,a

Stroke Risk Stratification and its Validation using Ultrasonic Echolucent Carotid Wall Plaque Morphology: A Machine Learning Paradigm.

PubMed

Araki, Tadashi; Jain, Pankaj K; Suri, Harman S; Londhe, Narendra D; Ikeda, Nobutaka; El-Baz, Ayman; Shrivastava, Vimal K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Gupta, Ajay; Suri, Jasjit S

2017-01-01

Stroke risk stratification based on grayscale morphology of the ultrasound carotid wall has recently been shown to have a promise in classification of high risk versus low risk plaque or symptomatic versus asymptomatic plaques. In previous studies, this stratification has been mainly based on analysis of the far wall of the carotid artery. Due to the multifocal nature of atherosclerotic disease, the plaque growth is not restricted to the far wall alone. This paper presents a new approach for stroke risk assessment by integrating assessment of both the near and far walls of the carotid artery using grayscale morphology of the plaque. Further, this paper presents a scientific validation system for stroke risk assessment. Both these innovations have never been presented before. The methodology consists of an automated segmentation system of the near wall and far wall regions in grayscale carotid B-mode ultrasound scans. Sixteen grayscale texture features are computed, and fed into the machine learning system. The training system utilizes the lumen diameter to create ground truth labels for the stratification of stroke risk. The cross-validation procedure is adapted in order to obtain the machine learning testing classification accuracy through the use of three sets of partition protocols: (5, 10, and Jack Knife). The mean classification accuracy over all the sets of partition protocols for the automated system in the far and near walls is 95.08% and 93.47%, respectively. The corresponding accuracies for the manual system are 94.06% and 92.02%, respectively. The precision of merit of the automated machine learning system when compared against manual risk assessment system are 98.05% and 97.53% for the far and near walls, respectively. The ROC of the risk assessment system for the far and near walls is close to 1.0 demonstrating high accuracy. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Assessment of Heavy/ Light Chain Pairs of Immunoglobulin (Hevylite assay) -  Benefit for Stratification of Multiple Myeloma?].

PubMed

Ščudla, V; Lochaman, P; Pika, T; Zapletalová, J; Minařík, J; Bačovský, J

2015-01-01

The aim of the study was the comparison of two novel stratification models in multiple myeloma (MM), ie. according to Avet- Loiseau (A L) and according to Ludwig (L), based on the HLC r index (ratio of serum levels of involved- HLC/ uninvolved HLC, ie. HLC κ/ HLC  λ assessed using ie. nephelometric/turbidimetric technique using specific polyclonal antibodies on a Binding Site SPA(PLUS)) technique) and β(2) microglobulin (β(2) M) with selected prognostic factors (PF) of MM and staging systems according to Durie- Salmon (D S) and International Staging System (ISS). In a cohort of 132 patients (94 with IgG and 38 with IgA type of MM) at the time of dia-gnosis, we assessed HLC r, select-ed PF and D S, ISS, A L and L stratification systems. Unlike in IgA isotype, in IgG isotype we found a significant relationship of HLC r to stratification according to D S and ISS with the difference between A and B substages according to D S (p = 0.049) and between ISS stages 1 vs. 3 (p = 0.001). In the IgG group, there was highly significant relationship of the depth of Hb and albumin decrease and β(2) M increase to the results of stratification according to ISS, A L and L model (p < 0.0001), increase of LDH in the ISS system and A L, and creatinine according to ISS and L but not the relationship of the stages according to any of the stratification systems to the values of FLC r (ratio of serum free light chains κ/ λ of immunoglobulin), thrombocytes and Ca. In the IgA type, there was a significant relationship of the depth of the decrease of Hb, thrombocytes, albumin and increase of β(2) M to the results of stratification according to ISS, A L and L and increase of creatinine in the case of ISS, but not of the values of FLC r, Ca and LDH in the case of any of the stratification systems. The degree of correlation of selected PF, especially of Hb, albumin and β(2) M, event. of thrombocytes, LDH and creatinine to the stages according to ISS and to stage 1-3 according to A L and L model was in IgG vs IgA isotype significantly different (p < 0.0001- 0.030). Staging system according to ISS had proportional distribution of stages 1- 3, whereas in the A L model prevailed in IgA and IgG isotype risk category 2, ie. intermediate-risk (47.3 and 44.7%) and in the L model prevailed risk category 3, ie. high-risk (41.5 and 52.6%) with low count of category 1, ie. low- risk category (23.4 and 10.5%). McNemar- Bowker test of symmetry showed in both types of MM the highest concordance between the stratification according to D S and L in category 3, ie. high-risk (31.9 vs. 28.9%) with overall accord only in 53.2 and 42.1% and with significant shift in the case of IgG isotype only (p = 0.036). In IgG and IgA isotype there was an overall concordance in the distribution of categories 1- 3 according to ISS vs. A L (62.4 and 63.2%) but with significant shift of the stratification (p = 0.002 and 0.028). In the case of IgG and IgA isotype there was a close relationship between the models A L and L (64.5 and 81.6%) with significant stratification shift (p < 0.0001 and 0.030). The new stratification models for MM according to A L and L are easily practically applicable, with close relationship to principal PF but they need separate assessment of IgG and IgA isotypes of MM. The choice of optimal model for routine practice needs a validation study aimed at progression free survival and overall survival.

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy.

PubMed

Yamashita, Shimpei; Kohjimoto, Yasuo; Iguchi, Takashi; Koike, Hiroyuki; Kusumoto, Hiroki; Iba, Akinori; Kikkawa, Kazuro; Kodama, Yoshiki; Matsumura, Nagahide; Hara, Isao

2016-03-22

While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors.

PubMed

Russo, Marco; Malandrino, Pasqualino; Moleti, Mariacarla; Vermiglio, Francesco; D'Angelo, Antonio; La Rosa, Giuliana; Sapuppo, Giulia; Calaciura, Francesca; Regalbuto, Concetto; Belfiore, Antonino; Vigneri, Riccardo; Pellegriti, Gabriella

2018-05-16

To correlate clinical and pathological characteristics at diagnosis with patient long-term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC). Retrospective analysis of clinical and pathological prognostic factors of 124 paediatric patients with DTC (age at diagnosis <19 years) followed up for 10.4 ± 8.4 years. Patients with a follow-up >3 years (n = 104) were re-classified 18 months after surgery on the basis of their response to therapy (ongoing risk stratification). Most patients had a papillary histotype (96.0%), were older than 15 years (75.0%) and were diagnosed because of clinical local symptoms (63.7%). Persistent/recurrent disease was present in 31.5% of cases during follow-up, but at the last evaluation, only 12.9% had biochemical or structural disease. The presence of metastases in the lymph nodes of the lateral compartment (OR 3.2, 95% CI, 1.28-7.16, P = 0.01) was the only independent factor associated with recurrent/persistent disease during follow-up. At the last evaluation, biochemical/structural disease was associated with node metastases (N1a, N1b) by univariate but not multivariate analysis. Ongoing risk stratification compared to the initial risk classification method better identified patients with a lower probability of persistent/recurrent disease (NPV = 100%). In spite of the aggressive presentations at diagnosis, paediatric patients with DTC show an excellent response to treatment and often a favourable outcome. N1b status should be considered a strong predictor of persistent/recurrent disease which, as in adults, is better predicted by ongoing risk stratification. © 2018 Wiley Periodicals, Inc.

Risk stratification using lean body mass in patients undergoing transcatheter aortic valve replacement.

PubMed

Hioki, Hirofumi; Watanabe, Yusuke; Kozuma, Ken; Yamamoto, Masanori; Naganuma, Toru; Araki, Motoharu; Tada, Norio; Shirai, Shinichi; Yamanaka, Futoshi; Higashimori, Akihiro; Mizutani, Kazuki; Tabata, Minoru; Takagi, Kensuke; Ueno, Hiroshi; Hayashida, Kentaro

2018-02-22

The prognostic impact of skeletal muscle mass, assessed using lean body mass (LBM), remain unclear in patients who underwent transcatheter aortic valve replacement (TAVR). The aim of this study to assess prognostic impact of LBM on mortality after TAVR. We assessed 1,613 patients (median age 85 years, 70% female) who underwent TAVI from October 2013 to April 2016 using OCEAN (Optimized transCathEter vAlvular interveNtion)-TAVI registry data. LBM was calculated using the James formula. The primary endpoint was all-cause death after TAVR. Median follow-up period was 287 days (interquartile range 110-462). The Kaplan-Meier analysis demonstrated that patients with low LBM had significantly higher incidence of all-cause death than those with high LBM in male (32.3% vs. 9.9%, log rank P < 0.001) and female (15.8% vs. 9.2%, log-rank P = 0.011). On contrary, the risk stratification using body mass index (BMI) could not validate into female patients who underwent TAVR. The multivariate analysis showed that the LBM was an independent predictor of all-cause death in male (Hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89-0.98) and female (HR 0.94; 95% CI 0.89-0.99). Inversely, the assessment using BMI could not identify the high-risk population in a female. The patients with low LBM had the higher incidence of all-cause death after TAVR than those with high LBM, regardless of gender. Thus, the risk stratification using LBM might provide further insight to identify the high-risk TAVR population, compared to conventional risk stratification using BMI. © 2018 Wiley Periodicals, Inc.

Electrophysiologic profile and results of invasive risk stratification in asymptomatic children and adolescents with the Wolff-Parkinson-White electrocardiographic pattern.

PubMed

Kubuš, Peter; Vít, Pavel; Gebauer, Roman A; Materna, Ondřej; Janoušek, Jan

2014-04-01

Data on the results and clinical effect of an invasive risk stratification strategy in asymptomatic young patients with the Wolff-Parkinson-White electrocardiographic pattern are scarce. Eighty-five consecutive patients aged<18 years with a Wolff-Parkinson-White pattern and persistent preexcitation at maximum exercise undergoing invasive risk stratification were retrospectively studied. Adverse accessory pathway (AP) properties were defined according to currently consented criteria as any of the following: shortest preexcited RR interval during atrial fibrillation/rapid atrial pacing≤250 ms (or antegrade effective refractory period≤250 ms if shortest preexcited RR interval was not available) or inducible atrioventricular re-entrant tachycardia. Age at evaluation was median 14.9 years. Eighty-two patients had a structurally normal heart and 3 had hypertrophic cardiomyopathy. A single manifest AP was present in 80, 1 manifest and 1 concealed AP in 4, and 2 manifest APs in 1 patient. Adverse AP properties were present in 32 of 85 patients (37.6%) at baseline and in additional 16 of 44 (36.4%) after isoproterenol. Ablation was performed in 41 of these 48 patients. Ablation was deferred in the remaining 7 for pathway proximity to the atrioventricular node. In addition, 18 of the low-risk patients were ablated based on patient/parental decision. Adverse AP properties at baseline were exhibited by 37.6% of the evaluated patients with an asymptomatic Wolff-Parkinson-White preexcitation persisting at peak exercise. Isoproterenol challenge yielded additional 36.4% of those tested at higher risk. Ablation was performed in a total of 69.4% of patients subjected to invasive risk stratification.

Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial.

PubMed

Hobbs, F D R; Roalfe, A K; Lip, G Y H; Fletcher, K; Fitzmaurice, D A; Mant, J

2011-06-23

To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation. Comparative cohort study of eight risk stratification scores. Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial. 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period. Events rates of stroke and thromboembolism. 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes. Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis.

PubMed

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 guide decision-making to reduce admissions, optimize utility of diagnostic imaging and prevent negative explorations. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Progress towards personalized therapeutics: biologic- and risk-directed therapy for neuroblastoma.

PubMed

Gustafson, William Clay; Matthay, Katherine K

2011-10-01

Neuroblastoma, a tumor of the developing peripheral sympathetic nervous system, is the most common and deadly extracranial solid tumor of childhood. Risk-stratification and risk-adapted therapy play a large role in the modern treatment of neuroblastoma. Recently, through extensive international collaboration, new guidelines for risk stratification have emerged that will aid in international cooperative studies, as well as clarifying therapeutic options for patients. Current therapies for low- and intermediate-risk neuroblastoma have resulted in excellent prognoses for these risk strata, and current efforts are concentrated on chemotherapy reduction. By contrast, much more gradual progress has been made in improving survival for high-risk neuroblastoma patients, despite significant chemotherapy intensification. Current investigations focus on overcoming resistance by elucidating the molecular/genetic causes of neuroblastoma tumorigenesis and progression, with the aim of developing more effective biologically targeted therapies for this disease.

FOCIS: A forest classification and inventory system using LANDSAT and digital terrain data

NASA Technical Reports Server (NTRS)

Strahler, A. H.; Franklin, J.; Woodcook, C. E.; Logan, T. L.

1981-01-01

Accurate, cost-effective stratification of forest vegetation and timber inventory is the primary goal of a Forest Classification and Inventory System (FOCIS). Conventional timber stratification using photointerpretation can be time-consuming, costly, and inconsistent from analyst to analyst. FOCIS was designed to overcome these problems by using machine processing techniques to extract and process tonal, textural, and terrain information from registered LANDSAT multispectral and digital terrain data. Comparison of samples from timber strata identified by conventional procedures showed that both have about the same potential to reduce the variance of timber volume estimates over simple random sampling.

Impact of self-reported fasting duration on lipid profile variability, cardiovascular risk stratification and metabolic syndrome diagnosis.

PubMed

Janovsky, Carolina Castro Porto Silva; Laurinavicius, Antonio; Cesena, Fernando; Valente, Viviane; Ferreira, Carlos Eduardo; Mangueira, Cristovão; Conceição, Raquel; Santos, Raul D; Bittencourt, Marcio Sommer

2018-01-01

We sought to investigate the impact of self-reported fasting duration times on the lipid profile results and its impact on the cardiovascular risk stratification and metabolic syndrome diagnosis. We analyzed data from all consecutive individuals evaluated in a comprehensive health examination at the Hospital Israelita Albert Einstein from January to December 2015. We divided these patients in three groups, according to the fasting duration recalled (< 8h, 8-12h and > 12h). We calculated the global cardiovascular risk and diagnosed metabolic syndrome according to the current criteria and estimated their change according to fasting duration. A total of 12,196 (42.3 ± 9.2 years-old, 30.2% females) patients were evaluated. The distribution of cardiovascular risk was not different among groups defined by fasting duration in both men and women (p = 0.547 for women and p = 0.329 for men). Similarly, the prevalence of metabolic syndrome was not influenced by the fasting duration (p = 0.431 for women and p = 0.166 for men). Self-reported fasting duration had no significant impact on the lipid profile results, including triglyceride levels. Consequently, no changes on the cardiovascular risk stratification using the Framingham risk score nor changes on the prevalence of metabolic syndrome were noted.

Risk-stratification, resource availability, and choice of surgical location for the management of parturients with abnormal placentation: a survey of United States-based obstetric anesthesiologists.

PubMed

Grant, T R; Ellinas, E H; Kula, A O; Muravyeva, M Y

2018-05-01

Parturients with abnormally adherent placentas present anesthetic challenges that include risk-stratification, management planning and resource utilization. The labor and delivery unit may be remote from the main operating room services. Division chiefs of North American obstetric anesthesiology services were surveyed about their practices and management of parturients with an abnormally adherent placenta. Eighty-four of 122 chiefs, representing 103 hospital sites, responded to the survey (response rate 69%). Sixty-one percent of respondents agreed that women with preoperative placental imaging that was "suspicious" of placenta accreta represented a lower risk category; all other suggested descriptions fell into a higher risk category. Seventy-nine percent of respondents indicated that lower risk cases were managed on the labor and delivery unit, while 71% indicated that higher risk cases would be managed in the main operating room. Institutions where all cases were managed on the labor and delivery unit had better access to human and technical resources, were less remote from their main operating areas, and promoted neuraxial rather than general anesthesia, even for parturients perceived to be at higher risk. Obstetric anesthesia leaders identified patients at lower clinical risk and those less likely to require greater resources. Additional resources were available in institutions where all abnormal placentation cases were managed on the labor and delivery unit. Practitioners should consider risk-stratification and resource availability when planning high-risk cases. Copyright © 2018 Elsevier Ltd. All rights reserved.

68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients.

PubMed

Liu, Chen; Liu, Teli; Zhang, Ning; Liu, Yiqiang; Li, Nan; Du, Peng; Yang, Yong; Liu, Ming; Gong, Kan; Yang, Xing; Zhu, Hua; Yan, Kun; Yang, Zhi

2018-05-02

The purpose of this study was to investigate the performance of 68 Ga-PSMA-617 PET/CT in predicting risk stratification and metastatic risk of prostate cancer. Fifty newly diagnosed patients with prostate cancer as confirmed by needle biopsy were continuously included, 40 in a train set and ten in a test set. 68 Ga-PSMA-617 PET/CT and clinical data of all patients were retrospectively analyzed. Semi-quantitative analysis of PET images provided maximum standardized uptake (SUVmax) of primary prostate cancer and volumetric parameters including intraprostatic PSMA-derived tumor volume (iPSMA-TV) and intraprostatic total lesion PSMA (iTL-PSMA). According to prostate cancer risk stratification criteria of the NCCN Guideline, all patients were simplified into a low-intermediate risk group or a high-risk group. The semi-quantitative parameters of 68 Ga-PSMA-617 PET/CT were used to establish a univariate logistic regression model for high-risk prostate cancer and its metastatic risk, and to evaluate the diagnostic efficacy of the predictive model. In the train set, 30/40 (75%) patients had high-risk prostate cancer and 10/40 (25%) patients had low-to-moderate-risk prostate cancer; in the test set, 8/10 (80%) patients had high-risk prostate cancer while 2/10 (20%) had low-intermediate risk prostate cancer. The univariate logistic regression model established with SUVmax, iPSMA-TV and iTL-PSMA could all effectively predict high-risk prostate cancer; the AUC of ROC were 0.843, 0.802 and 0.900, respectively. Based on the test set, the sensitivity and specificity of each model were 87.5% and 50% for SUVmax, 62.5% and 100% for iPSMA-TV, and 87.5% and 100% for iTL-PSMA, respectively. The iPSMA-TV and iTL-PSMA-based predictive model could predict the metastatic risk of prostate cancer, the AUC of ROC was 0.863 and 0.848, respectively, but the SUVmax-based prediction model could not predict metastatic risk. Semi-quantitative analysis indexes of 68 Ga-PSMA-617 PET/CT imaging can be used as "imaging biomarkers" to predict risk stratification and metastatic risk of prostate cancer.

The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism.

PubMed

Lankeit, Mareike; Dellas, Claudia; Benz, Viola; Hasenfuß, Gerd; Konstantinides, Stavros

2013-11-01

Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism (PE). In patients with acute myocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE. We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE. Patients with acute (<24 hours; n=150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p<0.001) compared to patients with symptoms ≥ 24 hours (n=107); other baseline characteristics, comorbidities, and risk factors were distributed equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42 [1.92-5.42] ng/ml; p<0.001). However, the proportion of patients with H-FABP levels ≥ 6 ng/ml did not differ among patients with acute symptom onset and late presentation (p=0.104). Only tachycardia and elevation of H-FABP were associated with an increased risk of an adverse 30-day outcome both in patients with acute symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p=0.016; tachycardia: 7.0 [1.4-36.0]; p=0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p=0.004 and tachycardia: 12.3 [1.5-103.6]; p=0.021). The prognostic value could further be improved by the use of a simple H-FABP-based clinical prediction score. Our findings indicate that H-FABP is a useful biomarker for risk stratification of normotensive patients with PE regardless of symptom duration prior to diagnosis. © 2013.

Diagnosis of acute myocardial infarction.

PubMed

Pandey, Rudradev; Gupta, Naveen K; Wander, Gurpreet S

2011-12-01

Diagnosis of acute myocardial infarction (AMI) has to be made early in the emergency triage since maximal mortality occurs within first hour and the benefits of all interventions are greater once these are instituted early. Diagnosis is easy and based on simple principals of good history, physical examination, early and complete 12 lead electrocardiogram and use of echocardiography which should be available in the emergency triage area. Subsequently biomarkers are also available for documentation and risk stratification. The other causes of acute severe chest pain should be kept in mind and ruled out. The role of myocardial perfusion imaging for diagnosis of AMI is limited. The diagnosis also involves an estimation of the size of infarct, duration since onset of the process, any acute complications of AMI and the likely vessel involved since these have significant therapeutic implications.

A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children.

PubMed

Sutton, Rosemary; Venn, Nicola C; Law, Tamara; Boer, Judith M; Trahair, Toby N; Ng, Anthea; Den Boer, Monique L; Dissanayake, Anuruddhika; Giles, Jodie E; Dalzell, Pauline; Mayoh, Chelsea; Barbaric, Draga; Revesz, Tamas; Alvaro, Frank; Pieters, Rob; Haber, Michelle; Norris, Murray D; Schrappe, Martin; Dalla Pozza, Luciano; Marshall, Glenn M

2018-02-01

To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10 -5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL. © 2017 John Wiley & Sons Ltd.

Overview and recent advances in the treatment of neuroblastoma.

PubMed

Whittle, Sarah B; Smith, Valeria; Doherty, Erin; Zhao, Sibo; McCarty, Scott; Zage, Peter E

2017-04-01

Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.

Outlining a Population “at Risk” of Parkinson's Disease: Evidence from a Case-Control Study

PubMed Central

Schirinzi, Tommaso; Martella, Giuseppina; D'Elia, Alessio; Di Lazzaro, Giulia; Imbriani, Paola; Madeo, Graziella; Monaco, Leonardo; Maltese, Marta

2016-01-01

The multifactorial pathogenesis of Parkinson's Disease (PD) requires a careful identification of populations “at risk” of developing the disease. In this case-control study we analyzed a large Italian population, in an attempt to outline general criteria to define a population “at risk” of PD. We enrolled 300 PD patients and 300 controls, gender and age matched, from the same urban geographical area. All subjects were interviewed on demographics, family history of PD, occupational and environmental toxicants exposure, smoking status, and alcohol consumption. A sample of 65 patients and 65 controls also underwent serum dosing of iron, copper, mercury, and manganese by means of Inductively Coupled-Plasma-Mass-Spectrometry (ICP-MS). Positive family history, toxicants exposure, non-current-smoker, and alcohol nonconsumer status occurred as significant risk factors in our population. The number of concurring risk factors overlapping in the same subject impressively increased the overall risk. No significant differences were measured in the metal serum levels. Our findings indicate that combination of three to four concurrent PD-risk factors defines a condition “at risk” of PD. A simple stratification, based on these questionnaires, might be of help in identifying subjects suitable for neuroprotective strategies. PMID:27651975

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder

PubMed Central

Lawton, Michael; Rolinski, Michal; Evetts, Samuel; Baig, Fahd; Ruffmann, Claudio; Gornall, Aimie; Klein, Johannes C; Lo, Christine; Dennis, Gary; Bandmann, Oliver; Quinnell, Timothy; Zaiwalla, Zenobia; Ben-Shlomo, Yoav; Hu, Michele TM

2017-01-01

Abstract Objectives Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Methods Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson’s (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations. Results Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson’s Disease Rating Scale (UPDRS)-III, timed “get-up-and-go”, Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson’s compared to 0.3% (95% CI 0.009%, 2%) of controls. Conclusions RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions. PMID:28472425

Evaluation of prognostic models developed using standardised image features from different PET automated segmentation methods.

PubMed

Parkinson, Craig; Foley, Kieran; Whybra, Philip; Hills, Robert; Roberts, Ashley; Marshall, Chris; Staffurth, John; Spezi, Emiliano

2018-04-11

Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification. Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated. Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group. Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.

The evolving field of prognostication and risk stratification in MDS: Recent developments and future directions.

PubMed

Lee, Eun-Ju; Podoltsev, Nikolai; Gore, Steven D; Zeidan, Amer M

2016-01-01

The clinical course of patients with myelodysplastic syndromes (MDS) is characterized by wide variability reflecting the underlying genetic and biological heterogeneity of the disease. Accurate prediction of outcomes for individual patients is an integral part of the evidence-based risk/benefit calculations that are necessary for tailoring the aggressiveness of therapeutic interventions. While several prognostication tools have been developed and validated for risk stratification, each of these systems has limitations. The recent progress in genomic sequencing techniques has led to discoveries of recurrent molecular mutations in MDS patients with independent impact on relevant clinical outcomes. Reliable assays of these mutations have already entered the clinic and efforts are currently ongoing to formally incorporate mutational analysis into the existing clinicopathologic risk stratification tools. Additionally, mutational analysis holds promise for going beyond prognostication to therapeutic selection and individualized treatment-specific prediction of outcomes; abilities that would revolutionize MDS patient care. Despite these exciting developments, the best way of incorporating molecular testing for use in prognostication and prediction of outcomes in clinical practice remains undefined and further research is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Proposals for enhanced health risk assessment and stratification in an integrated care scenario

PubMed Central

Dueñas-Espín, Ivan; Vela, Emili; Pauws, Steffen; Bescos, Cristina; Cano, Isaac; Cleries, Montserrat; Contel, Joan Carles; de Manuel Keenoy, Esteban; Garcia-Aymerich, Judith; Gomez-Cabrero, David; Kaye, Rachelle; Lahr, Maarten M H; Lluch-Ariet, Magí; Moharra, Montserrat; Monterde, David; Mora, Joana; Nalin, Marco; Pavlickova, Andrea; Piera, Jordi; Ponce, Sara; Santaeugenia, Sebastià; Schonenberg, Helen; Störk, Stefan; Tegner, Jesper; Velickovski, Filip; Westerteicher, Christoph; Roca, Josep

2016-01-01

Objectives Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. Settings The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Participants Responsible teams for regional data management in the five ACT regions. Primary and secondary outcome measures We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. Results There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. Conclusions The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation. PMID:27084274

Improving risk-stratification of Diabetes complications using temporal data mining.

PubMed

Sacchi, Lucia; Dagliati, Arianna; Segagni, Daniele; Leporati, Paola; Chiovato, Luca; Bellazzi, Riccardo

2015-01-01

To understand which factor trigger worsened disease control is a crucial step in Type 2 Diabetes (T2D) patient management. The MOSAIC project, funded by the European Commission under the FP7 program, has been designed to integrate heterogeneous data sources and provide decision support in chronic T2D management through patients' continuous stratification. In this work we show how temporal data mining can be fruitfully exploited to improve risk stratification. In particular, we exploit administrative data on drug purchases to divide patients in meaningful groups. The detection of drug consumption patterns allows stratifying the population on the basis of subjects' purchasing attitude. Merging these findings with clinical values indicates the relevance of the applied methods while showing significant differences in the identified groups. This extensive approach emphasized the exploitation of administrative data to identify patterns able to explain clinical conditions.

Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study.

PubMed

Gergei, Ingrid; Krämer, Bernhard K; Scharnagl, Hubert; Stojakovic, Tatjana; März, Winfried; Mondorf, Ulrich

The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF). We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP). Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years). Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF. The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF. Big-ET-1improves risk stratification in patients referred for coronary angiography.

Measurement of the Specific Heat Using a Gravity Cancellation Approach

NASA Technical Reports Server (NTRS)

Zhong, Fang

2003-01-01

The specific heat at constant volume C(sob V) of a simple fluid diverges near its liquid-vapor critical point. However, gravity-induced density stratification due to the divergence of isothermal susceptibility hinders the direct comparison of the experimental data with the predictions of renormalization group theory. In the past, a microgravity environment has been considered essential to eliminate the density stratification. We propose to perform specific heat measurements of He-3 on the ground using a method to cancel the density stratification. A He-3 fluid layer will be heated from below, using the thermal expansion of the fluid to cancel the hydrostatic compression. A 6% density stratification at a reduced temperature of 10(exp -5) can be cancelled to better than 0.1% with a steady 1.7 micro K temperature difference across a 0.05 cm thick fluid layer. A conventional AC calorimetry technique will be used to determine the heat capacity. The minimized bulk density stratification with a relaxation time 6500 sec at a reduced temperature of 10(exp -5) will stay unchanged during 1 Hz AC heating. The smear of the specific heat divergence due to the temperature difference across the cell is about 0.1% at a reduced temperature of 10(exp -6). The combination of using High Resolution Thermometry with a 0.5 n K temperature resolution in the AC technique and the cancellation of the density stratification will enable C(sub V) to be measured down to a reduced temperature of 10(exp -6) with less than a 1% systematic error.

Clinical Risk Stratification for Primary Prevention Implantable Cardioverter Defibrillators

PubMed Central

Hardy, Judy; Yee, Raymond; Healey, Jeffrey S.; Birnie, David; Simpson, Christopher S.; Crystal, Eugene; Mangat, Iqwal; Nanthakumar, Kumaraswamy; Wang, Xuesong; Krahn, Andrew D.; Dorian, Paul; Austin, Peter C.; Tu, Jack V.

2015-01-01

Background— A conceptualized model may be useful for understanding risk stratification of primary prevention implantable cardioverter defibrillators considering the competing risks of appropriate implantable cardioverter defibrillator shock versus mortality. Methods and Results— In a prospective, multicenter, population-based cohort with left ventricular ejection fraction ≤35% referred for primary prevention implantable cardioverter defibrillator, we developed dual risk stratification models to determine the competing risks of appropriate defibrillator shock versus mortality using a Fine-Gray subdistribution hazard model. Among 7020 patients referred, 3445 underwent defibrillator implant (79.7% men, median, 66 years [25th, 75th: 58–73]). During 5918 person-years of follow-up, appropriate shock occurred in 204 patients (3.6 shocks/100 person-years) and 292 died (4.9 deaths/100 person-years). Competing risk predictors of appropriate shock included nonsustained ventricular tachycardia, atrial fibrillation, serum creatinine concentration, digoxin or amiodarone use, and QRS duration near 130-ms peak. One-year cumulative incidence of appropriate shock was 0.9% in the lowest risk category, and 1.7%, 2.5%, 4.9%, and 9.3% in low, intermediate, high, and highest risk groups, respectively. Hazard ratios for appropriate shock ranged from 4.04 to 7.79 in the highest 3 deciles (all P≤0.001 versus lowest risk). Cumulative incidence of 1-year death was 0.6%, 1.9%, 3.3%, 6.2%, and 17.7% in lowest, low, intermediate, high, and highest risk groups, respectively. Mortality hazard ratios ranged from 11.48 to 36.22 in the highest 3 deciles (all P<0.001 versus lowest risk). Conclusions— Simultaneous estimation of risks of appropriate shock and mortality can be performed using clinical variables, providing a potential framework for identification of patients who are unlikely to benefit from prophylactic implantable cardioverter defibrillator. PMID:26224792

Application of a prediction model for work-related sensitisation in bakery workers.

PubMed

Meijer, E; Suarthana, E; Rooijackers, J; Grobbee, D E; Jacobs, J H; Meijster, T; de Monchy, J G R; van Otterloo, E; van Rooy, F G B G J; Spithoven, J J G; Zaat, V A C; Heederik, D J J

2010-10-01

Identification of work-related allergy, particularly work-related asthma, in a (nationwide) medical surveillance programme among bakery workers requires an effective and efficient strategy. Bakers at high risk of having work-related allergy were indentified by use of a questionnaire-based prediction model for work-related sensitisation. The questionnaire was applied among 5,325 participating bakers. Sequential diagnostic investigations were performed only in those with an elevated risk. Performance of the model was evaluated in 674 randomly selected bakers who participated in the medical surveillance programme and the validation study. Clinical investigations were evaluated in the first 73 bakers referred at high risk. Overall 90% of bakers at risk of having asthma could be identified. Individuals at low risk showed 0.3-3.8% work-related respiratory symptoms, medication use or absenteeism. Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals. This prediction based stratification procedure appeared effective in detecting work-related allergy among bakers and can accurately be used for periodic examination, especially in small enterprises where delivery of adequate care is difficult. This approach may contribute to cost reduction.

Lessons from the Johns Hopkins Multi-Disciplinary Venous Thromboembolism (VTE) Prevention Collaborative

PubMed Central

Streiff, Michael B; Carolan, Howard T; Hobson, Deborah B; Kraus, Peggy S; Holzmueller, Christine G; Demski, Renee; Lau, Brandyn D; Biscup-Horn, Paula; Pronovost, Peter J

2012-01-01

Problem Venous thromboembolism (VTE) is a common cause of potentially preventable mortality, morbidity, and increased medical costs. Risk-appropriate prophylaxis can prevent most VTE events, but only a small fraction of patients at risk receive this treatment. Design Prospective quality improvement programme. Setting Johns Hopkins Hospital, Baltimore, Maryland, USA. Strategies for change A multidisciplinary team established a VTE Prevention Collaborative in 2005. The collaborative applied the four step TRIP (translating research into practice) model to develop and implement a mandatory clinical decision support tool for VTE risk stratification and risk-appropriate VTE prophylaxis for all hospitalised adult patients. Initially, paper based VTE order sets were implemented, which were then converted into 16 specialty-specific, mandatory, computerised, clinical decision support modules. Key measures for improvement VTE risk stratification within 24 hours of hospital admission and provision of risk-appropriate, evidence based VTE prophylaxis. Effects of change The VTE team was able to increase VTE risk assessment and ordering of risk-appropriate prophylaxis with paper based order sets to a limited extent, but achieved higher compliance with a computerised clinical decision support tool and the data feedback which it enabled. Risk-appropriate VTE prophylaxis increased from 26% to 80% for surgical patients and from 25% to 92% for medical patients in 2011. Lessons learnt A computerised clinical decision support tool can increase VTE risk stratification and risk-appropriate VTE prophylaxis among hospitalised adult patients admitted to a large urban academic medical centre. It is important to ensure the tool is part of the clinician’s normal workflow, is mandatory (computerised forcing function), and offers the requisite modules needed for every clinical specialty. PMID:22718994

The Value of Elastic Modulus Index as a Novel Surrogate Marker for Cardiovascular Risk Stratification by Dimensional Speckle-Tracking Carotid Ultrasonography

PubMed Central

Yoon, Ji Hyun; Cho, In-Jeong; Sung, Ji Min; Lee, Jinyong; Ryoo, Hojin; Shim, Chi Young; Hong, Geu-Ru; Chung, Namsik

2016-01-01

Background Carotid intima media thickness (CIMT) and the presence of carotid plaque have been used for risk stratification of cardiovascular disease (CVD). To date, however, the association between multi-directional functional properties of carotid artery and CVD has not been fully elucidated. We sought to explore the multi-directional mechanics of the carotid artery in relation to cardiovascular risk. Methods Four hundred one patients who underwent carotid ultrasound were enrolled between January 2010 and April 2013. A high risk of CVD was defined as more than 20% of 10-year risk based on the Framingham risk score. Using a speckle-tracking technique, the longitudinal and radial movements were analyzed in the B-mode images. Peak longitudinal and radial displacements, strain and strain rate were also measured. Beta stiffness and elastic modulus index were calculated from the radial measurements. Results Of the overall sample, 13% (52) of patients comprised the high-risk group. In multivariate logistic regression, CIMT and elastic modulus index were independently associated with a high-risk of CVD {odds ratio (OR): 1.810 [95% confidence interval (CI) 1.249–2.622] and OR: 1.767 (95% CI: 1.177–2.652); p = 0.002, 0.006, respectively}. The combination of CIMT and elastic modulus index correlated with a high-risk of CVD more so than CIMT alone. Conclusion The elastic modulus index of the carotid artery might serve as a novel surrogate marker of high-risk CVD. Measurement of the multi-directional mechanics of the carotid artery using the speckle tracking technique has potential for providing further information over conventional B-mode ultrasound for stratification of CVD risk. PMID:27721952

Surveillance of cardiovascular risk in the normotensive patient with repaired aortic coarctation

PubMed Central

Swan, Lorna; Kraidly, Mustafa; Muhll, Isabelle Vonder; Collins, Peter; Gatzoulis, Michael A.

2010-01-01

Background Repaired coarctation of the aorta is associated with premature atherosclerosis and an increased risk of cardiovascular events even in normotensive subjects. To date clinical risk stratification has focused on brachial blood pressures ignoring the complex pulsatility of the aortic wave form. The aim of this study was to assess components of this pulsatility in a clinical setting and to suggest possible techniques to improve risk stratification. Methods This was a prospective study recruiting patients from a tertiary referral centre. Pulse wave morphology was assessed using applanation tonometry. B-mode ultrasound and cardiac magnetic resonance were used to assess carotid intimal–medial thickness and left ventricular mass. Results Forty-six subjects with repaired coarctation of the aorta (range 16–62 years; mean 31 years) and 20 matched controls were studied. Baseline brachial systolic and diastolic blood pressures were not statistically different between the 2 groups. Peripheral (62.5 mmHg (11.3) vs. 50.6 mmHg (15.0), p = 0.0008) and central (34.5 mmHg (7.7) vs. 28.7 mmHg (4.7), p = 0.005) pulse pressures were elevated in the coarctation patients compared to controls. The reflected pressure wave returned to the ascending aorta earlier in the coarctation group (p = 0.007) and the tension time index (TTI) was increased (p = 0.03). The sub-endocardial viability index (SVI) was reduced in the coarctation subjects (159 (33) vs. 186 (31)%; p = 0.009) but there was no differences in central augmentation index (p = 0.35). Conclusions This study demonstrates that there are patients with repaired coarctation who have an excellent mid-term outcome free from ventricular hypertrophy, carotid intima medial thickening and with relatively preserved vascular reactivity. However even in this “best outcome” cohort there were abnormal vascular characteristics that may predispose to increased cardiovascular risk. Simple non-invasive investigations can more extensively characterise these sub-clinical abnormalities and by utilised in long-term surveillance. PMID:19059656

A Lagrangian cylindrical coordinate system for characterizing dynamic surface geometry of tubular anatomic structures.

PubMed

Lundh, Torbjörn; Suh, Ga-Young; DiGiacomo, Phillip; Cheng, Christopher

2018-03-03

Vascular morphology characterization is useful for disease diagnosis, risk stratification, treatment planning, and prediction of treatment durability. To quantify the dynamic surface geometry of tubular-shaped anatomic structures, we propose a simple, rigorous Lagrangian cylindrical coordinate system to monitor well-defined surface points. Specifically, the proposed system enables quantification of surface curvature and cross-sectional eccentricity. Using idealized software phantom examples, we validate the method's ability to accurately quantify longitudinal and circumferential surface curvature, as well as eccentricity and orientation of eccentricity. We then apply the method to several medical imaging data sets of human vascular structures to exemplify the utility of this coordinate system for analyzing morphology and dynamic geometric changes in blood vessels throughout the body. Graphical abstract Pointwise longitudinal curvature of a thoracic aortic endograft surface for systole and diastole, with their absolute difference.

Noninvasive Computed Tomography–based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial

PubMed Central

Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M.; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A.; Bartholmai, Brian J.

2015-01-01

Rationale: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. Objectives: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. Methods: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. Measurements and Main Results: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. Conclusions: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas. PMID:26052977

Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

PubMed

Maldonado, Fabien; Duan, Fenghai; Raghunath, Sushravya M; Rajagopalan, Srinivasan; Karwoski, Ronald A; Garg, Kavita; Greco, Erin; Nath, Hrudaya; Robb, Richard A; Bartholmai, Brian J; Peikert, Tobias

2015-09-15

Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Initial clinical validation of Health Heritage, a patient-facing tool for personal and family history collection and cancer risk assessment.

PubMed

Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A

2016-04-01

Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97% (sensitivity 98% and specificity 88%). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75%, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team.

Stratification of the Risk of Sudden Death in Nonischemic Heart Failure

PubMed Central

Pimentel, Maurício; Zimerman, Leandro Ioschpe; Rohde, Luis Eduardo

2014-01-01

Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure. PMID:25352509

Coronary heart disease risk stratification: pitfalls and possibilities.

PubMed

Negi, Smita; Nambi, Vijay

Atherosclerosis of the coronary arteries, or coronary heart disease (CHD), is the most common cause of mortality in U.S. adults. The pathobiology of atherosclerosis and its complications is a continuum. At one end of the spectrum are young individuals without atherosclerotic disease who have not yet been exposed to lifestyle or other risk factors, and at the other end are patients with manifest atherosclerosis - myocardial infarction, stroke, and disabling peripheral arterial disease - where risk of recurrent disease and death is driven by the same factors initially responsible for the emergence of disease. However, it is clear that while risk factors are important in the development of CHD, not everyone with risk factors develops the disease and not everyone with CHD has risk factors. Furthermore, even similar degrees of exposure to a risk factor leads to disease in some individuals and not in others. Risk prediction, which is crucial in predicting and hence preventing disease, therefore becomes very challenging. In this article we review the currently available risk stratification tools for predicting CHD risk and discuss potential ways to improve risk prediction.

Contemporary approach to essential thrombocythemia and polycythemia vera.

PubMed

Aruch, Daniel; Mascarenhas, John

2016-03-01

Management of polycythemia vera and essential thrombocythemia requires understanding of the key concepts regarding diagnosis, risk stratification, and management. Essential thrombocythemia and polycythemia vera are among the Philadelphia chromosome negative myeloproliferative neoplasms. They are characterized by overproduction of blood cells and their complications include thrombosis, hemorrhage, and progression to myelofibrosis or acute myeloid leukemia (AML). Management of essential thrombocythemia/polycythemia vera requires recognition of the risk factors for thrombosis and hemorrhage. Risk stratification allows the clinician to make a treatment plan that may include antiplatelet therapy with aspirin alone or in combination with therapeutic phlebotomy in the case of polycythemia vera, or cytoreductive therapy for high-risk patients with either essential thrombocythemia or polycythemia vera. Hydroxyurea remains first-line therapy for high-risk patients with essential thrombocythemia/polycythemia vera, whereas second-line options include anagrelide, pegylated-IFNα-2a, and the JAK1/2 inhibitor ruxolitinib. The current evaluation of pegylated-IFNα-2a in global phase II and III studies will provide clarity to the potential long-term benefit and risks associated with this biologic in patients with essential thrombocythemia/polycythemia vera. Novel therapeutics aimed at prevention of disease progression to myelofibrosis/AML are the focus of current clinical trials. Risk stratification of patients with essential thrombocythemia/polycythemia vera by age and/or history of thrombosis provides the basis of risk adapted therapeutic intervention. Aggressive control of modifiable cardiovascular risk factors, the use of antiplatelet agents, control of the hematocrit less than 45% in polycythemia vera, and cytoreductive therapy in high-risk essential thrombocythemia/polycythemia vera patients is the focus of management. The exact role of IFN-α remains undefined and under active investigation, and the recent approval of ruxolitinib provides patients with polycythemia vera a second-line option.

Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers

PubMed Central

Watson, Matthew J; George, Arvin K; Maruf, Mahir; Frye, Thomas P; Muthigi, Akhil; Kongnyuy, Michael; Valayil, Subin G; Pinto, Peter A

2016-01-01

Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice. PMID:27400645

The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy.

PubMed

Naito, Shiho; Hillebrand, Mathias; Bernhardt, Alexander Martin Justus; Jagodzinski, Annika; Conradi, Lenard; Detter, Christian; Sydow, Karsten; Reichenspurner, Hermann; Kodolitsch, Yskert von; Girdauskas, Evaldas

2018-06-01

Traditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV. Georg Thieme Verlag KG Stuttgart · New York.

A new gender-specific model for skin autofluorescence risk stratification

PubMed Central

Ahmad, Muhammad S.; Damanhouri, Zoheir A.; Kimhofer, Torben; Mosli, Hala H.; Holmes, Elaine

2015-01-01

Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79–4.84 AU) and 2.20 AU (0.75–4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis. PMID:25974028

Risk stratification, genomic data and the law.

PubMed

Hall, Alison; Finnegan, Thomas; Chowdhury, Susmita; Dent, Tom; Kroese, Mark; Burton, Hilary

2018-02-22

Risk prediction models have a key role in stratified disease prevention, and the incorporation of genomic data into these models promises more effective personalisation. Although the clinical utility of incorporating genomic data into risk prediction tools is increasingly compelling, at least for some applications and disease types, the legal and regulatory implications have not been examined and have been overshadowed by discussions about clinical and scientific utility and feasibility. We held a workshop to explore relevant legal and regulatory perspectives from four EU Member States: France, Germany, the Netherlands and the UK. While we found no absolute prohibition on the use of such data in those tools, there are considerable challenges. Currently, these are modest and result from genomic data being classified as sensitive data under existing Data Protection regulation. However, these challenges will increase in the future following the implementation of EU Regulations on data protection which take effect in 2018, and reforms to the governance of the manufacture, development and use of in vitro diagnostic devices to be implemented in 2022. Collectively these will increase the regulatory burden placed on these products as risk stratification tools will be brought within the scope of these new Regulations. The failure to respond to the challenges posed by the use of genomic data in disease risk stratification tools could therefore prove costly to those developing and using such tools.

Brugada syndrome: diagnosis, risk stratification, and management.

PubMed

Adler, Arnon

2016-01-01

Asymptomatic patients with Brugada syndrome (BrS) have a small, but not trivial, risk of cardiac events. Their risk stratification and its impact on their management are controversial. The review focuses on the clinical aspects of BrS with special emphasis on the asymptomatic patient. Emerging data suggest that drug and fever-induced type I Brugada patterns are more common than previously appreciated. Although preliminary, these data may imply that asymptomatic patients with induced Brugada pattern are at an even lower risk than currently estimated.The latest data regarding induced ventricular arrhythmias during electrophysiological studies support its use as an indication for an implantable cardioverter defibrillator; however, this issue remains highly controversial.Several new risk markers, such as presence of the Brugada pattern in infero-lateral leads or the concomitant finding of an early repolarization pattern, have recently been proposed. Most asymptomatic BrS patients are at low risk of cardiac events. The presence of new risk markers in this population may prompt consideration of primary prevention measures; however, data supporting this approach are still limited.

Lagged segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

PubMed

Voss, Andreas; Fischer, Claudia; Schroeder, Rico; Figulla, Hans R; Goernig, Matthias

2012-07-01

The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.

Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.

PubMed

Diotti, Roberta Antonia; Mancini, Nicasio; Clementi, Nicola; Sautto, Giuseppe; Moreno, Guisella Janett; Criscuolo, Elena; Cappelletti, Francesca; Man, Petr; Forest, Eric; Remy, Louise; Giannecchini, Simone; Clementi, Massimo; Burioni, Roberto

2014-08-01

JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Current approaches for risk stratification of infectious complications in pediatric oncology.

PubMed

Härtel, Christoph; Deuster, Maresa; Lehrnbecher, Thomas; Schultz, Christian

2007-11-01

Infections are serious complications of cytoreductive therapy in pediatric cancer patients presenting with febrile neutropenia. It is standard of care to initiate empirical intravenous broad-spectrum antibiotics until the fever and neutropenia resolve. However, it might be effective and safe to allow for early hospital discharge in certain subgroups of patients. Two strategies for risk stratification of pediatric cancer patients with regard to infectious complications are discussed in this review: (1) clinical risk parameters and laboratory measures to assist therapeutic management at presentation with fever in neutropenia, and (2) investigations of individual genetic susceptibility factors to tailor potential prophylactic approaches. Given the data available from a significant number of small studies, a large prospective non-inferiority trial is essential to assess low-risk clinical factors and additional laboratory or genetic markers for their predictive value. (c) 2007 Wiley-Liss, Inc.

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

PubMed Central

Maas, Paige; Barrdahl, Myrto; Joshi, Amit D.; Auer, Paul L.; Gaudet, Mia M.; Milne, Roger L.; Schumacher, Fredrick R.; Anderson, William F.; Check, David; Chattopadhyay, Subham; Baglietto, Laura; Berg, Christine D.; Chanock, Stephen J.; Cox, David G.; Figueroa, Jonine D.; Gail, Mitchell H.; Graubard, Barry I.; Haiman, Christopher A.; Hankinson, Susan E.; Hoover, Robert N.; Isaacs, Claudine; Kolonel, Laurence N.; Le Marchand, Loic; Lee, I-Min; Lindström, Sara; Overvad, Kim; Romieu, Isabelle; Sanchez, Maria-Jose; Southey, Melissa C.; Stram, Daniel O.; Tumino, Rosario; VanderWeele, Tyler J.; Willett, Walter C.; Zhang, Shumin; Buring, Julie E.; Canzian, Federico; Gapstur, Susan M.; Henderson, Brian E.; Hunter, David J.; Giles, Graham G; Prentice, Ross L.; Ziegler, Regina G.; Kraft, Peter; Garcia-Closas, Montse; Chatterjee, Nilanjan

2017-01-01

IMPORTANCE An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention. OBJECTIVE To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. DESIGN, SETTING, AND PARTICIPANTS Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality. EXPOSURES Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors. MAIN OUTCOMES AND MEASURES Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking). RESULTS The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population. CONCLUSIONS AND RELEVANCE This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation. PMID:27228256

Effect of Serum C-Reactive Protein Level on Admission to Predict Mortality After Transcatheter Aortic Valve Implantation.

PubMed

Hioki, Hirofumi; Watanabe, Yusuke; Kozuma, Ken; Yamamoto, Masanori; Naganuma, Toru; Araki, Motoharu; Tada, Norio; Shirai, Shinichi; Yamanaka, Futoshi; Higashimori, Akihiro; Mizutani, Kazuki; Tabata, Minoru; Takagi, Kensuke; Ueno, Hiroshi; Hayashida, Kentaro

2018-04-12

The relation between C-reactive protein (CRP) level on admission and mortality after transcatheter aortic valve implantation (TAVI) remains unclear. To evaluate the impact of serum CRP level on mortality after TAVI, we assessed 1,016 patients with CRP who underwent TAVI and 538 patients with high-sensitive CRP (hs-CRP) level who underwent TAVI on admission in the OCEAN (Optimized Transcatheter Valvular Intervention)-TAVI registry. Study population was stratified into 2 groups (high/low), according to the median of CRP and hs-CRP on admission. We assessed the impact of high CRP and hs-CRP level on all-cause death after TAVI. During 2-year follow-up, all-cause death after TAVI was 9.4% in patients with CRP and 11.9% in patients with hs-CRP. Median value of serum CRP was 0.10 mg/dl in both CRP and hs-CRP. Patients with high CRP (>0.10 mg/dl) had significantly higher incidence of all-cause death compared with those with low CRP (11.5% vs 7.6%, log-rank p = 0.015). Multivariate Cox regression analysis with a time-varying covariate demonstrated that high CRP was an independent predictor of all-cause death within the first 3 months (hazard ratio 2.78, 95% CI 1.30 to 5.95) compared with from 3 months to 2 years (hazard ratio 0.80, 95% CI 0.47 to 1.36) (P for interaction = 0.008). Inversely, these results were not observed in the stratification using hs-CRP on admission. In conclusion, high CRP on admission was significantly associated with an increased risk of all-cause death after TAVI, particularly within the first 3 months after TAVI. Risk stratification using CRP may be a simple and useful strategy to identify high-risk patients who undergo TAVI. Copyright © 2018 Elsevier Inc. All rights reserved.

Stratification of risk to the surgical team in removal of small arms ammunition implanted in the craniofacial region: case report.

PubMed

Forbes, Jonathan A; Laughlin, Ian; Newberry, Shane; Ryhn, Michael; Pasley, Jason; Newberry, Travis

2016-09-01

In cases of penetrating injury with implantation of small arms ammunition, it can often be difficult to tell the difference between simple ballistics and ballistics associated with unexploded ordnances (UXOs). In the operative environment, where highly flammable substances are often close to the surgical site, detonation of UXOs could have catastrophic consequences for both the patient and surgical team. There is a paucity of information in the literature regarding how to evaluate whether an implanted munition contains explosive material. This report describes a patient who presented during Operation Enduring Freedom with an implanted munition suspicious for a UXO and the subsequent workup organized by Explosive Ordnance Disposal (EOD) Company prior to surgical removal. Clinical risk factors for UXOs include assassination attempts and/or wartime settings. Specific radiological features suggestive of a UXO include projectile size greater than 7.62-mm caliber, alterations in density of the tip, as well as radiological evidence of a hollowed-out core. If an implanted UXO is suspected, risks to the surgical and anesthesia teams can be minimized by notifying the nearest military installation with EOD capabilities and following clinical practice guidelines set forth by the Joint Theater Trauma System.

Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria.

PubMed

Goh, Brian K P; Chow, Pierce K H; Yap, Wai-Ming; Kesavan, Sittampalam M; Song, In-Chin; Paul, Pradeep G; Ooi, Boon-Swee; Chung, Yaw-Fui A; Wong, Wai-Keong

2008-08-01

This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.

Recruitment of Hexagenia mayfly nymphs in western Lake Erie linked to environmental variability

USGS Publications Warehouse

Bridgeman, Thomas B.; Schloesser, Don W.; Krause, Ann E.

2006-01-01

After a 40-year absence caused by pollution and eutrophication, burrowing mayflies (Hexagenia spp.) recolonized western Lake Erie in the mid 1990s as water quality improved. Mayflies are an important food resource for the economically valuable yellow perch fishery and are considered to be major indicator species of the ecological condition of the lake. Since their reappearance, however, mayfly populations have suffered occasional unexplained recruitment failures. In 2002, a failure of fall recruitment followed an unusually warm summer in which western Lake Erie became temporarily stratified, resulting in low dissolved oxygen levels near the lake floor. In the present study, we examined a possible link between Hexagenia recruitment and periods of intermittent stratification for the years 1997-2002. A simple model was developed using surface temperature, wind speed, and water column data from 2003 to predict stratification. The model was then used to detect episodes of stratification in past years for which water column data are unavailable. Low or undetectable mayfly recruitment occurred in 1997 and 2002, years in which there was frequent or extended stratification between June and September. Highest mayfly reproduction in 2000 corresponded to the fewest stratified periods. These results suggest that even relatively brief periods of stratification can result in loss of larval mayfly recruitment, probably through the effects of hypoxia. A trend toward increasing frequency of hot summers in the Great Lakes region could result in recurrent loss of mayfly larvae in western Lake Erie and other shallow areas in the Great Lakes.

Stratification of a closed region containing two buoyancy sources

NASA Astrophysics Data System (ADS)

Thompson, Andrew; Linden, Paul

2005-11-01

Many closed systems such as lakes, ocean basins, rooms etc. have inputs of buoyancy at different levels. We address the question of how the resulting stratification depends on the location of these sources. For example a lake is heated and cooled at the surface, while for a room cool air may be applied at the ceiling but the heat source may be a person standing on the floor. We present an experimental study of convection in a finite box in which we systematically vary the vertical location of two well-separated, constant buoyancy sources. We specifically consider the case of a dense source and a light source so that there is no net buoyancy flux into the tank. We study the development of the large-time stratification in the tank, which falls between one of two limits. When the location of the dense source is significantly higher than the light source, the fluid is well mixed and the system remains largely unstratified. When the location of the light source is significantly higher than the dense source, a two- layer stratification develops. We find that the circulation pattern is dominated by counter-flowing shear layers (Wong, Griffiths & Hughes, 2001), whose number and strength are strongly influenced by the buoyancy source locations. The shear layers are the primary means of communication between the plumes and thus play a large role in the resulting stratification. We support our findings with a simple numerical model.

Risk stratification personalised model for prediction of life-threatening ventricular tachyarrhythmias in patients with chronic heart failure.

PubMed

Frolov, Alexander Vladimirovich; Vaikhanskaya, Tatjana Gennadjevna; Melnikova, Olga Petrovna; Vorobiev, Anatoly Pavlovich; Guel, Ludmila Michajlovna

2017-01-01

The development of prognostic factors of life-threatening ventricular tachyarrhythmias (VTA) and sudden cardiac death (SCD) continues to maintain its priority and relevance in cardiology. The development of a method of personalised prognosis based on multifactorial analysis of the risk factors associated with life-threatening heart rhythm disturbances is considered a key research and clinical task. To design a prognostic and mathematical model to define personalised risk for life-threatening VTA in patients with chronic heart failure (CHF). The study included 240 patients with CHF (mean-age of 50.5 ± 12.1 years; left ventricular ejection fraction 32.8 ± 10.9%; follow-up period 36.8 ± 5.7 months). The participants received basic therapy for heart failure. The elec-trocardiogram (ECG) markers of myocardial electrical instability were assessed including microvolt T-wave alternans, heart rate turbulence, heart rate deceleration, and QT dispersion. Additionally, echocardiography and Holter monitoring (HM) were performed. The cardiovascular events were considered as primary endpoints, including SCD, paroxysmal ventricular tachycardia/ventricular fibrillation (VT/VF) based on HM-ECG data, and data obtained from implantable device interrogation (CRT-D, ICD) as well as appropriated shocks. During the follow-up period, 66 (27.5%) subjects with CHF showed adverse arrhythmic events, including nine SCD events and 57 VTAs. Data from a stepwise discriminant analysis of cumulative ECG-markers of myocardial electrical instability were used to make a mathematical model of preliminary VTA risk stratification. Uni- and multivariate Cox logistic regression analysis were performed to define an individualised risk stratification model of SCD/VTA. A binary logistic regression model demonstrated a high prognostic significance of discriminant function with a classification sensitivity of 80.8% and specificity of 99.1% (F = 31.2; c2 = 143.2; p < 0.0001). The method of personalised risk stratification using Cox logistic regression allows correct classification of more than 93.9% of CHF cases. A robust body of evidence concerning logistic regression prognostic significance to define VTA risk allows inclusion of this method into the algorithm of subsequent control and selection of the optimal treatment modality to treat patients with CHF.

Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies.

PubMed

González-Torrecilla, Esteban; Arenal, Angel; Atienza, Felipe; Datino, Tomás; Bravo, Loreto; Ruiz, Pablo; Ávila, Pablo; Fernández-Avilés, Francisco

2015-01-01

Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions do support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk evaluation and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.

External validation of the simple clinical score and the HOTEL score, two scores for predicting short-term mortality after admission to an acute medical unit.

PubMed

Stræde, Mia; Brabrand, Mikkel

2014-01-01

Clinical scores can be of aid to predict early mortality after admission to a medical admission unit. A developed scoring system needs to be externally validated to minimise the risk of the discriminatory power and calibration to be falsely elevated. We performed the present study with the objective of validating the Simple Clinical Score (SCS) and the HOTEL score, two existing risk stratification systems that predict mortality for medical patients based solely on clinical information, but not only vital signs. Pre-planned prospective observational cohort study. Danish 460-bed regional teaching hospital. We included 3046 consecutive patients from 2 October 2008 until 19 February 2009. 26 (0.9%) died within one calendar day and 196 (6.4%) died within 30 days. We calculated SCS for 1080 patients. We found an AUROC of 0.960 (95% confidence interval [CI], 0.932 to 0.988) for 24-hours mortality and 0.826 (95% CI, 0.774-0.879) for 30-day mortality, and goodness-of-fit test, χ(2) = 2.68 (10 degrees of freedom), P = 0.998 and χ(2) = 4.00, P = 0.947, respectively. We included 1470 patients when calculating the HOTEL score. Discriminatory power (AUROC) was 0.931 (95% CI, 0.901-0.962) for 24-hours mortality and goodness-of-fit test, χ(2) = 5.56 (10 degrees of freedom), P = 0.234. We find that both the SCS and HOTEL scores showed an excellent to outstanding ability in identifying patients at high risk of dying with good or acceptable precision.

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

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 < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Emergence of molecular imaging of aortic aneurysm; implications for risk stratification and management

PubMed Central

Golestani, Reza; Sadeghi, Mehran M.

2014-01-01

Summary Imaging cellular and molecular processes associated with aneurysm expansion, dissection, and rupture can potentially transform the management of patients with thoracic and abdominal aortic aneurysm (TAA and AAA). Here, we review recent advances in molecular imaging of aortic aneurysm, focusing on imaging modalities with the greatest potential for clinical translation and application, PET, SPECT and MRI. Inflammation (e.g., with 18F-FDG, nanoparticles) and matrix remodeling (e.g., with matrix metalloproteinase-targeted tracers) are highlighted as promising targets for molecular imaging of aneurysm. Potential alternative or complementary approaches to molecular imaging for aneurysm risk stratification are briefly discussed. PMID:24381115

Quantitative modeling of clinical, cellular, and extracellular matrix variables suggest prognostic indicators in cancer: a model in neuroblastoma.

PubMed

Tadeo, Irene; Piqueras, Marta; Montaner, David; Villamón, Eva; Berbegall, Ana P; Cañete, Adela; Navarro, Samuel; Noguera, Rosa

2014-02-01

Risk classification and treatment stratification for cancer patients is restricted by our incomplete picture of the complex and unknown interactions between the patient's organism and tumor tissues (transformed cells supported by tumor stroma). Moreover, all clinical factors and laboratory studies used to indicate treatment effectiveness and outcomes are by their nature a simplification of the biological system of cancer, and cannot yet incorporate all possible prognostic indicators. A multiparametric analysis on 184 tumor cylinders was performed. To highlight the benefit of integrating digitized medical imaging into this field, we present the results of computational studies carried out on quantitative measurements, taken from stromal and cancer cells and various extracellular matrix fibers interpenetrated by glycosaminoglycans, and eight current approaches to risk stratification systems in patients with primary and nonprimary neuroblastoma. New tumor tissue indicators from both fields, the cellular and the extracellular elements, emerge as reliable prognostic markers for risk stratification and could be used as molecular targets of specific therapies. The key to dealing with personalized therapy lies in the mathematical modeling. The use of bioinformatics in patient-tumor-microenvironment data management allows a predictive model in neuroblastoma.

Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

PubMed Central

Schley, Gunnar; Köberle, Carmen; Manuilova, Ekaterina; Rutz, Sandra; Forster, Christian; Weyand, Michael; Formentini, Ivan; Kientsch-Engel, Rosemarie; Eckardt, Kai-Uwe; Willam, Carsten

2015-01-01

Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease. PMID:26669323

Proposals for enhanced health risk assessment and stratification in an integrated care scenario.

PubMed

Dueñas-Espín, Ivan; Vela, Emili; Pauws, Steffen; Bescos, Cristina; Cano, Isaac; Cleries, Montserrat; Contel, Joan Carles; de Manuel Keenoy, Esteban; Garcia-Aymerich, Judith; Gomez-Cabrero, David; Kaye, Rachelle; Lahr, Maarten M H; Lluch-Ariet, Magí; Moharra, Montserrat; Monterde, David; Mora, Joana; Nalin, Marco; Pavlickova, Andrea; Piera, Jordi; Ponce, Sara; Santaeugenia, Sebastià; Schonenberg, Helen; Störk, Stefan; Tegner, Jesper; Velickovski, Filip; Westerteicher, Christoph; Roca, Josep

2016-04-15

Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Responsible teams for regional data management in the five ACT regions. We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Modeling the periodic stratification and gravitational circulation in San Francisco Bay, California

USGS Publications Warehouse

Cheng, Ralph T.; Casulli, Vincenzo

1996-01-01

A high resolution, three-dimensional (3-D) hydrodynamic numerical model is applied to San Francisco Bay, California to simulate the periodic tidal stratification caused by tidal straining and stirring and their long-term effects on gravitational circulation. The numerical model is formulated using fixed levels in the vertical and uniform computational mesh on horizontal planes. The governing conservation equations, the 3-D shallow water equations, are solved by a semi-implicit finite-difference scheme. Numerical simulations for estuarine flows in San Francisco Bay have been performed to reproduce the hydrodynamic properties of tides, tidal and residual currents, and salt transport. All simulations were carried out to cover at least 30 days, so that the spring-neap variance in the model results could be analyzed. High grid resolution used in the model permits the use of a simple turbulence closure scheme which has been shown to be sufficient to reproduce the tidal cyclic stratification and well-mixed conditions in the water column. Low-pass filtered 3-D time-series reveals the classic estuarine gravitational circulation with a surface layer flowing down-estuary and an up-estuary flow near the bottom. The intensity of the gravitational circulation depends upon the amount of freshwater inflow, the degree of stratification, and spring-neap tidal variations.

Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy.

PubMed

Vriesendorp, Pieter A; Schinkel, Arend F L; Liebregts, Max; Theuns, Dominic A M J; van Cleemput, Johan; Ten Cate, Folkert J; Willems, Rik; Michels, Michelle

2015-08-01

The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57-0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47-0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50-0.70; P=0.07). The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD. © 2015 American Heart Association, Inc.

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

PubMed

Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

2013-01-01

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Impact of screening for metabolic syndrome on the evaluation of obese living kidney donors.

PubMed

Marcusa, Daniel P; Schaubel, Douglas E; Woodside, Kenneth J; Sung, Randall S

2018-01-01

We report our experience with metabolic syndrome screening for obese living kidney donor candidates to mitigate the long-term risk of CKD. We retrospectively reviewed 814 obese (BMI≥30) and 993 nonobese living kidney donor evaluations over 12 years. Using logistic regression, we explored interactions between social/clinical variables and candidate acceptance before and after policy implementation. Obese donor candidate acceptance decreased after metabolic syndrome screening began (56.3%, 46.3%, p < 0.01), while nonobese candidate acceptance remained similar (59.6%, 59.2%, p = 0.59). Adjusting for age, gender, race, BMI, and number of prior evaluations, acceptance of obese candidates decreased significantly more than nonobese (p = 0.025). In candidates without metabolic syndrome, there was no significant change in how age, sex, race, or BMI affected a donor candidate's probability of acceptance. Metabolic syndrome screening is a simple stratification tool for centers with liberal absolute BMI cut-offs to exclude potentially higher-risk obese candidates. Copyright © 2017 Elsevier Inc. All rights reserved.

Combining risk markers improves cardiovascular risk prediction in women.

PubMed

Holewijn, Suzanne; den Heijer, Martin; Kiemeney, Lambertus A; Stalenhoef, Anton F H; de Graaf, Jacqueline

2014-01-01

Cardiovascular risk stratification could be improved by adding measures of atherosclerosis to current risk scores, especially in intermediate-risk individuals. We prospectively evaluated the additive value of different non-invasive risk markers (both individual and combined) for gender-specific cardiovascular risk stratification on top of traditional risk factors in a middle-aged population-based cohort. Carotid-plaques, IMT (intima-media thickness), ABI (ankle-brachial index), PWV (pulse-wave velocity), AIx (augmentation index), CAP (central augmented pressure) and CSP (central-systolic pressure) were measured in 1367 CVD (cardiovascular disease)-free participants aged 50-70 years old. Cardiovascular events were validated after a mean follow-up of 3.8 years. AUC (area-under-the-curve) and NRI (net reclassification improvement) analyses (total-NRI for all and clinical-NRI for intermediate-risk groups) were used to determine the additive value of individual and combined risk markers. Cardiovascular events occurred in 32 women and 39 men. Traditional cardiovascular risk factors explained 6.2% and 12.5% of the variance in CVD in women and men respectively. AUCs did not substantially increase by adding individual or combined non-invasive risk markers. Individual risk markers only improved reclassification in intermediate-risk women and more than in men; clinical-NRIs ranged between 48.0 and 173.1% in women and 8.9 and 20% in men. Combined non-invasive-risk markers improved reclassification in all women and even more in those at intermediate risk; 'IMT-presence-thickness-of-plaques' showed largest reclassification [total-NRI=33.8%, P=0.012; IDI (integrated-discrimination-improvement)=0.048, P=0.066; clinical-NRI=168.0%]. In men, combined non-invasive risk markers improved reclassification only in those at intermediate risk; 'PWV-AIx-CSP-CAP-IMT' showed the largest reclassification (total-NRI=14.5%, P=0.087; IDI=0.016, P=0.148; clinical-NRI=46.0%). In all women, cardiovascular risk stratification improved by adding combinations and in women at intermediate risk also by adding individual non-invasive risk markers. The additive value of individual and combined non-invasive risk markers in men is limited to men at intermediate risk only, and to a lesser extent than in women.

Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer.

PubMed

Lubbock, Alexander L R; Stewart, Grant D; O'Mahony, Fiach C; Laird, Alexander; Mullen, Peter; O'Donnell, Marie; Powles, Thomas; Harrison, David J; Overton, Ian M

2017-06-26

Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification. We investigated the influence of confounding ITH on the performance of a novel molecular prognostic model, enabled by pathologist-guided multiregion sampling (n = 183) of geographically separated mccRCC cohorts from the SuMR trial (development, n = 22) and the SCOTRRCC study (validation, n = 22). Tumour protein levels quantified by reverse phase protein array (RPPA) were investigated alongside clinical variables. Regularised wrapper selection identified features for Cox multivariate analysis with overall survival as the primary endpoint. The optimal subset of variables in the final stratification model consisted of N-cadherin, EPCAM, Age, mTOR (NEAT). Risk groups from NEAT had a markedly different prognosis in the validation cohort (log-rank p = 7.62 × 10 -7 ; hazard ratio (HR) 37.9, 95% confidence interval 4.1-353.8) and 2-year survival rates (accuracy = 82%, Matthews correlation coefficient = 0.62). Comparisons with established clinico-pathological scores suggest favourable performance for NEAT (Net reclassification improvement 7.1% vs International Metastatic Database Consortium score, 25.4% vs Memorial Sloan Kettering Cancer Center score). Limitations include the relatively small cohorts and associated wide confidence intervals on predictive performance. Our multiregion sampling approach enabled investigation of NEAT validation when limiting the number of samples analysed per tumour, which significantly degraded performance. Indeed, sample selection could change risk group assignment for 64% of patients, and prognostication with one sample per patient performed only slightly better than random expectation (median logHR = 0.109). Low grade tissue was associated with 3.5-fold greater variation in predicted risk than high grade (p = 0.044). This case study in mccRCC quantitatively demonstrates the critical importance of tumour sampling for the success of molecular biomarker studies research where ITH is a factor. The NEAT model shows promise for mccRCC prognostication and warrants follow-up in larger cohorts. Our work evidences actionable parameters to guide sample collection (tumour coverage, size, grade) to inform the development of reproducible molecular risk stratification methods.

An externally validated model for predicting long-term survival after exercise treadmill testing in patients with suspected coronary artery disease and a normal electrocardiogram.

PubMed

Lauer, Michael S; Pothier, Claire E; Magid, David J; Smith, S Scott; Kattan, Michael W

2007-12-18

The exercise treadmill test is recommended for risk stratification among patients with intermediate to high pretest probability of coronary artery disease. Posttest risk stratification is based on the Duke treadmill score, which includes only functional capacity and measures of ischemia. To develop and externally validate a post-treadmill test, multivariable mortality prediction rule for adults with suspected coronary artery disease and normal electrocardiograms. Prospective cohort study conducted from September 1990 to May 2004. Exercise treadmill laboratories in a major medical center (derivation set) and a separate HMO (validation set). 33,268 patients in the derivation set and 5821 in the validation set. All patients had normal electrocardiograms and were referred for evaluation of suspected coronary artery disease. The derivation set patients were followed for a median of 6.2 years. A nomogram-illustrated model was derived on the basis of variables easily obtained in the stress laboratory, including age; sex; history of smoking, hypertension, diabetes, or typical angina; and exercise findings of functional capacity, ST-segment changes, symptoms, heart rate recovery, and frequent ventricular ectopy in recovery. The derivation data set included 1619 deaths. Although both the Duke treadmill score and our nomogram-illustrated model were significantly associated with death (P < 0.001), the nomogram was better at discrimination (concordance index for right-censored data, 0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate- to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The model also predicted 3-year mortality rates well in the validation set: Based on an optimal cut-point for a negative predictive value of 0.97, derivation and validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25% and 29% above the cut-point. Blood test-based measures or left ventricular ejection fraction were not included. The nomogram can be applied only to patients with a normal electrocardiogram. Clinical utility remains to be tested. A simple nomogram based on easily obtained pretest and exercise test variables predicted all-cause mortality in adults with suspected coronary artery disease and normal electrocardiograms.

Risk Stratification of Acute Kidney Injury Using the Blood Urea Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.

PubMed

Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei

2015-01-01

Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality. In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine. The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.

All men with vasculogenic erectile dysfunction require a cardiovascular workup.

PubMed

Miner, Martin; Nehra, Ajay; Jackson, Graham; Bhasin, Shalender; Billups, Kevin; Burnett, Arthur L; Buvat, Jacques; Carson, Culley; Cunningham, Glenn; Ganz, Peter; Goldstein, Irwin; Guay, Andre; Hackett, Geoff; Kloner, Robert A; Kostis, John B; LaFlamme, K Elizabeth; Montorsi, Piero; Ramsey, Melinda; Rosen, Raymond; Sadovsky, Richard; Seftel, Allen; Shabsigh, Ridwan; Vlachopoulos, Charalambos; Wu, Frederick

2014-03-01

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

Piraud, Marie; Menze, Bjoern H.; Hielscher, Thomas; Hofmanninger, Johannes; Wagner, Barbara; Kauczor, Hans-Ulrich; Merz, Maximilian; Hillengass, Jens; Langs, Georg; Weber, Marc-André

2018-01-01

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 114mm3/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. PMID:29861868

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.

PubMed

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.

Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation.

PubMed

Pun, Shawn C; Landau, Heather J; Riedel, Elyn R; Jordan, Jonathan; Yu, Anthony F; Hassoun, Hani; Chen, Carol L; Steingart, Richard M; Liu, Jennifer E

2018-01-01

Autologous hematopoietic cell transplantation (HCT) is a first-line therapy for prolonging survival in patients with light-chain (AL) amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT because of high risk for transplantation-related mortality and poor overall survival. Whether baseline left ventricular global longitudinal strain (GLS) can provide additional risk stratification and predict survival after HCT in this high-risk population remains unclear. The aim of this study was to evaluate the prognostic implication of baseline GLS and the added value of GLS beyond circulating cardiac biomarkers for risk stratification in patients with AL amyloidosis undergoing HCT. Eighty-two patients with newly diagnosed AL amyloidosis who underwent upfront HCT between January 2007 and April 2014 were included in the study. Clinical, echocardiographic, and serum cardiac biomarker data were collected at baseline and 12 months following HCT. GLS measurements were performed using a vendor-independent offline system. The median follow-up time for survivors was 58 months. Sixty-four percent of patients were in biomarker-based Mayo stage II or III. GLS, brain natriuretic peptide, troponin, and mitral E/A ratio were identified as the strongest predictors of survival (P < .0001). Other predictors included sex, creatinine, free AL, wall thickness, and ejection fraction. Mayo stage was significantly associated with outcome, with 5-year survival of 93%, 72% and 31% in stage I, II, and III patients, respectively. GLS of 17% was identified as the value that best discriminated survivors from nonsurvivors, and the application of this cutoff value provided further mortality risk stratification within each Mayo stage. GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

ADVANCIS Score Predicts Acute Kidney Injury After Percutaneous Coronary Intervention for Acute Coronary Syndrome.

PubMed

Fan, Pei-Chun; Chen, Tien-Hsing; Lee, Cheng-Chia; Tsai, Tsung-Yu; Chen, Yung-Chang; Chang, Chih-Hsiang

2018-01-01

Acute kidney injury (AKI), a common and crucial complication of acute coronary syndrome (ACS) after receiving percutaneous coronary intervention (PCI), is associated with increased mortality and adverse outcomes. This study aimed to develop and validate a risk prediction model for incident AKI after PCI for ACS. We included 82,186 patients admitted for ACS and receiving PCI between 1997 and 2011 from the Taiwan National Health Insurance Research Database and randomly divided them into a training cohort (n = 57,630) and validation cohort (n = 24,656) for risk model development and validation, respectively. Risk factor analysis revealed that age, diabetes mellitus, ventilator use, prior AKI, number of intervened vessels, chronic kidney disease (CKD), intra-aortic balloon pump (IABP) use, cardiogenic shock, female sex, prior stroke, peripheral arterial disease, hypertension, and heart failure were significant risk factors for incident AKI after PCI for ACS. The reduced model, ADVANCIS, comprised 8 clinical parameters (age, diabetes mellitus, ventilator use, prior AKI, number of intervened vessels, CKD, IABP use, cardiogenic shock), with a score scale ranging from 0 to 22, and performed comparably with the full model (area under the receiver operating characteristic curve, 87.4% vs 87.9%). An ADVANCIS score of ≥6 was associated with higher in-hospital mortality risk. In conclusion, the ADVANCIS score is a novel, simple, robust tool for predicting the risk of incident AKI after PCI for ACS, and it can aid in risk stratification to monitor patient care.

Maximization of the usage of coronary CTA derived plaque information using a machine learning based algorithm to improve risk stratification; insights from the CONFIRM registry.

PubMed

van Rosendael, Alexander R; Maliakal, Gabriel; Kolli, Kranthi K; Beecy, Ashley; Al'Aref, Subhi J; Dwivedi, Aeshita; Singh, Gurpreet; Panday, Mohit; Kumar, Amit; Ma, Xiaoyue; Achenbach, Stephan; Al-Mallah, Mouaz H; Andreini, Daniele; Bax, Jeroen J; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Cury, Ricardo C; DeLago, Augustin; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon A; Maffei, Erica; Marques, Hugo; Pontone, Gianluca; Raff, Gilbert L; Rubinshtein, Ronen; Shaw, Leslee J; Villines, Todd C; Gransar, Heidi; Lu, Yao; Jones, Erica C; Peña, Jessica M; Lin, Fay Y; Min, James K

Machine learning (ML) is a field in computer science that demonstrated to effectively integrate clinical and imaging data for the creation of prognostic scores. The current study investigated whether a ML score, incorporating only the 16 segment coronary tree information derived from coronary computed tomography angiography (CCTA), provides enhanced risk stratification compared with current CCTA based risk scores. From the multi-center CONFIRM registry, patients were included with complete CCTA risk score information and ≥3 year follow-up for myocardial infarction and death (primary endpoint). Patients with prior coronary artery disease were excluded. Conventional CCTA risk scores (conventional CCTA approach, segment involvement score, duke prognostic index, segment stenosis score, and the Leaman risk score) and a score created using ML were compared for the area under the receiver operating characteristic curve (AUC). Only 16 segment based coronary stenosis (0%, 1-24%, 25-49%, 50-69%, 70-99% and 100%) and composition (calcified, mixed and non-calcified plaque) were provided to the ML model. A boosted ensemble algorithm (extreme gradient boosting; XGBoost) was used and the entire data was randomly split into a training set (80%) and testing set (20%). First, tuned hyperparameters were used to generate a trained model from the training data set (80% of data). Second, the performance of this trained model was independently tested on the unseen test set (20% of data). In total, 8844 patients (mean age 58.0 ± 11.5 years, 57.7% male) were included. During a mean follow-up time of 4.6 ± 1.5 years, 609 events occurred (6.9%). No CAD was observed in 48.7% (3.5% event), non-obstructive CAD in 31.8% (6.8% event), and obstructive CAD in 19.5% (15.6% event). Discrimination of events as expressed by AUC was significantly better for the ML based approach (0.771) vs the other scores (ranging from 0.685 to 0.701), P < 0.001. Net reclassification improvement analysis showed that the improved risk stratification was the result of down-classification of risk among patients that did not experience events (non-events). A risk score created by a ML based algorithm, that utilizes standard 16 coronary segment stenosis and composition information derived from detailed CCTA reading, has greater prognostic accuracy than current CCTA integrated risk scores. These findings indicate that a ML based algorithm can improve the integration of CCTA derived plaque information to improve risk stratification. Published by Elsevier Inc.

[Syncope and work: role of the occupational physician and global risk stratification].

PubMed

Barbic, F; Angaroni, L; Orlandi, M; Costantino, G; Dipaola, E; Borleri, D; Borchini, R; D'Adda, F; Perego, F; Borella, M; Galli, A; Solbiati, M; Scanella, E; Casazza, G; Seghizzi, P; Furlan, R

2011-01-01

Safety risk for subjects suffering from syncope while working has not been as yet addressed by occupational medicine. The present study was aimed at evaluating a new developed methodology for job tasks risk stratification in patients with syncope. During a work-shop on syncope and occupational risk, 149 occupational physicians (OP) with about 10 years of clinical experience were asked to fulfil a Visual Analogue Scale (VAS) concerning the doctor's estimated potential damage (D) to the worker and the probability of a damage to occur (P) should syncope take place during the job task. Five job tasks characterized by different risk for safety (1, driving; 2, toxic products handling; 3, job performed closed to hot surfaces o free flames; 4, surgical activity; 5, office job) were identified. OP correctly stratified the risk associated to the different job tasks in patients with syncope. Unexpectedly, task #3 was given a risk similar to that obtained in drivers. This might be of paramount clinical and social importance when patients with syncope have to return to their job tasks.

Risk stratification in secondary cardiovascular prevention.

PubMed

Lazzeroni, Davide; Coruzzi, Paolo

2018-02-19

Worldwide, more than 7 million people experience acute myocardial infarction (AMI) every year (1), and although substantial reduction in mortality has been obtained in recent decades, one-year mortality rates are still in the range of 10%. Among patients who survive AMI, 20% suffer a second cardiovascular event in the first year and approximately 50% of major coronary events occur in those with a previous hospital discharge diagnosis of AMI (2). Despite the evidence that lifestyle changes and risk factors management strongly improve long-term prognosis, preventive care post-AMI remains sub-optimal. Cross-sectional data from the serially conducted EUROASPIRE surveys in patients with established ischemic heart disease (IHD) and people at high cardiovascular risk have demonstrated a high prevalence of unhealthy lifestyle, modifiable risk factors and inadequate use of drug therapies to achieve blood pressure and lipid goals (3). Secondary prevention programmes, defined as the level of preventive care focusing on early risk stratification, are highly recommended in all IHD patients, to restore quality of life, maintain or improve functional capacity and prevent recurrence.

Prediction of breast cancer risk based on profiling with common genetic variants.

PubMed

Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; Dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Figueroa, Jonine; Chanock, Stephen J; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M; Hunter, David J; Lindstrom, Sara; Tamimi, Rulla M; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J; Doody, Michele M; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G; Milne, Roger L; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Koppert, Linetta B; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Eccles, Diana M; Tapper, William J; Rafiq, Sajjad; John, Esther M; Whittemore, Alice S; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E; Yao, Song; Zheng, Wei; Halverson, Sandra L; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Simard, Jacques; Hall, Per; Easton, Douglas F; Garcia-Closas, Montserrat

2015-05-01

Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © The Author 2015. Published by Oxford University Press.

Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

PubMed Central

Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Pankratz, Vernon S.; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M.; Hunter, David J.; Lindstrom, Sara; Tamimi, Rulla M.; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J.; Doody, Michele M.; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Koppert, Linetta B.; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Eccles, Diana M.; Tapper, William J.; Rafiq, Sajjad; John, Esther M.; Whittemore, Alice S.; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E.; Yao, Song; Zheng, Wei; Halverson, Sandra L.; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Simard, Jacques; Hall, Per; Easton, Douglas F.; Garcia-Closas, Montserrat

2015-01-01

Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. PMID:25855707

Contemporary post surgical management of differentiated thyroid carcinoma.

PubMed

Tala, H; Tuttle, R M

2010-08-01

Risk assessment is the cornerstone of contemporary management of thyroid cancer. Following thyroid surgery, an initial risk assessment of recurrence and disease-specific mortality is made using important intra-operative findings, histologic characteristics of the tumor, molecular profile of the tumor, post-operative serum thyroglobulin and any available cross-sectional imaging studies. This initial risk assessment is used to guide recommendations regarding the need for remnant ablation, external beam irradiation, systemic therapy, degree of TSH suppression, and follow-up disease detection strategy over the first 2 years after initial therapy. While this initial risk stratification provides valuable information, it is a static representation of the patient in the first few weeks post-operatively that does not change over time. Depending on how the patient responds to our initial therapies, the risk of recurrence and death may change significantly during follow-up. In order to account for differences in response to therapy in individual patients and to incorporate the impact of treatment on our initial risk estimates, we recommend a re-stratification of risk at the 2-year point of follow-up. This re-stratification provides an updated risk estimate that can be used to guide ongoing management recommendations including the frequency and intensity of follow-up, degree of ongoing TSH suppression, and need for additional therapies. Ongoing management recommendations must be tailored to realistic, evolving risk estimates that are actively updated during follow-up. By individualizing therapy on the basis of initial and ongoing risk assessments, we can maximize the beneficial effects of aggressive therapy in patients with thyroid cancer who are likely to benefit from it, while minimizing potential complications and side effects in low-risk patients destined to have a full healthy and productive life after minimal therapeutic intervention. Copyright (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

CMV-Specific T Cell Monitoring Offers Superior Risk Stratification of CMV-Seronegative Kidney Transplant Recipients of a CMV-Seropositive Donor.

PubMed

Schachtner, Thomas; Stein, Maik; Reinke, Petra

2017-10-01

Detectable cytomegalovirus (CMV)-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV replication. Three hundred twenty-six KTRs were studied and classified with respect to CMV serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-γ Elispot assay. Nineteen (28%) of 67 D+R- KTRs showed pretransplant CMV-specific T cells. Although no differences were observed for CMV replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV loads (P < 0.05). KTRs with decreasing/undetectable CMV-IE1-specific T cells pretransplantation and posttransplantation were at greatest risk of CMV replication. KTRs with stable/increasing CMV-IE1-specific T cells from pretransplantation to posttransplantation, however, showed low risk of CMV replication (P < 0.001). One hundred sixty-two (80%) of 203 R+ KTRs showed pretransplant CMV-specific T cells. Decreasing/undetectable CMV-IE1-specific T cells from pretransplantation and posttransplantation identified those R+ KTRs at increased risk of CMV replication (65/80 KTRs; 81%; P < 0.001). Despite CMV prophylaxis, D+R- KTRs are at greatest risk of CMV disease. Our data suggest that monitoring CMV-specific T cell kinetics from pretransplantation to posttransplantation, particularly directed to CMV-IE1, offers superior risk stratification compared with CMV serostatus alone.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

PubMed

Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

2011-12-01

Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients.

PubMed

Hummel, Scott L; Ghalib, Hussam H; Ratz, David; Koelling, Todd M

2013-11-01

Most heart failure (HF) risk stratification models were developed for inpatient use, and available outpatient models use a complex set of variables. We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients. Using a quality improvement database and multivariable Cox modeling, we derived the Heart Failure Patient Severity Index (HFPSI) in the University of Michigan HF clinic (UM cohort, n = 1,536; 314 reached primary outcome). We externally validated the HFPSI in the Ann Arbor Veterans' Affairs HF clinic (VA cohort, n = 445; 106 outcomes) and explored "real-time" HFPSI use (VA-RT cohort, n = 486; 141 outcomes) by tracking VA patients for 6 months from their most recently calculated HFPSI, rather than using an arbitrary start date for the cohort. The HFPSI model included blood urea nitrogen, B-type natriuretic peptide, New York Heart Association class, diabetes status, history of atrial fibrillation/flutter, and all-cause hospitalization within the prior 1 and 2 to 6 months. The concordance c statistics in the UM/VA/VA-RT cohorts were 0.71/0.68/0.74. Kaplan-Meier curves and log-rank testing demonstrated excellent risk stratification, particularly between a large, low-risk group (40% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 8%/12%/12%) and a small, high-risk group (10% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 57%/58%/79%). The HFPSI uses readily available data to predict the 6-month risk of death and/or all-cause medical hospitalization in HF clinic outpatients and could potentially help allocate specialized HF resources within health systems. © 2013.

Evaluation of screening methods for identification of patients with chronic rheumatological disease requiring tuberculosis chemoprophylaxis prior to commencement of TNF-α antagonist therapy.

PubMed

Singanayagam, Aran; Manalan, Kavina; Sridhar, Saranya; Molyneaux, Philip L; Connell, David W; George, Peter M; Kindelerer, Anne; Seneviratne, Suranjith; Lalvani, Ajit; Wickremasinghe, Melissa; Kon, Onn Min

2013-10-01

Patients undergoing tumour necrosis factor (TNF)-α antagonist therapy are at increased risk of latent tuberculosis infection (LTBI) reactivation. The aim of this study was to determine the optimum available screening strategy for identifying patients for tuberculosis (TB) chemoprophylaxis. We conducted a prospective observational study of consecutive adults with chronic rheumatological disease referred for LTBI screening prior to commencement of TNF-α antagonist therapy. All patients included had calculation of TB risk according to age, ethnicity and year of UK entry, as described in the 2005 British Thoracic Society (BTS) guidelines and measurement of tuberculin skin test (TST) and T.Spot.TB. There were 187 patients included in the study, with 157 patients (84%) taking immunosuppressants. 137 patients would require further risk stratification according to the BTS algorithm, with 110 (80.3%) classified as being at low risk of having LTBI. There were 39 patients (35.5%) who were categorised as low risk but were either TST and/or T.Spot positive and would not have received chemoprophylaxis according to the BTS algorithm. Combination of all three methods (risk stratification and/or positive T.Spot and/or positive TST) identified 66 patients out of 137 who would potentially be offered chemoprophylaxis, which was greater than any single test or two-test combination. Performing both a TST and T.Spot in patients on immunosuppressants prior to commencement of TNF-α antagonist therapy gives an additional yield of potential LTBI compared with use of risk stratification tables alone. Our results suggest that use of all three screening modalities gives the highest yield of patients potentially requiring chemoprophylaxis.

Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation

PubMed Central

Huh, Jung Wook; Kim, Sung Chun; Sohn, Insuk; Jung, Sin-Ho; Kim, Hee Cheol

2016-01-01

Background In this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum. Methods Bloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance. Results During a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations). Conclusion Aptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients. PMID:26908450

Blood pressure load does not add to ambulatory blood pressure level for cardiovascular risk stratification.

PubMed

Li, Yan; Thijs, Lutgarde; Boggia, José; Asayama, Kei; Hansen, Tine W; Kikuya, Masahiro; Björklund-Bodegård, Kristina; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Kuznetsova, Tatiana; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Sandoya, Edgardo; Kawecka-Jaszcz, Kalina; Filipovsky, Jan; Imai, Yutaka; Ibsen, Hans; O'Brien, Eoin; Wang, Jiguang; Staessen, Jan A

2014-05-01

Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings ≥135/≥85 mm Hg and ≥120/≥70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hg×h) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R(2) statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hg×h conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)≤0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.

Deep Vein Thrombosis Prophylaxis: State of the Art.

PubMed

Lieberman, Jay R

2018-03-21

The selection of a prophylaxis regimen to prevent symptomatic pulmonary embolism and deep vein thrombosis is a balance between efficacy and safety. The latest American Academy of Orthopaedic Surgeons guideline recommended that either chemoprophylaxis or mechanical prophylaxis be used after total joint arthroplasty but did not recommend specific agents. However, the latest evidence-based American College of Chest Physicians guideline recommended a variety of chemoprophylaxis and mechanical agents for a minimum of 10 to 14 days after total joint arthroplasty. Risk stratification is the key to the selection of the appropriate prophylaxis regimen for the individual patient, but the optimal risk stratification protocol still needs to be developed. Copyright © 2018. Published by Elsevier Inc.

Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Wong, Hector R

2018-01-01

The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Prospective observational cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome. Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome.

Sampling estimators of total mill receipts for use in timber product output studies

Treesearch

John P. Brown; Richard G. Oderwald

2012-01-01

Data from the 2001 timber product output study for Georgia was explored to determine new methods for stratifying mills and finding suitable sampling estimators. Estimators for roundwood receipts totals comprised several types: simple random sample, ratio, stratified sample, and combined ratio. Two stratification methods were examined: the Dalenius-Hodges (DH) square...

Prevention of Cardiovascular Disease in Women.

PubMed

Saeed, Anum; Kampangkaew, June; Nambi, Vijay

2017-01-01

Cardiovascular diseases are the leading cause of morbidity and mortality among women worldwide. The pathophysiological basis of cardiovascular health among men and women is not identical. This leads to variable cardiovascular responses to stimulus and presentation of cardiovascular disease symptoms, both of which can have a direct effect on treatment outcomes. Traditionally, the enrollment of women in clinical trials has been minimal, resulting in a lack of gender-specific analysis of clinical trial data and, therefore, the absence of concrete risk factor assessment among women. However, scientific progress in the past decade has identified a spectrum of risk factors for cardiovascular diseases that may be specific to women. These risk factors, which may include menopause, hypertensive disease of pregnancy, and depression, confer additional risk in women besides the traditional risk factors. The current state of knowledge and awareness about these risk factors is suboptimal at this time. Therefore, although the treatment of cardiovascular diseases is similar in both genders, appropriate risk stratification may be limited in women compared to men. The purpose of this review is to describe the recent trends in identifying female-specific risk factors for cardiovascular diseases, their utility in risk stratification, and current pharmacological options for women with regard to cardiovascular disease prevention.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

PubMed

Bertoluci, Marcello Casaccia; Moreira, Rodrigo Oliveira; Faludi, André; Izar, Maria Cristina; Schaan, Beatriz D; Valerio, Cynthia Melissa; Bertolami, Marcelo Chiara; Chacra, Ana Paula; Malachias, Marcus Vinicius Bolivar; Vencio, Sérgio; Saraiva, José Francisco Kerr; Betti, Roberto; Turatti, Luiz; Fonseca, Francisco Antonio Helfenstein; Bianco, Henrique Tria; Sulzbach, Marta; Bertolami, Adriana; Salles, João Eduardo Nunes; Hohl, Alexandre; Trujilho, Fábio; Lima, Eduardo Gomes; Miname, Marcio Hiroshi; Zanella, Maria Teresa; Lamounier, Rodrigo; Sá, João Roberto; Amodeo, Celso; Pires, Antonio Carlos; Santos, Raul D

2017-01-01

Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.

World Health Organization cardiovascular risk stratification and target organ damage.

PubMed

Piskorz, D; Bongarzoni, L; Citta, L; Citta, N; Citta, P; Keller, L; Mata, L; Tommasi, A

2016-01-01

Prediction charts allow treatment to be targeted according to simple markers of cardiovascular risk; many algorithms do not recommend screening asymptomatic target organ damage which could change dramatically the assessment. To demonstrate that target organ damage is present in low cardiovascular risk hypertensive patients and it is more frequent and severe as global cardiovascular risk increases. Consecutive hypertensive patients treated at a single Latin American center. Cardiovascular risk stratified according to 2013 WHO/ISH risk prediction chart America B. Left ventricular mass assessed by Devereux method, left ventricular hypertrophy considered >95g/m(2) in women and >115g/m(2) in men. Transmitral diastolic peak early flow velocity to average septal/lateral peak early diastolic relaxation velocity (E/e' ratio) measured cut off value >13. Systolic function assessed by tissue Doppler average interventricular septum/lateral wall mitral annulus rate systolic excursion (s wave). A total of 292 patients were included of whom 159 patients (54.5%) had cardiovascular risk of <10%, 90 (30.8%) had cardiovascular risk of 10-20% and 43 (14.7%) had cardiovascular risk of >20%. Left ventricular hypertrophy was detected in 17.6% low risk patients, 27.8% in medium risk and 23.3% in high risk (p<0.05), abnormal E/e' ratio was found in 13.8%, 31.1% and 27.9%, respectively (p<0.05). Mean s wave was 8.03+8, 8.1+9 and 8.7+1cm/s for low, intermediate and high risk patients, respectively (p<0.025). Target organ damage is more frequent and severe in high risk; one over four subjects was misclassified due to the presence of asymptomatic target organ damage. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

Correction of Population Stratification in Large Multi-Ethnic Association Studies

PubMed Central

Serre, David; Montpetit, Alexandre; Paré, Guillaume; Engert, James C.; Yusuf, Salim; Keavney, Bernard; Hudson, Thomas J.; Anand, Sonia

2008-01-01

Background The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification. Methodology/Principal Findings We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification. Conclusions/Significance Our results highlight the importance of carefully addressing population stratification and of carefully “cleaning” the sample prior to analyses to obtain stronger signals of association and to avoid spurious results. PMID:18196181

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

PubMed

Anderson, Nigel J; Jackson, James E; Smith, Jennifer G; Wada, Morikatsu; Schneider, Michal; Poulsen, Michael; Rolfo, Maureen; Fahandej, Maziar; Gan, Hui; Joon, Daryl Lim; Khoo, Vincent

2018-05-13

The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use. © 2018 Wiley Periodicals, Inc.

Use of risk stratification to guide ambulatory management of neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee.

PubMed

Worth, L J; Lingaratnam, S; Taylor, A; Hayward, A M; Morrissey, S; Cooney, J; Bastick, P A; Eek, R W; Wei, A; Thursky, K A

2011-01-01

Utilization of risk-stratification tools in the setting of neutropenic fever is currently limited by inadequate knowledge and lack of awareness. Within this context, the approach to management of low-risk patients with neutropenic fever is inconsistent with the available evidence across many Australian treating centres. These clinical guidelines define and clarify an accepted standard of care for this patient group given the current evidence base. The Multinational Association for Supportive Care in Cancer risk index is presented as the preferred risk assessment tool for determining patient risk. Suitability of ambulatory care within specific patient populations is discussed, with defined eligibility criteria provided to guide clinical decision-making. Detailed recommendations for implementing appropriate ambulatory strategies, such as early discharge and outpatient antibiotic therapy, are also provided. Due consideration is given to infrastructural requirements and other supportive measures at a resourcing and operational level. An analysis of the relevant health economics is also presented. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Model of the discrete destruction process of a solid body

NASA Astrophysics Data System (ADS)

Glagolev, V. V.; Markin, A. A.

2018-03-01

Destruction is considered as a discrete thermomechanical process, in which the deformation of a solid body is achieved by changing the boundary stresses acting on the part of the volume being destroyed with the external load unchanged. On the basis of the proposed concept, a model for adhesive stratification of a composite material is constructed. When adhesive stratification is used, the stress state of one or two boundaries of the adhesive layer changes to zero if the bonds with the joined body are broken. As a result of the stratification, the interaction between the part of the composite, which may include an adhesive layer and the rest of the body stops. When solving the elastoplastic problem of cohesive stratification, the region in which the destruction criterion is achieved is identified. With the help of a repeated solution of the problem of subcritical deformation with the known law of motion of the boundary of the region, the distribution of the load (nodal forces) acting from the region to the body is located. The next step considers the change in the stress–strain state of the body in the process of destruction of the selected area. The elastoplastic problem is solved with a simple unloading of the formed surface of the body and preservation of the external load corresponding to the beginning of the process of destruction.

External Validation of the Simple Clinical Score and the HOTEL Score, Two Scores for Predicting Short-Term Mortality after Admission to an Acute Medical Unit

PubMed Central

Stræde, Mia; Brabrand, Mikkel

2014-01-01

Background Clinical scores can be of aid to predict early mortality after admission to a medical admission unit. A developed scoring system needs to be externally validated to minimise the risk of the discriminatory power and calibration to be falsely elevated. We performed the present study with the objective of validating the Simple Clinical Score (SCS) and the HOTEL score, two existing risk stratification systems that predict mortality for medical patients based solely on clinical information, but not only vital signs. Methods Pre-planned prospective observational cohort study. Setting Danish 460-bed regional teaching hospital. Findings We included 3046 consecutive patients from 2 October 2008 until 19 February 2009. 26 (0.9%) died within one calendar day and 196 (6.4%) died within 30 days. We calculated SCS for 1080 patients. We found an AUROC of 0.960 (95% confidence interval [CI], 0.932 to 0.988) for 24-hours mortality and 0.826 (95% CI, 0.774–0.879) for 30-day mortality, and goodness-of-fit test, χ2 = 2.68 (10 degrees of freedom), P = 0.998 and χ2 = 4.00, P = 0.947, respectively. We included 1470 patients when calculating the HOTEL score. Discriminatory power (AUROC) was 0.931 (95% CI, 0.901–0.962) for 24-hours mortality and goodness-of-fit test, χ2 = 5.56 (10 degrees of freedom), P = 0.234. Conclusion We find that both the SCS and HOTEL scores showed an excellent to outstanding ability in identifying patients at high risk of dying with good or acceptable precision. PMID:25144186

Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia.

PubMed

Zuna, Jan; Moericke, Anja; Arens, Mari; Koehler, Rolf; Panzer-Grümayer, Renate; Bartram, Claus R; Fischer, Susanna; Fronkova, Eva; Zaliova, Marketa; Schrauder, André; Stanulla, Martin; Zimmermann, Martin; Trka, Jan; Stary, Jan; Attarbaschi, Andishe; Mann, Georg; Schrappe, Martin; Cario, Gunnar

2016-06-01

Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment. © 2016 John Wiley & Sons Ltd.

Less is More: Comparing the 2015 and 2009 American Thyroid Association Guidelines for Thyroid Nodules and Cancer.

PubMed

Kim, Brian W; Yousman, Wina; Wong, Wei Xiang; Cheng, Cheng; McAninch, Elizabeth A

2016-06-01

The American Thyroid Association (ATA) has recently revised its guidance pertaining to thyroid nodules and follicular cell-derived thyroid cancer. The 2015 guidelines are massive in both scope and scale, with changes in the organizational approach to risk stratification of nodules and cancer, as well as multiple sections covering new material. This review highlights the major structural and organizational changes, focusing attention on the most dramatically changed recommendations, that is, those recommendations that clinicians will find striking because they call for significant divergence from prior clinical practice. The revised approach to thyroid nodule risk stratification is based on sonographic pattern, with an emphasis on pattern rather than growth in the long-term surveillance of nodules. Accumulating data have also been incorporated into an updated risk stratification scheme for thyroid cancer that increases the size of the low-risk pool, in part because low-volume lymph nodal metastases are now considered low risk. The most fundamentally altered recommendation is that lobectomy might be considered as the initial surgical approach for follicular cell-derived thyroid cancers from 1 to 4 cm in size. The underlying theme of the 2015 ATA guidelines is that "less is more." As these new recommendations are adopted, fewer fine-needle aspiration biopsies will need to be done, less extensive surgeries will become more common, less radioactive iodine will be used either for treatment or for diagnostics, and less stimulated thyroglobulin testing will be done. Mastery of these guidelines will help clinicians know when it is reasonable to do less, thus providing responsibly individualized therapy for their patients.

Accurate and robust genomic prediction of celiac disease using statistical learning.

PubMed

Abraham, Gad; Tye-Din, Jason A; Bhalala, Oneil G; Kowalczyk, Adam; Zobel, Justin; Inouye, Michael

2014-02-01

Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87-0.89) and in independent replication across cohorts (AUC of 0.86-0.9), despite differences in ethnicity. The models explained 30-35% of disease variance and up to ∼43% of heritability. The GRS's utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases.

Risk stratification of gallbladder polyps (1-2 cm) for surgical intervention with 18F-FDG PET/CT.

PubMed

Lee, Jaehoon; Yun, Mijin; Kim, Kyoung-Sik; Lee, Jong-Doo; Kim, Chun K

2012-03-01

We assessed the value of (18)F-FDG uptake in the gallbladder polyp (GP) in risk stratification for surgical intervention and the optimal cutoff level of the parameters derived from GP (18)F-FDG uptake for differentiating malignant from benign etiologies in a select, homogeneous group of patients with 1- to 2-cm GPs. Fifty patients with 1- to 2-cm GPs incidentally found on the CT portion of PET/CT were retrospectively analyzed. All patients had histologic diagnoses. GP (18)F-FDG activity was visually scored positive (≥liver) or negative (

Speckle-Tracking Echocardiography Improves Pre-operative Risk Stratification Before the Total Cavopulmonary Connection.

PubMed

Park, Patsy W; Atz, Andrew M; Taylor, Carolyn L; Chowdhury, Shahryar M

2017-05-01

Single-ventricle patients with elevated pulmonary vascular resistance (PVR) or end-diastolic pressure (EDP) are excluded from undergoing total cavopulmonary connection (TCPC). However, a subset of patients deemed to be at acceptable risk experience prolonged length of stay (LOS) after TCPC. Routine assessment of ventricular function has been inadequate in identifying these high-risk patients. Speckle-tracking echocardiography (STE) is a novel method for assessment of myocardial deformation that may be useful in single-ventricle patients. The aim of this study was to perform a contemporary preoperative risk assessment for prolonged LOS to determine whether STE improves risk stratification before TCPC. Our single institution's perioperative data were retrospectively collected. The primary outcome was postoperative LOS >14 days. Longitudinal and circumferential STE deformation measures were analyzed on echocardiograms obtained during preoperative catheterization. Patient-specific, echocardiographic, and catheterization data were included in multivariable logistic regression. Receiver operating characteristic area under the curves (AUC) were analyzed. From 2007 to 2014, 135 patients who underwent TCPC were included in the analysis. The median LOS was 11 (IQR 9-14) days. The PVR (P < .01) and circumferential strain rate (CSR) (P < .01) were the only variables independently associated with LOS >14 days. For every 0.1 s -1 CSR increased, there was a 20% increased odds of prolonged LOS. The AUC for CSR was 0.70. The AUC for PVR and EDP combined was 0.68. The AUC for PVR, EDP, and CSR combined was 0.73. Preoperative CSR is independently associated with LOS >14 days and improves preoperative risk stratification in patients undergoing TCPC. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Major bleeding events and risk stratification of antithrombotic agents in hemodialysis: Results from the DOPPS

PubMed Central

Sood, Manish M.; Larkina, Maria; Thumma, Jyothi R.; Tentori, Francesca; Gillespie, Brenda W.; Fukuhara, Shunichi; Mendelssohn, David C.; Chan, Kevin; de Sequera, Patricia; Komenda, Paul; Rigatto, Claudio; Robinson, Bruce M.

2013-01-01

Benefits and risks of antithrombotic agents remain unclear in the hemodialysis population. We aimed to determine variation in antithrombotic agent use, rates of major bleeding events, and to determine factors predictive of stroke and bleeding to allow for risk stratification, enabling more rational decisions about using antithrombotic agents. The sample included 48,144 patients in 12 countries in the Dialysis Outcomes and Practice Patterns Study Phase I–IV. Antithrombotic agents included oral anticoagulants (OAC), ASA and anti-platelet agents (APA). OAC prescription, comorbidities and vascular access were assessed at study entry; data on clinical events including hospitalization due to bleeding were collected every four months during follow-up. There was wide variation in OAC (0.3–18%), APA (3–25%) and ASA use (8–36%), and major bleeding rates (0.05–0.22 events/year) among countries. Rates of all-cause mortality, cardiovascular mortality, and bleeding events requiring hospitalization were elevated in patients prescribed OAC across adjusted models. The CHADS2 score predicted the risk of stroke in atrial fibrillation patients. Gastrointestinal bleeding in the past 12 months was highly predictive of major bleeding events; for patients with previous gastrointestinal bleeding, the rate of bleeding exceeded the rate of stroke by at least 2-fold across categories of CHADS2 score. Prescription of antithrombotic agents varied greatly. The CHADS2 score and a history of gastrointestinal bleeding were predictive of stroke and bleeding events, respectively, with bleeding rates substantially exceeding stroke rates in all groups including patients at high stroke risk. Appropriate risk stratification and a cautious approach should be considered before OAC use in the dialysis population. PMID:23677245

Hyperuricemia and the risk of ischemic stroke in patients with atrial fibrillation--could it refine clinical risk stratification in AF?

PubMed

Chao, Tze-Fan; Liu, Chia-Jen; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Tsao, Hsuan-Ming; Chen, Shih-Ann

2014-01-01

Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF. This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed. During the follow up of 3.0±2.7 years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4. Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

PubMed

Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

2018-05-01

In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient

PubMed Central

Budoff, Matthew J.; Raggi, Paolo; Beller, George A.; Berman, Daniel S.; Druz, Regina S.; Malik, Shaista; Rigolin, Vera H.; Weigold, Wm. Guy; Soman, Prem

2017-01-01

Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a “coronary risk equivalent,” implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data. PMID:26846937

Gastric Cancer Screening by Combined Determination of Serum Helicobacter pylori Antibody and Pepsinogen Concentrations: ABC Method for Gastric Cancer Screening.

PubMed

Chen, Xian-Zhe; Huang, Cheng-Zhi; Hu, Wei-Xian; Liu, Ying; Yao, Xue-Qing

2018-05-20

Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice. The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords "Helicobacter pylori," "Pepsinogens," and "Stomach Neoplasms." Original articles and reviews on the topics were selected. Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval. The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.

Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer

PubMed Central

Honda, Kazufumi; Srivastava, Sudhir

2016-01-01

Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer. PMID:27673558

Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification

PubMed Central

Toczek, Jakub; Meadows, Judith L.; Sadeghi, Mehran M.

2015-01-01

Selection of patients for abdominal aortic aneurysm (AAA) repair is currently based on aneurysm size, growth rate and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, e.g., inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in AAA morbidity and mortality. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ultrasmall superparamagnetic particles of iron oxide (USPIO) magnetic resonance imaging are two novel approaches to AAA imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (e.g., integrin αvβ3 and matrix metalloproteinases), have proven effective in preclinical models of AAA and show great potential for clinical translation. PMID:26763279

Primary thrombocytosis in children

PubMed Central

Kucine, Nicole; Chastain, Katherine M.; Mahler, Michelle B.; Bussel, James B.

2014-01-01

Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outcomes in adults have been well delineated with defined recommendations for risk stratification and treatment. This is not the case for pediatric patients, for whom there is neither a standard approach to workup nor any consensus regarding management. This review will discuss thrombocytosis in children, including causes of thrombocytosis in children, the limited knowledge we have regarding pediatric primary thrombocytosis, and our thoughts on potential risk stratification and management, and future questions to be answered by laboratory research and collaborative clinical study. PMID:24688110

Risk stratification in myelodysplastic syndromes: is there a role for gene expression profiling?

PubMed

Zeidan, Amer M; Prebet, Thomas; Saad Aldin, Ehab; Gore, Steven David

2014-04-01

Evaluation of: Pellagatti A, Benner A, Mills KI et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J. Clin. Oncol. 31(28), 3557-3564 (2013). Patients with myelodysplastic syndromes (MDS) exhibit wide heterogeneity in clinical outcomes making accurate risk-stratification an integral part of the risk-adaptive management paradigm. Current prognostic schemes for MDS rely on clinicopathological parameters. Despite the increasing knowledge of the genetic landscape of MDS and the prognostic impact of many newly discovered molecular aberrations, none to date has been incorporated formally into the major risk models. Efforts are ongoing to use data generated from genome-wide high-throughput techniques to improve the 'individualized' outcome prediction for patients. We here discuss an important paper in which gene expression profiling (GEP) technology was applied to marrow CD34(+) cells from 125 MDS patients to generate and validate a standardized GEP-based prognostic signature.

Syncope: risk stratification and clinical decision making.

PubMed

Peeters, Suzanne Y G; Hoek, Amber E; Mollink, Susan M; Huff, J Stephen

2014-04-01

Syncope is a common occurrence in the emergency department, accounting for approximately 1% to 3% of presentations. Syncope is best defined as a brief loss of consciousness and postural tone followed by spontaneous and complete recovery. The spectrum of etiologies ranges from benign to life threatening, and a structured approach to evaluating these patients is key to providing care that is thorough, yet cost-effective. This issue reviews the most relevant evidence for managing and risk stratifying the syncope patient, beginning with a focused history, physical examination, electrocardiogram, and tailored diagnostic testing. Several risk stratification decision rules are compared for performance in various scenarios, including how age and associated comorbidities may predict short-term and long-term adverse events. An algorithm for structured, evidence-based care of the syncope patient is included to ensure that patients requiring hospitalization are managed appropriately and those with benign causes are discharged safely.

Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.

PubMed

Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Bailey, Simon; Clifford, Steven C; Doz, Francois; Kool, Marcel; Dufour, Christelle; Vassal, Gilles; Milde, Till; Witt, Olaf; von Hoff, Katja; Pietsch, Torsten; Northcott, Paul A; Gajjar, Amar; Robinson, Giles W; Padovani, Laetitia; André, Nicolas; Massimino, Maura; Pizer, Barry; Packer, Roger; Rutkowski, Stefan; Pfister, Stefan M; Taylor, Michael D; Pomeroy, Scott L

2016-06-01

Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3-17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75-90 % survival), high risk (50-75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.

Risk stratification of childhood medulloblastoma in the molecular era: The Current Consensus

PubMed Central

Ramaswamy, Vijay; Remke, Marc; Bouffet, Eric; Bailey, Simon; Clifford, Steven C.; Doz, Francois; Kool, Marcel; Dufour, Christelle; Vassal, Gilles; Milde, Till; Witt, Olaf; von Hoff, Katja; Pietsch, Torsten; Northcott, Paul A.; Gajjar, Amar; Robinson, Giles W.; Padovani, Laetitia; André, Nicolas; Massimino, Maura; Pizer, Barry; Packer, Roger; Rutkowski, Stefan; Pfister, Stefan M.; Taylor, Michael D.; Pomeroy, Scott L.

2016-01-01

Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3–17). Published and unpublished data over the past five years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90% survival), average (standard) risk (75–90% survival), high risk (50–75% survival) and very high risk (<50% survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials. PMID:27040285

Experimental and CFD evidence of multiple solutions in a naturally ventilated building.

PubMed

Heiselberg, P; Li, Y; Andersen, A; Bjerre, M; Chen, Z

2004-02-01

This paper considers the existence of multiple solutions to natural ventilation of a simple one-zone building, driven by combined thermal and opposing wind forces. The present analysis is an extension of an earlier analytical study of natural ventilation in a fully mixed building, and includes the effect of thermal stratification. Both computational and experimental investigations were carried out in parallel with an analytical investigation. When flow is dominated by thermal buoyancy, it was found experimentally that there is thermal stratification. When the flow is wind-dominated, the room is fully mixed. Results from all three methods have shown that the hysteresis phenomena exist. Under certain conditions, two different stable steady-state solutions are found to exist by all three methods for the same set of parameters. As shown by both the computational fluid dynamics (CFD) and experimental results, one of the solutions can shift to another when there is a sufficient perturbation. These results have probably provided the strongest evidence so far for the conclusion that multiple states exist in natural ventilation of simple buildings. Different initial conditions in the CFD simulations led to different solutions, suggesting that caution must be taken when adopting the commonly used 'zero initialization'.

Do Health Professionals Need Additional Competencies for Stratified Cancer Prevention Based on Genetic Risk Profiling?

PubMed Central

Chowdhury, Susmita; Henneman, Lidewij; Dent, Tom; Hall, Alison; Burton, Alice; Pharoah, Paul; Pashayan, Nora; Burton, Hilary

2015-01-01

There is growing evidence that inclusion of genetic information about known common susceptibility variants may enable population risk-stratification and personalized prevention for common diseases including cancer. This would require the inclusion of genetic testing as an integral part of individual risk assessment of an asymptomatic individual. Front line health professionals would be expected to interact with and assist asymptomatic individuals through the risk stratification process. In that case, additional knowledge and skills may be needed. Current guidelines and frameworks for genetic competencies of non-specialist health professionals place an emphasis on rare inherited genetic diseases. For common diseases, health professionals do use risk assessment tools but such tools currently do not assess genetic susceptibility of individuals. In this article, we compare the skills and knowledge needed by non-genetic health professionals, if risk-stratified prevention is implemented, with existing competence recommendations from the UK, USA and Europe, in order to assess the gaps in current competences. We found that health professionals would benefit from understanding the contribution of common genetic variations in disease risk, the rationale for a risk-stratified prevention pathway, and the implications of using genomic information in risk-assessment and risk management of asymptomatic individuals for common disease prevention. PMID:26068647

Heart rate variability as predictive factor for sudden cardiac death.

PubMed

Sessa, Francesco; Anna, Valenzano; Messina, Giovanni; Cibelli, Giuseppe; Monda, Vincenzo; Marsala, Gabriella; Ruberto, Maria; Biondi, Antonio; Cascio, Orazio; Bertozzi, Giuseppe; Pisanelli, Daniela; Maglietta, Francesca; Messina, Antonietta; Mollica, Maria P; Salerno, Monica

2018-02-23

Sudden cardiac death (SCD) represents about 25% of deaths in clinical cardiology. The identification of risk factors for SCD is the philosopher's stone of cardiology and the identification of non-invasive markers of risk of SCD remains one of the most important goals for the scientific community.The aim of this review is to analyze the state of the art around the heart rate variability (HRV) as a predictor factor for SCD.HRV is probably the most analyzed index in cardiovascular risk stratification technical literature, therefore an important number of models and methods have been developed.Nowadays, low HRV has been shown to be independently predictive of increased mortality in post- myocardial infarction patients, heart failure patients, in contrast with the data of the general population.Contrariwise, the relationship between HRV and SCD has received scarce attention in low-risk cohorts. Furthermore, in general population the attributable risk is modest and the cost/benefit ratio is not always convenient.The HRV evaluation could become an important tool for health status in risks population, even though the use of HRV alone for risk stratification of SCD is limited and further studies are needed.

Evaluation of Quantra Hologic Volumetric Computerized Breast Density Software in Comparison With Manual Interpretation in a Diverse Population

PubMed Central

Richard-Davis, Gloria; Whittemore, Brianna; Disher, Anthony; Rice, Valerie Montgomery; Lenin, Rathinasamy B; Dollins, Camille; Siegel, Eric R; Eswaran, Hari

2018-01-01

Objective: Increased mammographic breast density is a well-established risk factor for breast cancer development, regardless of age or ethnic background. The current gold standard for categorizing breast density consists of a radiologist estimation of percent density according to the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) criteria. This study compares paired qualitative interpretations of breast density on digital mammograms with quantitative measurement of density using Hologic’s Food and Drug Administration–approved R2 Quantra volumetric breast density assessment tool. Our goal was to find the best cutoff value of Quantra-calculated breast density for stratifying patients accurately into high-risk and low-risk breast density categories. Methods: Screening digital mammograms from 385 subjects, aged 18 to 64 years, were evaluated. These mammograms were interpreted by a radiologist using the ACR’s BI-RADS density method, and had quantitative density measured using the R2 Quantra breast density assessment tool. The appropriate cutoff for breast density–based risk stratification using Quantra software was calculated using manually determined BI-RADS scores as a gold standard, in which scores of D3/D4 denoted high-risk densities and D1/D2 denoted low-risk densities. Results: The best cutoff value for risk stratification using Quantra-calculated breast density was found to be 14.0%, yielding a sensitivity of 65%, specificity of 77%, and positive and negative predictive values of 75% and 69%, respectively. Under bootstrap analysis, the best cutoff value had a mean ± SD of 13.70% ± 0.89%. Conclusions: Our study is the first to publish on a North American population that assesses the accuracy of the R2 Quantra system at breast density stratification. Quantitative breast density measures will improve accuracy and reliability of density determination, assisting future researchers to accurately calculate breast cancer risks associated with density increase. PMID:29511356

Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification.

PubMed

Oberthuer, André; Berthold, Frank; Warnat, Patrick; Hero, Barbara; Kahlert, Yvonne; Spitz, Rüdiger; Ernestus, Karen; König, Rainer; Haas, Stefan; Eils, Roland; Schwab, Manfred; Brors, Benedikt; Westermann, Frank; Fischer, Matthias

2006-11-01

To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease. Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States. The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]). Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.

Evaluation of Quantra Hologic Volumetric Computerized Breast Density Software in Comparison With Manual Interpretation in a Diverse Population.

PubMed

Richard-Davis, Gloria; Whittemore, Brianna; Disher, Anthony; Rice, Valerie Montgomery; Lenin, Rathinasamy B; Dollins, Camille; Siegel, Eric R; Eswaran, Hari

2018-01-01

Increased mammographic breast density is a well-established risk factor for breast cancer development, regardless of age or ethnic background. The current gold standard for categorizing breast density consists of a radiologist estimation of percent density according to the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) criteria. This study compares paired qualitative interpretations of breast density on digital mammograms with quantitative measurement of density using Hologic's Food and Drug Administration-approved R2 Quantra volumetric breast density assessment tool. Our goal was to find the best cutoff value of Quantra-calculated breast density for stratifying patients accurately into high-risk and low-risk breast density categories. Screening digital mammograms from 385 subjects, aged 18 to 64 years, were evaluated. These mammograms were interpreted by a radiologist using the ACR's BI-RADS density method, and had quantitative density measured using the R2 Quantra breast density assessment tool. The appropriate cutoff for breast density-based risk stratification using Quantra software was calculated using manually determined BI-RADS scores as a gold standard, in which scores of D3/D4 denoted high-risk densities and D1/D2 denoted low-risk densities. The best cutoff value for risk stratification using Quantra-calculated breast density was found to be 14.0%, yielding a sensitivity of 65%, specificity of 77%, and positive and negative predictive values of 75% and 69%, respectively. Under bootstrap analysis, the best cutoff value had a mean ± SD of 13.70% ± 0.89%. Our study is the first to publish on a North American population that assesses the accuracy of the R2 Quantra system at breast density stratification. Quantitative breast density measures will improve accuracy and reliability of density determination, assisting future researchers to accurately calculate breast cancer risks associated with density increase.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study

PubMed Central

Hausfater, Pierre; Amin, Devendra; Amin, Adina; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Conca, Antoinette; Haubitz, Sebastian; Struja, Tristan; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

2016-01-01

Introduction The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. Methods We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. Results Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75–1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). Conclusions Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out). PMID:28005916

Advantages of new cardiovascular risk-assessment strategies in high-risk patients with hypertension.

PubMed

Ruilope, Luis M; Segura, Julian

2005-10-01

Accurate assessment of cardiovascular disease (CVD) risk in patients with hypertension is important when planning appropriate treatment of modifiable risk factors. The causes of CVD are multifactorial, and hypertension seldom exists as an isolated risk factor. Classic models of risk assessment are more accurate than a simple counting of risk factors, but they are not generalizable to all populations. In addition, the risk associated with hypertension is graded, continuous, and independent of other risk factors, and this is not reflected in classic models of risk assessment. This article is intended to review both classic and newer models of CVD risk assessment. MEDLINE was searched for articles published between 1990 and 2005 that contained the terms cardiovascular disease, hypertension, or risk assessment. Articles describing major clinical trials, new data about cardiovascular risk, or global risk stratification were selected for review. Some patients at high long-term risk for CVD events (eg, patients aged <50 years with multiple risk factors) may go untreated because they do not meet the absolute risk-intervention threshold of 20% risk over 10 years with the classic model. Recognition of the limitations of classic risk-assessment models led to new guidelines, particularly those of the European Society of Hypertension-European Society of Cardiology. These guidelines view hypertension as one of many risk and disease factors that require treatment to decrease risk. These newer guidelines include a more comprehensive range of risk factors and more finely graded blood pressure ranges to stratify patients by degree of risk. Whether they accurately predict CVD risk in most populations is not known. Evidence from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study, which stratified patients by several risk and disease factors, highlights the predictive value of some newer CVD risk assessments. Modern risk assessments, which include blood pressure along with a wide array of modifiable risk factors, may be more accurate than classic models for CVD risk prediction.

Risk Associated with Pulse Pressure on Out-of-Office Blood Pressure Measurement

PubMed Central

Gu, Yu-Mei; Aparicio, Lucas S.; Liu, Yan-Ping; Asayama, Kei; Hansen, Tine W.; Niiranen, Teemu J.; Boggia, José; Thijs, Lutgarde; Staessen, Jan A.

2014-01-01

Background Longitudinal studies have demonstrated that the risk of cardiovascular disease increases with pulse pressure (PP). However, PP remains an elusive cardiovascular risk factor with findings being inconsistent between studies. The 2013 ESH/ESC guideline proposed that PP is useful in stratification and suggested a threshold of 60 mm Hg, which is 10 mm Hg higher compared to that in the 2007 guideline; however, no justification for this increase was provided. Methodology Published thresholds of PP are based on office blood pressure measurement and often on arbitrary categorical analyses. In the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) and the International Database on HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO), we determined outcome-driven thresholds for PP based on ambulatory or home blood pressure measurement, respectively. Results The main findings were that for people aged <60 years, PP did not refine risk stratification, whereas in older people the thresholds were 64 and 76 mm Hg for the ambulatory and home PP, respectively. However, PP provided little added predictive value over and beyond classical risk factors. PMID:26587443

Chromosome 9p21 In Ischemic Stroke: Population Structure and Meta-Analysis

PubMed Central

Anderson, CD; Biffi, A; Rost, NS; Cortellini, L; Furie, KL; Rosand, J

2011-01-01

Background and Purpose Sequence variants on chromosome 9p21.3 are implicated in coronary artery disease (CAD) and myocardial infarction (MI), but studies in ischemic stroke have produced inconsistent results. We investigated whether these conflicting findings were due to false positive studies confounded by population stratification, or false negative studies that failed to account for effects specific to certain stroke subtypes. Methods After assessing for population stratification at 9p21.3 using genome-wide data, we meta-analyzed 8 ischemic stroke studies. This analysis focused on two single nucleotide polymorphisms (SNPs), rs1537378 and rs10757278, as these variants are in strong linkage disequilibrium with most SNPs analyzed in prior studies of the region. Results Principal component analysis of the genome-wide data showed no evidence of population stratification at that locus. Meta-analysis confirmed that both rs1537378 and rs10757278 are risk factors for ischemic stroke (odds ratios 1.09, [p = 0.0014], and 1.11, [p = 0.001] respectively). Subtype analysis revealed a substantial increase in the effect of each SNP for risk of large artery (LA) stroke, achieving an effect size similar to that seen in CAD/MI. Conclusions Variants on 9p21.3 are associated with ischemic stroke, and restriction of analysis to LA stroke increases effect size towards that observed in prior association studies of CAD/MI. Previous inconsistent findings are best explained by this subtype-specificity rather than any unmeasured confounding by population stratification. PMID:20395606

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online.

PubMed

Jahn, Beate; Rochau, Ursula; Kurzthaler, Christina; Hubalek, Michael; Miksad, Rebecca; Sroczynski, Gaby; Paulden, Mike; Bundo, Marvin; Stenehjem, David; Brixner, Diana; Krahn, Murray; Siebert, Uwe

2017-10-16

Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high ODX risk. In other words, low ODX risk suggests chemotherapy should not be considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our analysis suggests that risk-group specific cost-effectiveness analysis, which includes companion prognostic tests are essential in PM.

Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

PubMed Central

Galper, Benjamin Z.; Wang, Y. Claire; Einstein, Andrew J.

2015-01-01

Background Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown. Methods We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe. Results Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event. Conclusions Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers. PMID:26422204

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status--do we need specificity for sex and beta-blockers?

PubMed

Frankenstein, L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Nelles, M; Katus, H A; Clark, A L; Cleland, J G F; Zugck, C

2011-02-17

It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

A Risk Prediction Index for Advanced Colorectal Neoplasia at Screening Colonoscopy.

PubMed

Schroy, Paul C; Wong, John B; O'Brien, Michael J; Chen, Clara A; Griffith, John L

2015-07-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability of ACN at screening colonoscopy. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average-risk patients 50-79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods. The final index consisted of five independent predictors of risk (age, smoking, alcohol intake, height, and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement (NRI), 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% confidence interval (CI), 2.6-3.9) for the low-risk group (score ≤2) to 8.6% (95% CI, 7.4-9.7) for the intermediate/high-risk group (score 3-11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66-0.72) and good calibration (P=0.73-0.93). A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ.

Update on techniques to prevent infections associated with prostate needle biopsy.

PubMed

Fontana, Matteo; Boeri, Luca; Montanari, Emanuele

2018-04-24

Postbiopsy infections (PBIs) are among the most common complications associated with transrectal ultrasound-guided prostate biopsy (TRUSPB). This article discusses the pathogenesis of TRUSPB-associated infectious complications and reviews the most recent findings on techniques to prevent PBIs. Risk stratification is a powerful tool for identifying TRUSPB candidates whom warrant additional preventive measures. Bowel preparation with povidone-iodine-based enemas and needle disinfection with formalin solution are simple and attractive strategies, but their effectiveness needs to be thoroughly assessed. Antibiotic prophylaxis represents the mainstay for the prevention of PBIs: the prophylactic regimen must respect the principles of antimicrobial stewardship, and local antibiotic resistance patterns among uropathogens should always be considered. Augmented and targeted antibiotic prophylaxes are powerful options, but their role in current clinical practice has yet to be clarified. The transperineal approach has shown a near-zero rate of PBIs, and should therefore be considered for the highest-risk patients. Several procedures have been introduced to prevent TRUSPB-related infectious complication, but their utility and applicability in the clinical practice has yet to be elucidated. More robust evidence based on randomized control trials is needed to establish the efficacy of these tools in improving patient outcomes.

Qualified Fitness and Exercise as Professionals and Exercise Prescription: Evolution of the PAR-Q and Canadian Aerobic Fitness Test.

PubMed

Shephard, Roy J

2015-04-01

Traditional approaches to exercise prescription have included a preliminary medical screening followed by exercise tests of varying sophistication. To maximize population involvement, qualified fitness and exercise professionals (QFEPs) have used a self-administered screening questionnaire (the Physical Activity Readiness Questionnaire, PAR-Q) and a simple measure of aerobic performance (the Canadian Aerobic Fitness Test, CAFT). However, problems have arisen in applying the original protocol to those with chronic disease. Recent developments have addressed these issues. Evolution of the PAR-Q and CAFT protocol is reviewed from their origins in 1974 to the current electronic decision tree model of exercise screening and prescription. About a fifth of apparently healthy adults responded positively to the original PAR-Q instrument, thus requiring an often unwarranted referral to a physician. Minor changes of wording did not overcome this problem. However, a consensus process has now developed an electronic decision tree for stratification of exercise risk not only for healthy individuals, but also for those with various types of chronic disease. The new approach to clearance greatly reduces physician referrals and extends the role of QFEPs. The availability of effective screening and simple fitness testing should contribute to the goal of maximizing physical activity in the entire population.

Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding.

PubMed

Jensen, Dennis M; Ohning, Gordon V; Kovacs, Thomas O G; Ghassemi, Kevin A; Jutabha, Rome; Dulai, Gareth S; Machicado, Gustavo A

2016-01-01

For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P < .0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P < .05). (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB. Published by Elsevier Inc.

Power of resting echocardiographic measurements to classify pulmonary hypertension patients according to European society of cardiology exercise testing risk stratification cut-offs.

PubMed

Rehman, Michaela B; Garcia, Rodrigue; Christiaens, Luc; Larrieu-Ardilouze, Elisa; Howard, Luke S; Nihoyannopoulos, Petros

2018-04-15

Right ventricular function is the major determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). The ESC risk assessment strategy for PAH is based on clinical status, exercise testing, NTproBNP, imaging and haemodynamics but does not include right ventricular function. Our aims were to test the power of resting echocardiographic measurements to classify PAH patients according to ESC exercise testing risk stratification cut-offs and to determine if the classification power of echocardiographic parameters varied in chronic thrombo-embolic pulmonary hypertension (CTEPH). We prospectively and consecutively recruited 46 PAH patients and 42 CTEPH patients referred for cardio-pulmonary exercise testing and comprehensive transthoracic echocardiography. Exercise testing parameters analyzed were peak oxygen consumption, percentage of predicted maximal oxygen consumption and the slope of ventilation against carbon dioxide production. Receiver operator characteristic curves were used to determine the optimal diagnostic cut-off values of echocardiographic parameters for classifying the patients in intermediate or high risk category according to exercise testing. Measurements of right ventricular systolic function were the best for classifying in PAH (area under the curve 0.815 to 0.935). Measurements of right ventricular pressure overload (0.810 to 0.909) were optimal for classifying according to exercise testing in CTEPH. Measurements of left ventricular function were of no use in either group. Measurements of right ventricular systolic function can classify according to exercise testing risk stratification cut-offs in PAH. However, this is not the case in CTEPH where pressure overload, rather than right ventricular function seems to be linked to exercise performance. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic value of the Ortho Vitros cardiac troponin I assay in patients with symptoms of myocardial ischemia. Risk stratification using European Society of Cardiology/American College of Cardiology recommended cutoff values.

PubMed

Apple, Fred S; Murakami, MaryAnn M; Quist, Heidi H; Pearce, Lesly A; Wieczorek, Stacey; Wu, Alan H B

2003-07-01

We evaluated the risk assessment value of a commercial cardiac troponin (cTn; Ortho Vitros ECi, Ortho-Clinical Diagnostics, Raritan, NJ) I assay in patients with symptoms of myocardial ischemia suggestive of acute coronary syndrome and compared findings with those for a commercial cTnT assay in the same population. The cTn levels were measured by both assays in plasma samples from 273 patients during 24 hours after admission. Baseline and maximum concentrations were used for risk stratification; cutoffs were the 99th percentile and 10% coefficient of variation. End points were all-cause death and cardiac events within 60 days. Relative risks (RRs) were estimated using Cox proportional hazards regression models and Kaplan-Meier curves. RRs of cardiac events and death were significantly higher with increased baseline and maximum concentrations using either cTnI cutoff. The respective mortality rates for baseline cTnI of more than 0.08 microgram/L vs 0.08 microgram/L or less were 17.4% vs 2.9% (P = .001); cardiac event rates were 11.5% vs 3.6% (P = .03). Exclusion of patients with ST-segment elevation had no significant effect on rates for either assay. Mortality was higher in the intermediate (0.09-0.2 microgram/L) than in the low (< or = 0.08 microgram/L) group for cTnI, with directionally similar results for cTnT. Our findings validate the Ortho cTnI assay as a risk stratification biomarker in patients with symptoms of myocardial ischemia.

Doppler Endoscopic Probe as a Guide to Risk Stratification and Definitive Hemostasis of Peptic Ulcer Bleeding

PubMed Central

Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas OG; Ghassemi, Kevin A.; Jutabha, Rome; Dulai, Gareth S.; Machicado, Gustavo A.

2015-01-01

Background and Aims For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUBs), we used Doppler endoscopic probe (DEP) for: 1. detection of blood flow underlying stigmata of recent hemorrhage (SRH), 2. quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and 3. comparing risks of rebleeding and actual 30 day rebleed rates for spurting arterial bleeding (Forrest – FIA) and oozing bleeding (FIB). Methods Prospective cohort study of 163 consecutive patients with severe PUBs and different SRH. Results All blood flow detected by DEP was arterial. Detection rates were 87.4% in major SRH - spurting arterial bleeding (FIA), non bleeding visible vessel (FIIA), clot (FIIB) - and significantly lower at 42.3% (p<0.0001) for intermediate group of oozing bleeding (FIB) or flat spot (FIIC). For spurting bleeding (FIA) vs. oozing (FIB), baseline DEP arterial flow was 100% vs. 46.7%; residual blood flow detected after endoscopic hemostasis was 35.7% vs. 0%; and 30 day rebleed rates were 28.6% vs. 0% (all p<0.05). Conclusions 1. For major SRH vs. oozing or spot, the arterial blood flow detection rates by DEP was significantly higher, indicating a higher rebleed risk. 2. Before and after endoscopic treatment, spurting FIA PUB’s had significantly higher rates of blood flow detection than oozing FIB PUB’s and a significantly higher 30 rebleed rate. 3. DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUBs. PMID:26318834

Application of the National Early Warning Score (NEWS) as a stratification tool on admission in an Italian acute medical ward: A perspective study.

PubMed

Spagnolli, Walter; Rigoni, Marta; Torri, Emanuele; Cozzio, Susanna; Vettorato, Elisa; Nollo, Giandomenico

2017-03-01

We aimed to assess the performance of the National Early Warning Score (NEWS) as tool for patient risk stratification at admission in an acute Internal Medicine ward and to ensure patient placement in ward areas with the required and most appropriate intensity of care. As secondary objective, we considered NEWS performance in two subgroups of patients: sudden cardiac events (acute coronary syndromes and arrhythmic events), and chronic respiratory insufficiency. We conducted a perspective cohort single centre study on 2,677 unselected patients consecutively admitted from July 2013 to March 2015 in the Internal Medicine ward of the hospital of Trento, Italy. The NEWS was mandatory collected on ward admission. We defined three risk categories for clinical deterioration: low score (NEWS 0-4), medium score (NEWS 5-6), and high score (NEWS≥7). Following adverse outcomes were considered: total and early (<72 hours) in-hospital mortality, urgent transfers to a higher intensity of care. A logistic regression model quantified the association between outcomes and NEWS. For patients with NEWS >4 vs patients with NEWS <4, the risk of early death increased from 12 to 36 times, total mortality from 3.5 to 9, and urgent transfers from 3.5 to 7. In patients with sudden cardiac events, lower scores were significantly associated with higher risk of transfer to a higher intensity of care. In patients affected by chronic hypoxaemia, adverse outcomes occurred less in medium and high score categories of NEWS. National Early Warning Score assessed on ward admission may enable risk stratification of clinical deterioration and can be a good predictor of in-hospital serious adverse outcomes, although sudden cardiac events and chronic hypoxaemia could constitute some limits. © 2017 John Wiley & Sons Ltd.

Evaluation and Management of Wolff-Parkinson-White in Athletes

PubMed Central

Rao, Ashwin L.; Salerno, Jack C.; Asif, Irfan M.; Drezner, Jonathan A.

2014-01-01

Context: Wolff-Parkinson-White (WPW) is a cardiac conduction system disorder characterized by abnormal accessory conduction pathways between the atria and the ventricles. Symptomatic patients classically present with palpitations, presyncope, or syncope that results from supraventricular tachycardia. While rare, sudden cardiac death may be the first manifestation of underlying disease and occurs more frequently in exercising individuals. Evidence Acquisition: Medline and PubMed databases were evaluated through 2012, with the following keywords: WPW, Wolff-Parkinson-White, pre-excitation, sudden cardiac death, risk stratification, and athletes. Selected articles identified through the primary search, along with relevant references from those articles, were reviewed for pertinent clinical information regarding the identification, evaluation, risk stratification, and management of WPW as they pertained to the care of athletes. Study Design: Systematic review. Level of Evidence: Level 1. Results: Diagnosis of WPW is confirmed by characteristic electrocardiogram changes, which include a delta wave, short PR interval, and widened QRS complex. Utilization of the electrocardiogram as part of the preparticipation physical evaluation may allow for early identification of asymptomatic individuals with a WPW pattern. Risk stratification techniques identify individuals at risk for malignant arrhythmias who may be candidates for curative therapy through transcatheter ablation. Conclusion: WPW accounts for at least 1% of sudden death in athletes and has a prevalence of at least 1 to 4.5 per 1000 children and adults. The risk of lethal arrhythmia appears to be higher in asymptomatic children than in adults, and sudden cardiac death is often the sentinel event. The athlete with WPW should be evaluated for symptoms and the presence of intermittent or persistent pre-excitation, which dictates further consultation, treatment, and monitoring strategies as well as return to play. PMID:24982705

Classification of drugs with different risk profiles.

PubMed

Saedder, Eva Aggerholm; Brock, Birgitte; Nielsen, Lars Peter; Bonnerup, Dorthe Krogsgaard; Lisby, Marianne

2015-08-01

A risk stratification approach is needed to identify patients at high risk of medication errors and a resulting high need of medication review. The aim of this study was to perform risk stratification (distinguishing between low-risk, medium-risk and high-risk drugs) for drugs found to cause serious adverse reactions due to medication errors. The study employed a modified Delphi technique. Drugs from a systematic literature search were included into two rounds of a Delphi process. A panel of experts was asked to evaluate each identified drug's potential for harm and for clinically relevant drug-drug interactions on a scale from 1 (low risk) to 9 (high risk). A total of 36 experts were appointed to serve on the panel. Consensus was reached for 29/57 (51%) drugs or drug classes that cause harm, and for 32/57 (56%) of the drugs or drug classes that cause interactions. For the remaining drugs, a decision was made based on the median score. Two lists, one stating the drugs' potential for causing harm and the other stating clinically relevant drug-drug interactions, were stratified into low-risk, medium-risk and high-risk drugs. Based on a modified Delphi technique, we created two lists of drugs stratified into a low-risk, a medium-risk and a high-risk group of clinically relevant interactions or risk of harm to patients. The lists could be incorporated into a risk-scoring tool that stratifies the performance of medication reviews according to patients' risk of experiencing adverse reactions. none. not relevant.

Numerical investigation of potential stratification caused by a cryogenic helium spill inside a tunnel

NASA Astrophysics Data System (ADS)

Sinclair, Cameron; Malecha, Ziemowit; Jedrusyna, Artur

2018-04-01

The sudden release of cryogenic fluid into an accelerator tunnel can pose a significant health and safety risk. For this reason, it is important to evaluate the consequences of such a spill. Previous publications concentrated on either Oxygen Deficiency Hazard or the evaluation of mathematical models using experimental data. No studies to date have focussed on the influence of cryogen inlet conditions on flow development. In this paper, the stratification behaviour of low-temperature helium released into an air-filled accelerator tunnel is investigated for varying helium inlet diameters. A numerical model was constructed using the OpenFOAM Toolbox of a generalised 3D geometry, with similar hydraulic characteristics to the CERN and SLAC tunnels. This model has been validated against published experimental and numerical data. A dimensionless parameter, based on Bakke number, was then determined for the onset of stratification, taking into account the helium inlet diameter; a dimensionless parameter for the degree of stratification was also employed. The simulated flow behaviour is described in terms of these dimensionless parameters, as well as the temperature and oxygen concentration at various heights throughout the tunnel.

Genomic Characterization of Paediatric Acute Lymphoblastic Leukaemia: an Opportunity for Precision Medicine Therapeutics

PubMed Central

Tasian, Sarah K; Hunger, Stephen P

2016-01-01

Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (1) underlying biological and clinical characteristics and (2) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies. PMID:27984637

Peri-procedural risk stratification and management of patients with Williams syndrome.

PubMed

Collins Ii, R Thomas; Collins, Margaret G; Schmitz, Michael L; Hamrick, Justin T

2017-03-01

Williams syndrome (WS) is a congenital, multisystem disorder affecting the cardiovascular, connective tissue, and central nervous systems in 1 in 10 000 live births. Cardiovascular involvement is the most common cause of morbidity and mortality in patients with WS, and noninvasive and invasive procedures are common. Sudden cardiovascular collapse in patients with WS is a well-known phenomenon, especially in the peri-procedural period. Detailed guidelines for peri-procedural management of patients with WS are limited. The goal of this review is to provide thoughtful, safe and effective management strategies for the peri-procedural care of patients with WS with careful consideration of hemodynamic impacts of anesthetic strategies. In addition, an expanded risk stratification system for anesthetic administration is provided. © 2017 Wiley Periodicals, Inc.

[Amyloidosis: Up-to-date].

PubMed

Magy-Bertrand, N

2016-08-01

Amyloidosis is mainly a systemic disease belonging to protein-folding diseases. The past 10 years have shown significant progress in typing and the clinical management of amyloidosis, in the identification of novel prognostic markers for risk-stratification, and also in the development of new therapeutic agents. Biological molecular techniques are now able to type amyloidosis which were unidentified. Cardiac MRI and biomarkers allow a precise risk-stratification, especially in AL amyloidosis. If necessary, this prognostic evaluation may lead to rapid changes in the chemotherapy treatment. Emerging treatments rely on biotherapies, gene therapy, immunotherapy and blocking analogous agents. They give hope about an increase of survival of patients with systemic amyloidosis. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics.

PubMed

Tasian, Sarah K; Hunger, Stephen P

2017-03-01

Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (i) underlying biological and clinical characteristics, and (ii) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies. © 2016 John Wiley & Sons Ltd.

Congenital and hereditary causes of sudden cardiac death in young adults: diagnosis, differential diagnosis, and risk stratification.

PubMed

Stojanovska, Jadranka; Garg, Anubhav; Patel, Smita; Melville, David M; Kazerooni, Ella A; Mueller, Gisela C

2013-01-01

Sudden cardiac death is defined as death from unexpected circulatory arrest-usually a result of cardiac arrhythmia-that occurs within 1 hour of the onset of symptoms. Proper and timely identification of individuals at risk for sudden cardiac death and the diagnosis of its predisposing conditions are vital. A careful history and physical examination, in addition to electrocardiography and cardiac imaging, are essential to identify conditions associated with sudden cardiac death. Among young adults (18-35 years), sudden cardiac death most commonly results from a previously undiagnosed congenital or hereditary condition, such as coronary artery anomalies and inherited cardiomyopathies (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy [ARVC], dilated cardiomyopathy, and noncompaction cardiomyopathy). Overall, the most common causes of sudden cardiac death in young adults are, in descending order of frequency, hypertrophic cardiomyopathy, coronary artery anomalies with an interarterial or intramural course, and ARVC. Often, sudden cardiac death is precipitated by ventricular tachycardia or fibrillation and may be prevented with an implantable cardioverter defibrillator (ICD). Risk stratification to determine the need for an ICD is challenging and involves imaging, particularly echocardiography and cardiac magnetic resonance (MR) imaging. Coronary artery anomalies, a diverse group of congenital disorders with a variable manifestation, may be depicted at coronary computed tomographic angiography or MR angiography. A thorough understanding of clinical risk stratification, imaging features, and complementary diagnostic tools for the evaluation of cardiac disorders that may lead to sudden cardiac death is essential to effectively use imaging to guide diagnosis and therapy.

A Patch-Based Approach for the Segmentation of Pathologies: Application to Glioma Labelling.

PubMed

Cordier, Nicolas; Delingette, Herve; Ayache, Nicholas

2016-04-01

In this paper, we describe a novel and generic approach to address fully-automatic segmentation of brain tumors by using multi-atlas patch-based voting techniques. In addition to avoiding the local search window assumption, the conventional patch-based framework is enhanced through several simple procedures: an improvement of the training dataset in terms of both label purity and intensity statistics, augmented features to implicitly guide the nearest-neighbor-search, multi-scale patches, invariance to cube isometries, stratification of the votes with respect to cases and labels. A probabilistic model automatically delineates regions of interest enclosing high-probability tumor volumes, which allows the algorithm to achieve highly competitive running time despite minimal processing power and resources. This method was evaluated on Multimodal Brain Tumor Image Segmentation challenge datasets. State-of-the-art results are achieved, with a limited learning stage thus restricting the risk of overfit. Moreover, segmentation smoothness does not involve any post-processing.

A new risk stratification algorithm for the management of patients with adrenal incidentalomas.

PubMed

Birsen, Onur; Akyuz, Muhammet; Dural, Cem; Aksoy, Erol; Aliyev, Shamil; Mitchell, Jamie; Siperstein, Allan; Berber, Eren

2014-10-01

Although adrenal incidentalomas (AI) are detected in ≤5% of patients undergoing chest and abdominal computed tomography (CT), their management is challenging. The current guidelines include recommendations from the National Institutes of Health, the American Association of Endocrine Surgeons (AAES), and the American Association for Cancer Education (AACE). The aim of this study was to develop a new risk stratification model and compare its performance against the existing guidelines for managing AI. A risk stratification model was designed by assigning points for adrenal size (1, 2, or 3 points for tumors <4, 4-6, or >6 cm, respectively) and Hounsfield unit (HU) density on noncontrast CT (1, 2, or 3 points for HU <10, 10-20, or >20, respectively). This model was applied retrospectively to 157 patients with AI managed in an endocrine surgery clinic to assign a score to each tumor. The utility of this model versus the AAES/AACE guidelines was assessed. Of the 157 patients, 54 (34%), had tumors <4 cm with HU <10 (a score of 2). One third of these were hormonally active on biochemical workup and underwent adrenalectomy. The remaining two thirds were nonsecretory lesions and have been followed conservatively with annual testing. In 103 patients (66%), the adrenal mass was >4 cm and/or had indeterminate features on noncontrast CT (HU >10, irregular borders, heterogeneity), and adrenalectomy was performed after hormonal evaluation was completed (10 were hormonally active on biochemical testing). Seven of these patients (7%) had adrenocortical cancer on final pathology with tumor size <4 cm in 0, 4-6 cm in 1, and >6 cm in 5 patients. Of the hormonally inactive patients, 32% had a score of 3, 38% 4, and 30% 5 or 6. The incidence of adrenocortical cancer in these subgroups was 0, 0, and 25%, respectively. This study shows that an algorithm that utilizes the hormonal activity at the first decision step followed by a consolidated risk stratification, based on tumor size and HU density, has a potential to spare a substantial number of patients from unnecessary "diagnostic" surgery for AI. Copyright © 2014 Elsevier Inc. All rights reserved.

Prediction of esophageal variceal bleeding in B-viral liver cirrhosis using the P2/MS noninvasive index based on complete blood counts.

PubMed

Kim, Beom Kyung; Ahn, Sang Hoon; Han, Kwang-Hyub; Park, Jun Yong; Han, Min Seok; Jo, Jung Hyun; Kim, Ja Kyung; Lee, Kwan Sik; Chon, Chae Yoon; Kim, Do Young

2012-01-01

Periodic endoscopy for esophageal varices (EVs) and prophylactic treatment of high-risk EVs, i.e., medium/large EVs, small EVs with the red-color sign or decompensation, are recommended in cirrhotic patients. We assessed the cumulative risks for future EV bleeding using the following simple P2/MS index: (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)]. We enrolled 475 consecutive B-viral cirrhosis patients for 4 years, none of whom experienced EV bleeding. All underwent laboratory work-ups, endoscopy and ultrasonography. Those with EV bleeding took a nonselective β-blocker as prophylaxis. The major endpoint was the first occurrence of EV bleeding, analyzed using the Kaplan-Meier and Cox regression methods. Among patients with EV bleeding (n = 131), 25 experienced their first EV bleeding during follow-up. To differentiate the risk for EV bleeding, we divided them into two subgroups according to their P2/MS value (subgroup 1: P2/MS ≥9 and subgroup 2: P2/MS <9). The risk was significantly higher in subgroup 2 (p = 0.029). From multivariate analysis, a lower P2/MS (p = 0.040) remained a significant predictor for EV bleeding along with large varix size (p = 0.015), red-color sign (p = 0.041) and Child-Pugh classification B/C (p = 0.001). In subgroup 1, the risk for EV bleeding was similar to that of patients with low-risk EVs (p = 0.164). The P2/MS is a reliable predictor for the risk of EV bleeding among patients with EV bleeding. According to risk stratification, different prophylactic treatments should be considered for the subgroup with a P2/MS <9. Copyright © 2012 S. Karger AG, Basel.

Integrated e-Health approach based on vascular ultrasound and pulse wave analysis for asymptomatic atherosclerosis detection and cardiovascular risk stratification in the community.

PubMed

Santana, Daniel Bia; Zócalo, Yanina A; Armentano, Ricardo L

2012-03-01

New strategies are urgently needed to identify subjects at increased risk of atherosclerotic cardiovascular disease (ACVD) development or complications. A National Public University Center (CUiiDARTE) was created in Uruguay, based on six main pillars: 1) integration of experts in different disciplines and creation of multidisciplinary teams, 2) incidence in public and professional education programs to give training in the use of new technologies and to shift the focus from ACVD treatment to disease prevention, 3) implementation of free vascular studies in the community (distributed rather than centralized healthcare), 4) innovation and application of e-Health and noninvasive technology and approaches, 5) design and development of a biomedical approach to determine the target population and patient workflow, and 6) improvement in individual risk estimation and differentiation between aging and ACVD-related arterial changes using population-based epidemiological and statistical patient-specific models. This work describes main features of CUiiDARTE project implementation, the scientific and technological steps and innovations done for individual risk stratification, and sub-clinical ACVD diagnosis. © 2012 IEEE

Role of risk stratification by SPECT, PET, and hybrid imaging in guiding management of stable patients with ischaemic heart disease: expert panel of the EANM cardiovascular committee and EACVI.

PubMed

Acampa, Wanda; Gaemperli, Oliver; Gimelli, Alessia; Knaapen, Paul; Schindler, Thomas H; Verberne, Hein J; Zellweger, Michael J

2015-12-01

Risk stratification has become increasingly important in the management of patients with suspected or known ischaemic heart disease (IHD). Recent guidelines recommend that these patients have their care driven by risk assessment. The purpose of this position statement is to summarize current evidence on the value of cardiac single-photon emission computed tomography, positron emission tomography, and hybrid imaging in risk stratifying asymptomatic or symptomatic patients with suspected IHD, patients with stable disease, patients after coronary revascularization, heart failure patients, and specific patient population. In addition, this position statement evaluates the impact of imaging results on clinical decision-making and thereby its role in patient management. The document represents the opinion of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee and of the European Association of Cardiovascular Imaging (EACVI) and intends to stimulate future research in this field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Risk stratification of patients with diabetes and the role of sodium glucose co-transporter inhibitors 2 during Ramadan fasting.

PubMed

Adnan, Zaina

2017-09-01

The month of Ramadan represents a golden opportunity for better management of patients with diabetes not only during Ramadan month, but also through the entire year. Pre Ramadan period is crucial for evaluating and preparing patients with diabetes intending to Fast Ramadan. The risk stratification categories should take into consideration patients with diabetes having specific conditions such as nephrotic syndrome who are predisposed to thrombosis independent to their estimated glomerular filtration rate and glycated haemoglobin. Furthermore, population-specific conditions such as nomadic Bedouins living in remote areas should be considered as part of the very high risk category for fasting Ramadan. Published data regarding the use of sodium glucose co-transporter 2 inhibitors during Ramadan is very limited. Dapagliflozin was the only agent studied during Ramadan. Therefore, it is suggested to categorize this group of agents differently from other agents such as metformin and incretin based therapy studied vastly during Ramadan. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroblastoma: clinical and biological approach to risk stratification and treatment.

PubMed

Tolbert, Vanessa P; Matthay, Katherine K

2018-05-01

Neuroblastoma is the most common extra-cranial solid tumor of childhood and the most common in the first year of life. It is a unique malignancy in that infants often present with either localized or metastatic disease that can spontaneously regress without intervention while older children can succumb to the disease after months to years of arduous therapy. Given this wide range of outcomes, the International Neuroblastoma Risk Group was created to stratify patients based on presenting characteristics and tumor biology in order to guide intensity of treatment strategies. The goal has been to decrease therapy for low-risk patients to avoid long-term complications while augmenting and targeting therapies for high-risk patients to improve overall survival. The international risk stratification depends on age, stage, histology, MYCN gene amplification status, tumor cell ploidy and segmental chromosomal abnormalities. Treatment for asymptomatic low-risk patients with an estimated survival of > 98% is often observation or surgical resection alone, whereas intermediate-risk patients with an estimated survival of > 90% require moderate doses of response-adjusted chemotherapy along with resection. High-risk patients undergo multiple cycles of combination chemotherapy before surgery, followed by consolidation with myeloablative autologous hematopoietic stem cell transplantation and local radiation and finally immunotherapy with differentiation therapy as maintenance phase. With this approach, outcome for patients with neuroblastoma has improved, as the field continues to expand efforts in more targeted therapies for high-risk patients.

Surveillance of Pediatric Cardiac Surgical Outcome Using Risk Stratifications at a Tertiary Care Center in Thailand

PubMed Central

Vijarnsorn, Chodchanok; Laohaprasitiporn, Duangmanee; Durongpisitkul, Kritvikrom; Chantong, Prakul; Soongswang, Jarupim; Cheungsomprasong, Paweena; Nana, Apichart; Sriyoschati, Somchai; Subtaweesin, Thawon; Thongcharoen, Punnarerk; Prakanrattana, Ungkab; Krobprachya, Jiraporn; Pooliam, Julaporn

2011-01-01

Objectives. To determine in-hospital mortality and complications of cardiac surgery in pediatric patients and identify predictors of hospital mortality. Methods. Records of pediatric patients who had undergone cardiac surgery in 2005 were reviewed retrospectively. The risk adjustment for congenital heart surgery (RACHS-1) method, the Aristotle basic complexity score (ABC score), and the Society of Thoracic Surgeons and the European Association for Cardiothoracic Surgery Mortality score (STS-EACTS score) were used as measures. Potential predictors were analyzed by risk analysis. Results. 230 pediatric patients had undergone congenital cardiac surgery. Overall, the mortality discharge was 6.1%. From the ROC curve of the RACHS-1, the ABC level, and the STS-EACTS categories, the validities were determined to be 0.78, 0.74, and 0.67, respectively. Mortality risks were found at the high complexity levels of the three tools, bypass time >85 min, and cross clamp time >60 min. Common morbidities were postoperative pyrexia, bleeding, and pleural effusion. Conclusions. Overall mortality and morbidities were 6.1%. The RACHS-1 method, ABC score, and STS-EACTS score were helpful for risk stratification. PMID:21738856

Barrett’s oesophagus: Current controversies

PubMed Central

Amadi, Chidi; Gatenby, Piers

2017-01-01

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett’s oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett’s oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett’s segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett’s segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus. PMID:28811703

Barrett's oesophagus: Current controversies.

PubMed

Amadi, Chidi; Gatenby, Piers

2017-07-28

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.

Physical Therapists' Ability to Identify Psychological Factors and Their Self-Reported Competence to Manage Chronic Low Back Pain.

PubMed

Brunner, Emanuel; Dankaerts, Wim; Meichtry, André; O'Sullivan, Kieran; Probst, Michel

2018-06-01

In the management of chronic low back pain (LBP), identifying and managing more patients who are at high risk and who have psychological barriers to recovery is important yet difficult. The objective of this study was to test physical therapists' ability to allocate patients into risk stratification groups, test correlations between therapists' assessments of psychological factors and patient questionnaires, and explore relationships between psychological factors and therapists' self-reported competence to manage patients with chronic LBP. This was a pragmatic, observational study. Patients completed the STarT Back Tool (SBT, for risk stratification), the Four-Dimensional Symptom Questionnaire (distress, depression, anxiety), and the Tampa Scale of Kinesiophobia (kinesiophobia) prior to the intake session. After this session, physical therapists estimated patient prognostic risk using the 3 SBT categories and rated patient psychological factors using a 0-to-10 scale. Finally, therapists reported their self-reported competence to manage the patient. Intraclass and Spearman rank correlations tested correlations between therapists' intuitive assessments and patient questionnaires. A linear-mixed model explored relationships between psychological factors and therapists' self-reported competence. Forty-nine patients were managed by 20 therapists. Therapists accurately estimated SBT risk allocation in only 41% of patients. Correlations between therapist perceptions and patient questionnaires were moderate for distress (r = 0.602) and fair for depression (r = 0.304) and anxiety (r = 0.327). There was no correlation for kinesiophobia (r = -0.007). Patient distress was identified as a negative predictor of therapists' self-reported competence. This was a cross-sectional study, conducted in only 1 center. Physical therapists were not very accurate at allocating patients into risk stratification groups or identifying psychological factors. Therapists' self-reported competence in managing patients was lowest when patients reported higher distress.

Development of Technologies for Early Detection and Stratification of Breast Cancer

DTIC Science & Technology

2015-10-01

fatal disease progression, or in the cases of over-treatment, unnecessary physical and emotional trauma.4 ELISA, the most common immunoassay for...laboratory to discover new biomarkers that meet these requirements within serum so that a simple blood test can be implemented. We are also working to...microspheres and tested first on standard samples. Assay performance characteristics will be determined to ascertain that they will address

Noninvasive esthetic treatment for hypomaturation amelogenesis imperfecta: a case report.

PubMed

Nahsan, Flávia Pardo Salata; Silva, Luciana Mendonça da; Lima, Thiago Mendes de; Bertocco, Verônica Pereira de Lima; Chui, Fabíola Mendonça da Silva; Martins, Leandro de Moura

2016-01-01

Enamel alterations, such as amelogenesis imperfecta, can compromise the harmony of the smile and the patient's self-esteem and may cause tooth sensitivity. A simple and effective treatment approach uses the natural stratification of composite resins to mask deficient enamel formation and mimic the natural appearance of the substrate. The operative steps and principles for restorative success are described in this case report with 36-month follow-up.

Plaque hemorrhage in carotid artery disease: pathogenesis, clinical and biomechanical considerations.

PubMed

Teng, Zhongzhao; Sadat, Umar; Brown, Adam J; Gillard, Jonathan H

2014-03-03

Stroke remains the most prevalent disabling illness today, with internal carotid artery luminal stenosis due to atheroma formation responsible for the majority of ischemic cerebrovascular events. Severity of luminal stenosis continues to dictate both patient risk stratification and the likelihood of surgical intervention. But there is growing evidence to suggest that plaque morphology may help improve pre-existing risk stratification criteria. Plaque components such a fibrous tissue, lipid rich necrotic core and calcium have been well investigated but plaque hemorrhage (PH) has been somewhat overlooked. In this review we discuss the pathogenesis of PH, its role in dictating plaque vulnerability, PH imaging techniques, marterial properties of atherosclerotic tissues, in particular, those obtained based on in vivo measurements and effect of PH in modulating local biomechanics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preventing tomorrow's sudden cardiac death today: part I: Current data on risk stratification for sudden cardiac death.

PubMed

Al-Khatib, Sana M; Sanders, Gillian D; Bigger, J Thomas; Buxton, Alfred E; Califf, Robert M; Carlson, Mark; Curtis, Anne; Curtis, Jeptha; Fain, Eric; Gersh, Bernard J; Gold, Michael R; Haghighi-Mood, Ali; Hammill, Stephen C; Healey, Jeff; Hlatky, Mark; Hohnloser, Stefan; Kim, Raymond J; Lee, Kerry; Mark, Daniel; Mianulli, Marcus; Mitchell, Brent; Prystowsky, Eric N; Smith, Joseph; Steinhaus, David; Zareba, Wojciech

2007-06-01

Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.

Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

PubMed

Singh, Neeraj; Parikh, Samir; Bhatt, Udayan; Vonvisger, Jon; Nori, Uday; Hasan, Ayesha; Samavedi, Srinivas; Andreoni, Kenneth; Henry, Mitchell; Pelletier, Ronald; Rajab, Amer; Elkhammas, Elmahdi; Pesavento, Todd

2012-12-27

The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers. We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results. Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results. In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

Standardized reporting guidelines for emergency department syncope risk-stratification research.

PubMed

Sun, Benjamin C; Thiruganasambandamoorthy, Venkatesh; Cruz, Jeffrey Dela

2012-06-01

There is increasing research interest in the risk stratification of emergency department (ED) syncope patients. A major barrier to comparing and synthesizing existing research is wide variation in the conduct and reporting of studies. The authors wanted to create standardized reporting guidelines for ED syncope risk-stratification research using an expert consensus process. In that pursuit, a panel of syncope researchers was convened and a literature review was performed to identify candidate reporting guideline elements. Candidate elements were grouped into four sections: eligibility criteria, outcomes, electrocardiogram (ECG) findings, and predictors. A two-round, modified Delphi consensus process was conducted using an Internet-based survey application. In the first round, candidate elements were rated on a five-point Likert scale. In the second round, panelists rerated items after receiving information about group ratings from the first round. Items that were rated by >80% of the panelists at the two highest levels of the Likert scale were included in the final guidelines. There were 24 panelists from eight countries who represented five clinical specialties. The panel identified an initial set of 183 candidate elements. After two survey rounds, the final reporting guidelines included 92 items that achieved >80% consensus. These included 10 items for study eligibility, 23 items for outcomes, nine items for ECG abnormalities, and 50 items for candidate predictors. Adherence to these guidelines should facilitate comparison of future research in this area. © 2012 by the Society for Academic Emergency Medicine.

Predicting Geriatric Falls Following an Episode of Emergency Department Care: A Systematic Review

PubMed Central

Carpenter, Christopher R.; Avidan, Michael S.; Wildes, Tanya; Stark, Susan; Fowler, Susan A.; Lo, Alexander X.

2015-01-01

Background Falls are the leading cause of traumatic mortality in geriatric adults. Despite recent multispecialty guideline recommendations that advocate for proactive fall prevention protocols in the emergency department (ED), the ability of risk factors or risk stratification instruments to identify subsets of geriatric patients at increased risk for short-term falls is largely unexplored. Objectives This was a systematic review and meta-analysis of ED-based history, physical examination, and fall risk stratification instruments with the primary objective of providing a quantitative estimate for each risk factor’s accuracy to predict future falls. A secondary objective was to quantify ED fall risk assessment test and treatment thresholds using derived estimates of sensitivity and specificity. Methods A medical librarian and two emergency physicians (EPs) conducted a medical literature search of PUBMED, EMBASE, CINAHL, CENTRAL, DARE, the Cochrane Registry, and Clinical Trials. Unpublished research was located by a hand search of emergency medicine (EM) research abstracts from national meetings. Inclusion criteria for original studies included ED-based assessment of pre-ED or post-ED fall risk in patients 65 years and older with sufficient detail to reproduce contingency tables for meta-analysis. Original study authors were contacted for additional details when necessary. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used to assess individual study quality for those studies that met inclusion criteria. When more than one qualitatively similar study assessed the same risk factor for falls at the same interval following an ED evaluation, then meta-analysis was performed using Meta-DiSc software. The primary outcomes were sensitivity, specificity, and likelihood ratios for fall risk factors or risk stratification instruments. Secondary outcomes included estimates of test and treatment thresholds using the Pauker method based on accuracy, screening risk, and the projected benefits or harms of fall prevention interventions in the ED. Results A total of 608 unique and potentially relevant studies were identified, but only three met our inclusion criteria. Two studies that included 660 patients assessed 29 risk factors and two risk stratification instruments for falls in geriatric patients in the 6 months following an ED evaluation, while one study of 107 patients assessed the risk of falls in the preceding 12 months. A self-report of depression was associated with the highest positive likelihood ratio (LR) of 6.55 (95% confidence interval [CI] = 1.41 to 30.48). Six fall predictors were identified in more than one study (past falls, living alone, use of walking aid, depression, cognitive deficit, and more than six medications) and meta-analysis was performed for these risk factors. One screening instrument was sufficiently accurate to identify a subset of geriatric ED patients at low risk for falls with a negative LR of 0.11 (95% CI = 0.06 to 0.20). The test threshold was 6.6% and the treatment threshold was 27.5%. Conclusions This study demonstrates the paucity of evidence in the literature regarding ED-based screening for risk of future falls among older adults. The screening tools and individual characteristics identified in this study provide an evidentiary basis on which to develop screening protocols for geriatrics adults in the ED to reduce fall risk PMID:25293956

Predicting geriatric falls following an episode of emergency department care: a systematic review.

PubMed

Carpenter, Christopher R; Avidan, Michael S; Wildes, Tanya; Stark, Susan; Fowler, Susan A; Lo, Alexander X

2014-10-01

Falls are the leading cause of traumatic mortality in geriatric adults. Despite recent multispecialty guideline recommendations that advocate for proactive fall prevention protocols in the emergency department (ED), the ability of risk factors or risk stratification instruments to identify subsets of geriatric patients at increased risk for short-term falls is largely unexplored. This was a systematic review and meta-analysis of ED-based history, physical examination, and fall risk stratification instruments with the primary objective of providing a quantitative estimate for each risk factor's accuracy to predict future falls. A secondary objective was to quantify ED fall risk assessment test and treatment thresholds using derived estimates of sensitivity and specificity. A medical librarian and two emergency physicians (EPs) conducted a medical literature search of PUBMED, EMBASE, CINAHL, CENTRAL, DARE, the Cochrane Registry, and Clinical Trials. Unpublished research was located by a hand search of emergency medicine (EM) research abstracts from national meetings. Inclusion criteria for original studies included ED-based assessment of pre-ED or post-ED fall risk in patients 65 years and older with sufficient detail to reproduce contingency tables for meta-analysis. Original study authors were contacted for additional details when necessary. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used to assess individual study quality for those studies that met inclusion criteria. When more than one qualitatively similar study assessed the same risk factor for falls at the same interval following an ED evaluation, then meta-analysis was performed using Meta-DiSc software. The primary outcomes were sensitivity, specificity, and likelihood ratios for fall risk factors or risk stratification instruments. Secondary outcomes included estimates of test and treatment thresholds using the Pauker method based on accuracy, screening risk, and the projected benefits or harms of fall prevention interventions in the ED. A total of 608 unique and potentially relevant studies were identified, but only three met our inclusion criteria. Two studies that included 660 patients assessed 29 risk factors and two risk stratification instruments for falls in geriatric patients in the 6 months following an ED evaluation, while one study of 107 patients assessed the risk of falls in the preceding 12 months. A self-report of depression was associated with the highest positive likelihood ratio (LR) of 6.55 (95% confidence interval [CI] = 1.41 to 30.48). Six fall predictors were identified in more than one study (past falls, living alone, use of walking aid, depression, cognitive deficit, and more than six medications) and meta-analysis was performed for these risk factors. One screening instrument was sufficiently accurate to identify a subset of geriatric ED patients at low risk for falls with a negative LR of 0.11 (95% CI = 0.06 to 0.20). The test threshold was 6.6% and the treatment threshold was 27.5%. This study demonstrates the paucity of evidence in the literature regarding ED-based screening for risk of future falls among older adults. The screening tools and individual characteristics identified in this study provide an evidentiary basis on which to develop screening protocols for geriatrics adults in the ED to reduce fall risk. © 2014 by the Society for Academic Emergency Medicine.

Improving rural and remote practitioners' knowledge of the diabetic foot: findings from an educational intervention.

PubMed

Schoen, Deborah E; Gausia, Kaniz; Glance, David G; Thompson, Sandra C

2016-01-01

This study aimed to determine knowledge of national guidelines for diabetic foot assessment and risk stratification by rural and remote healthcare professionals in Western Australia and their implementation in practice. Assessment of diabetic foot knowledge, availability of equipment and delivery of foot care education in a primary healthcare setting at baseline enabled evaluation of the effectiveness of a diabetic foot education and training program for generalist healthcare professionals. This study employed a quasi-experimental pre-test/post-test study design. Healthcare practitioners' knowledge, attitudes and practice of diabetic foot assessment, diabetic foot risks, risk stratification, and use of the 2011 National Health and Medical Research Council Guidelines were investigated with an electronic pre-test survey(.) Healthcare professionals then undertook a 3-h education and training workshop before completing the electronic post-test knowledge, attitudes and practice survey. Comparison of pre-test/post-test survey findings was used to assess the change in knowledge, attitudes and intended practice due to the workshops. Two hundred and forty-six healthcare professionals from two rural and remote health regions of Western Australia participated in training workshops. Monofilaments and diabetes foot care education brochures, particularly brochures for Aboriginal people, were reported as not readily available in rural and remote health services. For most participants (58 %), their post-test knowledge score increased significantly from the pre-test score. Use of the Guidelines in clinical settings was low (19 %). The healthcare professionals' baseline diabetic foot knowledge was adequate to correctly identify the high risk category. However, stratification of the intermediate risk category was poor, even after training. This study reports the first assessment of Western Australia's rural and remote health professionals' knowledge, attitudes and practices regarding the diabetic foot. It shows that without training, generalists' levels of knowledge concerning the diabetic foot was low and they were unlikely to assess foot risk. The findings from this study in a rural and remote setting cast doubt on the ability of generalist healthcare professionals to stratify risk appropriately, especially for those at intermediate risk, without clinical decision support tools.

Therapeutic Decisions in Atrial Fibrillation for Stroke Prevention: The Role of Aversion to Ambiguity and Physicians' Risk Preferences.

PubMed

Sposato, Luciano A; Stirling, Devin; Saposnik, Gustavo

2018-04-09

Knowledge-to-action gaps influence therapeutic decisions in atrial fibrillation (AF). Physician-related factors are common, but the least studied. We evaluated the prevalence and determinants of physician-related factors and knowledge-to-action gaps among physicians involved in the management of AF patients. In this cross-sectional study, participants from 6 South American countries recruited during an educational program answered questions regarding 16 case scenarios of patients with AF and completed experiments assessing 3 outcome measures: therapeutic inertia, herding, and errors in risk stratification knowledge translated into action (ERSKTA) based on commonly used stratification tools (Congestive heart failure, Hypertension, Age ≥75 years (double), Diabetes mellitus, previous Stroke/transient ischemic attack/thromboembolism (double), Vascular disease, Age 65-74 years, and female gender (score of 0 for males and 1 for female) (CHA 2 DS 2 -VASc) and Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, and previous Stroke/transient ischemic attack (double) (CHADS 2 )). Logistic regression analysis was conducted to determine factors associated with the outcomes. Overall, 149 physicians were invited to participate, of which 88 (59.1%) completed the online assessment tool. Cardiology was the most frequent specialty (69.3%). Therapeutic inertia was present in 53 participants (60.2%), herding in 66 (75.0%), and ERSKTA in 46 (52.3%). Therapeutic inertia was inversely associated with willingness to take financial risks (odds ratio [OR] .72, 95% confidence interval [CI] .59-.89 per point in the financial risk propensity score), herding was associated with aversion to ambiguity in the medical domain (OR 5.35, 95% CI 1.40-20.46), and ERSKTA was associated with the willingness to take risks (OR 1.70, 95% CI 1.15-2.50, per point in score). Among physicians involved in stroke prevention in AF, individual risk preferences and aversion to ambiguity lead to therapeutic inertia, herding, and errors in risk stratification and subsequent use of oral anticoagulants. Educational interventions, including formal training in risk management and decision-making are needed. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype

PubMed Central

Domingues, Patrícia Henriques; Sousa, Pablo; Otero, Álvaro; Gonçalves, Jesus Maria; Ruiz, Laura; de Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto; Tabernero, Maria Dolores

2014-01-01

Background Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Methods Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Results Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Conclusions Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse. PMID:24536048

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol

PubMed Central

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-01-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23–3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. PMID:26137961

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

PubMed

Ghazavi, Farzaneh; Clappier, Emmanuelle; Lammens, Tim; Suciu, Stefan; Caye, Aurélie; Zegrari, Samira; Bakkus, Marleen; Grardel, Nathalie; Benoit, Yves; Bertrand, Yves; Minckes, Odile; Costa, Vitor; Ferster, Alina; Mazingue, Françoise; Plat, Geneviève; Plouvier, Emmanuel; Poirée, Marilyne; Uyttebroeck, Anne; van der Werff-Ten Bosch, Jutte; Yakouben, Karima; Helsmoortel, Hetty; Meul, Magali; Van Roy, Nadine; Philippé, Jan; Speleman, Frank; Cavé, Hélène; Van Vlierberghe, Pieter; De Moerloose, Barbara

2015-10-01

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728. Copyright© Ferrata Storti Foundation.

The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Fang, Yingying; Shao, Rui

2018-01-01

To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score.

PubMed

Tapper, Elliot B; Hunink, M G Myriam; Afdhal, Nezam H; Lai, Michelle; Sengupta, Neil

2016-01-01

The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.

Value of the Definition of Severe Familial Hypercholesterolemia for Stratification of Heterozygous Patients.

PubMed

Pérez-Calahorra, Sofia; Sánchez-Hernández, Rosa María; Plana, Núria; Marco-Benedi, Victoria; Pedro-Botet, Juan; Almagro, Fátima; Brea, Angel; Ascaso, Juan Francisco; Lahoz, Carlos; Civeira, Fernando

2017-03-01

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem. Copyright © 2016 Elsevier Inc. All rights reserved.

Doppler Endoscopic Probe Monitoring of Blood Flow Improves Risk Stratification and Outcomes of Patients With Severe Nonvariceal Upper Gastrointestinal Hemorrhage.

PubMed

Jensen, Dennis M; Kovacs, Thomas O G; Ohning, Gordon V; Ghassemi, Kevin; Machicado, Gustavo A; Dulai, Gareth S; Sedarat, Alireza; Jutabha, Rome; Gornbein, Jeffrey

2017-05-01

For 4 decades, stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis. The arterial blood flow that underlies the stigmata rarely is monitored, but can be used to determine risk for rebleeding. We performed a randomized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage. In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding (125 with ulcers, 19 with Dieulafoy's lesions, and 4 with Mallory Weiss tears) to groups that underwent standard, visually guided endoscopic hemostasis (control, n = 76), or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata (n = 72). The primary outcome was the rate of rebleeding after 30 days; secondary outcomes were complications, death, and need for transfusions, surgery, or angiography. There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group (26.3%) vs the Doppler group (11.1%) (P = .0214). The odds ratio for rebleeding with Doppler monitoring was 0.35 (95% confidence interval, 0.143-0.8565) and the number needed to treat was 7. In a randomized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions, Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis. Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results. ClinicalTrials.gov no: NCT00732212 (CLIN-013-07F). Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

The new dyslipidemia guidelines: what is the debate?

PubMed

Anderson, Todd J; Mancini, G B John; Genest, Jacques; Grégoire, Jean; Lonn, Eva M; Hegele, Robert A

2015-05-01

Dyslipidemia is a major risk factor for the development of atherosclerotic disease. Therefore, lifestyle interventions and pharmacological approaches to decrease cholesterol are widely used in cardiovascular disease prevention. The introduction and widespread use of 3-hydroxy-3 methylglutaryl coenzyme A inhibitors (statins) for individuals at risk of atherosclerotic disease has been an important advance in cardiovascular care. There can be no doubt that better control of dyslipidemia, even in subjects whose low-density lipoprotein cholesterol level is not particularly high, has reduced overall event rates. On a background of lifestyle interventions, statins are routinely used to decrease risk along with aspirin and interventions to control hypertension and diabetes. More than other risk factors, the approach to the identification and treatment of dyslipidemia has been heterogeneous and widely debated. The recent release of the 2013 American College of Cardiology/American Heart Association dyslipidemia guidelines has reignited the controversy over the best approach for risk stratification and treatment. In this article we review the importance of statin therapy for global cardiovascular risk reduction, compare the Canadian Cardiovascular Society dyslipidemia guidelines with other standards, and discuss the points of debate. Despite the seeming variety of recommendations, their common link is a systematic approach to risk stratification and treatment, which will continue to benefit our patients at risk. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Public health implications from COGS and potential for risk stratification and screening.

PubMed

Burton, Hilary; Chowdhury, Susmita; Dent, Tom; Hall, Alison; Pashayan, Nora; Pharoah, Paul

2013-04-01

The PHG Foundation led a multidisciplinary program, which used results from COGS research identifying genetic variants associated with breast, ovarian and prostate cancers to model risk-stratified prevention for breast and prostate cancers. Implementing such strategies would require attention to the use and storage of genetic information, the development of risk assessment tools, new protocols for consent and programs of professional education and public engagement.

A Nationwide Epidemiologic Modeling Study of LD: Risk, Protection, and Unintended Impact

ERIC Educational Resources Information Center

McDermott, Paul A.; Goldberg, Michelle M.; Watkins, Marley W.; Stanley, Jeanne L.; Glutting, Joseph J.

2006-01-01

Through multiple logistic regression modeling, this article explores the relative importance of risk and protective factors associated with learning disabilities (LD). A representative national sample of 6- to 17-year-old students (N = 1,268) was drawn by random stratification and classified by the presence versus absence of LD in reading,…

Stratification of breast cancer risk in women with atypia: a Mayo cohort study.

PubMed

Degnim, Amy C; Visscher, Daniel W; Berman, Hal K; Frost, Marlene H; Sellers, Thomas A; Vierkant, Robert A; Maloney, Shaun D; Pankratz, V Shane; de Groen, Piet C; Lingle, Wilma L; Ghosh, Karthik; Penheiter, Lois; Tlsty, Thea; Melton, L Joseph; Reynolds, Carol A; Hartmann, Lynn C

2007-07-01

Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed. Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time. With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (< 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years. Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate "very high risk" status (> 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.

Understanding the Effect of Stratification on Vertical and Temporal Heterogenieties of Cyanobacteria Blooms in Lakes Using a Long Term in-situ Monitoring Station

NASA Astrophysics Data System (ADS)

Wilkinson, A.; Guala, M.; Hondzo, M.

2017-12-01

Harmful Algal Blooms (HAB) are made up of potentially toxic freshwater microorganisms called cyanobacteria, because of this they are a ecological and public health hazard. The occurrences of toxic HAB are unpredictable and highly spatially and temporary variable in freshwater ecosystems. To study the abiotic drivers for toxic HAB, a floating research station has been deployed in a hyper-eutrophic lake in Madison Lake, Minnesota, from June-October 2016. This research station provides full depth water quality (hourly) and meteorological monitoring (5 minutes). Water quality monitoring is performed by an autonomously traversed water quality sonde that provides chemical, physical and biological measurements; including phycocyanin, a photosynthetic pigment distinct to cyanobacteria. A bloom of cyanobacteria recorded in the epiliminion in mid-July was driven by prolonged strong thermal stratification in the water column, high surface water temperatures and high phosphate concentrations in the epiliminion. The high biovolume (BV) persisted until late September and was sustained below the surface after stratification weakened, when the thermocline did not confine cyanobacteria-rich layers any more, and cyanobacteria vertical heterogeneities decayed in the water column. High correlations among BV stratification, surface water temperature, and stratification stability informed the development of a quantitative relationship to determine how BV heterogeneities vary with thermal structure in the water column. The BV heterogeneity decreased with thermal stratification stability and surface water temperature, and the dynamic lake stability described by the Lake Number. Finally the location of maximum BV accumulation showed diurnal patterns ie. BV peaks were observed at 1 m depth during the day and deeper layers during the night, which followed patterns in light penetration and thermocline depth. These findings capture cyanobacteria vertical and temporal heterogeneities on a on full depth, seasonal scale and quantify BV distribution throughout the water column under different stratification conditions, which can be important for mitigating risks of contamination of drinking water and recreational exposure.

A validation study of the 2003 American College of Cardiology/European Society of Cardiology and 2011 American College of Cardiology Foundation/American Heart Association risk stratification and treatment algorithms for sudden cardiac death in patients with hypertrophic cardiomyopathy.

PubMed

O'Mahony, Constantinos; Tome-Esteban, Maite; Lambiase, Pier D; Pantazis, Antonios; Dickie, Shaughan; McKenna, William J; Elliott, Perry M

2013-04-01

Sudden cardiac death (SCD) is a common mode of death in hypertrophic cardiomyopathy (HCM), but identification of patients who are at a high risk of SCD is challenging as current risk stratification guidelines have never been formally validated. The objective of this study was to assess the power of the 2003 American College of Cardiology (ACC)/European Society of Cardiology (ESC) and 2011 ACC Foundation (ACCF)/American Heart Association (AHA) SCD risk stratification algorithms to distinguish high risk patients who might be eligible for an implantable cardioverter defibrillator (ICD) from low risk individuals. We studied 1606 consecutively evaluated HCM patients in an observational, retrospective cohort study. Five risk factors (RF) for SCD were assessed: non-sustained ventricular tachycardia, severe left ventricular hypertrophy, family history of SCD, unexplained syncope and abnormal blood pressure response to exercise. During a follow-up period of 11 712 patient years (median 6.6 years), SCD/appropriate ICD shock occurred in 20 (3%) of 660 patients without RF (annual rate 0.45%), 31 (4.8%) of 636 patients with 1 RF (annual rate 0.65%), 27 (10.8%) of 249 patients with 2 RF (annual rate 1.3%), 7 (13.7%) of 51 patients with 3 RF (annual rate 1.9%) and 4 (40%) of 10 patients with ≥4 RF (annual rate 5.0%). The risk of SCD increased with multiple RF (2 RF: HR 2.87, p≤0.001; 3 RF: HR 4.32, p=0.001; ≥4 RF: HR 11.37, p<0.0001), but not with a single RF (HR 1.43 p=0.21). The area under time-dependent receiver operating characteristic curves (representing the probability of correctly identifying a patient at risk of SCD on the basis of RF profile) was 0.63 at 1 year and 0.64 at 5 years for the 2003 ACC/ESC algorithm and 0.61 at 1 year and 0.63 at 5 years for the 2011 ACCF/AHA algorithm. The risk of SCD increases with the aggregation of RF. The 2003 ACC/ESC and 2011 ACCF/AHA guidelines distinguish high from low risk individuals with limited power.

Characterisation of the Subaquatic Groundwater Discharge That Maintains the Permanent Stratification within Lake Kivu; East Africa

PubMed Central

Ross, Kelly Ann; Gashugi, Elisée; Gafasi, Augustin; Wüest, Alfred; Schmid, Martin

2015-01-01

Warm and cold subaquatic groundwater discharge into Lake Kivu forms the large-scale density gradients presently observed in the lake. This structure is pertinent to maintaining the stratification that locks the high volume of gases in the deepwater. Our research presents the first characterisation of these inflows. Temperature and conductivity profiling was conducted from January 2010 to March 2013 to map the locations of groundwater discharge. Water samples were obtained within the lake at the locations of the greatest temperature anomalies observed from the background lake-profile. The isotopic and chemical signatures of the groundwater were applied to assess how these inflows contribute to the overall stratification. It is inferred that Lake Kivu’s deepwater has not been completely recharged by the groundwater inflows since its turnover that is speculated to have occurred within the last ~1000 yrs. Given a recent salinity increase in the lake constrained to within months of seismic activity measured beneath the basin, it is plausible that increased hydrothermal-groundwater inflows into the deep basin are correlated with episodic geologic events. These results invalidate the simple two-component end-member mixing regime that has been postulated up to now, and indicate the importance of monitoring this potentially explosive lake. PMID:25799098

Management of acute paracetamol (acetaminophen) toxicity: a standardised proforma improves risk assessment and overall risk stratification by emergency medicine doctors.

PubMed

McQuade, David J; Aknuri, Srikanth; Dargan, Paul I; Wood, David M

2012-12-01

Paracetamol (acetaminophen) poisoning is the most common toxicological presentation in the UK. Doctors managing patients with paracetamol poisoning need to assess the risk of their patient developing hepatotoxicity before determining appropriate treatment. Patients deemed to be at 'high risk' of hepatotoxicity have lower treatment thresholds than those deemed to be at 'normal risk'. Errors in this process can lead to harmful or potentially fatal under or over treatment. To determine how well treating doctors assess risk factor status and whether a standardised proforma is useful in the risk stratification process. Retrospective 12-month case note review of all patients presenting with paracetamol poisoning to our large inner-city emergency department. Data were collected on the documentation of risk factors, the presence of a local hospital proforma and treatment outcomes. 249 presentations were analysed and only 59 (23.7%) had full documentation of all the risk factors required to make a complete risk assessment. 56 of the 59 (94.9%) had the local hospital proforma included in the notes; the remaining 3 (5.1%) had full documentation of risk factors despite the absence of a proforma. A local hospital proforma was more likely to be included in the emergency department notes in those with 'adequate documentation' (78 out of 120 (65%)) than for those with 'inadequate documentation' (16 out of 129 (12.4%)); X(2), p<0.001. Despite a low overall uptake of the proforma, use of a standardised proforma significantly increased the likelihood of documentation of the risk factors which increase risk for hepatotoxicity following paracetamol poisoning.

TCGA's Testicular Germ Cell Tumor Study - TCGA

Cancer.gov

TCGA network researchers identify molecular characteristics that classify testicular germ cell tumor types, including a separate subset of seminomas defined by KIT mutations. This provides a set of candidate biomarkers for risk stratification and potential therapeutic targeting.

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

PubMed Central

2012-01-01

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department. PMID:22264220

Hypertrophic Cardiomyopathy: Clinical Update.

PubMed

Geske, Jeffrey B; Ommen, Steve R; Gersh, Bernard J

2018-05-01

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy in the absence of a secondary cause. The genetic underpinnings of HCM arise largely from mutations of sarcomeric proteins; however, the specific underlying mutation often remains undetermined. Patient presentation is phenotypically diverse, ranging from asymptomatic to heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in most patients. The goal of therapeutic interventions is largely to reduce dynamic obstruction, with treatment modalities spanning lifestyle modifications, pharmacotherapies, and septal reduction therapies. A small subset of patients with HCM will experience sudden cardiac death, and risk stratification remains a clinical challenge. This paper presents a clinical update for diagnosis, family screening, clinical imaging, risk stratification, and management of symptoms in patients with HCM. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The assessment and management of chest pain in primary care: A focus on acute coronary syndrome

PubMed

Thomsett, Richard; Cullen, Louise

2018-05-01

Chest pain is a common presentation and diagnosis can be challenging. There are many causes for chest pain, including life-threatening conditions such as acute coronary syndrome (ACS), which can prove difficult to diagnose. This article focuses on diagnosis and early management of patients with possible ACS. Key differentials and essential primary care investigations and management are outlined. Hospital-based risk stratification and management are described, providing an outline of what patients can expect if referred to hospital. In primary care, an electrocardiogram (ECG) is the only investigation required for most patients while referral is made to hospital. Troponin testing should rarely be requested to investigate patients with suspected ACS in the primary care setting. Initial treatment may include aspirin, glyceryl trinitrate and oxygen if required. If ACS is suspected as the cause of the symptoms, urgent referral for definitive risk stratification is required.

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up

PubMed Central

Frobisher, Clare; Glaser, Adam; Levitt, Gill A; Cutter, David J; Winter, David L; Lancashire, Emma R; Oeffinger, Kevin C; Guha, Joyeeta; Kelly, Julie; Reulen, Raoul C; Hawkins, Michael M

2017-01-01

Background: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. Methods: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. Results: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs—5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death—2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition—14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. Conclusions: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes. PMID:29065109

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art.

PubMed

Kamal, Muhammad Umar; Riaz, Irbaz Bin; Janardhanan, Rajesh

2016-01-01

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1:500 (0.2%) in the general population. Sudden cardiac death (SCD) is the most feared presentation of HCM. Therefore, it is essential to identify individuals at high risk in order to prevent SCD. The absence of conventional risk factors does not nullify the risk of HCM related SCD. Although echocardiography is currently the most widely used imaging modality, cardiac magnetic resonance (CMR) allows detailed characterization of the HCM phenotype, which makes it possible to differentiate HCM from other causes of left ventricular hypertrophy. CMR has the potential to further refine risk stratification. Late gadolinium enhancement (LGE) on CMR is a high-risk feature and there is emerging data to suggest that the presence of LGE should be employed as a marker for major adverse outcomes such as SCD, arrhythmias, systolic and diastolic heart failure. Hence, LGE on CMR may be considered an additional risk factor for SCD in HCM patients and should be incorporated in decision-making for implant-able cardioverter defibrillator implantation to aid primary prevention. Novel markers such as the extent of myocardial fibrosis on CMR must be accounted for comprehensive risk stratifica-tion of HCM patients. The purpose of this review is to discuss the current status and emerging role of CMR in HCM.

Risk stratification following acute myocardial infarction.

PubMed

Singh, Mandeep

2007-07-01

This article reviews the current risk assessment models available for patients presenting with myocardial infarction (MI). These practical tools enhance the health care provider's ability to rapidly and accurately assess patient risk from the event or revascularization therapy, and are of paramount importance in managing patients presenting with MI. This article highlights the models used for ST-elevation MI (STEMI) and non-ST elevation MI (NSTEMI) and provides an additional description of models used to assess risks after primary angioplasty (ie, angioplasty performed for STEMI).

Analysis of the individual risk of altitude decompression sickness under repeated exposures

NASA Technical Reports Server (NTRS)

Kumar, K. Vasantha; Horrigan, David J.; Waligora, James M.; Gilbert, John H.

1991-01-01

In a case-control study, researchers examined the risk of decompression sickness (DCS) in individual subjects with higher number of exposures. Of the 126 subjects, 42 showed one or more episodes of DCS. Examination of the exposure-DCS relationship by odds ratio showed a linear relationship. Stratification analysis showed that sex, tissue ratio, and the presence of Doppler microbubbles were cofounders of this risk. A higher number of exposures increased the risk of DCS in this analysis.

[Sports medical aspects in cardiac risk stratification--heart rate variability and exercise capacity].

PubMed

Banzer, W; Lucki, K; Bürklein, M; Rosenhagen, A; Vogt, L

2006-12-01

The present study investigates the association of the predicted CHD-risk (PROCAM) with the individual endurance capacity and heart rate variability (HRV) in a population-based sample of sedentary elderly. After stratification, in 57 men (48.1+/-9.5 yrs.) with an overall PROCAM-risk <10% (28.7+/-10.9 points) and 22 men (54.5+/-7.7 yrs.) with a coronary 10-year risk > or =10% (50.8+/-5.6 points) cycle ergometries and short-term HRV analysis of time (RRMEAN, SDNN, RMSSD) and frequency domain parameters (LF, HF, TP, LF/HF) were conducted. Additionally the autonomic stress index (SI) was calculated. Nonparametric tests were used for statistical correlation analysis (Spearman rho) and group comparisons (Mann-Whitney). For endurance capacity [W/kg] (r=-0.469, p<0.001), SDNN (r=-0.302, p<0.05), RMSSD (r= -0.311, p<0.05), LF (r=-0.325, p<0.05), HF (r= -0.311, p<0.05) and TP (r= -0.307, p<0.05) negative monotone correlations with the coronary score-risk were determined. Significant positive correlations were calculated for SI (r=0.476, p<0.001). Except for RRMEAN and LF/HF significant group differences (p<0.05) were computed for SDNN (30.0+/-20.0 vs 20.0+/-10.0 ms), RMSSD (22.2+/-18.3 vs 18.0+/-8.7 ms), LF (90.9+/-241.5 vs 41.35+/-81.1 ms(2)), HF (43.0+/-105.1 vs 18.0+/-27.0 ms(2)) and TP (189.0+/-457.1 vs 100.0+/-157.6 ms(2)). Significant differences (p<0.01) were evaluated for exercise capacity (2.4+/-0.5 vs 1.8+/-0.3 W/kg) and SI (90+/-183 vs 322+/-291). The results underline the predictive value of HRV analysis in risk stratification and outline the interrelation of a decreased exercise capacity and autonomic function with a raised individual 10-year cardiac risk. As an independent parameter of the vegetative regulatory state the stress index may contribute to an increased practical relevance of short-time HRV analysis.

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

PubMed

Schuetz, Philipp; Hausfater, Pierre; Amin, Devendra; Amin, Adina; Haubitz, Sebastian; Faessler, Lukas; Kutz, Alexander; Conca, Antoinette; Reutlinger, Barbara; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Huber, Andreas; Mueller, Beat

2015-10-29

Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

PCA-based polling strategy in machine learning framework for coronary artery disease risk assessment in intravascular ultrasound: A link between carotid and coronary grayscale plaque morphology.

PubMed

Araki, Tadashi; Ikeda, Nobutaka; Shukla, Devarshi; Jain, Pankaj K; Londhe, Narendra D; Shrivastava, Vimal K; Banchhor, Sumit K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Suri, Jasjit S

2016-05-01

Percutaneous coronary interventional procedures need advance planning prior to stenting or an endarterectomy. Cardiologists use intravascular ultrasound (IVUS) for screening, risk assessment and stratification of coronary artery disease (CAD). We hypothesize that plaque components are vulnerable to rupture due to plaque progression. Currently, there are no standard grayscale IVUS tools for risk assessment of plaque rupture. This paper presents a novel strategy for risk stratification based on plaque morphology embedded with principal component analysis (PCA) for plaque feature dimensionality reduction and dominant feature selection technique. The risk assessment utilizes 56 grayscale coronary features in a machine learning framework while linking information from carotid and coronary plaque burdens due to their common genetic makeup. This system consists of a machine learning paradigm which uses a support vector machine (SVM) combined with PCA for optimal and dominant coronary artery morphological feature extraction. Carotid artery proven intima-media thickness (cIMT) biomarker is adapted as a gold standard during the training phase of the machine learning system. For the performance evaluation, K-fold cross validation protocol is adapted with 20 trials per fold. For choosing the dominant features out of the 56 grayscale features, a polling strategy of PCA is adapted where the original value of the features is unaltered. Different protocols are designed for establishing the stability and reliability criteria of the coronary risk assessment system (cRAS). Using the PCA-based machine learning paradigm and cross-validation protocol, a classification accuracy of 98.43% (AUC 0.98) with K=10 folds using an SVM radial basis function (RBF) kernel was achieved. A reliability index of 97.32% and machine learning stability criteria of 5% were met for the cRAS. This is the first Computer aided design (CADx) system of its kind that is able to demonstrate the ability of coronary risk assessment and stratification while demonstrating a successful design of the machine learning system based on our assumptions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Risk Stratification of Stress Fractures and Prediction of Return to Duty

DTIC Science & Technology

2015-12-01

enrollment. In study Task 1 we aim to determine the sex- and race -ethnicity-specific bone traits that may contribute to stress fracture risk in military...SUBJECT TERMS bone microarchitecture, HRpQCT, race , gender, sex, bone mineral density, vBMD, bone geometry, stress fracture 16. SECURITY...sectional study aimed at identifying the bone properties that may be related to the well-known sex and race /ethnicity differences in risk for stress

Risk stratification of gallbladder polyps larger than 10 mm using high-resolution ultrasonography and texture analysis.

PubMed

Choi, Tae Won; Kim, Jung Hoon; Park, Sang Joon; Ahn, Su Joa; Joo, Ijin; Han, Joon Koo

2018-01-01

To assess important features for risk stratification of gallbladder (GB) polyps >10 mm using high-resolution ultrasonography (HRUS) and texture analysis. We included 136 patients with GB polyps (>10 mm) who underwent both HRUS and cholecystectomy (non-neoplastic, n = 58; adenomatous, n = 32; and carcinoma, n = 46). Two radiologists retrospectively assessed HRUS findings and texture analysis. Multivariate analysis was performed to identify significant predictors for neoplastic polyps and carcinomas. Single polyp (OR, 3.680-3.856) and larger size (OR, 1.450-1.477) were independently associated with neoplastic polyps (p < 0.05). In a single or polyp >14 mm, sensitivity for differentiating neoplastic from non-neoplastic polyps was 92.3%. To differentiate carcinoma from adenoma, sessile shape (OR, 9.485-41.257), larger size (OR, 1.267-1.303), higher skewness (OR, 6.382) and lower grey-level co-occurrence matrices (GLCM) contrast (OR, 0.963) were significant predictors (p < 0.05). In a polyp >22 mm or sessile, sensitivity for differentiating carcinomas from adenomas was 93.5-95.7%. If a polyp demonstrated at least one HRUS finding and at least one texture feature, the specificity for diagnosing carcinoma was increased to 90.6-93.8%. In a GB polyp >10 mm, single and diameter >14 mm were useful for predicting neoplastic polyps. In neoplastic polyps, sessile shape, diameter >22 mm, higher skewness and lower GLCM contrast were useful for predicting carcinoma. • Risk of neoplastic polyp is low in <14 mm and multiple polyps • A sessile polyp or >22 mm has increased risk for GB carcinomas • Higher skewness and lower GLCM contrast are predictors of GB carcinoma • HRUS is useful for risk stratification of GB polyps >1 cm.

Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study.

PubMed

Jensen, Annette S; Broberg, Craig S; Rydman, Riikka; Diller, Gerhard-Paul; Li, Wei; Dimopoulos, Konstantinos; Wort, Stephen J; Pennell, Dudley J; Gatzoulis, Michael A; Babu-Narayan, Sonya V

2015-12-01

Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up. © 2015 American Heart Association, Inc.

Current indications for transplantation: stratification of severe heart failure and shared decision-making

PubMed Central

Vucicevic, Darko; Honoris, Lily; Raia, Federica

2018-01-01

Heart failure (HF) is a complex clinical syndrome that results from structural or functional cardiovascular disorders causing a mismatch between demand and supply of oxygenated blood and consecutive failure of the body’s organs. For those patients with stage D HF, advanced therapies, such as mechanical circulatory support (MCS) or heart transplantation (HTx), are potentially life-saving options. The role of risk stratification of patients with stage D HF in a value-based healthcare framework is to predict which subset might benefit from advanced HF (AdHF) therapies, to improve outcomes related to the individual patient including mortality, morbidity and patient experience as well as to optimize health care delivery system outcomes such as cost-effectiveness. Risk stratification and subsequent outcome prediction as well as therapeutic recommendation-making need to be based on the comparative survival benefit rationale. A robust model needs to (I) have the power to discriminate (i.e., to correctly risk stratify patients); (II) calibrate (i.e., to show agreement between the predicted and observed risk); (III) to be applicable to the general population; and (IV) provide good external validation. The Seattle Heart Failure Model (SHFM) and the Heart Failure Survival Score (HFSS) are two of the most widely utilized scores. However, outcomes for patients with HF are highly variable which make clinical predictions challenging. Despite our clinical expertise and current prediction tools, the best short- and long-term survival for the individual patient, particularly the sickest patient, is not easy to identify because among the most severely ill, elderly and frail patients, most preoperative prediction tools have the tendency to be imprecise in estimating risk. They should be used as a guide in a clinical encounter grounded in a culture of shared decision-making, with the expert healthcare professional team as consultants and the patient as an empowered decision-maker in a trustful safe therapeutic relationship. PMID:29492383

Current indications for transplantation: stratification of severe heart failure and shared decision-making.

PubMed

Vucicevic, Darko; Honoris, Lily; Raia, Federica; Deng, Mario

2018-01-01

Heart failure (HF) is a complex clinical syndrome that results from structural or functional cardiovascular disorders causing a mismatch between demand and supply of oxygenated blood and consecutive failure of the body's organs. For those patients with stage D HF, advanced therapies, such as mechanical circulatory support (MCS) or heart transplantation (HTx), are potentially life-saving options. The role of risk stratification of patients with stage D HF in a value-based healthcare framework is to predict which subset might benefit from advanced HF (AdHF) therapies, to improve outcomes related to the individual patient including mortality, morbidity and patient experience as well as to optimize health care delivery system outcomes such as cost-effectiveness. Risk stratification and subsequent outcome prediction as well as therapeutic recommendation-making need to be based on the comparative survival benefit rationale. A robust model needs to (I) have the power to discriminate (i.e., to correctly risk stratify patients); (II) calibrate (i.e., to show agreement between the predicted and observed risk); (III) to be applicable to the general population; and (IV) provide good external validation. The Seattle Heart Failure Model (SHFM) and the Heart Failure Survival Score (HFSS) are two of the most widely utilized scores. However, outcomes for patients with HF are highly variable which make clinical predictions challenging. Despite our clinical expertise and current prediction tools, the best short- and long-term survival for the individual patient, particularly the sickest patient, is not easy to identify because among the most severely ill, elderly and frail patients, most preoperative prediction tools have the tendency to be imprecise in estimating risk. They should be used as a guide in a clinical encounter grounded in a culture of shared decision-making, with the expert healthcare professional team as consultants and the patient as an empowered decision-maker in a trustful safe therapeutic relationship.

Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival.

PubMed

Mughal, Muhammad Kashif; Akhter, Ariz; Street, Lesley; Pournazari, Payam; Shabani-Rad, Meer-Taher; Mansoor, Adnan

2017-09-01

Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Predictive genetic testing for the identification of high-risk groups: a simulation study on the impact of predictive ability

PubMed Central

2011-01-01

Background Genetic risk models could potentially be useful in identifying high-risk groups for the prevention of complex diseases. We investigated the performance of this risk stratification strategy by examining epidemiological parameters that impact the predictive ability of risk models. Methods We assessed sensitivity, specificity, and positive and negative predictive value for all possible risk thresholds that can define high-risk groups and investigated how these measures depend on the frequency of disease in the population, the frequency of the high-risk group, and the discriminative accuracy of the risk model, as assessed by the area under the receiver-operating characteristic curve (AUC). In a simulation study, we modeled genetic risk scores of 50 genes with equal odds ratios and genotype frequencies, and varied the odds ratios and the disease frequency across scenarios. We also performed a simulation of age-related macular degeneration risk prediction based on published odds ratios and frequencies for six genetic risk variants. Results We show that when the frequency of the high-risk group was lower than the disease frequency, positive predictive value increased with the AUC but sensitivity remained low. When the frequency of the high-risk group was higher than the disease frequency, sensitivity was high but positive predictive value remained low. When both frequencies were equal, both positive predictive value and sensitivity increased with increasing AUC, but higher AUC was needed to maximize both measures. Conclusions The performance of risk stratification is strongly determined by the frequency of the high-risk group relative to the frequency of disease in the population. The identification of high-risk groups with appreciable combinations of sensitivity and positive predictive value requires higher AUC. PMID:21797996

Development and applications of the Veterans Health Administration's Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide.

PubMed

Oliva, Elizabeth M; Bowe, Thomas; Tavakoli, Sara; Martins, Susana; Lewis, Eleanor T; Paik, Meenah; Wiechers, Ilse; Henderson, Patricia; Harvey, Michael; Avoundjian, Tigran; Medhanie, Amanuel; Trafton, Jodie A

2017-02-01

Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Current challenges and opportunities in treating adult patients with Philadelphia-negative acute lymphoblastic leukaemia.

PubMed

Wolach, Ofir; Amitai, Irina; DeAngelo, Daniel J

2017-12-01

Significant advances have been made in recent years in the field of Philadelphia-negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk-stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric-inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk-adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk-stratification, choice of induction and post-remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL. © 2017 John Wiley & Sons Ltd.

Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients : Recommendations for updated ESUR Contrast Medium Safety Committee guidelines.

PubMed

van der Molen, Aart J; Reimer, Peter; Dekkers, Ilona A; Bongartz, Georg; Bellin, Marie-France; Bertolotto, Michele; Clement, Olivier; Heinz-Peer, Gertraud; Stacul, Fulvio; Webb, Judith A W; Thomsen, Henrik S

2018-07-01

The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. AREAS COVERED IN PART 2: Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC-AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium. • In CKD, hydration reduces the PC-AKI risk • Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis • No drugs have been consistently shown to reduce the risk of PC-AKI • Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/1.73 m 2 • Dialysis schedules need not change when intravascular contrast medium is given.

Chronic Kidney Disease in Pregnancy.

PubMed

Koratala, Abhilash; Bhattacharya, Deepti; Kazory, Amir

2017-09-01

With the increasing prevalence of chronic kidney disease (CKD) worldwide, the number of pregnant women with various degrees of renal dysfunction is expected to increase. There is a bidirectional relation between CKD and pregnancy in which renal dysfunction negatively affects pregnancy outcomes, and the pregnancy can have a deleterious impact on various aspects of kidney disease. It has been shown that even mild renal dysfunction can increase considerably the risk of adverse maternal and fetal outcomes. Moreover, data suggest that a history of recovery from acute kidney injury is associated with adverse pregnancy outcomes. In addition to kidney dysfunction, maternal hypertension and proteinuria predispose women to negative outcomes and are important factors to consider in preconception counseling and the process of risk stratification. In this review, we provide an overview of the physiologic renal changes during pregnancy as well as available data regarding CKD and pregnancy outcomes. We also highlight the important management strategies in women with certain selected renal conditions that are seen commonly during the childbearing years. We call for future research on underexplored areas such as the concept of renal functional reserve to develop a potential clinical tool for prognostication and risk stratification of women at higher risk for complications during pregnancy.

Risk stratification for large artery or chronic coronary artery disease-related ischemic stroke in octogenarians undergoing exercise stress myocardial perfusion imaging: A cohort study.

PubMed

Katsikis, Athanasios; Theodorakos, Athanasios; Drosatos, Alexandros; Konstantinou, Konstantinos; Papaioannou, Spyridon; Koutelou, Maria

2017-04-01

To test, if in octogenarians, treadmill exercise with myocardial perfusion imaging (exercise-MPI) can risk stratify for large artery or chronic CAD-related ischemic stroke (LACCIS). Exercise-MPI-related data of 237 octogenarians (55% prior MI or revascularization) without previous stroke were registered and prospective follow-up was performed to document LACCIS. LACCIS was defined as acute onset of neurological symptoms with CT/MRI findings of non-lacunar-type infarcts in the absence of atrial fibrillation or intracardiac embolic sources. After 7.3 years, 10 LACCIS were documented. SSS [HR 1.08 (1.02-1.13 95% CIs), SDS [HR 1.1 (1.04-1.16 95% CIs)], and non-sustained VT or transient AV block during exercise [HR 3.9 (1.7-9.0 95% CIs)] were predictors of LACCIS (P < .01 for all). A SSS threshold of 16 had 81% specificity for identification of future LACCIS and risk groups formed according to this cut-off had significantly different LACCIS-free survival (P = .015). Exercise-MPI in octogenarians can provide risk stratification markers for LACCIS.

Papanicolaou Society of Cytopathology new guidelines have a greater ability of risk stratification for pancreatic endoscopic ultrasound-guided fine-needle aspiration specimens

PubMed Central

Chen, Bo; Zhao, Yu; Gu, Jiangang; Wu, Huanwen; Liang, Zhiyong; Meng, Zhilan

2017-01-01

The Papanicolaou Society of Cytopathology has recently proposed a standardized terminology and nomenclature guidelines for pancreatic cytology. However the risk of malignancy associated with the new guidelines has been scarcely studied. In this study, a series of pancreatic cytology cases obtained by endoscopic ultrasound-guided fine-needle aspiration from 294 Chinese patients were retrospectively re-categorized into six categories according the new guidelines. The risks of malignancy were 18.1% for “negative,” 20.0% for “neoplastic,” 57.1% for “nondiagnostic,” 69.2% for “atypical,” 87.5% for “suspicious,” and 100.0% for “positive” respectively. The area under the receiver operating characteristic curve was 0.93 (95% Confidence Interval, 0.90-0.96), which was significantly higher than that associated with old classification system (0.82; 95% Confidence Interval, 0.77-0.87) conventionally used in China. Our investigation demonstrated that the new guidelines have a greater ability of risk stratification than the old classification system conventionally used in China. This may be helpful in giving better predictions of malignancy, thus leading to more personalized treatment strategies. PMID:28042957

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.

PubMed

Zang, Shiming; Shao, Guoqiang; Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-02-14

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.

Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker treatment.

PubMed

Frankenstein, L; Nelles, M; Hallerbach, M; Dukic, D; Fluegel, A; Schellberg, D; Katus, H A; Remppis, A; Zugck, C

2007-11-15

Peak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL. 194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7+/-1.5 months after V1 and patients were followed >12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n=62; EPN, end-point negative; n=113). Initial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: -0.6+/-2.6 ml/kg min; EPN: +2.5+/-3.3 ml/kg min; p<0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2. Serial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL.

Updated systematic review and meta-analysis of the performance of risk prediction rules in children and young people with febrile neutropenia.

PubMed

Phillips, Robert S; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia.

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients

PubMed Central

Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-01-01

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis. PMID:28103574

Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

PubMed Central

Phillips, Robert S.; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Introduction Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia. PMID:22693615

Applying Latent Class Analysis to Risk Stratification for Perioperative Mortality in Patients Undergoing Intraabdominal General Surgery.

PubMed

Kim, Minjae; Wall, Melanie M; Li, Guohua

2016-07-01

Perioperative risk stratification is often performed using individual risk factors without consideration of the syndemic of these risk factors. We used latent class analysis (LCA) to identify the classes of comorbidities and risk factors associated with perioperative mortality in patients presenting for intraabdominal general surgery. The 2005 to 2010 American College of Surgeons National Surgical Quality Improvement Program was used to obtain a cohort of patients undergoing intraabdominal general surgery. Risk factors and comorbidities were entered into LCA models to identify the latent classes, and individuals were assigned to a class based on the highest posterior probability of class membership. Relative risk regression was used to determine the associations between the latent classes and 30-day mortality, with adjustments for procedure. A 9-class model was fit using LCA on 466,177 observations. After combining classes with similar adjusted mortality risks, 5 risk classes were obtained. Compared with the class with average mortality risk (class 4), the risk ratios (95% confidence interval) ranged from 0.020 (0.014-0.027) in the lowest risk class (class 1) to 6.75 (6.46-7.02) in the highest risk class. After adjusting for procedure and ASA physical status, the latent classes remained significantly associated with 30-day mortality. The addition of the risk class variable to a model containing ASA physical status and surgical procedure demonstrated a significant increase in the area under the receiver operator characteristic curve (0.892 vs 0.915; P < 0.0001). Latent classes of risk factors and comorbidities in patients undergoing intraabdominal surgery are predictive of 30-day mortality independent of the ASA physical status and improve risk prediction with the ASA physical status.

Home telemonitoring of vital signs--technical challenges and future directions.

PubMed

Celler, Branko G; Sparks, Ross S

2015-01-01

The telemonitoring of vital signs from the home is an essential element of telehealth services for the management of patients with chronic conditions, such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), diabetes, or poorly controlled hypertension. Telehealth is now being deployed widely in both rural and urban settings, and in this paper, we discuss the contribution made by biomedical instrumentation, user interfaces, and automated risk stratification algorithms in developing a clinical diagnostic quality longitudinal health record at home. We identify technical challenges in the acquisition of high-quality biometric signals from unsupervised patients at home, identify new technical solutions and user interfaces, and propose new measurement modalities and signal processing techniques for increasing the quality and value of vital signs monitoring at home. We also discuss use of vital signs data for the automated risk stratification of patients, so that clinical resources can be targeted to those most at risk of unscheduled admission to hospital. New research is also proposed to integrate primary care, hospital, personal genomic, and telehealth electronic health records, and apply predictive analytics and data mining for enhancing clinical decision support.

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

PubMed

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.

Resonant Tidal Excitation of Internal Waves in the Earth's Fluid Core

NASA Technical Reports Server (NTRS)

Tyler, Robert H.; Kuang, Weijia

2014-01-01

It has long been speculated that there is a stably stratified layer below the core-mantle boundary, and two recent studies have improved the constraints on the parameters describing this stratification. Here we consider the dynamical implications of this layer using a simplified model. We first show that the stratification in this surface layer has sensitive control over the rate at which tidal energy is transferred to the core. We then show that when the stratification parameters from the recent studies are used in this model, a resonant configuration arrives whereby tidal forces perform elevated rates of work in exciting core flow. Specifically, the internal wave speed derived from the two independent studies (150 and 155 m/s) are in remarkable agreement with the speed (152 m/s) required for excitation of the primary normal mode of oscillation as calculated from full solutions of the Laplace Tidal Equations applied to a reduced-gravity idealized model representing the stratified layer. In evaluating this agreement it is noteworthy that the idealized model assumed may be regarded as the most reduced representation of the stratified dynamics of the layer, in that there are no non-essential dynamical terms in the governing equations assumed. While it is certainly possible that a more realistic treatment may require additional dynamical terms or coupling, it is also clear that this reduced representation includes no freedom for coercing the correlation described. This suggests that one must accept either (1) that tidal forces resonantly excite core flow and this is predicted by a simple model or (2) that either the independent estimates or the dynamical model does not accurately portray the core surface layer and there has simply been an unlikely coincidence between three estimates of a stratification parameter which would otherwise have a broad plausible range.

Turbulent entrainment in a strongly stratified barrier layer

NASA Astrophysics Data System (ADS)

Pham, H. T.; Sarkar, S.

2017-06-01

Large-eddy simulation (LES) is used to investigate how turbulence in the wind-driven ocean mixed layer erodes the stratification of barrier layers. The model consists of a stratified Ekman layer that is driven by a surface wind. Simulations at a wide range of N0/f are performed to quantify the effect of turbulence and stratification on the entrainment rate. Here, N0 is the buoyancy frequency in the barrier layer and f is the Coriolis parameter. The evolution of the mixed layer follows two stages: a rapid initial deepening and a late-time growth at a considerably slower rate. During the first stage, the mixed layer thickens to the depth that is proportional to u∗/fN0 where u∗ is the frictional velocity. During the second stage, the turbulence in the mixed layer continues to deepen further into the barrier layer, and the turbulent length scale is shown to scale with u∗/N0, independent of f. The late-time entrainment rate E follows the law of E=0.035Ri∗-1/2 where Ri∗ is the Richardson number. The exponent of -1/2 is identical but the coefficient of 0.035 is much smaller relative to the value of 2-3/2 for the nonrotating boundary layer. Simulations using the KPP model (version applicable to this simple case without additional effects of Langmuir turbulence or surface buoyancy flux) also yield the entrainment scaling of E∝Ri∗-1/2; however, the proportionality coefficient varies with the stratification. The structure of the Ekman current is examined to illustrate the strong effect of stratification in the limit of large N0/f.

The Global Spine Care Initiative: a consensus process to develop and validate a stratification scheme for surgical care of spinal disorders as a guide for improved resource utilization in low- and middle-income communities.

PubMed

Acaroğlu, Emre; Mmopelwa, Tiro; Yüksel, Selcen; Ayhan, Selim; Nordin, Margareta; Randhawa, Kristi; Haldeman, Scott

2017-10-16

The purpose of this study was to develop a stratification scheme for surgical spinal care to serve as a framework for referrals and distribution of patients with spinal disorders. We used a modified Delphi process. A literature search identified experts for the consensus panel and the panel was expanded by inviting spine surgeons known to be global opinion leaders. After creating a seed document of five hierarchical levels of surgical care, a four-step modified Delphi process (question validation, collection of factors, evaluation of factors, re-evaluation of factors) was performed. Of 78 invited experts, 19 participated in round 1, and of the 19, 14 participated in 2, and 12 in 3 and 4. Consensus was fairly heterogeneous for levels of care 2-4 (moderate resources). Only simple assessment methods based on the clinical skills of the medical personnel were considered feasible and safe in low-resource settings. Diagnosis, staging, and treatment were deemed feasible and safe in a specialized spine center. Accurate diagnostic workup was deemed feasible and safe for lower levels of care complexity (from level 3 upwards) compared to non-invasive procedures (level 4) and the full range of invasive procedures (level 5). This study introduces a five-level stratification scheme for the surgical care of spinal disorders. This stratification may provide input into the Global Spine Care Initiative care pathway that will be applied in medically underserved areas and low- and middle-income countries. These slides can be retrieved under Electronic Supplementary Material.

Simulating rotating fluid bodies: When is vorticity generation via density-stratification important?

NASA Astrophysics Data System (ADS)

Evonuk, M.; Samuel, H.

2012-04-01

Differential rotation is one of the key components needed to maintain a magnetic dynamo, therefore it is important to understand the processes that generate differential rotation in rotating bodies. In a rotating density-stratified fluid, local vorticity generation occurs as fluid parcels move radially, expanding or contracting with respect to the background density stratification. The convergence of this vorticity forms zonal flow structures as a function of the radius and the slope of the background density profile. While this effect is thought to be of importance in bodies that are quickly rotating and highly turbulent with large density stratifications such as Jupiter, it is generally neglected in bodies such as the Earth's outer core, where the density change is small. Simulations of thermal convection in the 2D rotating equatorial plane are conducted to determine the parameter regime where local vorticity generation plays a significant role in organizing the fluid flow. Three regimes are found: a dipolar flow regime, where the flow is not organized by the rotation, a transitional flow regime, and a differential flow regime, where the flow is strongly organized into differential rotation with multiple jets. A scaling law is determined based on the convective Rossby number and the density contrast across the equatorial plane, providing a simple way to determine in which regime a given body lies. While a giant planet such as Jupiter lies firmly in the differential flow regime as expected, the Earth's outer core is also found to lie in the differential flow regime indicating that, even in the Earth's outer core, where the density contrast is small, vorticity contributions via fluid movement through the density stratification may be non-negligible.

Simulating rotating fluid bodies: When is vorticity generation via density-stratification important?

NASA Astrophysics Data System (ADS)

Evonuk, M.; Samuel, H.

2012-12-01

Differential rotation is one of the key components needed to maintain a magnetic dynamo, therefore it is important to understand the processes that generate differential rotation in rotating bodies. In a rotating density-stratified fluid, local vorticity generation occurs as fluid parcels move radially, expanding or contracting with respect to the background density stratification. The convergence of this vorticity forms zonal flow structures as a function of the radius and the slope of the background density profile. While this effect is thought to be of importance in bodies that are quickly rotating and highly turbulent with large density stratifications such as Jupiter, it is generally neglected in bodies such as the Earth's outer core, where the density change is small. Simulations of thermal convection in the 2D rotating equatorial plane are conducted to determine the parameter regime where local vorticity generation plays a significant role in organizing the fluid flow. Three regimes are found: a dipolar flow regime, where the flow is not organized by the rotation, a transitional flow regime, and a differential flow regime, where the flow is strongly organized into differential rotation with multiple jets. A scaling law is determined based on the convective Rossby number and the density contrast across the equatorial plane, providing a simple way to determine in which regime a given body lies. While a giant planet such as Jupiter lies firmly in the differential flow regime as expected, the Earth's outer core is also found to lie in the differential flow regime indicating that, even in the Earth's outer core, where the density contrast is small, vorticity contributions via fluid movement through the density stratification may be non-negligible.

Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: the ATRIA Study

PubMed Central

Go, Alan S.; Fang, Margaret C.; Udaltsova, Natalia; Chang, Yuchiao; Pomernacki, Niela K.; Borowsky, Leila; Singer, Daniel E.

2009-01-01

Background Atrial fibrillation (AF) substantially increases the risk of ischemic stroke but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown. Methods and Results We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. Results During 33,165 person-years off anticoagulation among 10,908 patients with atrial fibrillation, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk [RR] 1.54, 1.29 to 1.85) and there was a graded, increased risk of stroke associated with progressively lower level of eGFR compared with eGFR ≥60 (in units of ml/min/1.73 m2): RR 1.16 (95% CI: 0.95−1.40) for eGFR 45−59 and RR 1.39 (95% CI: 1.13−1.71) for eGFR <45 (P=0.0082 for trend). Conclusions . Chronic kidney disease increases the risk of thromboembolism in AF independent of other risk factors. Knowing the level of kidney function and presence of proteinuria may improve risk stratification for decision-making about the use of antithrombotic therapy for stroke prevention in AF. PMID:19255343

ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias

PubMed Central

Hieken, Tina J; Carter, Jodi M; Hawse, John R; Hoskin, Tanya L; Bois, Melanie; Frost, Marlene; Hartmann, Lynn C; Radisky, Derek C; Visscher, Daniel W; Degnim, Amy C

2015-01-01

Estrogen receptor beta (ERβ) is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171 women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15 years median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules than normal lobules, by percent staining and intensity (both p<0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2 (p=0.04) and 2.5-fold (p=0.006). High normal lobule ERβ expression conferred the strongest protective effect in pre-menopausal women: the 20-year cumulative incidence of breast cancer was 0% for women

Predicting Long-Term Outcomes in Pleural Infections. RAPID Score for Risk Stratification.

PubMed

White, Heath D; Henry, Christopher; Stock, Eileen M; Arroliga, Alejandro C; Ghamande, Shekhar

2015-09-01

Pleural infections are associated with significant morbidity and mortality. The recently developed RAPID (renal, age, purulence, infection source, and dietary factors) score consists of five clinical factors that can identify patients at risk for increased mortality. The objective of this study was to further validate the RAPID score in a diverse cohort, identify factors associated with mortality, and provide long-term outcomes. We evaluated a single-center retrospective cohort of 187 patients with culture-positive pleural infections. Patients were classified by RAPID scores into low-risk (0-2), medium-risk (3-4), and high-risk (5-7) groups. The Social Security Death Index was used to determine date of death. All-cause mortality was assessed at 3 months, 1 year, 3 years, and 5 years. Clinical factors and comorbid conditions were evaluated for association. Three-month mortality for low-, medium-, and high-risk groups was 1.5, 17.8, and 47.8%, respectively. Increased odds were observed among medium-risk (odds ratio, 14.3; 95% confidence interval, 1.8-112.6; P = 0.01) and high-risk groups (odds ratio, 53.3; 95% confidence interval, 6.8-416.8; P < 0.01). This trend continued at 1, 3, and 5 years. Factors associated with high-risk scores include gram-negative rod infections, heart disease, diabetes, cancer, lung disease, and increased length of stay. When applied to a diverse patient cohort, the RAPID score predicts outcomes in patients up to 5 years and may aid in long-term risk stratification on presentation.

Role of cardiopulmonary exercise testing in clinical stratification in heart failure. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology.

PubMed

Corrà, Ugo; Agostoni, Pier Giuseppe; Anker, Stefan D; Coats, Andrew J S; Crespo Leiro, Maria G; de Boer, Rudolph A; Hairola, Veli-Pekka; Hill, Loreena; Lainscak, Mitja; Lund, Lars H; Metra, Marco; Ponikowski, Piotr; Riley, Jillian; Seferović, Petar M; Piepoli, Massimo F

2018-01-01

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Prognostic stratification improvement by integrating ID1/ID3/IGJ gene expression signature and immunophenotypic profile in adult patients with B-ALL.

PubMed

Cruz-Rodriguez, Nataly; Combita, Alba L; Enciso, Leonardo J; Raney, Lauren F; Pinzon, Paula L; Lozano, Olga C; Campos, Alba M; Peñaloza, Niyireth; Solano, Julio; Herrera, Maria V; Zabaleta, Jovanny; Quijano, Sandra

2017-02-28

Survival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction. To improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples. Both techniques were correlated to stratify patients into prognostic groups. An inverse relationship between survival and expression of the three-genes signature was observed and an immunophenotypic profile associated with clinical outcome was identified. Markers CD10 and CD20 were correlated with simultaneous overexpression of ID1, ID3 and IGJ. Patients with simultaneous expression of the poor prognosis gene signature and overexpression of CD10 or CD20, had worse Event Free Survival and Overall Survival than patients who had either the poor prognosis gene expression signature or only CD20 or CD10 overexpressed. By utilizing the combined evaluation of these two immunophenotypic markers along with the poor prognosis gene expression signature, the risk stratification can be significantly strengthened. Further studies including a large number of patients are needed to confirm these findings.

Genetic Modifiers of Ovarian Cancer

DTIC Science & Technology

2014-08-01

samples from many countries. To account for population stratification, the genotyping data in combination with HapMap data (CEU, Yoruban, Han Chinese...Cambridge, we evaluated associations with both breast and ovarian cancer using a retrospective likelihood model. This accounts for the age extremes of...carriers we used a competing risk analysis that accounted for the effects on breast and ovarian cancer in parallel. In this competing risk analysis

Prognostic Usefulness of Cardiac Stress Test Modalities in Patients With Type 2 Diabetes Mellitus Who Underwent Myocardial Perfusion Scintigraphy (from the Basel Asymptomatic High-Risk Diabetics' Outcome Trial).

PubMed

Caobelli, Federico; Haaf, Philip; Chronis, Joannis; Haenny, Gianluca; Brinkert, Miriam; Pfisterer, Matthias E; Zellweger, Michael J

2017-10-01

Our study aimed to assess predictors of the stress test technique used and to evaluate the impact of exercise level achieved on risk stratification in patients with asymptomatic type 2 diabetes without a previous coronary artery disease. Little is known whether co-morbidities of these patients predict the stress technique and whether physical performance provides risk stratification: 400 patients underwent clinical evaluation and myocardial perfusion scintigraphy (MPS) using physical or pharmacological stress. Physical patients were divided into 2 groups: achieving <6 and ≥6 METs, respectively. The mean follow-up time was 2 years. Major cardiac events (MACEs) included myocardial infarction and/or cardiac death. Independent predictors of pharmacological stress were a body mass index of >30 kg/m 2 (hazard ratio 1.076, 95% confidence interval 1.027 to 1.127, p = 0.002) and a peripheral arterial disease (hazard ratio 2.888, 95% confidence interval 1.446 to 5.769, p = 0.003). Pharmacological patients had more MACE than physical patients (3.2% vs 1.0%, p = 0.03). Patients achieving <6 METs had a similar MACE rate as pharmacological patients (3.0% vs 3.2%, p = not significant) and more MACE than patients achieving ≥6 METs (3.0% vs 0.4%, p = 0.01). In patients achieving <6 METs and in pharmacological patients, MPS added an incremental prognostic value to pretest information (p values for global chi-square 0.012 and 0.04, respectively). In high-risk asymptomatic diabetic patients, co-morbidities were predictive of the stress technique used. Pharmacological patients had more MACE, similar to those unable to achieve 6 METs. MPS provided an incremental prognostic value in pharmacological patients and in patients with <6METs. In contrast, patients who were able to achieve ≥6 METs were at low risk and do not need further risk stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

Intermediate outcomes in randomized clinical trials: an introduction

PubMed Central

2013-01-01

Background Intermediate outcomes are common and typically on the causal pathway to the final outcome. Some examples include noncompliance, missing data, and truncation by death like pregnancy (e.g. when the trial intervention is given to non-pregnant women and the final outcome is preeclampsia, defined only on pregnant women). The intention-to-treat approach does not account properly for them, and more appropriate alternative approaches like principal stratification are not yet widely known. The purposes of this study are to inform researchers that the intention-to-treat approach unfortunately does not fit all problems we face in experimental research, to introduce the principal stratification approach for dealing with intermediate outcomes, and to illustrate its application to a trial of long term calcium supplementation in women at high risk of preeclampsia. Methods Principal stratification and related concepts are introduced. Two ways for estimating causal effects are discussed and their application is illustrated using the calcium trial, where noncompliance and pregnancy are considered as intermediate outcomes, and preeclampsia is the main final outcome. Results The limitations of traditional approaches and methods for dealing with intermediate outcomes are demonstrated. The steps, assumptions and required calculations involved in the application of the principal stratification approach are discussed in detail in the case of our calcium trial. Conclusions The intention-to-treat approach is a very sound one but unfortunately it does not fit all problems we find in randomized clinical trials; this is particularly the case for intermediate outcomes, where alternative approaches like principal stratification should be considered. PMID:23510143

A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

PubMed

Amland, Robert C; Lyons, Jason J; Greene, Tracy L; Haley, James M

2015-10-01

To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction.

PubMed

Xie, Yi; Xu, Hua; Fang, Fang; Li, Zhiheng; Zhou, Huiting; Pan, Jian; Guo, Wanliang; Zhu, Xueming; Wang, Jian; Wu, Yi

2018-05-22

Neuroblastoma (NB) is the most common extracranial solid tumor in children with contrasting outcomes. Precise risk assessment contributes to prognosis prediction, which is critical for treatment strategy decisions. In this study, we developed a 3-protein predictor model, including the neural stem cell marker Msi1, neural differentiation marker ID1, and proliferation marker proliferating cell nuclear antigen (PCNA), to improve clinical risk assessment of patients with NB. Kaplan-Meier analysis in the microarray data (GSE16476) revealed that low expression of ID1 and high expression of Msi1 and PCNA were associated with poor prognosis in NB patients. Combined application of these 3 markers to constitute a signature further stratified NB patients into different risk subgroups can help obtain more accurate prediction performance. Survival prognostic power of age and Msi1_ID1_PCNA signature by receiver operating characteristics analysis showed that this signature predicted more effectively and sensitively compared with classic risk stratification system, compensating for the deficiency of the prediction function of the age. Furthermore, we validated the expressions of these 3 proteins in neuroblastic tumor spectrum tissues by immunohistochemistry revealed that Msi1 and PCNA exhibited increased expression in NB compared with intermedial ganglioneuroblastoma and benign ganglioneuroma, whereas ID1 levels were reduced in NB. In conclusion, we established a robust risk assessment predictor model based on simple immunohistochemistry for therapeutic decisions of NB patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Risk-adjusted predictive models of mortality after index arterial operations using a minimal data set.

PubMed

Prytherch, D R; Ridler, B M F; Ashley, S

2005-06-01

Reducing the data required for a national vascular database (NVD) without compromising the statistical basis of comparative audit is an important goal. This work attempted to model outcomes (mortality and morbidity) from a small and simple subset of the NVD data items, specifically urea, sodium, potassium, haemoglobin, white cell count, age and mode of admission. Logistic regression models of risk of adverse outcome were built from the 2001 submission to the NVD using all records that contained the complete data required by the models. These models were applied prospectively against the equivalent data from the 2002 submission to the NVD. As had previously been found using the P-POSSUM (Portsmouth POSSUM) approach, although elective abdominal aortic aneurysm (AAA) repair and infrainguinal bypass (IIB) operations could be described by the same model, separate models were required for carotid endarterectomy (CEA) and emergency AAA repair. For CEA there were insufficient adverse events recorded to allow prospective testing of the models. The overall mean predicted risk of death in 530 patients undergoing elective AAA repair or IIB operations was 5.6 per cent, predicting 30 deaths. There were 28 reported deaths (chi(2) = 2.75, 4 d.f., P = 0.600; no evidence of lack of fit). Similarly, accurate predictions were obtained across a range of predicted risks as well as for patients undergoing repair of ruptured AAA and for morbidity. A 'data economic' model for risk stratification of national data is feasible. The ability to use a minimal data set may facilitate the process of comparative audit within the NVD. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age.

PubMed

Sung, Tae-Yon; Cho, Jae Won; Lee, Yu-Mi; Lee, Yi Ho; Kwon, Hyemi; Jeon, Min Ji; Kim, Won Gu; Choi, Young Jun; Song, Dong Eun; Chung, Ki-Wook; Yoon, Jong Ho; Hong, Suck Joon

2017-11-01

This study validated the dynamic risk stratification (DRS) system with regard to its association with structural recurrence and risk factors associated with non-excellent responses in patients <45 years with stage I classical papillary thyroid cancer (PTC). This historical cohort study included 598 patients with stage I classical PTC <45 years of age treated with total thyroidectomy followed by radioactive iodine remnant ablation (n = 440), total thyroidectomy without radioactive iodine remnant ablation (n = 23), and thyroid lobectomy alone (n = 135). The median follow-up period was 123 months. Structural recurrence occurred in 4.2% (n = 18/432) of the patients with an excellent response, 17.1% (18/105) of patients with an indeterminate response, 44.7% (17/38) of patients with a biochemically incomplete response, and 82.6% (19/23) of patients with a structurally incomplete response (p < 0.001) during the follow-up. The disease-free survival curves of each response showed significant differences (p < 0.001). Extensive extrathyroidal extension and extranodal extension were the independent risk factors associated with non-excellent response (p < 0.05). DRS may reduce unnecessary additional treatments by reclassifying initial risk estimates of structural recurrence. Furthermore, applying the risk factors associated with non-excellent response to initial therapy may be a more useful and viable surrogate of the risk for structural recurrence in stage I PTC patients <45 years of age.

Effect of Neurocognition and Concussion on Musculoskeletal Injury Risk

PubMed Central

Herman, Daniel C.; Zaremski, Jason L.; Vincent, Heather K.; Vincent, Kevin R.

2015-01-01

Research regarding musculoskeletal injury risk has focused primarily on anatomical, neuromuscular, hormonal, and environmental risk factors; however, subsequent injury risk screening and intervention programs have been largely limited to neuromuscular factors and have faced challenges in both implementation and efficacy. Recent studies indicate that poor neurocognitive performance, either at baseline or in the aftermath of a concussion, is associated with elevated risk of musculoskeletal injury. Despite the relatively limited current understanding regarding the nature of the relationship between different aspects of neurocognitive performance and musculoskeletal injury risk, this is a promising area of research that may yield significant advances in musculoskeletal injury risk stratification, rehabilitation, and prevention. PMID:25968852

Systemic risk score evaluation in ischemic stroke patients (SCALA): a prospective cross sectional study in 85 German stroke units.

PubMed

Weimar, Christian; Goertler, Michael; Röther, Joachim; Ringelstein, E Bernd; Darius, Harald; Nabavi, Darius Günther; Kim, In-Ha; Theobald, Karlheinz; Diener, Han-Christoph

2007-11-01

Stratification of patients with transient ischemic attack (TIA) or ischemic stroke (IS) by risk of recurrent stroke can contribute to optimized secondary prevention. We therefore aimed to assess cardiovascular risk factor profiles of consecutive patients hospitalized with TIA/IS to stratify the risk of recurrent stroke according to the Essen Stroke Risk Score (ESRS) and of future cardiovascular events according to the ankle brachial index (ABI) as a marker of generalized atherosclerosis In this cross-sectional observational study, 85 neurological stroke units throughout Germany documented cardiovascular risk factor profiles of 10 consecutive TIA/IS patients on standardized questionnaires. Screening for PAD was done with Doppler ultrasonography to calculate the ABI. A total of 852 patients (57% men) with a mean age of 67+/-12.4 years were included of whom 82.9 % had IS. The median National Institutes of Health stroke sum score was 4 (TIA: 1). Arterial hypertension was reported in 71%, diabetes mellitus in 26%, clinical PAD in 10%, and an ABI < or = 0.9 in 51%. An ESRS > or = 3 was observed in 58%, which in two previous retrospective analyses corresponded to a recurrent stroke risk of > or = 4%/year. The correlation between the ESRS and the ABI was low (r = 0.21). A high proportion of patients had asymptomatic atherosclerotic disease and a considerable risk of recurrent stroke according to the ABI and ESRS category. The prognostic accuracy as well as the potential benefit of various risk stratification scores in secondary stroke prevention require validation in a larger prospective study.

Dynamic TIMI Risk Score for STEMI

PubMed Central

Amin, Sameer T.; Morrow, David A.; Braunwald, Eugene; Sloan, Sarah; Contant, Charles; Murphy, Sabina; Antman, Elliott M.

2013-01-01

Background Although there are multiple methods of risk stratification for ST‐elevation myocardial infarction (STEMI), this study presents a prospectively validated method for reclassification of patients based on in‐hospital events. A dynamic risk score provides an initial risk stratification and reassessment at discharge. Methods and Results The dynamic TIMI risk score for STEMI was derived in ExTRACT‐TIMI 25 and validated in TRITON‐TIMI 38. Baseline variables were from the original TIMI risk score for STEMI. New variables were major clinical events occurring during the index hospitalization. Each variable was tested individually in a univariate Cox proportional hazards regression. Variables with P<0.05 were incorporated into a full multivariable Cox model to assess the risk of death at 1 year. Each variable was assigned an integer value based on the odds ratio, and the final score was the sum of these values. The dynamic score included the development of in‐hospital MI, arrhythmia, major bleed, stroke, congestive heart failure, recurrent ischemia, and renal failure. The C‐statistic produced by the dynamic score in the derivation database was 0.76, with a net reclassification improvement (NRI) of 0.33 (P<0.0001) from the inclusion of dynamic events to the original TIMI risk score. In the validation database, the C‐statistic was 0.81, with a NRI of 0.35 (P=0.01). Conclusions This score is a prospectively derived, validated means of estimating 1‐year mortality of STEMI at hospital discharge and can serve as a clinically useful tool. By incorporating events during the index hospitalization, it can better define risk and help to guide treatment decisions. PMID:23525425

Dynamic TIMI risk score for STEMI.

PubMed

Amin, Sameer T; Morrow, David A; Braunwald, Eugene; Sloan, Sarah; Contant, Charles; Murphy, Sabina; Antman, Elliott M

2013-01-29

Although there are multiple methods of risk stratification for ST-elevation myocardial infarction (STEMI), this study presents a prospectively validated method for reclassification of patients based on in-hospital events. A dynamic risk score provides an initial risk stratification and reassessment at discharge. The dynamic TIMI risk score for STEMI was derived in ExTRACT-TIMI 25 and validated in TRITON-TIMI 38. Baseline variables were from the original TIMI risk score for STEMI. New variables were major clinical events occurring during the index hospitalization. Each variable was tested individually in a univariate Cox proportional hazards regression. Variables with P<0.05 were incorporated into a full multivariable Cox model to assess the risk of death at 1 year. Each variable was assigned an integer value based on the odds ratio, and the final score was the sum of these values. The dynamic score included the development of in-hospital MI, arrhythmia, major bleed, stroke, congestive heart failure, recurrent ischemia, and renal failure. The C-statistic produced by the dynamic score in the derivation database was 0.76, with a net reclassification improvement (NRI) of 0.33 (P<0.0001) from the inclusion of dynamic events to the original TIMI risk score. In the validation database, the C-statistic was 0.81, with a NRI of 0.35 (P=0.01). This score is a prospectively derived, validated means of estimating 1-year mortality of STEMI at hospital discharge and can serve as a clinically useful tool. By incorporating events during the index hospitalization, it can better define risk and help to guide treatment decisions.

External Validation of the HERNIAscore: An Observational Study.

PubMed

Cherla, Deepa V; Moses, Maya L; Mueck, Krislynn M; Hannon, Craig; Ko, Tien C; Kao, Lillian S; Liang, Mike K

2017-09-01

The HERNIAscore is a ventral incisional hernia (VIH) risk assessment tool that uses only preoperative variables and predictable intraoperative variables. The aim of this study was to validate and modify, if needed, the HERNIAscore in an external dataset. This was a retrospective observational study of all patients undergoing resection for gastrointestinal malignancy from 2011 through 2015 at a safety-net hospital. The primary end point was clinical postoperative VIH. Patients were stratified into low-risk, medium-risk, and high-risk groups based on HERNIAscore. A revised HERNIAscore was calculated with the addition of earlier abdominal operation as a categorical variable. Cox regression of incisional hernia with stratification by risk class was performed. Incidence rates of clinical VIH formation within each risk class were also calculated. Two hundred and forty-seven patents were enrolled. On Cox regression, in addition to the 3 variables of the HERNIAscore (BMI, COPD, and incision length), earlier abdominal operation was also predictive of VIH. The revised HERNIAscore demonstrated improved predictive accuracy for clinical VIH. Although the original HERNIAscore effectively stratified the risk of an incisional radiographic VIH developing, the revised HERNIAscore provided a statistically significant stratification for both clinical and radiographic VIHs in this patient cohort. We have externally validated and improved the HERNIAscore. The revised HERNIAscore uses BMI, incision length, COPD, and earlier abdominal operation to predict risk of postoperative incisional hernia. Future research should assess methods to prevent incisional hernias in moderate-to-high risk patients. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

An Asian validation of the TIMI risk score for ST-segment elevation myocardial infarction.

PubMed

Selvarajah, Sharmini; Fong, Alan Yean Yip; Selvaraj, Gunavathy; Haniff, Jamaiyah; Uiterwaal, Cuno S P M; Bots, Michiel L

2012-01-01

Risk stratification in ST-elevation myocardial infarction (STEMI) is important, such that the most resource intensive strategy is used to achieve the greatest clinical benefit. This is essential in developing countries with wide variation in health care facilities, scarce resources and increasing burden of cardiovascular diseases. This study sought to validate the Thrombolysis In Myocardial Infarction (TIMI) risk score for STEMI in a multi-ethnic developing country. Data from a national, prospective, observational registry of acute coronary syndromes was used. The TIMI risk score was evaluated in 4701 patients who presented with STEMI. Model discrimination and calibration was tested in the overall population and in subgroups of patients that were at higher risk of mortality; i.e., diabetics and those with renal impairment. Compared to the TIMI population, this study population was younger, had more chronic conditions, more severe index events and received treatment later. The TIMI risk score was strongly associated with 30-day mortality. Discrimination was good for the overall study population (c statistic 0.785) and in the high risk subgroups; diabetics (c statistic 0.764) and renal impairment (c statistic 0.761). Calibration was good for the overall study population and diabetics, with χ2 goodness of fit test p value of 0.936 and 0.983 respectively, but poor for those with renal impairment, χ2 goodness of fit test p value of 0.006. The TIMI risk score is valid and can be used for risk stratification of STEMI patients for better targeted treatment.

Travel cost demand model based river recreation benefit estimates with on-site and household surveys: Comparative results and a correction procedure

NASA Astrophysics Data System (ADS)

Loomis, John

2003-04-01

Past recreation studies have noted that on-site or visitor intercept surveys are subject to over-sampling of avid users (i.e., endogenous stratification) and have offered econometric solutions to correct for this. However, past papers do not estimate the empirical magnitude of the bias in benefit estimates with a real data set, nor do they compare the corrected estimates to benefit estimates derived from a population sample. This paper empirically examines the magnitude of the recreation benefits per trip bias by comparing estimates from an on-site river visitor intercept survey to a household survey. The difference in average benefits is quite large, with the on-site visitor survey yielding 24 per day trip, while the household survey yields 9.67 per day trip. A simple econometric correction for endogenous stratification in our count data model lowers the benefit estimate to $9.60 per day trip, a mean value nearly identical and not statistically different from the household survey estimate.

Setting the stage for equity-sensitive monitoring of the maternal and child health Millennium Development Goals.

PubMed Central

Wirth, Meg E.; Balk, Deborah; Delamonica, Enrique; Storeygard, Adam; Sacks, Emma; Minujin, Alberto

2006-01-01

OBJECTIVE: This analysis seeks to set the stage for equity-sensitive monitoring of the health-related Millennium Development Goals (MDGs). METHODS: We use data from international household-level surveys (Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS)) to demonstrate that establishing an equity baseline is necessary and feasible, even in low-income and data-poor countries. We assess data from six countries using 11 health indicators and six social stratifiers. Simple bivariate stratification is complemented by simultaneous stratification to expose the compound effect of multiple forms of vulnerability. FINDINGS: The data reveal that inequities are complex and interactive: inferences cannot be drawn about the nature or extent of inequities in health outcomes from a single stratifier or indicator. CONCLUSION: The MDGs and other development initiatives must become more comprehensive and explicit in their analysis and tracking of inequities. The design of policies to narrow health gaps must take into account country-specific inequities. PMID:16878225

Coronary risk assessment by point-based vs. equation-based Framingham models: significant implications for clinical care.

PubMed

Gordon, William J; Polansky, Jesse M; Boscardin, W John; Fung, Kathy Z; Steinman, Michael A

2010-11-01

US cholesterol guidelines use original and simplified versions of the Framingham model to estimate future coronary risk and thereby classify patients into risk groups with different treatment strategies. We sought to compare risk estimates and risk group classification generated by the original, complex Framingham model and the simplified, point-based version. We assessed 2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III) guidelines recommend formal risk stratification. For each subject, we calculated the 10-year risk of major coronary events using the original and point-based Framingham models, and then compared differences in these risk estimates and whether these differences would place subjects into different ATP-III risk groups (<10% risk, 10-20% risk, or >20% risk). Using standard procedures, all analyses were adjusted for survey weights, clustering, and stratification to make our results nationally representative. Among 39 million eligible adults, the original Framingham model categorized 71% of subjects as having "moderate" risk (<10% risk of a major coronary event in the next 10 years), 22% as having "moderately high" (10-20%) risk, and 7% as having "high" (>20%) risk. Estimates of coronary risk by the original and point-based models often differed substantially. The point-based system classified 15% of adults (5.7 million) into different risk groups than the original model, with 10% (3.9 million) misclassified into higher risk groups and 5% (1.8 million) into lower risk groups, for a net impact of classifying 2.1 million adults into higher risk groups. These risk group misclassifications would impact guideline-recommended drug treatment strategies for 25-46% of affected subjects. Patterns of misclassifications varied significantly by gender, age, and underlying CHD risk. Compared to the original Framingham model, the point-based version misclassifies millions of Americans into risk groups for which guidelines recommend different treatment strategies.

The physical phenotype of frailty for risk stratification of older medical inpatients.

PubMed

Forti, P; Maioli, F; Zagni, E; Lucassenn, T; Montanari, L; Maltoni, B; Luca Pirazzoli, G; Bianchi, G; Zoli, M

2014-12-01

To determine the usefulness of physical phenotype of frailty, cognitive impairment, and serum albumin for risk stratification of elderly medical impatients. Prospective, observational cohort study. A general internal medicine unit of a university hospital in Italy. Inpatients with an average age of 80.8 ± 7.5 yr (N = 470). Frailty was defined using the Study of Osteoporotic Fractures Index, a parsimonious version of the physical phenotype (two of the following markers: weight loss, inability to rise five times from a chair, and exhaustion). Two frailty markers from non-physical dimensions were also evaluated: cognitive impairment (Mini-Cog score < 3) and low serum albumin on ward admission (< 3,5 gr/dl). Logistic regression adjusted for preadmission and admission-related confounders was used to investigate whether the physical phenotype of frailty and the two non-physical markers were associated with ward length of stay and unfavorable discharge (death plus any other ward discharge disposition different from direct return home). Areas Under the receiver operating characteristic Curve (AUCs) and Likelihood Ratios (LRs) were used for evaluation of discriminatory ability and clinical usefulness of significant predictors. The physical phenotype of frailty was associated with both study outcomes (p < 0.010) but the association was mainly mediated by chair standing ability. Non-physical markers were associated only with unfavourable discharge (p < 0.001). All of these predictors, either alone or in combination, had poor discriminatory ability (AUCs < 0.70) and poor clinical usefulness (+LRs near 1) for the study outcomes. The physical phenotype of frailty appears of limited clinical use for risk stratification of older medical inpatients. Combination with markers from non-physical dimensions does not improve its prognostic abilities.

Mental health in primary care: an evaluation using the Item Response Theory.

PubMed

Rocha, Hugo André da; Santos, Alaneir de Fátima Dos; Reis, Ilka Afonso; Santos, Marcos Antônio da Cunha; Cherchiglia, Mariângela Leal

2018-01-01

OBJECTIVE To determine the items of the Brazilian National Program for Improving Access and Quality of Primary Care that better evaluate the capacity to provide mental health care. METHODS This is a cross-sectional study carried out using the Graded Response Model of the Item Response Theory using secondary data from the second cycle of the National Program for Improving Access and Quality of Primary Care, which evaluates 30,523 primary care teams in the period from 2013 to 2014 in Brazil. The internal consistency, correlation between items, and correlation between items and the total score were tested using the Cronbach's alpha, Spearman's correlation, and point biserial coefficients, respectively. The assumptions of unidimensionality and local independence of the items were tested. Word clouds were used as one way to present the results. RESULTS The items with the greatest ability to discriminate were scheduling of the agenda according to risk stratification, keeping of records of the most serious cases of users in psychological distress, and provision of group care. The items that required a higher level of mental health care in the parameter of location were the provision of any type of group care and the provision of educational and mental health promotion activities. Total Cronbach's alpha coefficient was 0.87. The items that obtained the highest correlation with total score were the recording of the most serious cases of users in psychological distress and scheduling of the agenda according to risk stratification. The final scores obtained oscillated between -2.07 (minimum) and 1.95 (maximum). CONCLUSIONS There are important aspects in the discrimination of the capacity to provide mental health care by primary health care teams: risk stratification for care management, follow-up of the most serious cases, group care, and preventive and health promotion actions.

Comparison of Human Papillomavirus Detection by Aptima HPV and cobas HPV Tests in a Population of Women Referred for Colposcopy following Detection of Atypical Squamous Cells of Undetermined Significance by Pap Cytology

PubMed Central

Castle, Philip E.; Eaton, Barbara; Reid, Jennifer; Dockter, Janel

2015-01-01

Few studies have compared the cobas HPV test to the Aptima HPV assay (AHPV) and the Aptima HPV 16 18/45 genotype assay (AHPV GT) for high-risk human papillomavirus (hrHPV) detection, clinical performance in detecting cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) diagnoses, and risk stratification by partial HPV genotyping. The cobas HPV test is a DNA test that separately and concurrently detects HPV16, HPV18, and a pool of 12 other hrHPV types. AHPV is an RNA test for a pool of 14 hrHPV genotypes, and AHPV GT is an RNA test run on AHPV-positive results to detect HPV16 separately from HPV18 and HPV45, which are detected together. In a population of patients (n = 988) referred for colposcopy because of a cervical Pap cytology result of atypical squamous cells of undetermined significance (ASC-US), a cervical scrape specimen was taken, placed into a ThinPrep Pap test vial containing PreservCyt liquid cytology medium, and tested in a blinded fashion with cobas and AHPV and with AHPV GT for AHPV-positive results. The final diagnoses were based on a consensus panel review of the biopsy specimen histology. AHPV and cobas were equally sensitive for CIN2+ diagnoses (89.4% each; P = 1.000), and AHPV was more specific than cobas (63.1% versus 59.3%; P ≤ 0.001). The percent total agreement, percent positive agreement, and kappa value were 90.9%, 81.1%, and 0.815, respectively. Risk stratification using partial HPV genotyping was similar for the two assays. AHPV and AHPV GT had similar sensitivity and risk stratification to cobas HPV, but they were more specific than cobas HPV. PMID:25653409

Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft Loss

PubMed Central

Viglietti, Denis; Loupy, Alexandre; Vernerey, Dewi; Bentlejewski, Carol; Gosset, Clément; Aubert, Olivier; Duong van Huyen, Jean-Paul; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Zeevi, Adriana

2017-01-01

The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor–specific anti–HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post–transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post–transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients. Post–transplant DSA monitoring improved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q binding capacity increased discrimination performance of the traditional model at transplant and post-transplant. Compared with DSA mean fluorescence intensity, DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at lower or higher risk for allograft loss at transplant (category–free net reclassification index, 1.30; 95% CI, 0.94 to 1.67; P<0.001 and 0.93; 95% CI, 0.49 to 1.36; P<0.001, respectively) and post-transplant (category–free net reclassification index, 1.33; 95% CI, 1.03 to 1.62; P<0.001 and 0.95; 95% CI, 0.62 to 1.28; P<0.001, respectively). Thus, pre– and post–transplant DSA monitoring and characterization may improve individual risk stratification for kidney allograft loss. PMID:27493255

Wolff-Parkinson-White syndrome: a single exercise stress test might be misleading.

PubMed

Salavitabar, Arash; Silver, Eric S; Liberman, Leonardo

2017-05-01

Risk stratification of patients with Wolff-Parkinson-White syndrome for sudden death is a complex process, particularly in understanding the utility of the repeat exercise stress test. We report a case of an 18-year-old patient who was found to have a high-risk pathway by both invasive and exercise stress testing after an initial exercise stress test showing beat-to-beat loss of pre-excitation.

Using procalcitonin-guided algorithms to improve antimicrobial therapy in ICU patients with respiratory infections and sepsis.

PubMed

Schuetz, Philipp; Raad, Issam; Amin, Devendra N

2013-10-01

In patients with systemic bacterial infections hospitalized in ICUs, the inflammatory biomarker procalcitonin (PCT) has been shown to aid diagnosis, antibiotic stewardship, and risk stratification. Our aim is to summarize recent evidence about the utility of PCT in the critical care setting and discuss the potential benefits and limitations of PCT when used for clinical decision-making. A growing body of evidence supports PCT use to differentiate bacterial from viral respiratory infections (including influenza), to help risk stratify patients, and to guide decisions about optimal duration of antibiotic therapy. Different PCT protocols were evaluated for these and similar purposes in randomized controlled trials in patients with varying severities of predominantly respiratory tract infection and sepsis. These trials demonstrated effectiveness of monitoring PCT to de-escalate antibiotic treatment earlier without increasing rates of relapsing infections or other adverse outcomes. Although serial PCT measurement has shown value in risk stratification of ICU patients, PCT-guided antibiotic escalation protocols have not yet shown benefit for patients. Inclusion of PCT data in clinical algorithms improves individualized decision-making regarding antibiotic treatment in patients in critical care for respiratory infections or sepsis. Future research should focus on use of repeated PCT measurements to risk-stratify patients and guide treatment to improve their outcomes.

New Insight Into the Biology, Risk Stratification, and Targeted Treatment of Myelodysplastic Syndromes.

PubMed

Haider, Mintallah; Duncavage, Eric J; Afaneh, Khalid F; Bejar, Rafael; List, Alan F

2017-01-01

In myelodysplastic syndromes (MDS), somatic mutations occur in five major categories: RNA splicing, DNA methylation, activated cell signaling, myeloid transcription factors, and chromatin modifiers. Although many MDS cases harbor more than one somatic mutation, in general, there is mutual exclusivity of mutated genes within a class. In addition to the prognostic significance of individual somatic mutations, more somatic mutations in MDS have been associated with poor prognosis. Prognostic assessment remains a critical component of the personalization of care for patient with MDS because treatment is highly risk adapted. Multiple methods for risk stratification are available with the revised International Prognostic Scoring System (IPSS-R), currently considered the gold standard. Increasing access to myeloid gene panels and greater evidence for the diagnostic and predictive value of somatic mutations will soon make sequencing part of the standard evaluation of patients with MDS. In the absence of formal guidelines for their prognostic use, well-validated mutations can still refine estimates of risk made with the IPSS-R. Not only are somatic gene mutations advantageous in understanding the biology of MDS and prognosis, they also offer potential as biomarkers and targets for the treatment of patients with MDS. Examples include deletion 5q, spliceosome complex gene mutations, and TP53 mutations.

PAS positivity of erythroid precursor cells is associated with a poor prognosis in newly diagnosed myelodysplastic syndrome patients.

PubMed

Masuda, Kenta; Shiga, Shuichi; Kawabata, Hiroshi; Takaori-Kondo, Akifumi; Ichiyama, Satoshi; Kamikubo, Yasuhiko

2018-07-01

Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders characterized by hematopoietic insufficiency. The accurate risk stratification of patients with MDS is essential for selection of appropriate therapies. We herein conducted a retrospective cohort study to examine the prognostic value of periodic acid-Schiff (PAS) reaction-positive erythroblasts in MDS patients. We examined the PAS positivity of the bone marrow erythroblasts of 144 patients newly diagnosed with MDS; 26 (18.1%) of them had PAS-positive erythroblasts, whereas 118 (81.9%) did not. The PAS-positive group showed significantly poorer karyotypes as defined in the revised International Prognostic Scoring System (IPSS-R) and higher scores in age-adjusted IPSS-R (IPSS-RA) than the PAS-negative group. Overall survival (OS) and leukemia-free survival (LFS) were also significantly shorter in the PAS-positive group than in the PAS-negative group. Similar results were obtained when only high- and very high risk groups were analyzed using IPSS-RA. This retrospective study suggested that the PAS positivity of erythroblasts is an additional prognostic factor combined with other risk scores for OS and LFS in MDS, and our results may contribute to improved clinical decision-making and rapid risk stratification.

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

PubMed

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.

The Kid-Short Marfan Score (Kid-SMS) - an easy executable risk score for suspected paediatric patients with Marfan syndrome.

PubMed

Mueller, Goetz C; Stark, Veronika; Steiner, Kristoffer; Weil, Jochen; von Kodolitsch, Yskert; Mir, Thomas S

2013-02-01

Due to age-dependent manifestations, diagnosis of Marfan syndrome (MFS) in children and adolescents is sophisticated. Although revised Ghent criteria is a major step forward, its utility in children is still restricted due to expensive and technically advanced diagnostics. As early diagnosis submits long-term benefits concerning prognosis, the need of an appropriate diagnostic tool for risk stratification of suspected paediatric patients with Marfan is justified. Sixty paediatric patients with Marfan were subject to a standardized diagnostic programme. All clinical symptoms of the revised Ghent nosology were analysed concerning age at first clinical manifestation, prevalence and likelihood ratio for MFS. Symptoms with early onset, high prevalence and high positive likelihood ratio were identified and combined for a risk score called Kid-Short Marfan Score (Kid-SMS). Three risk categories for suspicion of Marfan syndrome were developed. Finally, the Kid-SMS was operated in 130 paediatric patients with suspected MFS. Kid-SMS identified significantly more suspected patients with Marfan compared with Ghent nosology, revised Ghent and genetics alone without oversensitivity. Whereas diagnosis of MFS in childhood is sophisticated, Kid-SMS is a useful tool for risk stratification of suspected paediatric patients with Marfan by easy executable diagnostics, especially for paediatricians and paediatric cardiologists. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

Urban Poverty and Neighborhood Effects on Crime: Incorporating Spatial and Network Perspectives

PubMed Central

Graif, Corina; Gladfelter, Andrew S.; Matthews, Stephen A.

2015-01-01

Research on neighborhoods and crime is on a remarkable growth trajectory. In this article, we survey important recent developments in the scholarship on neighborhood effects and the spatial stratification of poverty and urban crime. We advance the case that, in understanding the impact of neighborhoods and poverty on crime, sociological and criminological research would benefit from expanding the analytical focus from residential neighborhoods to the network of neighborhoods individuals are exposed to during their daily routine activities. This perspective is supported by reemerging scholarship on activity spaces and macro-level research on inter-neighborhood connections. We highlight work indicating that non-residential contexts add variation in criminogenic exposure, which in turn influence offending behavior and victimization risk. Also, we draw on recent insights from research on gang violence, social and institutional connections, and spatial mismatch, and call for advancements in the scholarship on urban poverty that investigates the salience of inter-neighborhood connections in evaluating the spatial stratification of criminogenic risk for individuals and communities. PMID:27375773

Recent Advances in the Biology and Treatment of T Cell Acute Lymphoblastic Leukemia.

PubMed

Hefazi, Mehrdad; Litzow, Mark R

2018-06-15

This article provides an overview of the current knowledge regarding the biology and treatment of T cell acute lymphoblastic leukemia (T-ALL) and highlights the most recent findings in this field over the past 5 years. Remarkable progress has been made in the genomic landscape of T-ALL over the past few years. The discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation, with several early phase clinical trials currently exploring these as potential therapeutic targets. Characterization of early T cell precursor ALL, incorporation of minimal residual disease assessment into therapeutic protocols, and use of pediatric-intensive regimens along with judicious use of allogeneic HCT have significantly improved risk stratification and treatment outcomes. Improved risk stratification and the use of novel targeted therapies based on recent genomic discoveries are expected to change the therapeutic landscape of T-ALL and hopefully improve the outcomes of this historically poor prognosis disease.

Developing a risk stratification tool for audit of outcome after surgery for head and neck squamous cell carcinoma.

PubMed

Tighe, David F; Thomas, Alan J; Sassoon, Isabel; Kinsman, Robin; McGurk, Mark

2017-07-01

Patients treated surgically for head and neck squamous cell carcinoma (HNSCC) represent a heterogeneous group. Adjusting for patient case mix and complexity of surgery is essential if reporting outcomes represent surgical performance and quality of care. A case note audit totaling 1075 patients receiving 1218 operations done for HNSCC in 4 cancer networks was completed. Logistic regression, decision tree analysis, an artificial neural network, and Naïve Bayes Classifier were used to adjust for patient case-mix using pertinent preoperative variables. Thirty-day complication rates varied widely (34%-51%; P < .015) between units. The predictive models allowed risk stratification. The artificial neural network demonstrated the best predictive performance (area under the curve [AUC] 0.85). Early postoperative complications are a measurable outcome that can be used to benchmark surgical performance and quality of care. Surgical outcome reporting in national clinical audits should be taking account of the patient case mix. © 2017 Wiley Periodicals, Inc.

Management of advanced NK/T-cell lymphoma.

PubMed

Tse, Eric; Kwong, Yok-Lam

2014-09-01

NK/T-cell lymphomas are aggressive malignancies, and the outlook is poor when conventional anthracycline-containing regimens designed for B-cell lymphomas are used. With the advent of L-asparaginase-containing regimens, treatment outcome has significantly improved. L-asparaginase-containing regimens are now considered the standard in the management of NK/T-cell lymphomas. In advanced diseases, however, outcome remains unsatisfactory, with durable remission achieved in only about 50% of cases. Stratification of patients with advanced NK/T-cell lymphomas is needed, so that poor-risk patients can be given additional therapy to improve outcome. Conventional presentation parameters are untested and appear inadequate for prognostication when L-asparaginase-containing regimens are used. Recent evidence suggests that dynamic factors during treatment and interim assessment, including Epstein-Barr virus (EBV) DNA quantification and positron emission tomography computed tomography findings, are more useful in patient stratification. The role of high-dose chemotherapy and haematopoietic stem cell transplantation requires evaluation in an overall risk-adapted treatment algorithm.

Cardiac PET/CT for the Evaluation of Known or Suspected Coronary Artery Disease

PubMed Central

Murthy, Venkatesh L.

2011-01-01

Positron emission tomography (PET) is increasingly being applied in the evaluation of myocardial perfusion. Cardiac PET can be performed with an increasing variety of cyclotron- and generator-produced radiotracers. Compared with single photon emission computed tomography, PET offers lower radiation exposure, fewer artifacts, improved spatial resolution, and, most important, improved diagnostic performance. With its capacity to quantify rest–peak stress left ventricular systolic function as well as coronary flow reserve, PET is superior to other methods for the detection of multivessel coronary artery disease and, potentially, for risk stratification. Coronary artery calcium scoring may be included for further risk stratification in patients with normal perfusion imaging findings. Furthermore, PET allows quantification of absolute myocardial perfusion, which also carries substantial prognostic value. Hybrid PET–computed tomography scanners allow functional evaluation of myocardial perfusion combined with anatomic characterization of the epicardial coronary arteries, thereby offering great potential for both diagnosis and management. Additional studies to further validate the prognostic value and cost effectiveness of PET are warranted. © RSNA, 2011 PMID:21918042

Genetic causes of sudden cardiac death in children: inherited arrhythmogenic diseases.

PubMed

Vacanti, Gaetano; Maragna, Riccardo; Priori, Silvia G; Mazzanti, Andrea

2017-10-01

In this chapter we will discuss the most recent and relevant evidences published in the field of inherited arrhythmogenic disorders, focusing on the so called 'channelopathies' that are associated with sudden cardiac death (SCD) in children: long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). We will discuss the latest diagnostic criteria for channelopathies released by the European Society of Cardiology, the new data on BrS in children and the recent evidence supporting a genotype-specific therapy for LQTS type 3. Moreover, we will present further insights into the risk stratification of the children affected by LQTS, analyzing the role of imaging for the prediction of life-threatening arrhythmias. In addition, we will offer a perspective on how to deal with genetic results in families affected by SCD at very young ages. The selected publications will aid pediatricians in their clinical work when managing little patients with inherited arrhythmias, providing the most recent information for diagnosis, risk stratification, and management.

Novel Biomarkers for Predicting Cardiovascular Disease in Patients With Diabetes.

PubMed

Retnakaran, Ravi

2018-05-01

It is generally acknowledged that patients with diabetes comprise a high-risk population for the development of cardiovascular disease. However, it is perhaps less well recognized that there actually exists considerable heterogeneity in vascular risk within this patient population, with a sizable subset of individuals seemingly at low risk for major cardiovascular events despite the presence of diabetes. Because traditional clinical risk calculators have shown wide variability in their performance in the setting of diabetes, there exists a need for additional risk predictors in this patient population. In this context, there has been considerable interest in the potential utility of circulating biomarkers as clinical tools that might facilitate risk stratification and thereby guide therapeutic and preventative decision-making. Coupled with the current era of dedicated cardiovascular outcome trials in type 2 diabetes, this interest has spawned a growing literature of recent studies that evaluated potential biomarkers. To date, these studies have identified N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponins, and growth differentiation factor-15 as cardiovascular biomarkers of particular potential in patients with diabetes. Furthermore, recognizing the potential benefit of collective consideration of different biomarkers reflecting distinct pathophysiologic processes that might contribute to the development of cardiovascular disease, there is emerging emphasis on the evaluation of combinations of biomarkers for optimal risk prediction. Although not currently ready for clinical practice, this rapidly-growing topic of biomarker research might ultimately facilitate the goal of individualized risk stratification and thereby enable truly personalized management of diabetes. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Advanced colorectal neoplasia risk stratification by penalized logistic regression.

PubMed

Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

2016-08-01

Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the [Formula: see text]-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance. © The Author(s) 2013.

Better Indigenous Risk stratification for Cardiac Health study (BIRCH) protocol: rationale and design of a cross-sectional and prospective cohort study to identify novel cardiovascular risk indicators in Aboriginal Australian and Torres Strait Islander adults.

PubMed

Rémond, Marc G W; Stewart, Simon; Carrington, Melinda J; Marwick, Thomas H; Kingwell, Bronwyn A; Meikle, Peter; O'Brien, Darren; Marshall, Nathaniel S; Maguire, Graeme P

2017-08-23

Of the estimated 10-11 year life expectancy gap between Indigenous (Aboriginal and Torres Strait Islander people) and non-Indigenous Australians, approximately one quarter is attributable to cardiovascular disease (CVD). Risk prediction of CVD is imperfect, but particularly limited for Indigenous Australians. The BIRCH (Better Indigenous Risk stratification for Cardiac Health) project aims to identify and assess existing and novel markers of early disease and risk in Indigenous Australians to optimise health outcomes in this disadvantaged population. It further aims to determine whether these markers are relevant in non-Indigenous Australians. BIRCH is a cross-sectional and prospective cohort study of Indigenous and non-Indigenous Australian adults (≥ 18 years) living in remote, regional and urban locations. Participants will be assessed for CVD risk factors, left ventricular mass and strain via echocardiography, sleep disordered breathing and quality via home-based polysomnography or actigraphy respectively, and plasma lipidomic profiles via mass spectrometry. Outcome data will comprise CVD events and death over a period of five years. Results of BIRCH may increase understanding regarding the factors underlying the increased burden of CVD in Indigenous Australians in this setting. Further, it may identify novel markers of early disease and risk to inform the development of more accurate prediction equations. Better identification of at-risk individuals will promote more effective primary and secondary preventive initiatives to reduce Indigenous Australian health disadvantage.

Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.

PubMed

Elyas, Salim; Shore, Angela C; Kingwell, Hayley; Keenan, Samantha; Boxall, Leigh; Stewart, Jane; James, Martin A; Strain, William David

2016-09-01

Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.

PubMed

Goldstein, Benjamin I; Carnethon, Mercedes R; Matthews, Karen A; McIntyre, Roger S; Miller, Gregory E; Raghuveer, Geetha; Stoney, Catherine M; Wasiak, Hank; McCrindle, Brian W

2015-09-08

In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. © 2015 American Heart Association, Inc.

Clinical severity score system in dogs with degenerative mitral valve disease.

PubMed

López-Alvarez, J; Elliott, J; Pfeiffer, D; Chang, Y-M; Mattin, M; Moonarmart, W; Hezzell, M J; Boswood, A

2015-01-01

Several risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE). Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification. Client-owned dogs (n = 244) with DMVD recruited from first opinion practice. Prospective longitudinal follow-up of dogs with DMVD. History and PE data were obtained at 6-month intervals and analyzed with time-dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken. History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes. Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Advantages of early diagnosis of diabetic neuropathy in the prevention of diabetic foot ulcers.

PubMed

Sanz-Corbalán, Irene; Lázaro-Martínez, José Luis; García-Morales, Esther; Molines-Barroso, Raúl; Álvaro-Afonso, Francisco; García-Álvarez, Yolanda

2017-12-26

to evaluate the utility of the sudomotor function test (SFT) as a clinical tool in the Risk Stratification System of diabetic patients and to demonstrate the earlier detection of the risk of developing diabetic foot ulcers (DFU) compared to the standard clinical tests. prospective follow-up study on 263 patients enrolled consecutively over 3.5 years. Diabetic patients without active DFU were classified according to the International Working Group Risk Stratification System (RSS) and categorized according to the results of the Semmes-Wenstein Monofilament (SWM) and biothesiometer measurements or the SFT. The main outcome evaluated was the development of DFU. median follow-up was 42 [38-44] months. Sixty patients (22.8%) developed DFU after a median of 6.2 [3-17] months. Ten patients that were included in the no-risk group (group 0) based on the SWM and biothesiometer results developed DFU. Thus the sensitivity of this approach was 83.33% and the specificity was 50.47%. Based on the SFT results, all patients that developed DFU were included in the correct risk group. This approach had 100% sensitivity and 31.53% specificity. Regarding the diagnostic accuracy of the two Methods, the respective AUC values were 0.776 (95% CI 0.702-0.849) and 0.816 (95% CI 0.757-0.874). SFT improved RSS in diabetic patients in a specialized diabetic foot unit. SFT categorized patients correctly according to the risk of developing DFU. Copyright © 2017 Elsevier B.V. All rights reserved.

[Exercise stress test and dobutamine stress echocardiography for the prognostic stratification after uncomplicated acute myocardial infarction].

PubMed

Vitiello, Nicola; Cirillo, Raffaele; Granato, Luigi; Coppola, Vincenzo; di Palma, Francesco

2007-05-01

Exercise stress test and dobutamine stress echocardiography are usually performed early after an uncomplicated acute myocardial infarction in the prognostic stratification of patients to define the optimal diagnostic and therapeutic procedure. The aim of this study was to evaluate if the association of an imaging test could increase exercise test capability to identify patients with residual ischemia and patients at high risk of events in the follow-up. Four hundred and forty-two consecutive patients underwent exercise stress testing and dobutamine stress echocardiography before discharge and subsequently coronary angiography within 30 days. In case of submaximal negative result at the exercise test, this was repeated 20 days after discharge. The follow-up lasted 26.8 +/- 9 months. The endpoints were death, reinfarction, and unstable angina requiring hospitalization or revascularization intervention. Both tests and their association showed a higher sensitivity in males; in females dobutamine stress echocardiography had a higher specificity. In females, the addition of dobutamine stress echocardiography increased either the negative or the positive prognostic values of exercise stress test by 31% and 5.6%, respectively. In males, the negative prognostic value increased by 15.5%, whereas the positive prognostic value decreased by 12%. A low exercise capability (<6 METs) showed an event predictive value independent of test results and any other variables. The event-free survival curves correlated with exercise capability differed shortly after the first months both in males and females. These results suggest different stratification procedures with regard to gender: in males, the exercise stress test might be sufficient at discharge, to be repeated 20 days later, if submaximal negative. In females, it seems to be useful to associate an imaging test at discharge. In any case, the exercise stress test remains the main step in the stratification procedure also for its capability to identify patients who are at high risk of events in the follow-up.

CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins

PubMed Central

Londin, Eric R.; Keller, Margaret A.; Maista, Cathleen; Smith, Gretchen; Mamounas, Laura A.; Zhang, Ran; Madore, Steven J.; Gwinn, Katrina; Corriveau, Roderick A.

2010-01-01

Background Genetic ancestry is known to impact outcomes of genotype-phenotype studies that are designed to identify risk for common diseases in human populations. Failure to control for population stratification due to genetic ancestry can significantly confound results of disease association studies. Moreover, ancestry is a critical factor in assessing lifetime risk of disease, and can play an important role in optimizing treatment. As modern medicine moves towards using personal genetic information for clinical applications, it is important to determine genetic ancestry in an accurate, cost-effective and efficient manner. Self-identified race is a common method used to track and control for population stratification; however, social constructs of race are not necessarily informative for genetic applications. The use of ancestry informative markers (AIMs) is a more accurate method for determining genetic ancestry for the purposes of population stratification. Methodology/Principal Findings Here we introduce a novel panel of 36 microsatellite (MSAT) AIMs that determines continental admixture proportions. This panel, which we have named Continental Ancestry Informative Markers or CoAIMs, consists of MSAT AIMs that were chosen based upon their measure of genetic variance (Fst), allele frequencies and their suitability for efficient genotyping. Genotype analysis using CoAIMs along with a Bayesian clustering method (STRUCTURE) is able to discern continental origins including Europe/Middle East (Caucasians), East Asia, Africa, Native America, and Oceania. In addition to determining continental ancestry for individuals without significant admixture, we applied CoAIMs to ascertain admixture proportions of individuals of self declared race. Conclusion/Significance CoAIMs can be used to efficiently and effectively determine continental admixture proportions in a sample set. The CoAIMs panel is a valuable resource for genetic researchers performing case-control genetic association studies, as it can control for the confounding effects of population stratification. The MSAT-based approach used here has potential for broad applicability as a cost effective tool toward determining admixture proportions. PMID:20976178

Sampling procedures for throughfall monitoring: A simulation study

NASA Astrophysics Data System (ADS)

Zimmermann, Beate; Zimmermann, Alexander; Lark, Richard Murray; Elsenbeer, Helmut

2010-01-01

What is the most appropriate sampling scheme to estimate event-based average throughfall? A satisfactory answer to this seemingly simple question has yet to be found, a failure which we attribute to previous efforts' dependence on empirical studies. Here we try to answer this question by simulating stochastic throughfall fields based on parameters for statistical models of large monitoring data sets. We subsequently sampled these fields with different sampling designs and variable sample supports. We evaluated the performance of a particular sampling scheme with respect to the uncertainty of possible estimated means of throughfall volumes. Even for a relative error limit of 20%, an impractically large number of small, funnel-type collectors would be required to estimate mean throughfall, particularly for small events. While stratification of the target area is not superior to simple random sampling, cluster random sampling involves the risk of being less efficient. A larger sample support, e.g., the use of trough-type collectors, considerably reduces the necessary sample sizes and eliminates the sensitivity of the mean to outliers. Since the gain in time associated with the manual handling of troughs versus funnels depends on the local precipitation regime, the employment of automatically recording clusters of long troughs emerges as the most promising sampling scheme. Even so, a relative error of less than 5% appears out of reach for throughfall under heterogeneous canopies. We therefore suspect a considerable uncertainty of input parameters for interception models derived from measured throughfall, in particular, for those requiring data of small throughfall events.

Acute myeloid leukemia in children: Current status and future directions.

PubMed

Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

2016-02-01

Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. © 2015 Japan Pediatric Society.

The use of adenosine and adenosine triphosphate testing in the diagnosis, risk stratification and management of patients with syncope: current evidence and future perspectives.

PubMed

Fragakis, Nikolaos; Antoniadis, Antonios P; Saviano, Massimo; Vassilikos, Vassilios; Pappone, Carlo

2015-03-15

Syncope is a significant source of cardiovascular-related morbidity yet the etiology is frequently obscure and the identification of patients at highest risk is challenging. Adenosine (AD) and adenosine triphosphate (ATP) administrations have been suggested as potentially useful non-invasive tools in the diagnostic workup of patients with neurally-mediated or bradycardia-related syncope. It has been postulated that both compounds by modulating the autonomic innervation in the heart and exerting negative chronotropic and dromotropic effects in the conduction system, may unmask the mechanism of syncope. However, the clinical implications derived from the efficacy of both tests in the investigation of syncope remain unclear mainly due to inconclusive and occasionally contradictory results of published studies. This review article summarizes recent and past information in the use of ATP and AD in the investigation of syncope with emphasis on clinical trials. We present the current level of evidence for the use of these agents in clinical practice, identify areas where further research is warranted and highlight the future perspectives of these agents as complements to an accurate risk-stratification of patients with syncope. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nonobstructive Coronary Artery Disease by Coronary CT Angiography Improves Risk Stratification and Allocation of Statin Therapy.

PubMed

Emami, Hamed; Takx, Richard A P; Mayrhofer, Thomas; Janjua, Sumbal; Park, Jakob; Pursnani, Amit; Tawakol, Ahmed; Lu, Michael T; Ferencik, Maros; Hoffmann, Udo

2017-09-01

This study sought to determine prognostic value of nonobstructive coronary artery disease (CAD) for atherosclerotic cardiovascular disease (ASCVD) events and to determine whether incorporation of this information into the pooled cohort equation reclassifies recommendations for statin therapy as defined by the 2013 guidelines for cholesterol management of the American College of Cardiology and American Heart Association (ACC/AHA). Detection of nonobstructive CAD by coronary computed tomography angiography may improve risk stratification and permit individualized and more appropriate allocation of statin therapy. This study determined the pooled hazard ratio of nonobstructive CAD for ASCVD events from published studies and incorporated this information into the ACC/AHA pooled cohort equation. The study calculated revised sex- and ethnicity-based 10-year ASCVD risk and determined boundaries corresponding to the original 7.5% risk for ASCVD events. It also assessed reclassification for statin eligibility by incorporating the results from meta-analysis to individual patients from a separate cohort. This study included 2 studies (2,295 subjects; 66% male; prevalence of nonobstructive CAD, 47%; median follow-up, 49 months; 67 ASCVD events). The hazard ratio of nonobstructive CAD for ASCVD events was 3.2 (95% confidence interval: 1.5 to 6.7). Incorporation of this information into the pooled cohort equation resulted in reclassification toward statin eligibility in individuals with nonobstructive CAD, with an original ASCVD score of 3.0% and 5.9% or higher in African-American women and men and a score of 4.4% and 4.6% or higher in Caucasian women and men, respectively. The absence of nonobstructive CAD resulted in reclassification toward statin ineligibility if the original ASCVD score was as 10.0% and 17.9% or lower in African-American women and men and 13.7% and 14.3% or lower in Caucasian women and men, respectively. Reclassification is observed in 14% of patients. Detection of nonobstructive CAD by coronary computed tomography angiography improves risk stratification and permits individualized and more appropriate allocation of statin therapy across sex and ethnicity groups. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Modelling the distribution of chickens, ducks, and geese in China

USGS Publications Warehouse

Prosser, Diann J.; Wu, Junxi; Ellis, Erie C.; Gale, Fred; Van Boeckel, Thomas P.; Wint, William; Robinson, Tim; Xiao, Xiangming; Gilbert, Marius

2011-01-01

Global concerns over the emergence of zoonotic pandemics emphasize the need for high-resolution population distribution mapping and spatial modelling. Ongoing efforts to model disease risk in China have been hindered by a lack of available species level distribution maps for poultry. The goal of this study was to develop 1 km resolution population density models for China's chickens, ducks, and geese. We used an information theoretic approach to predict poultry densities based on statistical relationships between poultry census data and high-resolution agro-ecological predictor variables. Model predictions were validated by comparing goodness of fit measures (root mean square error and correlation coefficient) for observed and predicted values for 1/4 of the sample data which were not used for model training. Final output included mean and coefficient of variation maps for each species. We tested the quality of models produced using three predictor datasets and 4 regional stratification methods. For predictor variables, a combination of traditional predictors for livestock mapping and land use predictors produced the best goodness of fit scores. Comparison of regional stratifications indicated that for chickens and ducks, a stratification based on livestock production systems produced the best results; for geese, an agro-ecological stratification produced best results. However, for all species, each method of regional stratification produced significantly better goodness of fit scores than the global model. Here we provide descriptive methods, analytical comparisons, and model output for China's first high resolution, species level poultry distribution maps. Output will be made available to the scientific and public community for use in a wide range of applications from epidemiological studies to livestock policy and management initiatives.

Stratification Pattern of Static and Scale-Invariant Dynamic Measures of Heartbeat Fluctuations Across Sleep Stages in Young and Elderly

PubMed Central

Schmitt, Daniel T.; Stein, Phyllis K.; Ivanov, Plamen Ch.

2010-01-01

Cardiac dynamics exhibit complex variability characterized by scale-invariant and nonlinear temporal organization related to the mechanism of neuroautonomic control, which changes with physiologic states and pathologic conditions. Changes in sleep regulation during sleep stages are also related to fluctuations in autonomic nervous activity. However, the interaction between sleep regulation and cardiac autonomic control remains not well understood. Even less is known how this interaction changes with age, as aspects of both cardiac dynamics and sleep regulation differ in healthy elderly compared to young subjects. We hypothesize that because of the neuroautonomic responsiveness in young subjects, fractal and nonlinear features of cardiac dynamics exhibit a pronounced stratification pattern across sleep stages, while in elderly these features will remain unchanged due to age-related loss of cardiac variability and decline of neuroautonomic responsiveness. We analyze the variability and the temporal fractal organization of heartbeat fluctuations across sleep stages in both young and elderly. We find that independent linear and nonlinear measures of cardiac control consistently exhibit the same ordering in their values across sleep stages, forming a robust stratification pattern. Despite changes in sleep architecture and reduced heart rate variability in elderly subjects, this stratification surprisingly does not break down with advanced age. Moreover, the difference between sleep stages for some linear, fractal, and nonlinear measures exceeds the difference between young and elderly, suggesting that the effect of sleep regulation on cardiac dynamics is significantly stronger than the effect of healthy aging. Quantifying changes in this stratification pattern may provide insights into how alterations in sleep regulation contribute to increased cardiac risk. PMID:19203874

Modelling the distribution of chickens, ducks, and geese in China

PubMed Central

Prosser, Diann J.; Wu, Junxi; Ellis, Erle C.; Gale, Fred; Van Boeckel, Thomas P.; Wint, William; Robinson, Tim; Xiao, Xiangming; Gilbert, Marius

2011-01-01

Global concerns over the emergence of zoonotic pandemics emphasize the need for high-resolution population distribution mapping and spatial modelling. Ongoing efforts to model disease risk in China have been hindered by a lack of available species level distribution maps for poultry. The goal of this study was to develop 1 km resolution population density models for China’s chickens, ducks, and geese. We used an information theoretic approach to predict poultry densities based on statistical relationships between poultry census data and high-resolution agro-ecological predictor variables. Model predictions were validated by comparing goodness of fit measures (root mean square error and correlation coefficient) for observed and predicted values for ¼ of the sample data which was not used for model training. Final output included mean and coefficient of variation maps for each species. We tested the quality of models produced using three predictor datasets and 4 regional stratification methods. For predictor variables, a combination of traditional predictors for livestock mapping and land use predictors produced the best goodness of fit scores. Comparison of regional stratifications indicated that for chickens and ducks, a stratification based on livestock production systems produced the best results; for geese, an agro-ecological stratification produced best results. However, for all species, each method of regional stratification produced significantly better goodness of fit scores than the global model. Here we provide descriptive methods, analytical comparisons, and model output for China’s first high resolution, species level poultry distribution maps. Output will be made available to the scientific and public community for use in a wide range of applications from epidemiological studies to livestock policy and management initiatives. PMID:21765567

A fast and cost-effective method for apolipoprotein E isotyping as an alternative to APOE genotyping for patient screening and stratification.

PubMed

Calero, Olga; García-Albert, Luis; Rodríguez-Martín, Andrés; Veiga, Sergio; Calero, Miguel

2018-04-13

Apolipoprotein E (apoE) is a 34 kDa glycoprotein involved in lipid metabolism. The human APOE gene encodes for three different apoE protein isoforms: E2, E3 and E4. The interest in apoE isoforms is high for epidemiological research, patient stratification and identification of those at increased risk for clinical trials and prevention. The isoform apoE4 is associated with increased risk for coronary heart and Alzheimer's diseases. This paper describes a method for specifically detecting the apoE4 isoform from biological fluids by taking advantage of the capacity of apoE to bind "specifically" to polystyrene surfaces as capture and a specific anti-apoE4 monoclonal antibody as reporter. Our results indicate that the apoE-polystyrene binding interaction is highly stable, resistant to detergents and acid and basic washes. The methodology here described is accurate, easily implementable, fast and cost-effective. Although at present, our technique is unable to discriminate homozygous APOE ε4/ε4 from APOE ε3/ε4 and ε2/ε4 heterozygous, it opens new avenues for the development of inexpensive, yet effective, tests for the detection of apoE4 for patients' stratification. Preliminary results indicated that this methodology is also adaptable into turbidimetric platforms, which make it a good candidate for clinical implementation through its translation to the clinical analysis routine.

Application of multivariate probabilistic (Bayesian) networks to substance use disorder risk stratification and cost estimation.

PubMed

Weinstein, Lawrence; Radano, Todd A; Jack, Timothy; Kalina, Philip; Eberhardt, John S

2009-09-16

This paper explores the use of machine learning and Bayesian classification models to develop broadly applicable risk stratification models to guide disease management of health plan enrollees with substance use disorder (SUD). While the high costs and morbidities associated with SUD are understood by payers, who manage it through utilization review, acute interventions, coverage and cost limitations, and disease management, the literature shows mixed results for these modalities in improving patient outcomes and controlling cost. Our objective is to evaluate the potential of data mining methods to identify novel risk factors for chronic disease and stratification of enrollee utilization, which can be used to develop new methods for targeting disease management services to maximize benefits to both enrollees and payers. For our evaluation, we used DecisionQ machine learning algorithms to build Bayesian network models of a representative sample of data licensed from Thomson-Reuters' MarketScan consisting of 185,322 enrollees with three full-year claim records. Data sets were prepared, and a stepwise learning process was used to train a series of Bayesian belief networks (BBNs). The BBNs were validated using a 10 percent holdout set. The networks were highly predictive, with the risk-stratification BBNs producing area under the curve (AUC) for SUD positive of 0.948 (95 percent confidence interval [CI], 0.944-0.951) and 0.736 (95 percent CI, 0.721-0.752), respectively, and SUD negative of 0.951 (95 percent CI, 0.947-0.954) and 0.738 (95 percent CI, 0.727-0.750), respectively. The cost estimation models produced area under the curve ranging from 0.72 (95 percent CI, 0.708-0.731) to 0.961 (95 percent CI, 0.95-0.971). We were able to successfully model a large, heterogeneous population of commercial enrollees, applying state-of-the-art machine learning technology to develop complex and accurate multivariate models that support near-real-time scoring of novel payer populations based on historic claims and diagnostic data. Initial validation results indicate that we can stratify enrollees with SUD diagnoses into different cost categories with a high degree of sensitivity and specificity, and the most challenging issue becomes one of policy. Due to the social stigma associated with the disease and ethical issues pertaining to access to care and individual versus societal benefit, a thoughtful dialogue needs to occur about the appropriate way to implement these technologies.

Burden of cardiovascular risk factors and disease among patients with type 1 diabetes: results of the Australian National Diabetes Audit (ANDA).

PubMed

Pease, Anthony; Earnest, Arul; Ranasinha, Sanjeeva; Nanayakkara, Natalie; Liew, Danny; Wischer, Natalie; Andrikopoulos, Sofianos; Zoungas, Sophia

2018-06-02

Cardiovascular risk stratification is complex in type 1 diabetes. We hypothesised that traditional and diabetes-specific cardiovascular risk factors were prevalent and strongly associated with cardiovascular disease (CVD) among adults with type 1 diabetes attending Australian diabetes centres. De-identified, prospectively collected data from patients with type 1 diabetes aged ≥ 18 years in the 2015 Australian National Diabetes Audit were analysed. The burden of cardiovascular risk factors [age, sex, diabetes duration, glycated haemoglobin (HbA1c), blood pressure, lipid profile, body mass index, smoking status, retinopathy, renal function and albuminuria] and associations with CVD inclusive of stroke, myocardial infarction, coronary artery bypass graft surgery/angioplasty and peripheral vascular disease were assessed. Restricted cubic splines assessed for non-linearity of diabetes duration and likelihood ratio test assessed for interactions between age, diabetes duration, centre type and cardiovascular outcomes of interest. Discriminatory ability of multivariable models were assessed with area under the receiver operating characteristic (ROC) curves. Data from 1169 patients were analysed. Mean (± SD) age and median diabetes duration was 40.0 (± 16.7) and 16.0 (8.0-27.0) years respectively. Cardiovascular risk factors were prevalent including hypertension (21.9%), dyslipidaemia (89.4%), overweight/obesity (56.4%), ever smoking (38.5%), albuminuria (31.1%), estimated glomerular filtration rate < 60 mL/min/1.73 m 2 (10.3%) and HbA1c > 7.0% (53 mmol/mol) (81.0%). Older age, longer diabetes duration, smoking and antihypertensive therapy use were positively associated with CVD, while high density lipoprotein-cholesterol and diastolic blood pressure were negatively associated (p < 0.05). Association with CVD and diabetes duration remained constant until 20 years when a linear increase was noted. Longer diabetes duration also had the highest population attributable risk of 6.5% (95% CI 1.4, 11.6). Further, the models for CVD demonstrated good discriminatory ability (area under the ROC curve 0.88; 95% CI 0.84, 0.92). Cardiovascular risk factors were prevalent and strongly associated with CVD among adults with type 1 diabetes attending Australian diabetes centres. Given the approximate J-shaped association between type 1 diabetes duration and CVD, the impact of cardiovascular risk stratification and management before and after 20 years duration needs to be further assessed longitudinally. Diabetes specific cardiovascular risk stratification tools incorporating diabetes duration should be an important consideration in future guideline development.

Ontology for heart rate turbulence domain from the conceptual model of SNOMED-CT.

PubMed

Soguero-Ruiz, Cristina; Lechuga-Suárez, Luis; Mora-Jiménez, Inmaculada; Ramos-López, Javier; Barquero-Pérez, Óscar; García-Alberola, Arcadi; Rojo-Álvarez, José L

2013-07-01

Electronic health record (EHR) automates the clinician workflow, allowing evidence-based decision support and quality management. We aimed to start a framework for domain standardization of cardiovascular risk stratification into the EHR, including risk indices whose calculation involves ECG signal processing. We propose the use of biomedical ontologies completely based on the conceptual model of SNOMED-CT, which allows us to implement our domain in the EHR. In this setting, the present study focused on the heart rate turbulence (HRT) domain, according to its concise guidelines and clear procedures for parameter calculations. We used 289 concepts from SNOMED-CT, and generated 19 local extensions (new concepts) for the HRT specific concepts not present in the current version of SNOMED-CT. New concepts included averaged and individual ventricular premature complex tachograms, initial sinus acceleration for turbulence onset, or sinusal oscillation for turbulence slope. Two representative use studies were implemented: first, a prototype was inserted in the hospital information system for supporting HRT recordings and their simple follow up by medical societies; second, an advanced support for a prospective scientific research, involving standard and emergent signal processing algorithms in the HRT indices, was generated and then tested in an example database of 27 Holter patients. Concepts of the proposed HRT ontology are publicly available through a terminology server, hence their use in any information system will be straightforward due to the interoperability provided by SNOMED-CT.

Interchangeable effects of gibberellic acid and temperature on embryo growth, seed germination and epicotyl emergence in Ribes multiflorum ssp. sandalioticum (Grossulariaceae).

PubMed

Mattana, E; Pritchard, H W; Porceddu, M; Stuppy, W H; Bacchetta, G

2012-01-01

Morphophysiological dormancy was investigated in seeds of Ribes multiflorum Kit ex Roem et Schult. ssp. sandalioticum Arrigoni, a rare mountain species endemic to Sardinia (Italy). There were no differences in imbibition rates between intact and scarified seeds, suggesting a lack of physical dormancy, while methylene blue solution (0.5%) highlighted a preferential pathway for solution entrance through the raphe. Embryos were small at seed dispersal, with an initial embryo:seed ratio (E:S) of ca. 0.2 (embryo length, ca. 0.5 mm), whereas the critical E:S ratio for germination was three times longer (ca. 0.6). Gibberellic acid (GA(3), 250 mg · l(-1)) and warm stratification (25 °C for 3 months) followed by low temperature (<15 °C) enhanced embryo growth rate (maximum of ca. 0.04 mm · day(-1) at 10 °C) and subsequent seed germination (radicle emergence; ca. 80% at 10 °C). Low germination occurred at warmer temperatures, and cold stratification (5 °C for 3 months) induced secondary dormancy. After radicle emergence, epicotyl emergence was delayed for ca. 2 months for seeds from three different populations. Mean time of epicotyl emergence was affected by GA(3) . Seeds of this species showed non-deep simple (root) - non-deep simple (epicotyl) morphophysiological dormancy, highlighting a high synchronisation with Mediterranean seasonality in all the investigated populations. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Kawasaki disease and giant coronary artery aneurysms: the role of echocardiography from diagnosis through follow-up.

PubMed

Adler, Adam C; Kodavatiganti, Ramesh

2016-08-01

Kawasaki disease is an acquired vasculitis that can affect the coronary arteries placing the patient at risk for coronary artery thrombosis, myocardial ischemia and infarction. The risk of complications related to coronary artery involvement persists for years despite recovery from the acute illness phase. The risk of late coronary disease progression necessitates long term follow-up generally accomplished by non-invasive echocardiography in pediatric patients. We review the utility of echocardiography in patients with Kawasaki disease as it relates to initial management, risk stratification and follow-up of these children. © 2016, Wiley Periodicals, Inc.

Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer.

PubMed

Fernández, Mario I; Williams, Stephen B; Willis, Daniel L; Slack, Rebecca S; Dickstein, Rian J; Parikh, Sahil; Chiong, Edmund; Siefker-Radtke, Arlene O; Guo, Charles C; Czerniak, Bogdan A; McConkey, David J; Shah, Jay B; Pisters, Louis L; Grossman, H Barton; Dinney, Colin P N; Kamat, Ashish M

2017-05-01

To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data. A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival. For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P < 0.001). Patients down-staged at RC

Cardiovascular risk stratification in overweight or obese patients in primary prevention. Implications for use of statins.

PubMed

Masson, Walter; Lobo, Martín; Huerín, Melina; Molinero, Graciela; Manente, Diego; Pángaro, Mario; Vitagliano, Laura; Zylbersztejn, Horacio

2015-02-01

Cardiovascular risk estimation in patients with overweight/obesity is not standardized. Our objectives were to stratify cardiovascular risk using different scores, to analyze use of statins, to report the prevalence of carotid atherosclerotic plaque (CAP), and to determine the optimal cut-off point (OCP) of scores that discriminate between subjects with or without CAP. Non-diabetic patients with overweight or obesity in primary prevention were enrolled. The Framingham score (FS), the European score (ES), and the score proposed by the new American guidelines (NS) were calculated, and statin indication was evaluated. Prevalence of CAP was determined by ultrasound examination. A ROC analysis was performed. A total of 474 patients (67% with overweight and 33% obese) were enrolled into the study. The FS classified the largest number of subjects as low risk. PAC prevalence was higher in obese as compared to overweight subjects (44.8% vs. 36.1%, P=.04). According to the FS, ES, and NS respectively, 26.7%, 39.1%, and 39.1% of overweight subjects and 28.6%, 39.0%, and 39.0% of obese subjects had an absolute indication for statins. All three scores were shown to acceptably discriminate between subjects with and without CAP (area under the curve>0.7). The OCPs evaluated did not agree with the risk category values. Risk stratification and use of statins varied in the overweight/obese population depending on the function used. Understanding of the relationship between scores and presence of CAP may optimize risk estimate. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Breast cancer screening in the era of density notification legislation: summary of 2014 Massachusetts experience and suggestion of an evidence-based management algorithm by multi-disciplinary expert panel.

PubMed

Freer, Phoebe E; Slanetz, Priscilla J; Haas, Jennifer S; Tung, Nadine M; Hughes, Kevin S; Armstrong, Katrina; Semine, A Alan; Troyan, Susan L; Birdwell, Robyn L

2015-09-01

Stemming from breast density notification legislation in Massachusetts effective 2015, we sought to develop a collaborative evidence-based approach to density notification that could be used by practitioners across the state. Our goal was to develop an evidence-based consensus management algorithm to help patients and health care providers follow best practices to implement a coordinated, evidence-based, cost-effective, sustainable practice and to standardize care in recommendations for supplemental screening. We formed the Massachusetts Breast Risk Education and Assessment Task Force (MA-BREAST) a multi-institutional, multi-disciplinary panel of expert radiologists, surgeons, primary care physicians, and oncologists to develop a collaborative approach to density notification legislation. Using evidence-based data from the Institute for Clinical and Economic Review, the Cochrane review, National Comprehensive Cancer Network guidelines, American Cancer Society recommendations, and American College of Radiology appropriateness criteria, the group collaboratively developed an evidence-based best-practices algorithm. The expert consensus algorithm uses breast density as one element in the risk stratification to determine the need for supplemental screening. Women with dense breasts and otherwise low risk (<15% lifetime risk), do not routinely require supplemental screening per the expert consensus. Women of high risk (>20% lifetime) should consider supplemental screening MRI in addition to routine mammography regardless of breast density. We report the development of the multi-disciplinary collaborative approach to density notification. We propose a risk stratification algorithm to assess personal level of risk to determine the need for supplemental screening for an individual woman.

Frequency Of Different Risk Factors Associated With Recurrent Urinary Tract Infection Among Postmenopausal Women.

PubMed

Jameel, Sadia; Mahmud, Syed Nayer

2016-01-01

Urinary Tract Infection is one of the most common infections encountered by women. These infections have the tendency to recur. In order to identify women at risk of recurrence there is a need to identify risk factors associated with it. Among women, factors predisposing to recurrent infections are not much explored. The study was done with an objective to determine different risk factors associated with recurrent UTI among postmenopausal women. This was a cross sectional study conducted at the Out Patient Department of Nephrology in Shifa International Hospital Islamabad over a period of six months, June 6th to December 5th 2012. Information regarding demographics and risk factors were recorded on a predesigned pro forma. A descriptive analysis was done for quantitative variables like age and qualitative variables like marital status and frequency of different risk factors. Stratification of risk factors according to age was also done. Hundred females were enrolled into the study after informed consent. The mean age of the study population was 64.4±9.48. 97% of the population was married. Out of 100 patients, 42 had high post-void volume, 35 had urinary incontinence and 17 patients were having cystocele. According to age stratification, most frequently affected age group was between 51-60 years (38%), followed by 61-70 years (36%), then 25% in more than 70 years, whereas only 1% was between 41-50 years. Recurrent UTI in postmenopausal females is most frequently associated with high post void volume and most frequently affected age group is between 51-60 years.

A scoring model for predicting advanced colorectal neoplasia in a screened population of asymptomatic Japanese individuals.

PubMed

Sekiguchi, Masau; Kakugawa, Yasuo; Matsumoto, Minori; Matsuda, Takahisa

2018-01-22

Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening. Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed. ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m 2 , and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of < 3, ≥ 3 to < 5, and ≥ 5, respectively. The c-statistic of the scoring model was 0.70 (95% confidence interval, 0.67-0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]. We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PubMed

Hingorani, Pooja; Missiaglia, Edoardo; Shipley, Janet; Anderson, James R; Triche, Timothy J; Delorenzi, Mauro; Gastier-Foster, Julie; Wing, Michele; Hawkins, Douglas S; Skapek, Stephen X

2015-10-15

Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. ©2015 American Association for Cancer Research.

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

PubMed Central

Kempny, Aleksander; Diller, Gerhard-Paul; Alonso-Gonzalez, Rafael; Uebing, Anselm; Rafiq, Isma; Li, Wei; Swan, Lorna; Hooper, James; Donovan, Jackie; Wort, Stephen J; Gatzoulis, Michael A; Dimopoulos, Konstantinos

2015-01-01

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population. PMID:25736048

Technical feasibility and validation of a coronary artery calcium scoring system using CT coronary angiography images.

PubMed

Pavitt, Christopher W; Harron, Katie; Lindsay, Alistair C; Zielke, Sayeh; Ray, Robin; Gordon, Daniel; Rubens, Michael B; Padley, Simon P; Nicol, Edward D

2016-05-01

We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system. Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (n = 168). Bland-Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated. Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (r = 0.95; p < 0.0001) and agreement (mean difference -10.4 [95% limits of agreement -258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups k = 0.88 and MESA centiles k = 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third. CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability. • Coronary calcium scores can be reliably determined on contrast-enhanced cardiac CT • This score can accurately risk stratify patients • Elimination of a dedicated calcium scan reduces patient radiation by a third.

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

Advanced techniques to prepare seed to sow

Treesearch

Robert P. Karrfalt

2013-01-01

This paper reviews research on improving the basic technique of cold stratification for tree and shrub seeds. Advanced stratification techniques include long stratification, stratification re-dry, or multiple cycles of warm-cold stratification. Research demonstrates that careful regulation of moisture levels and lengthening the stratification period have produced a...

A Risk Stratification Tool to Assess Commercial Influences on Continuing Medical Education

ERIC Educational Resources Information Center

Barnes, Barbara E.; Cole, Jeanne G.; King, Catherine Thomas; Zukowski, Rebecca; Allgier-Baker, Tracy; Rubio, Doris McGartland; Thorndyke, Luanne E.

2007-01-01

Introduction: Heightened concerns about industry influence on continuing medical education (CME) have prompted tighter controls on the management of commercial funding and conflict of interest. As a result, CME providers must closely monitor their activities and intervene if bias or noncompliance with accreditation standards is likely. Potential…

The Impact of School Choice and Public Policy on Segregation: Evidence from Chile

ERIC Educational Resources Information Center

Elacqua, Gregory

2012-01-01

Advocates argue that vouchers can make improved educational opportunity available to disadvantaged students. Critics contend that vouchers increase the risk of stratification. Researchers have found that Chile's voucher program has lead to increased socioeconomic school segregation. What has been overlooked, however, is segregation between schools…

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of the standardised extraction tool from the JBI-MAStARI. Prognostic factors and the accompanying odds ratio reported for the significance of these factors that were identified by multivariate regression, were extracted from each included study. Studies results were pooled in statistical meta-analysis using Review Manager 5.1. Where statistical pooling was not possible, the findings were presented in narrative form. Seven studies (four prospective cohort and three retrospective cohort) investigating 22 factors in total were included. Fixed effects meta-analysis showed: hypotension [OR=1.66, 95%CI, 1.14-2.41, p=0.008] and thrombocytopenia [OR=3.92, 95%CI, 2.19-7.01, p<0.00001)] were associated with high-risk of adverse outcomes for febrile neutropenia. Other factors that were statistically significant from single studies included: age of patients, clinical presentation at fever onset, presence or absence of co-morbidities, infections, duration and severity of neutropenia state. Five prognostic factors failed to demonstrate an association between the variables and the outcomes measured and they include: presence of pneumonia, total febrile days, median days to fever, recovery from neutropenia and presence of moderate clinical symptoms in association with Gram-negative bacteraemia. Despite the overall limitations identified in the included studies, this review has provided a synthesis of the best available evidence for the prognostic factors used in risk stratification of febrile neutropenia patients. However, the dynamic aspects of prognostic model development, validation and utilisation have not been addressed adequately thus far. Given the findings of this review, it is timely to address these issues and improve the utilisation of prognostic models in the management of febrile neutropenia patients. The identified factors are similar to the factors in current prognostic models. However, additional factors that were reported to be statistically significant in this review (thrombocytopenia, presence of central venous catheter, and duration and severity of neutropenia) have not previously been included in prognostic models. This review has found these factors may improve the performance of current models by adding or replacing some of the factors. The role of risk stratification of chemotherapy-induced febrile neutropenia patients continues to evolve as the practice of risk-based therapy has been demonstrated to be beneficial to patients, clinicians and health care organisations. Further research to identify new factors /markers is needed to develop a new model which is reliable and accurate for these patients, regardless of cancer types. A robust and well-validated prognostic model is the key to enhance patient safety in the risk-based management of cancer patients with chemotherapy-induced febrile neutropenia.

Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO) scoring system in septic patients in the emergency department: a cohort study.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2014-04-16

The predisposition, infection, response and organ dysfunction (PIRO) staging system was designed as a stratification tool to deal with the inherent heterogeneity of septic patients. The present study was conducted to assess the performance of PIRO in predicting multiple organ dysfunction (MOD), intensive care unit (ICU) admission, and 28-day mortality in septic patients in the emergency department (ED), and to compare this scoring system with the Mortality in Emergency Department Sepsis (MEDS) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Consecutive septic patients (n = 680) admitted to the ED of Beijing Chao-Yang Hospital were enrolled. PIRO, MEDS, and APACHE II scores were calculated for each patient on ED arrival. Organ function was reassessed within 3 days of enrollment. All patients were followed up for 28 days. Outcome criteria were the development of MOD within 3 days, ICU admission or death within 28 days after enrollment. The predictive ability of the four components of PIRO was analyzed separately. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess the prognostic and risk stratification value of the scoring systems. Organ dysfunction independently predicted ICU admission, MOD, and 28-day mortality, with areas under the ROC curve (AUC) of 0.888, 0.851, and 0.816, respectively. The predictive value of predisposition, infection, and response was weaker than that of organ dysfunction. A negative correlation was found between the response component and MOD, as well as mortality. PIRO, MEDS, and APACHE II scores significantly differed between patients who did and did not meet the outcome criteria (P < 0.001). PIRO and APACHE II independently predicted ICU admission and MOD, but MEDS did not. All three systems were independent predictors of 28-day mortality with similar AUC values. The AUC of PIRO was 0.889 for ICU admission, 0.817 for MOD, and 0.744 for 28-day mortality. The AUCs of PIRO were significantly greater than those of APACHE II and MEDS (P < 0.05) in predicting ICU admission and MOD. The study indicates that PIRO is helpful for risk stratification and prognostic determinations in septic patients in the ED.

Desmoplakin II expression is not restricted to stratified epithelia.

PubMed

Angst, B D; Nilles, L A; Green, K J

1990-10-01

Desmosomes are major intercellular junctions found in association with intermediate filaments in epithelial, cardiac and arachnoidal tissue. Desmoplakins I and II (DPI and II) are highly related proteins localized in the innermost part of the desmosomal plaque and are candidates for linking intermediate filaments (IF) to the desmosomal complex. While investigators agree that DPI is present in all epithelia, they disagree on the distribution of DPII. Some have reported DPII to be restricted to stratified tissue and have furthermore suggested that the expression of DPII may be linked to stratification. We have compared the expression of DPI and II at the mRNA and protein levels in cell lines derived from simple, transitional and stratified epithelia. Northern blot analysis revealed DPI and II mRNA to be present in all cell lines as well as simple and stratified epithelial tissues. However, DPII mRNA could not be detected in cardiac muscle tissue. Immunoblotting and immunoprecipitation demonstrated the presence of DPI and II in all cell lines at the whole-cell protein level as well as in association with cytoskeletal fractions. Immunofluorescence staining was used to correlate the biochemical findings with the localization of DPI and II. While most cell lines exhibited typical intercellular and in many cases cytoplasmic DP staining, T24 cells exhibited predominantly diffuse and dotty cytoplasmic staining. In addition, we investigated whether changes in DPI and II expression occurred following calcium-induced cell contact formation and stratification in the human pharyngeal cell line, FaDu. No significant changes in mRNA or whole-cell protein levels were observed during a period of 5 days following the calcium switch. However, immunoblotting revealed a significant increase in DPI and II levels in the insoluble protein pool during desmosome formation. These observations indicated a possible recruitment of soluble DPI/II into an insoluble pool after induction of desmosome assembly by the calcium switch, consistent with earlier reports for MDCK cells. In summary, our results suggest that the expression of DPII is not strictly linked to stratification or differentiation; however, the apparent absence of DPII mRNA from cardiac muscle suggests it may not be a constituent of all desmosomes.

Instability of 2D Flows to Hydrostatic 3D Perturbations.

NASA Astrophysics Data System (ADS)

Straub, David N.

2003-01-01

Considered here is the evolution of three-dimensional perturbations to the hydrostatic equations linearized about a two-dimensional base state U. Motivated by an argument by T. Warn, this study begins with the nonrotating, unstratified case, and draws analogies between the perturbation equations and equations describing evolution of material line elements and scalar gradients embedded in the same 2D flow. When U is chaotic, both scalar gradients and line elements are characterized by rapid growth, and this leads one to suspect that the perturbations behave similarly. A generalized Okubo-Weiss parameter is proposed, and it is argued that this gives a reasonable litmus test for identifying regions where growth is most probable. Rotation modifies the generalized Okubo-Weiss parameter and tends to curb growth of the perturbation fields, as expected. It is also pointed out that, in realistic geophysical settings, the stability parameter can be suggestive of growth locally, even when a globally defined Rossby number is small.Also considered is the effect of a constant stratification. The perturbation equations can then be separated into vertical modes that have simple sinusoidal structures. The equations describing the evolution of a given mode take a form analogous to the shallow water equations, linearized about U. Numerical simulations of these, assuming a simple but chaotic prescription of U, are carried out. For sufficiently strong stratification, a balance dynamics similar to that suggested by Riley, Metcalfe, and Weissman is recovered. For a given value of the buoyancy frequency N, however, this balance breaks down at high vertical wavenumbers. For high vertical wavenumbers, the modified Okubo-Weiss parameter once again appears to give a potentially useful indication of when growth should be expected. When the Rossby number is small, this criterion predicts stability, and growth occurs only when stratification effects are comparable to or larger than rotational effects. More specifically, growth is seen when the relevant Rossby radius is comparable to or larger than the characteristic length scale of U. It is also found in this limit that approximate geostrophic adjustment occurs prior to growth.

Generalized scaling of seasonal thermal stratification in lakes

NASA Astrophysics Data System (ADS)

Shatwell, T.; Kirillin, G.

2016-12-01

The mixing regime is fundamental to the biogeochemisty and ecology of lakes because it determines the vertical transport of matter such as gases, nutrients, and organic material. Whereas shallow lakes are usually polymictic and regularly mix to the bottom, deep lakes tend to stratify seasonally, separating surface water from deep sediments and deep water from the atmosphere. Although empirical relationships exist to predict the mixing regime, a physically based, quantitative criterion is lacking. Here we review our recent research on thermal stratification in lakes at the transition between polymictic and stratified regimes. Using the mechanistic balance between potential and kinetic energy in terms of the Richardson number, we derive a generalized physical scaling for seasonal stratification in a closed lake basin. The scaling parameter is the critical mean basin depth that delineates polymictic and seasonally stratified lakes based on lake water transparency (Secchi depth), lake length, and an annual mean estimate for the Monin-Obukhov length. We validated the scaling on available data of 374 global lakes using logistic regression and found it to perform better than other criteria including a conventional open basin scaling or a simple depth threshold. The scaling has potential applications in estimating large scale greenhouse gas fluxes from lakes because the required inputs, like water transparency and basin morphology, can be acquired using the latest remote sensing technologies. The generalized scaling is universal for freshwater lakes and allows the seasonal mixing regime to be estimated without numerically solving the heat transport equations.

T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers

NASA Technical Reports Server (NTRS)

Hohnloser, S. H.; Klingenheben, T.; Li, Y. G.; Zabel, M.; Peetermans, J.; Cohen, R. J.

1998-01-01

INTRODUCTION: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. METHODS AND RESULTS: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. CONCLUSIONS: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to be prospectively evaluated in such populations.

Personalized assessment and management of women at risk for breast cancer in North America.

PubMed

Pruthi, Sandhya; Heisey, Ruth; Bevers, Therese

2015-03-01

Many women at increased risk for breast cancer would benefit from referral for genetic testing, enhanced screening, preventive therapy or risk-reducing surgery. We present a visual model and a step-wise approach to assist with a personalized risk stratification and management of these women. We present current recommendations with respect to lifestyle behaviors and mammographic screening, and we review the current evidence regarding enhanced screening and risk-reducing therapies. We discuss the usefulness of three risk-assessment tools in determining whether a woman qualifies for genetic testing, enhanced screening or preventive therapy and present four cases to demonstrate the usefulness of this approach in the clinical setting.

Admission glucose does not improve GRACE score at 6 months and 5 years after myocardial infarction.

PubMed

de Mulder, Maarten; van der Ploeg, Tjeerd; de Waard, Guus A; Boersma, Eric; Umans, Victor A

2011-01-01

Admission plasma glucose (APG) is a biomarker that predicts mortality in myocardial infarction (MI) patients. Therefore, APG may improve risk stratification based on the GRACE risk score. We collected data on baseline characteristics and long-term (median 55 months) outcome of 550 MI patients who entered our hospital in 2003 and 2006. We determined the GRACE risk score at admission for each patient, which was entered in a logistic regression model, together with APG, to evaluate their prognostic value for 6-month and 5-year mortality. Patients with APG ≥7.8 mmol/l had a higher mortality than those with APG levels <7.8 mmol/l; 6 months: 13.7 versus 3.6%, p value <0.001; 5 years: 20.4 versus 11.1%, p value 0.003. After adjustment for the GRACE risk score variables, APG appeared a significant predictor of 6-month and 5-year mortality, adjusted OR 1.17 (1.06-1.29) and 1.12 (1.03-1.22). The combination of the GRACE risk score and APG increased the model's performance (discrimination C-index 0.87 vs. 0.85), although the difference was not significant (p = 0.095). Combining the GRACE risk score and APG reclassified 12.9% of the patients, but the net reclassification improvement was nonsignificant (p = 0.146). APG is a predictor of 6-month and 5-year mortality, each mmol/l increase in APG being associated with a mortality increase of 17 and 12%, respectively, independent of the GRACE risk score. However, adding APG to the GRACE model did not result in significantly improved clinical risk stratification. Copyright © 2012 S. Karger AG, Basel.

Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography.

PubMed

Bugiardini, Raffaele; Manfrini, Olivia; De Ferrari, Gaetano M

2006-07-10

The prognostic implication of chest pain associated with normal or near-normal findings on angiography is still unknown. We explored outcomes and methods of risk stratification in patients with nonobstructive coronary artery disease in the setting of non-ST-segment elevation acute coronary syndromes. Data were pooled from 3 Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 11B, TIMI 16, and TIMI 22). Angiographic data were available on 7656 patients with non-ST-segment elevation acute coronary syndromes. The primary end point of this analysis was the composite of the rates of death, myocardial infarction, unstable angina requiring rehospitalization, revascularization, and stroke at 1-year follow-up. Outcomes were evaluated by mean of the TIMI risk score for developing at least 1 component of the primary end point. Angiographic findings showed that 710 (9.1%) of 7656 patients had nonobstructive coronary artery disease; 48.7% of these had normal coronary arteries (0% stenosis), and 51.3% had mild coronary artery disease (>0% to <50% stenosis). A primary end-point event occurred in 101 patients (12.1%). It is noteworthy that a 2% event rate of deaths and myocardial infarctions had occurred in these patients at the 1-year follow-up. Event rates of death and myocardial infarction increased significantly as the TIMI risk score increased from 0.6% for a score of 1 to 4.0% for a score greater than 4. Patients with non-ST-segment elevation acute coronary syndromes with nonobstructive coronary artery disease detected by angiography have a substantial risk of subsequent coronary events within 1 year. The risk is not univariately high, and the TIMI risk score helps to reveal patients at high risk.

Adding Complex Terrain and Stable Atmospheric Condition Capability to the Simulator for On/Offshore Wind Farm Applications (SOWFA) (Presentation)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Churchfield, M. J.

This presentation describes changes made to NREL's OpenFOAM-based wind plant aerodynamics solver so that it can compute the stably stratified atmospheric boundary layer and flow over terrain. Background about the flow solver, the Simulator for Off/Onshore Wind Farm Applications (SOWFA) is given, followed by details of the stable stratification/complex terrain modifications to SOWFA, along with some preliminary results calculations of a stable atmospheric boundary layer and flow over a simple set of hills.

Wake Vortex Prediction Models for Decay and Transport Within Stratified Environments

NASA Astrophysics Data System (ADS)

Switzer, George F.; Proctor, Fred H.

2002-01-01

This paper proposes two simple models to predict vortex transport and decay. The models are determined empirically from results of three-dimensional large eddy simulations, and are applicable to wake vortices out of ground effect and not subjected to environmental winds. The results, from the large eddy simulations assume a range of ambient turbulence and stratification levels. The models and the results from the large eddy simulations support the hypothesis that the decay of the vortex hazard is decoupled from its change in descent rate.

Risk stratification and management of acute pulmonary embolism.

PubMed

Becattini, Cecilia; Agnelli, Giancarlo

2016-12-02

The clinical management of patients with acute pulmonary embolism is rapidly changing over the years. The widening spectrum of clinical management strategies for these patients requires effective tools for risk stratification. Patients at low risk for death could be candidates for home treatment or early discharge. Clinical models with high negative predictive value have been validated that could be used to select patients at low risk for death. In a major study and in several meta-analyses, thrombolysis in hemodynamically stable patients was associated with unacceptably high risk for major bleeding complications or intracranial hemorrhage. Thus, the presence of shock or sustained hypotension continues to be the criterion for the selection of candidates for thrombolytic treatment. Interventional procedures for early revascularization should be reserved to selected patients until further evidence is available. No clinical advantage is expected with the insertion of a vena cava filter in the acute-phase management of patients with acute pulmonary embolism. Direct oral anticoagulants used in fixed doses without laboratory monitoring showed similar efficacy (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.70-1.12) and safety (OR, 0.89; 95% CI, 0.77-1.03) in comparison with conventional anticoagulation in patients with acute pulmonary embolism. Based on these results and on their practicality, direct oral anticoagulants are the agents of choice for the treatment of the majority of patients with acute pulmonary embolism. © 2016 by The American Society of Hematology. All rights reserved.

Best practice in the use of natalizumab in multiple sclerosis.

PubMed

Fernández, Oscar

2013-03-01

Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use.

Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.

PubMed

Hansen, T W; Thijs, L; Li, Y; Boggia, J; Liu, Y; Asayama, K; Kikuya, M; Björklund-Bodegård, K; Ohkubo, T; Jeppesen, J; Torp-Pedersen, C; Dolan, E; Kuznetsova, T; Stolarz-Skrzypek, K; Tikhonoff, V; Malyutina, S; Casiglia, E; Nikitin, Y; Lind, L; Sandoya, E; Kawecka-Jaszcz, K; Filipovský, J; Imai, Y; Wang, J; O'Brien, E; Staessen, J A

2014-09-01

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

[Essential thrombocythemia: baseline characteristics and risk factors for survival and thrombosis in a series of 214 patients].

PubMed

Angona, Anna; Alvarez-Larrán, Alberto; Bellosillo, Beatriz; Martínez-Avilés, Luz; Garcia-Pallarols, Francesc; Longarón, Raquel; Ancochea, Àgueda; Besses, Carles

2015-03-15

Two prognostic models to predict overall survival and thrombosis-free survival have been proposed: International Prognostic Score for Essential Thrombocythemia (IPSET) and IPSET-Thrombosis, respectively, based on age, leukocytes count, history of previous thrombosis, the presence of cardiovascular risk factors and the JAK2 mutational status. The aim of the present study was to assess the clinical and biological characteristics at diagnosis and during evolution in essential thrombocythemia (ET) patients as well as the factors associated with survival and thrombosis and the usefulness of these new prognostic models. We have evaluated the clinical data and the mutation status of JAK2, MPL and calreticulin of 214 ET patients diagnosed in a single center between 1985 and 2012, classified according to classical risk stratification, IPSET and IPSET-Thrombosis. With a median follow-up of 6.9 years, overall survival was not associated with any variable by multivariate analysis. Thrombotic history and leukocytes>10×10(9)/l were associated with thrombosis-free survival (TFS). In our series, IPSET prognostic systems of survival and thrombosis did not provide more clinically relevant information regarding the classic risk of thrombosis stratification. Thrombotic history and leukocytosis>10×10(9)/l were significantly associated with lower TFS, while the prognostic IPSET-Thrombosis system did not provide more information than classical thrombotic risk assessment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Recursive partition analysis of peritoneal and systemic recurrence in patients with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant therapy consideration.

PubMed

Chang, Jee Suk; Kim, Kyung Hwan; Keum, Ki Chang; Noh, Sung Hoon; Lim, Joon Seok; Kim, Hyo Song; Rha, Sun Young; Lee, Yong Chan; Hyung, Woo Jin; Koom, Woong Sub

2016-12-01

To classify patients with nonmetastatic advanced gastric cancer who underwent D2-gastrectomy into prognostic groups based on peritoneal and systemic recurrence risks. Between 2004 and 2007, 1,090 patients with T3-4 or N+ gastric cancer were identified from our registry. Recurrence rates were estimated using a competing-risk analysis. Different prognostic groups were defined using recursive partitioning analysis (RPA). Median follow-up was 7 years. In the RPA-model for peritoneal recurrence risk, the initial node was split by T stage, indicating that differences between patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were 34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact on high-risk patients. The RPA model for systemic relapse incorporated N stage alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year cumulative incidences were 7.7% and 24.5%, respectively. We proposed risk stratification models of peritoneal and systemic recurrence in patients undergoing D2-gastrectomy. This classification could be used for stratification protocols in future studies evaluating adjuvant therapies such as preoperative chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genotype-Specific Minimal Residual Disease Interpretation Improves Stratification in Pediatric Acute Lymphoblastic Leukemia

PubMed Central

O’Connor, David; Enshaei, Amir; Bartram, Jack; Hancock, Jeremy; Harrison, Christine J.; Hough, Rachael; Samarasinghe, Sujith; Schwab, Claire; Vora, Ajay; Wade, Rachel; Moppett, John; Moorman, Anthony V.; Goulden, Nick

2018-01-01

Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current risk algorithms dichotomize MRD data and do not assimilate genetics when assigning MRD risk, which reduces predictive accuracy. The aim of our study was to exploit the full power of MRD by examining it as a continuous variable and to integrate it with genetics. Patients and Methods We used a population-based cohort of 3,113 patients who were treated in UKALL2003, with a median follow-up of 7 years. MRD was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements, and patients were assigned to a genetic subtype on the basis of immunophenotype, cytogenetics, and fluorescence in situ hybridization. To examine response kinetics at the end of induction, we log-transformed the absolute MRD value and examined its distribution across subgroups. Results MRD was log normally distributed at the end of induction. MRD distributions of patients with distinct genetic subtypes were different (P < .001). Patients with good-risk cytogenetics demonstrated the fastest disease clearance, whereas patients with high-risk genetics and T-cell acute lymphoblastic leukemia responded more slowly. The risk of relapse was correlated with MRD kinetics, and each log reduction in disease level reduced the risk by 20% (hazard ratio, 0.80; 95% CI, 0.77 to 0.83; P < .001). Although the risk of relapse was directly proportional to the MRD level within each genetic risk group, absolute relapse rate that was associated with a specific MRD value or category varied significantly by genetic subtype. Integration of genetic subtype–specific MRD values allowed more refined risk group stratification. Conclusion A single threshold for assigning patients to an MRD risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with MRD to accurately identify patients with the lowest and highest risk of relapse. PMID:29131699

Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study.

PubMed

Olesen, Jonas Bjerring; Lip, Gregory Y H; Hansen, Morten Lock; Hansen, Peter Riis; Tolstrup, Janne Schurmann; Lindhardsen, Jesper; Selmer, Christian; Ahlehoff, Ole; Olsen, Anne-Marie Schjerning; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2011-01-31

To evaluate the individual risk factors composing the CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score and the CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. Registry based cohort study. Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. Stroke and thromboembolism. Of 121,280 patients with non-valvular atrial fibrillation, 73,538 (60.6%) fulfilled the study inclusion criteria. In patients at "low risk" (score = 0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS(2) and 0.78 (0.58 to 1.04) with CHA(2)DS(2)-VASc at one year's follow-up. In patients at "intermediate risk" (score = 1), this rate was 4.75 (4.45 to 5.07) with CHADS(2) and 2.01 (1.70 to 2.36) with CHA(2)DS(2)-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years' follow-up were 0.812 (0.796 to 0.827) with CHADS(2) and 0.888 (0.875 to 0.900) with CHA(2)DS(2)-VASc. The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA(2)DS(2)-VASc performed better than CHADS(2) in predicting patients at high risk, and those categorised as low risk by CHA(2)DS(2)-VASc were truly at low risk for thromboembolism.

Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system.

PubMed

Snozek, C L H; Katzmann, J A; Kyle, R A; Dispenzieri, A; Larson, D R; Therneau, T M; Melton, L J; Kumar, S; Greipp, P R; Clark, R J; Rajkumar, S V

2008-10-01

To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as kappa/lambda (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint kappa/lambda FLC ratio of <0.03 or >32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of <0.03 or >32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin <3.5 g/dl and serum beta(2)-microglobulin >or=3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.

Effect of root length on epicotyl dormancy release in seeds of Paeonia ludlowii, Tibetan peony.

PubMed

Hao, Hai-ping; He, Zhi; Li, Hui; Shi, Lei; Tang, Yu-Dan

2014-02-01

Epicotyl dormancy break in seeds that have deep simple epicotyl morphophysiological dormancy (MPD) requires radicle emergence and even a certain root length in some species. However, the mechanisms by which root length affects epicotyl dormancy break are not clear at present. This study aims to explore the relationship between root length and epicotyl dormancy release in radicle-emerged seeds of Tibetan peony, Paeonia ludlowii, with discussion of the possible mechanisms. Radicle-emerged seeds (radicle length 1.5, 3.0, 4.5 and 6.0 cm) were incubated at 5, 10 and 15 °C. During the stratification, some seeds were transferred to 15 °C and monitored for epicotyl-plumule growth. Hormone content was determined by ELISA, and the role of hormones in epicotyl dormancy release was tested by exogenous hormone and embryo culture. Cold stratification did not break the epicotyl dormancy until the root length was ≥6 cm. The indole-3-actic acid (IAA) and GA3 contents of seeds having 6 cm roots were significantly higher than those of seeds with other root lengths, but the abscisic acid (ABA) content was lowest among radicle-emerged seeds. GA3 (400 mg L(-1)) could break epicotyl dormancy of all radicle-emerged seeds, while IAA (200 mg L(-1)) had little or no effect. When grown on MS medium, radicles of naked embryos grew and cotyledons turned green, but epicotyls did not elongate. Naked embryos developed into seedlings on a mixed medium of MS + 100 mg L(-1) GA3. A root length of ≥6.0 cm is necessary for epicotyl dormancy release by cold stratification. The underlying reason for root length affecting epicotyl dormancy release is a difference in the GA3/ABA ratio in the epicotyl within radicle-emerged seeds, which is mainly as a result of a difference in ABA accumulation before cold stratification.

Effect of root length on epicotyl dormancy release in seeds of Paeonia ludlowii, Tibetan peony

PubMed Central

Hao, Hai-ping; He, Zhi; Li, Hui; Shi, Lei; Tang, Yu-Dan

2014-01-01

Background and Aims Epicotyl dormancy break in seeds that have deep simple epicotyl morphophysiological dormancy (MPD) requires radicle emergence and even a certain root length in some species. However, the mechanisms by which root length affects epicotyl dormancy break are not clear at present. This study aims to explore the relationship between root length and epicotyl dormancy release in radicle-emerged seeds of Tibetan peony, Paeonia ludlowii, with discussion of the possible mechanisms. Methods Radicle-emerged seeds (radicle length 1·5, 3·0, 4·5 and 6·0 cm) were incubated at 5, 10 and 15 °C. During the stratification, some seeds were transferred to 15 °C and monitored for epicotyl–plumule growth. Hormone content was determined by ELISA, and the role of hormones in epicotyl dormancy release was tested by exogenous hormone and embryo culture. Key Results Cold stratification did not break the epicotyl dormancy until the root length was ≥6 cm. The indole-3-actic acid (IAA) and GA3 contents of seeds having 6 cm roots were significantly higher than those of seeds with other root lengths, but the abscisic acid (ABA) content was lowest among radicle-emerged seeds. GA3 (400 mg L−1) could break epicotyl dormancy of all radicle-emerged seeds, while IAA (200 mg L−1) had little or no effect. When grown on MS medium, radicles of naked embryos grew and cotyledons turned green, but epicotyls did not elongate. Naked embryos developed into seedlings on a mixed medium of MS + 100 mg L−1 GA3. Conclusions A root length of ≥6·0 cm is necessary for epicotyl dormancy release by cold stratification. The underlying reason for root length affecting epicotyl dormancy release is a difference in the GA3/ABA ratio in the epicotyl within radicle-emerged seeds, which is mainly as a result of a difference in ABA accumulation before cold stratification. PMID:24284815

Dormancy induction by summer temperatures and/or desiccation in imbibed seeds of trumpet daffodils Narcissus alcaracensis and N. longispathus (Amaryllidaceae).

PubMed

Herranz, J M; Copete, E; Copete, M A; Márquez, J; Ferrandis, P

2017-01-01

We analysed the effects of summer temperatures (28/14 °C) and/or desiccation (from 48% to 8% humidity) on imbibed Narcissus alcaracensis and N. longispathus seeds with an elongating embryo. In the N. alcaracensis seeds that overcame dormancy (embryo elongation = 27.14%), exposure to high temperatures induced secondary dormancy and reduced subsequent embryo growth. A further 3-month cold stratification (5 °C) was required to break secondary dormancy. Desiccation in early embryo growth stages (elongation = 11.42%) also reduced germination. Desiccation in the seeds in a more advanced growth stage (i.e. embryo elongation = 27.14%) induced secondary dormancy, which the further 3-month cold stratification did not overcome. When desiccation was preceded by high temperatures, seeds better overcame secondary dormancy (i.e. longer embryo elongation and seed germination). Treatments did not affect seed viability. In the N. longispathus seeds that overcame dormancy (embryo elongation = 59.21%), exposure to high temperatures induced secondary dormancy and they needed a further 1-month stratification at 15/4 °C + 2 months at 5 °C to reactivate the germination process. When embryo elongation was 42.10%, seed desiccation totally impeded subsequent germination. When embryo elongation reached 59.21%, desiccation induced secondary dormancy, which was not overcome by the above-described stratification treatment. When desiccation was preceded by high temperatures, seeds better overcame dormancy. Stress treatments killed 5-10% of seeds. This study suggests that the seeds of species with complex morphophysiological dormancy (MPD) levels are sensitive to desiccation in early embryo development stages, as opposed to the seeds of species with deep simple epicotyl MPD, which better tolerate water stress. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

Cytogenetic prognostication within medulloblastoma subgroups.

PubMed

Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

2014-03-20

Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Plaque Tissue Morphology-Based Stroke Risk Stratification Using Carotid Ultrasound: A Polling-Based PCA Learning Paradigm.

PubMed

Saba, Luca; Jain, Pankaj K; Suri, Harman S; Ikeda, Nobutaka; Araki, Tadashi; Singh, Bikesh K; Nicolaides, Andrew; Shafique, Shoaib; Gupta, Ajay; Laird, John R; Suri, Jasjit S

2017-06-01

Severe atherosclerosis disease in carotid arteries causes stenosis which in turn leads to stroke. Machine learning systems have been previously developed for plaque wall risk assessment using morphology-based characterization. The fundamental assumption in such systems is the extraction of the grayscale features of the plaque region. Even though these systems have the ability to perform risk stratification, they lack the ability to achieve higher performance due their inability to select and retain dominant features. This paper introduces a polling-based principal component analysis (PCA) strategy embedded in the machine learning framework to select and retain dominant features, resulting in superior performance. This leads to more stability and reliability. The automated system uses offline image data along with the ground truth labels to generate the parameters, which are then used to transform the online grayscale features to predict the risk of stroke. A set of sixteen grayscale plaque features is computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of 0.995, the machine learning system is able to achieve an accuracy of 98.55 and 98.83%corresponding to the carotidfar wall and near wall plaques, respectively. The corresponding reliability of the system was 94.56 and 95.63%, respectively. The automated system was validated against the manual risk assessment system and the precision of merit for same cross-validation settings and PCA cutoffs are 98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded morphology-based plaque characterization shows a powerful strategy for risk assessment and can be adapted in clinical settings.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PubMed Central

Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

2014-01-01

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID:24493713

Evaluating the Laboratory Risk Indicator to Differentiate Cellulitis from Necrotizing Fasciitis in the Emergency Department

PubMed Central

Neeki, Michael M.; Dong, Fanglong; Au, Christine; Toy, Jake; Khoshab, Nima; Lee, Carol; Kwong, Eugene; Yuen, Ho Wang; Lee, Jonathan; Ayvazian, Arbi; Lux, Pamela; Borger, Rodney

2017-01-01

Introduction Necrotizing fasciitis (NF) is an uncommon but rapidly progressive infection that results in gross morbidity and mortality if not treated in its early stages. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is used to distinguish NF from other soft tissue infections such as cellulitis or abscess. This study analyzed the ability of the LRINEC score to accurately rule out NF in patients who were confirmed to have cellulitis, as well as the capability to differentiate cellulitis from NF. Methods This was a 10-year retrospective chart-review study that included emergency department (ED) patients ≥18 years old with a diagnosis of cellulitis or NF. We calculated a LRINEC score ranging from 0–13 for each patient with all pertinent laboratory values. Three categories were developed per the original LRINEC score guidelines denoting NF risk stratification: high risk (LRINEC score ≥8), moderate risk (LRINEC score 6–7), and low risk (LRINEC score ≤5). All cases missing laboratory values were due to the absence of a C-reactive protein (CRP) value. Since the score for a negative or positive CRP value for the LRINEC score was 0 or 4 respectively, a LRINEC score of 0 or 1 without a CRP value would have placed the patient in the “low risk” group and a LRINEC score of 8 or greater without CRP value would have placed the patient in the “high risk” group. These patients missing CRP values were added to these respective groups. Results Among the 948 ED patients with cellulitis, more than one-tenth (10.7%, n=102 of 948) were moderate or high risk for NF based on LRINEC score. Of the 135 ED patients with a diagnosis of NF, 22 patients had valid CRP laboratory values and LRINEC scores were calculated. Among the other 113 patients without CRP values, six patients had a LRINEC score ≥ 8, and 19 patients had a LRINEC score ≤ 1. Thus, a total of 47 patients were further classified based on LRINEC score without a CRP value. More than half of the NF group (63.8%, n=30 of 47) had a low risk based on LRINEC ≤5. Moreover, LRINEC appeared to perform better in the diabetes population than in the non-diabetes population. Conclusion The LRINEC score may not be an accurate tool for NF risk stratification and differentiation between cellulitis and NF in the ED setting. This decision instrument demonstrated a high false positive rate when determining NF risk stratification in confirmed cases of cellulitis and a high false negative rate in cases of confirmed NF. PMID:28611889

Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome.

PubMed

Villar, Jesús; Ambrós, Alfonso; Soler, Juan Alfonso; Martínez, Domingo; Ferrando, Carlos; Solano, Rosario; Mosteiro, Fernando; Blanco, Jesús; Martín-Rodríguez, Carmen; Fernández, María Del Mar; López, Julia; Díaz-Domínguez, Francisco J; Andaluz-Ojeda, David; Merayo, Eleuterio; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M

2016-07-01

Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis. A prospective, multicenter, observational, descriptive, and validation study. A network of multidisciplinary ICUs. Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation. None. Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an independent cohort of 300 acute respiratory distress syndrome patients. Primary outcome was in-hospital mortality. We found that a 9-point score based on patient's age, PaO2/FIO2 ratio, and plateau pressure at 24 hours after acute respiratory distress syndrome diagnosis was associated with death. Patients with a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0-11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p < 0.0000001). We confirmed the predictive validity of the score in a validation cohort. A simple 9-point score based on the values of age, PaO2/FIO2 ratio, and plateau pressure calculated at 24 hours on protective ventilation after acute respiratory distress syndrome diagnosis could be used in real time for rating prognosis of acute respiratory distress syndrome patients with high probability.

T-wave alternans and dispersion of the QT interval as risk stratification markers in patients susceptible to sustained ventricular arrhythmias

NASA Technical Reports Server (NTRS)

Armoundas, A. A.; Osaka, M.; Mela, T.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

1998-01-01

T-wave alternans and QT dispersion were compared as predictors of the outcome of electrophysiologic study and arrhythmia-free survival in patients undergoing electrophysiologic evaluation. T-wave alternans was a highly significant predictor of these 2 outcome variables, whereas QT dispersion was not.

Stratification of Recanalization for Patients with Endovascular Treatment of Intracranial Aneurysms

PubMed Central

Ogilvy, Christopher S.; Chua, Michelle H.; Fusco, Matthew R.; Reddy, Arra S.; Thomas, Ajith J.

2015-01-01

Background With increasing utilization of endovascular techniques in the treatment of both ruptured and unruptured intracranial aneurysms, the issue of obliteration efficacy has become increasingly important. Objective Our goal was to systematically develop a comprehensive model for predicting retreatment with various types of endovascular treatment. Methods We retrospectively reviewed medical records that were prospectively collected for 305 patients who received endovascular treatment for intracranial aneurysms from 2007 to 2013. Multivariable logistic regression was performed on candidate predictors identified by univariable screening analysis to detect independent predictors of retreatment. A composite risk score was constructed based on the proportional contribution of independent predictors in the multivariable model. Results Size (>10 mm), aneurysm rupture, stent assistance, and post-treatment degree of aneurysm occlusion were independently associated with retreatment while intraluminal thrombosis and flow diversion demonstrated a trend towards retreatment. The Aneurysm Recanalization Stratification Scale was constructed by assigning the following weights to statistically and clinically significant predictors. Aneurysm-specific factors: Size (>10 mm), 2 points; rupture, 2 points; presence of thrombus, 2 points. Treatment-related factors: Stent assistance, -1 point; flow diversion, -2 points; Raymond Roy 2 occlusion, 1 point; Raymond Roy 3 occlusion, 2 points. This scale demonstrated good discrimination with a C-statistic of 0.799. Conclusion Surgical decision-making and patient-centered informed consent require comprehensive and accessible information on treatment efficacy. We have constructed the Aneurysm Recanalization Stratification Scale to enhance this decision-making process. This is the first comprehensive model that has been developed to quantitatively predict the risk of retreatment following endovascular therapy. PMID:25621984

Pediatric Minor Head Injury 2.0: Moving from Injury Exclusion to Risk Stratification.

PubMed

Homme, James Jim L

2018-05-01

Visits for pediatric minor blunt head trauma continue to increase. Variability exists in clinician evaluation and management of this generally low-risk population. Clinical decision rules identify very low-risk children who can forgo neuroimaging. Observation before imaging decreases neuroimaging rates. Outcome data can be used to risk stratify children into more discrete categories. Decision aids improves knowledge and accuracy of risk perception and facilitates identification of caregiver preferences, allowing for shared decision making. For children in whom imaging is performed and is normal or shows isolated linear skull fractures, deterioration and neurosurgical intervention are rare and hospital admission can be avoided. Copyright © 2018 The Author. Published by Elsevier Inc. All rights reserved.

[Myocardial viability: update in nuclear cardiology].

PubMed

Vallejo, Enrique

2007-01-01

Evaluation of myocardial viability with the aid of radionuclides, is a technique that offers reliable, reproducible information, with an attractive cost-benefit relationship, in the study of the myocardial viability, integrating cardiac molecular, metabolic, and functional aspects. Nowadays, coronary risk stratification in post-myocardial infarction patients pretends to locate them as low-, intermediate, and high risk-subjects that can suffer cardiovascular complications in the very near future. Low-risk patients are characterized by a cardiac-related mortality below 1%, whereas high-risk mortality is greater than 3%. Because of clinical complications following a myocardial infarction are observed during the first month of evolution, clinical guidelines suggest to evaluate the cardiovascular risk before hospital discharge.

Breast Cancer Screening in the Era of Density Notification Legislation: Summary of 2014 Massachusetts Experience and Suggestion of An Evidence-Based Management Algorithm by Multi-disciplinary Expert Panel

PubMed Central

Freer, Phoebe E.; Slanetz, Priscilla J.; Haas, Jennifer S.; Tung, Nadine M.; Hughes, Kevin S.; Armstrong, Katrina; Semine, A. Alan; Troyan, Susan L.; Birdwell, Robyn L.

2015-01-01

Purpose Stemming from breast density notification legislation in Massachusetts effective 2015, we sought to develop a collaborative evidence-based approach to density notification that could be used by practitioners across the state. Our goal was to develop an evidence-based consensus management algorithm to help patients and health care providers follow best practices to implement a coordinated, evidence-based, cost-effective, sustainable practice and to standardize care in recommendations for supplemental screening. Methods We formed the Massachusetts Breast Risk Education and Assessment Task Force (MA-BREAST) a multi-institutional, multi-disciplinary panel of expert radiologists, surgeons, primary care physicians, and oncologists to develop a collaborative approach to density notification legislation. Using evidence-based data from the Institute for Clinical and Economic Review (ICER), the Cochrane review, National Comprehensive Cancer Network (NCCN) guidelines, American Cancer Society (ACS) recommendations, and American College of Radiology (ACR) appropriateness criteria, the group collaboratively developed an evidence-based best-practices algorithm. Results The expert consensus algorithm uses breast density as one element in the risk stratification to determine the need for supplemental screening. Women with dense breasts and otherwise low risk (<15% lifetime risk), do not routinely require supplemental screening per the expert consensus. Women of high risk (>20% lifetime) should consider supplemental screening MRI in addition to routine mammography regardless of breast density. Conclusion We report the development of the multi-disciplinary collaborative approach to density notification. We propose a risk stratification algorithm to assess personal level of risk to determine the need for supplemental screening for an individual woman. PMID:26290416

Utility of both Carotid Intima-media Thickness and Endothelial Function for Cardiovascular Risk Stratification in Patients with Angina-like Symptoms

PubMed Central

Matsuzawa, Yasushi; Svedlund, Sara; Aoki, Tatsuo; Guddeti, Raviteja R.; Kwon, Taek-Geun; Cilluffo, Rebecca; Widmer, R.Jay.; Nelson, Rebecca E.; Lennon, Ryan J.; Lerman, Lilach O.; Gao, Sinsia; Ganz, Peter; Gan, Li-Ming; Lerman, Amir

2015-01-01

Background Myocardial perfusion scintigraphy (MPS) is used widely to assess cardiovascular risk in patients with chest pain. The utility of carotid intima-media thickness (CIMT) and endothelial function as assessed by reactive hyperemia-peripheral arterial tonometry index (RHI) in risk stratifying patients with angina-like symptom needs to be defined. We investigated whether addition of CIMT and RHI to Framingham Cardiovascular Risk Score (FCVRS) and MPS improves comprehensive cardiovascular risk prediction in patients presenting with angina-like symptom. Methods We enrolled 343 consecutive patients with angina-like symptom suspected of having stable angina. MPS, CIMT, and RHI were performed and patients were followed for cardiovascular events for a median of 5.3 years (range 4.4-6.2). Patients were stratified by FCVRS and MPS. Results During the follow-up, 57 patients (16.6%) had cardiovascular events. Among patients without perfusion defect, low RHI was significantly associated with cardiovascular events in the intermediate and high FCVRS groups (Hazard ratio (HR) [95% confidence interval (CI)] of RHI≤2.11 was 6.99 [1.34-128] in the intermediate FCVRS group and 6.08 [1.08-114] in the high FCVRS group). Furthermore, although MPS did not predict, only RHI predicted hard cardiovascular events (cardiovascular death, myocardial infarction, and stroke) independent from FCVRS, and adding RHI to FCVRS improved net reclassification index (20.9%, 95% CI 0.8-41.1, p=0.04). Especially, RHI was significantly associated with hard cardiovascular events in the high FCVRS group (HR [95% CI] of RHI≤1.93 was 5.66 [1.54-36.4], p=0.007). Conclusions Peripheral endothelial function may improve discrimination in identifying at-risk patients for future cardiovascular events when added to FCVRS-MPS-based risk stratification. PMID:25918056

Office-Based Spirometry: A New Model of Care in Preoperative Assessment for Low-Risk Lung Resections.

PubMed

Hudson, Jessica L; Bell, Jennifer M; Crabtree, Traves D; Kreisel, Daniel; Patterson, G Alexander; Meyers, Bryan F; Puri, Varun

2018-01-01

Formal pulmonary function testing with laboratory spirometry (LS) is the standard of care for risk stratification before lung resection. LS and handheld office spirometry (OS) are clinically comparable for forced expiratory volume in 1 second and forced vital capacity. We investigated the safety of preoperative risk stratification based solely on OS. Patients at low-risk for cardiopulmonary complications were enrolled in a single-center prospective study and underwent preoperative OS. Formal LS was not performed when forced expiratory volume in 1 second was more than 60% by OS. Propensity score matching was used to compare patients in the OS group to low-risk institutional database patients (2008 to 2015) who underwent LS and lung resection. Standardized mean differences determined model covariate balance. The McNemar test and log-rank test were performed, respectively, for categorical and continuous paired outcome data. There were 66 prospectively enrolled patients who received OS and underwent pulmonary resection, and 1,290 patients received preoperative LS, resulting in 52 propensity score-matched pairs (83%). There were no deaths and two 30-day readmissions per group. The major morbidity risk was similar in each group (7.7%). All analyses of discordant pair morbidity had p exceeding 0.56. There was no association between length of stay and exposure to OS vs LS (p = 0.31). The estimated annual institutional cost savings from performing OS only and avoiding LS was $38,000. Low-risk patients undergoing lung resection can be adequately and safely assessed using OS without formal LS, with significant cost savings. With upcoming bundled care reimbursement paradigms, such safe and effective strategies are likely to be more widely used. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study

PubMed Central

Timmer, Margriet R.; Martinez, Pierre; Lau, Chiu T.; Westra, Wytske M.; Calpe, Silvia; Rygiel, Agnieszka M.; Rosmolen, Wilda D.; Meijer, Sybren L.; ten Kate, Fiebo J.W.; Dijkgraaf, Marcel G.W.; Mallant-Hent, Rosalie C.; Naber, Anton H.J.; van Oijen, Arnoud H.A.M.; Baak, Lubbertus C.; Scholten, Pieter; Böhmer, Clarisse J.M.; Fockens, Paul; Maley, Carlo C.; Graham, Trevor A.; Bergman, Jacques J.G.H.M.; Krishnadath, Kausilia K.

2016-01-01

Objective The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. Methods In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC, and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver-operating-characteristic curves and a leave-one-out analysis. Results A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain, and aneusomy, were significantly associated with progression on univariate analysis. We defined an ‘Abnormal Marker Count’ that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI, 2.6 to 29.8) increased hazard ratio compared with the low-risk group, with an area under the curve of 0.76 (95% CI, 0.66 to 0.86). Conclusion A prediction model based on age, Barrett's length, and the markers p16, MYC, and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. PMID:26104750

Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients.

PubMed

Ely, Scott; Forsberg, Peter; Ouansafi, Ihsane; Rossi, Adriana; Modin, Alvin; Pearse, Roger; Pekle, Karen; Perry, Arthur; Coleman, Morton; Jayabalan, David; Di Liberto, Maurizio; Chen-Kiang, Selina; Niesvizky, Ruben; Mark, Tomer M

2017-12-01

Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138 + ) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

A genetic fuzzy system for unstable angina risk assessment.

PubMed

Dong, Wei; Huang, Zhengxing; Ji, Lei; Duan, Huilong

2014-02-18

Unstable Angina (UA) is widely accepted as a critical phase of coronary heart disease with patients exhibiting widely varying risks. Early risk assessment of UA is at the center of the management program, which allows physicians to categorize patients according to the clinical characteristics and stratification of risk and different prognosis. Although many prognostic models have been widely used for UA risk assessment in clinical practice, a number of studies have highlighted possible shortcomings. One serious drawback is that existing models lack the ability to deal with the intrinsic uncertainty about the variables utilized. In order to help physicians refine knowledge for the stratification of UA risk with respect to vagueness in information, this paper develops an intelligent system combining genetic algorithm and fuzzy association rule mining. In detail, it models the input information's vagueness through fuzzy sets, and then applies a genetic fuzzy system on the acquired fuzzy sets to extract the fuzzy rule set for the problem of UA risk assessment. The proposed system is evaluated using a real data-set collected from the cardiology department of a Chinese hospital, which consists of 54 patient cases. 9 numerical patient features and 17 categorical patient features that appear in the data-set are selected in the experiments. The proposed system made the same decisions as the physician in 46 (out of a total of 54) tested cases (85.2%). By comparing the results that are obtained through the proposed system with those resulting from the physician's decision, it has been found that the developed model is highly reflective of reality. The proposed system could be used for educational purposes, and with further improvements, could assist and guide young physicians in their daily work.

Is atherosclerosis imaging the most sensitive way to assess patients' risk and the best way to conduct future drug trials? A pros-and-cons debate.

PubMed

Nanchen, David; Raggi, Paolo

2017-11-01

Atherosclerosis imaging has been the focus of intense debate and research for several decades. Among its primary applications are risk stratification of asymptomatic individuals and follow-up of atherosclerosis progression under a variety of treatments designed to retard or regress the development of arterial disease. Although endorsed and supported by many, this approach has been fiercely opposed by several key opinion leaders over the years. Similarly, regulatory agencies have raised a number of objections to resist the approval of new drugs and devices based on surrogate imaging markers. However, there is a large body of evidence in the medical literature that shows that risk stratification is improved with implementation of atherosclerosis imaging. Additionally, numerous lipid-modifying agents have been tested as far as their ability to affect progression of atherosclerosis, and in many cases the information obtained with imaging was in line with the outcome of subsequent clinical trials. This pros-and-cons debate was staged to bring up in a fun and provoking way the main arguments in favour or against the application of atherosclerosis imaging in the main settings described above. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention

PubMed Central

Gradíssimo, Ana

2018-01-01

INTRODUCTION Human papillomavirus (HPV)-related cancers can be averted by type-specific vaccination (primary prevention) and/or through detection and ablation of precancerous cervical lesions (secondary prevention). This review presents current challenges to cervical cancer screening programs, focusing on recent molecular advances in HPV testing and potential improvements on risk stratification. AREAS COVERED High-risk (HR)-HPV DNA detection has been progressively incorporated into cervix cancer prevention programs based on its increased sensitivity. Advances in next-generation sequencing (NGS) are being rapidly applied to HPV typing. However, current HPV DNA tests lack specificity for identification of cervical precancer (CIN3). HPV typing methods were reviewed based on published literature, with a focus on these applications for screening and risk stratification in the emerging complex clinical scenario post-vaccine introduction. In addition, the potential for NGS technologies to increase specificity is discussed in regards to reflex testing of specimens for emerging biomarkers for cervix precancer/cancer. EXPERT COMMENTARY Integrative multi-disciplinary molecular tests accurately triaging exfoliated cervical specimens will improve cervical cancer prevention programs while simplifying healthcare procedures in HPV-infected women. Hence, the concept of a “liquid-biopsy” (i.e., “molecular” Pap test) highly specific for early identification of cervical precancerous lesions is of critical importance in the years to come. PMID:28277144

Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial

PubMed Central

Tramsen, Lars; Salzmann-Manrique, Emilia; Bochennek, Konrad; Klingebiel, Thomas; Reinhardt, Dirk; Creutzig, Ursula; Sung, Lillian

2016-01-01

Purpose Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. Patients and Methods We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. Results Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. Conclusion The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti-infective policies. PMID:27269945

Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial.

PubMed

Tramsen, Lars; Salzmann-Manrique, Emilia; Bochennek, Konrad; Klingebiel, Thomas; Reinhardt, Dirk; Creutzig, Ursula; Sung, Lillian; Lehrnbecher, Thomas

2016-08-10

Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti-infective policies. © 2016 by American Society of Clinical Oncology.

Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case-control study.

PubMed

Zhu, Yanping; Liu, Kuo; Tang, Xun; Wang, Jinwei; Yu, Zhiping; Wu, Yiqun; Chen, Dafang; Wang, Xueyin; Fang, Kai; Li, Na; Huang, Shaoping; Hu, Yonghua

2014-11-01

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene-environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95% CI 1.04-3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95% CI 1.06-6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95% CI 1.54-8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.

The molecular genetic makeup of acute lymphoblastic leukemia.

PubMed

Mullighan, Charles G

2012-01-01

Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy.

Left main coronary artery disease: pathophysiology, diagnosis, and treatment.

PubMed

Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W

2018-06-01

The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.

Prognostic value of exercise echocardiography: validation of a new risk index combining echocardiographic, treadmill, and exercise electrocardiographic parameters.

PubMed

Mazur, Wojciech; Rivera, Jose M; Khoury, Alexander F; Basu, Abhijeet G; Perez-Verdia, Alejandro; Marks, Gary F; Chang, Su Min; Olmos, Leopoldo; Quiñones, Miguel A; Zoghbi, William A

2003-04-01

Exercise (Ex) echocardiography has been shown to have significant prognostic power, independent of other known predictors of risk from an Ex stress test. The purpose of this study was to evaluate a risk index, incorporating echocardiographic and conventional Ex variables, for a more comprehensive risk stratification and identification of a very low-risk group. Two consecutive, mutually exclusive populations referred for treadmill Ex echocardiography with the Bruce protocol were investigated: hypothesis-generating (388 patients; 268 males; age 55 +/- 13 years) and hypothesis-testing (105 patients; 61 males age: 54 +/- 14 years).Cardiac events included cardiac death, myocardial infarction, late revascularization (>90 days), hospital admission for unstable angina, and admission for heart failure. Mean follow-up in the hypothesis-generating population was 3.1 years. There were 38 cardiac events. Independent predictors of events by multivariate analysis were: Ex wall motion score index (odds ratio [OR] = 2.77/Unit; P <.001); ischemic S-T depression > or = 1 mm (OR = 2.84; P =.002); and treadmill time (OR = 0.87/min; P =.037). A risk index was generated on the basis of the multivariate Cox regression model as: risk index = 1.02 (Ex wall motion score index) + 1.04 (S-T change) - 0.14 (treadmill time). The validity of this index was tested in the hypothesis-testing population. Event rates at 3 years were lowest (0%) in the lower quartile of risk index (-1.22 to -0.47), highest (29.6%) in the upper quartile (+0.66 to +2.02), and intermediate (19.2% to 15.3%) in the intermediate quartiles. The OR of the risk index for predicting cardiac events was 2.94/Unit ([95% confidence interval: 1.4 to 6.2]; P =.0043). Echocardiographic and Ex parameters are independent powerful predictors of cardiac events after treadmill stress testing. A risk index can be derived with these parameters for a more comprehensive risk stratification with Ex echocardiography.

Health care professionals' attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.

PubMed

Hann, Katie E J; Fraser, Lindsay; Side, Lucy; Gessler, Sue; Waller, Jo; Sanderson, Saskia C; Freeman, Madeleine; Jacobs, Ian; Lanceley, Anne

2017-12-16

Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non-genetic information including epidemiological information is rolled out on a population basis, training will be needed for HCPs in primary care to enable them to provide appropriate support to women at each stage of the process.

Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study

PubMed Central

Lip, Gregory Y H; Hansen, Morten Lock; Hansen, Peter Riis; Tolstrup, Janne Schurmann; Lindhardsen, Jesper; Selmer, Christian; Ahlehoff, Ole; Olsen, Anne-Marie Schjerning; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2011-01-01

Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. Design Registry based cohort study. Setting Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. Main outcome measures Stroke and thromboembolism. Results Of 121 280 patients with non-valvular atrial fibrillation, 73 538 (60.6%) fulfilled the study inclusion criteria. In patients at “low risk” (score=0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS2 and 0.78 (0.58 to 1.04) with CHA2DS2-VASc at one year’s follow-up. In patients at “intermediate risk” (score=1), this rate was 4.75 (4.45 to 5.07) with CHADS2 and 2.01 (1.70 to 2.36) with CHA2DS2-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years’ follow-up were 0.812 (0.796 to 0.827) with CHADS2 and 0.888 (0.875 to 0.900) with CHA2DS2-VASc. Conclusions The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA2DS2-VASc performed better than CHADS2 in predicting patients at high risk, and those categorised as low risk by CHA2DS2-VASc were truly at low risk for thromboembolism. PMID:21282258

Hydra: A web-based system for cardiovascular analysis, diagnosis and treatment.

PubMed

Novo, J; Hermida, A; Ortega, M; Barreira, N; Penedo, M G; López, J E; Calvo, C

2017-02-01

Cardiovascular (CV) risk stratification is a highly complex process involving an extensive set of clinical trials to support the clinical decision-making process. There are many clinical conditions (e.g. diabetes, obesity, stress, etc.) that can lead to the early diagnosis or establishment of cardiovascular disease. In order to determine all these clinical conditions, a complete set of clinical patient analyses is typically performed, including a physical examination, blood analysis, electrocardiogram, blood pressure (BP) analysis, etc. This article presents a web-based system, called Hydra, which integrates a full and detailed set of services and functionalities for clinical decision support in order to help and improve the work of clinicians in cardiovascular patient diagnosis, risk assessment, treatment and monitoring over time. Hydra integrates a number of different services: a service for inputting all the information gathered by specialists (physical examination, habits, BP, blood analysis, electrocardiogram, etc.); a tool to automatically determine the CV risk stratification, including well-known standard risk stratification tables; and, finally, various tools to incorporate, analyze and graphically present the records of the ambulatory BP monitoring that provides BP analysis over a given period of time (24 or 48 hours). In addition, the platform presents a set of reports derived from all the information gathered from the patient in order to support physicians in their clinical decisions. Hydra was tested and validated in a real domain. In particular, internal medicine specialists at the Hypertension Unit of the Santiago de Compostela University Hospital (CHUS) validated the platform and used it in different clinical studies to demonstrate its utility. It was observed that the platform increased productivity and accuracy in the assessment of patient data yielding a cost reduction in clinical practice. This paper proposes a complete platform that includes different services for cardiovascular clinical decision support. It was also run as a web-based application to facilitate its use by clinicians, who can access the platform from any remote computer with Internet access. Hydra also includes different automated methods to facilitate the physicians' work and avoid potential errors in the analysis of patient data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation.

PubMed

Kato, Tomoko S; Stevens, Gerin R; Jiang, Jeffrey; Schulze, P Christian; Gukasyan, Natalie; Lippel, Matthew; Levin, Alison; Homma, Shunichi; Mancini, Donna; Farr, Maryjane

2013-03-01

Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)<14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS <4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors. We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation. Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI<5gm-m(2)/beat (OR 6.70, p < 0.01), PCWP>20 mm Hg (OR 5.48, p < 0.01), MELD-A>14 (OR 3.72, p< 0.01) and peak VO(2)<14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A>14 and peak VO(2)<14-1 point each; and PCWP>20 and RVSWI<5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events. Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

External Validation of a risk stratification model to assist shared decision making for patients starting renal replacement therapy.

PubMed

Peeters, Patrick; Van Biesen, Wim; Veys, Nic; Lemahieu, Wim; De Moor, Bart; De Meester, Johan

2016-04-07

Shared decision making is nowadays acknowledged as an essential step when deciding on starting renal replacement therapy. Valid risk stratification of prognosis is, besides discussing quality of life, crucial in this regard. We intended to validate a recently published risk stratification model in a large cohort of incident patients starting renal replacement therapy in Flanders. During 3 years (2001-2003), the data set collected for the Nederlandstalige Belgische Vereniging voor Nefrologie (NBVN) registry was expanded with parameters of comorbidity. For all incident patients, the abbreviated REIN score(aREIN), being the REIN score without the parameter "mobility", was calculated, and prognostication of mortality at 3, 6 and 12 month after start of renal replacement therapy (RRT) was evaluated. Three thousand four hundred seventy-two patients started RRT in Flanders during the observation period (mean age 67.6 ± 14.3, 56.7 % men, 33.6 % diabetes). The mean aREIN score was 4.1 ± 2.8, and 56.8, 23.1, 12.6 and 7.4 % of patients had a score of ≤4, 5-6, 7-8 or ≥9 respectively. Mortality at 3, 6 and 12 months was 8.6, 14.1 and 19.6 % in the overall and 13.2, 21.5 and 31.9 % in the group with age >75 respectively. In RoC analysis, the aREIN score had an AUC of 0.74 for prediction of survival at 3, 6 and 12 months. There was an incremental increase in mortality with the aREIN score from 5.6 to 45.8 % mortality at 6 months for those with a score ≤4 or ≥9 respectively. The aREIN score is a useful tool to predict short term prognosis of patients starting renal replacement therapy as based on comorbidity and age, and delivers meaningful discrimination between low and high risk populations. As such, it can be a useful instrument to be incorporated in shared decision making on whether or not start of dialysis is worthwhile.

Gastrointestinal Bleeding.

PubMed

Nable, Jose V; Graham, Autumn C

2016-05-01

Acute gastrointestinal bleeding is a commonly encountered chief complaint with a high morbidity and mortality. The emergency physician is challenged with prompt diagnosis, accurate risk assessment, and appropriate resuscitation of patients with gastrointestinal bleeding. Goals of care aim to prevent end-organ injury, manage comorbid illnesses, identify the source of bleeding, stop continued bleeding, support oxygen carrying capacity, and prevent rebleeding. This article reviews current strategies for risk stratification, diagnostic modalities, localization of bleeding, transfusion strategies, adjunct therapies, and reversal of anticoagulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Mental health in primary care: an evaluation using the Item Response Theory

PubMed Central

da Rocha, Hugo André; dos Santos, Alaneir de Fátima; Reis, Ilka Afonso; Santos, Marcos Antônio da Cunha; Cherchiglia, Mariângela Leal

2018-01-01

ABSTRACT OBJECTIVE To determine the items of the Brazilian National Program for Improving Access and Quality of Primary Care that better evaluate the capacity to provide mental health care. METHODS This is a cross-sectional study carried out using the Graded Response Model of the Item Response Theory using secondary data from the second cycle of the National Program for Improving Access and Quality of Primary Care, which evaluates 30,523 primary care teams in the period from 2013 to 2014 in Brazil. The internal consistency, correlation between items, and correlation between items and the total score were tested using the Cronbach’s alpha, Spearman’s correlation, and point biserial coefficients, respectively. The assumptions of unidimensionality and local independence of the items were tested. Word clouds were used as one way to present the results. RESULTS The items with the greatest ability to discriminate were scheduling of the agenda according to risk stratification, keeping of records of the most serious cases of users in psychological distress, and provision of group care. The items that required a higher level of mental health care in the parameter of location were the provision of any type of group care and the provision of educational and mental health promotion activities. Total Cronbach’s alpha coefficient was 0.87. The items that obtained the highest correlation with total score were the recording of the most serious cases of users in psychological distress and scheduling of the agenda according to risk stratification. The final scores obtained oscillated between -2.07 (minimum) and 1.95 (maximum). CONCLUSIONS There are important aspects in the discrimination of the capacity to provide mental health care by primary health care teams: risk stratification for care management, follow-up of the most serious cases, group care, and preventive and health promotion actions. PMID:29489992

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PubMed

Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J

2017-10-01

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.

A Personalized Risk Stratification Platform for Population Lifetime Healthcare.

PubMed

Daowd, Ali; Abidi, Samina Raza; Abusharekh, Ashraf; Abidi, Syed Sibte Raza

2018-01-01

Chronic diseases are the leading cause of death worldwide. It is well understood that if modifiable risk factors are targeted, most chronic diseases can be prevented. Lifetime health is an emerging health paradigm that aims to assist individuals to achieve desired health targets, and avoid harmful lifecycle choices to mitigate the risk of chronic diseases. Early risk identification is central to lifetime health. In this paper, we present a digital health-based platform (PRISM) that leverages artificial intelligence, data visualization and mobile health technologies to empower citizens to self-assess, self-monitor and self-manage their overall risk of major chronic diseases and pursue personalized chronic disease prevention programs. PRISM offers risk assessment tools for 5 chronic conditions, 2 psychiatric disorders and 8 different cancers.

Continuous opioid treatment for chronic noncancer pain: a time for moderation in prescribing.

PubMed

Colameco, Stephen; Coren, Joshua S; Ciervo, Carman A

2009-07-01

Physicians have embraced the concept of long-term opioid treatment for chronic noncancer pain (CNCP), as evidenced by increased prescribing. Many patients have benefited from more liberal opioid prescribing, but many have not, and prescription opioid abuse has risen significantly coincident with increased prescribing. Because of the potentially serious adverse effects of opioids, physicians must balance potential benefits against risks, especially in individuals at risk for opioid misuse, abuse, or dependence. This article reviews long-term, continuous opioid treatment of CNCP, current treatment guidelines, addiction risk stratification, opioid-induced hyperalgesia, and endocrine dysfunction.

Natriuretic Peptide and High-Sensitivity Troponin for Cardiovascular Risk Prediction in Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Gori, Mauro; Gupta, Deepak K.; Claggett, Brian; Selvin, Elizabeth; Folsom, Aaron R.; Matsushita, Kunihiro; Bello, Natalie A.; Cheng, Susan; Shah, Amil; Skali, Hicham; Vardeny, Orly; Ni, Hanyu; Ballantyne, Christie M.; Astor, Brad C.; Klein, Barbara E.; Aguilar, David

2016-01-01

OBJECTIVE Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes. RESEARCH DESIGN AND METHODS Among 8,402 participants without prevalent CVD at visit 4 (1996–1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive). RESULTS Over a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57–2.46]) and NTproBNP >125 pg/mL (1.61 [1.29–1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07–0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95–1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59–2.50] and 2.80 [2.34–3.35], respectively). CONCLUSIONS Abnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk. PMID:26740635

The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report

PubMed Central

Cohn, Susan L.; Pearson, Andrew D.J.; London, Wendy B.; Monclair, Tom; Ambros, Peter F.; Brodeur, Garrett M.; Faldum, Andreas; Hero, Barbara; Iehara, Tomoko; Machin, David; Mosseri, Veronique; Simon, Thorsten; Garaventa, Alberto; Castel, Victoria; Matthay, Katherine K.

2009-01-01

Purpose Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Patients and Methods The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Results Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to ≤ 85%, ≥ 50% to ≤ 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. Conclusion By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies. PMID:19047291

The effect of cost construction based on either DRG or ICD-9 codes or risk group stratification on the resulting cost-effectiveness ratios.

PubMed

Chumney, Elinor C G; Biddle, Andrea K; Simpson, Kit N; Weinberger, Morris; Magruder, Kathryn M; Zelman, William N

2004-01-01

As cost-effectiveness analyses (CEAs) are increasingly used to inform policy decisions, there is a need for more information on how different cost determination methods affect cost estimates and the degree to which the resulting cost-effectiveness ratios (CERs) may be affected. The lack of specificity of diagnosis-related groups (DRGs) could mean that they are ill-suited for costing applications in CEAs. Yet, the implications of using International Classification of Diseases-9th edition (ICD-9) codes or a form of disease-specific risk group stratification instead of DRGs has yet to be clearly documented. To demonstrate the implications of different disease coding mechanisms on costs and the magnitude of error that could be introduced in head-to-head comparisons of resulting CERs. We based our analyses on a previously published Markov model for HIV/AIDS therapies. We used the Healthcare Cost and Utilisation Project Nationwide Inpatient Sample (HCUP-NIS) data release 6, which contains all-payer data on hospital inpatient stays from selected states. We added costs for the mean number of hospitalisations, derived from analyses based on either DRG or ICD-9 codes or risk group stratification cost weights, to the standard outpatient and prescription drug costs to yield an estimate of total charges for each AIDS-defining illness (ADI). Finally, we estimated the Markov model three times with the appropriate ADI cost weights to obtain CERs specific to the use of either DRG or ICD-9 codes or risk group. Contrary to expectations, we found that the choice of coding/grouping assumptions that are disease-specific by either DRG codes, ICD-9 codes or risk group resulted in very similar CER estimates for highly active antiretroviral therapy. The large variations in the specific ADI cost weights across the three different coding approaches was especially interesting. However, because no one approach produced consistently higher estimates than the others, the Markov model's weighted cost per event and resulting CERs were remarkably close in value to one another. Although DRG codes are based on broader categories and contain less information than ICD-9 codes, in practice the choice of whether to use DRGs or ICD-9 codes may have little effect on the CEA results in heterogeneous conditions such as HIV/AIDS.

Risk stratification and rapid geriatric screening in an emergency department - a quasi-randomised controlled trial.

PubMed

Foo, Chik Loon; Siu, Vivan Wing Yin; Ang, Hou; Phuah, Madeline Wei Ling; Ooi, Chee Kheong

2014-08-30

To determine if risk stratification followed by rapid geriatric screening in an emergency department (ED) reduced functional decline, ED reattendance and hospitalisation. This was a quasi-randomised controlled trial. Patients were randomised by the last digit of their national registration identity card (NRIC). Odd number controls received standard ED care; even number patients received geriatric screening, followed by intervention and/or onward referrals. Patients were followed up for 12 months. There were 500 and 280 patients in the control and intervention groups. The intervention group had higher Triage Risk Screening Tool (TRST) scores (34.3% vs 25.4% TRST ≥3, p = 0.01) and lower baseline Instrumental Activity of Daily Living (IADL) scores (22.84 vs 24.18, p < 0.01). 82.9% of the intervention group had unmet needs; 62.1% accepted our interventions. Common positive findings were fall risk (65.0%), vision (61.4%), and footwear (58.2%). 28.2% were referred to a geriatric clinic and 11.8% were admitted. 425 (85.0%) controls and 234 (83.6%) in the intervention group completed their follow-up. After adjusting for TRST and baseline IADL, the intervention group had significant preservation in function (Basic ADL -0.99 vs -0.24, p < 0.01; IADL -2.57 vs +0.45, p < 0.01) at 12 months. The reduction in ED reattendance (OR0.75, CI 0.55-1.03, p = 0.07) and hospitalization (OR0.77, CI0.57-1.04, p = 0.09) were not significant, however the real difference would have been wider as 21.2% of the control group received geriatric screening at the request of the ED doctor. A major limitation was that a large proportion of patients who were randomized to the intervention group either refused (18.8%) or left the ED before being approached (32.0%). These two groups were not followed up, and hence were excluded in our analysis. Risk stratification and focused geriatric screening in ED resulted in significant preservation of patients' function at 12 months. National Healthcare Group (NHG) Domain Specific Review Board (DSRB) C/09/023. Registered 5th March 2009.

Risk stratification and rapid geriatric screening in an emergency department – a quasi-randomised controlled trial

PubMed Central

2014-01-01

Background To determine if risk stratification followed by rapid geriatric screening in an emergency department (ED) reduced functional decline, ED reattendance and hospitalisation. Method This was a quasi-randomised controlled trial. Patients were randomised by the last digit of their national registration identity card (NRIC). Odd number controls received standard ED care; even number patients received geriatric screening, followed by intervention and/or onward referrals. Patients were followed up for 12 months. Results There were 500 and 280 patients in the control and intervention groups. The intervention group had higher Triage Risk Screening Tool (TRST) scores (34.3% vs 25.4% TRST ≥3, p = 0.01) and lower baseline Instrumental Activity of Daily Living (IADL) scores (22.84 vs 24.18, p < 0.01). 82.9% of the intervention group had unmet needs; 62.1% accepted our interventions. Common positive findings were fall risk (65.0%), vision (61.4%), and footwear (58.2%). 28.2% were referred to a geriatric clinic and 11.8% were admitted. 425 (85.0%) controls and 234 (83.6%) in the intervention group completed their follow-up. After adjusting for TRST and baseline IADL, the intervention group had significant preservation in function (Basic ADL -0.99 vs -0.24, p < 0.01; IADL -2.57 vs +0.45, p < 0.01) at 12 months. The reduction in ED reattendance (OR0.75, CI 0.55-1.03, p = 0.07) and hospitalization (OR0.77, CI0.57-1.04, p = 0.09) were not significant, however the real difference would have been wider as 21.2% of the control group received geriatric screening at the request of the ED doctor. A major limitation was that a large proportion of patients who were randomized to the intervention group either refused (18.8%) or left the ED before being approached (32.0%). These two groups were not followed up, and hence were excluded in our analysis. Conclusion Risk stratification and focused geriatric screening in ED resulted in significant preservation of patients’ function at 12 months. Trial registration National Healthcare Group (NHG) Domain Specific Review Board (DSRB) C/09/023. Registered 5th March 2009. PMID:25178312

Detection and risk stratification of women at high risk of preterm birth in rural communities near Nagpur, India.

PubMed

Patel, Archana; Prakash, Amber Abhijeet; Pusdekar, Yamini V; Kulkarni, Hemant; Hibberd, Patricia

2017-09-19

Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB. Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community health workers actively monitored these women from 24 to 36 weeks of gestation for these signs or symptoms. If they were present (HRPB positive) the identified women were brought to government health facilities for assessment and management. HRPB positive could also be determined by the provider if the woman presented directly to the facility. Risk stratification was based on the number of signs or symptoms present. The outcome of preterm birth was based on the clinical assessment of gestational age < 37 weeks at delivery or a birth weight of <2000 g. Between July 1, 2012 and 30 November, 2013, 686 of 7050 (9.7%) pregnant women studied, delivered preterm. 732 (10.4%) women were HRPB positive, of whom 333 (45.5%) delivered preterm. Of the remaining 6318(89.6%) HRPB negative women 353 (5.6%) delivered preterm. The likelihood ratio (LR) of a preterm birth in the HRPB positives was 8.14 (95% confidence interval 7.16-9.26). The LR of a preterm birth increased in women who had more signs or symptoms of HRBP (p < 0.00001). More signs or symptoms of HRPB were also associated with a shorter time to delivery, lower birth weight and higher rates of stillbirths, neonatal deaths and postnatal complications. Addition of risk stratification improved the prediction of preterm delivery (Integrated Discrimination Improvement 17% (95% CI 15-19%)). The package for detection of signs and symptoms of HRPB is feasible, promising and likely to improve management of preterm labor. NCT01073475 on February 21, 2010 and NCT01084096 on March 9, 2010.

Changes in oxidative patterns during dormancy break by warm and cold stratification in seeds of an edible fruit tree.

PubMed

Shalimu, Dilinuer; Sun, Jia; Baskin, Carol C; Baskin, Jerry M; Sun, Liwei; Liu, Yujun

2016-01-01

The transition from seed dormancy to germination is triggered by environmental factors, and in pomegranate (Punica granatum) seeds higher germination percentages are achieved by warm + cold stratification rather than by cold stratification alone. Our objective was to define the pattern of internal oxidative changes in pomegranate seeds as dormancy was being broken by warm + cold stratification and by cold stratification alone. Embryos isolated from seeds after 1-42 days of warm stratification, after 56 days of warm stratification + 7, 28 or 56 days of cold stratification, and after 1-84 days of cold stratification alone, were used in biochemical tests. Hydrogen peroxide (H2O2), nitric oxide (NO), proline, lipid peroxidation, protein carbonylation, and activities of the scavenging enzymes superoxide dismutase (SOD), hydrogen peroxide enzyme and peroxidase in the embryos were assessed by colorimetric methods. Our results indicated that warm + cold stratification had a stronger dormancy-breaking effect than cold stratification (85% versus 50% germination), which may be attributed to a higher yield of H2O2, NO, lipid peroxidation and protein carbonylation in warm + cold stratification. Furthermore, warm + cold stratification-induced H2O2 change led to greater changes (elevation followed by attenuation) in activities of the scavenging enzymes than that induced by cold stratification alone. These results indicated that restriction of the level of reactive oxygen species change within a positive and safe range by such enzymes promoted seed germination. In addition, a relatively strong elevation of proline during warm + cold stratification also contributed to dormancy breakage and subsequent germination. In conclusion, the strong dormancy alleviating effect of warm + cold stratification on pomegranate seeds may be attributed to the corresponding active oxidative change via H2O2, NO, proline, malondialdehyde, protein carbonylation and scavenging enzymes. Published by Oxford University Press on behalf of the Annals of Botany Company.

Changes in oxidative patterns during dormancy break by warm and cold stratification in seeds of an edible fruit tree

PubMed Central

Shalimu, Dilinuer; Sun, Jia; Baskin, Carol C.; Baskin, Jerry M.; Sun, Liwei; Liu, Yujun

2016-01-01

The transition from seed dormancy to germination is triggered by environmental factors, and in pomegranate (Punica granatum) seeds higher germination percentages are achieved by warm + cold stratification rather than by cold stratification alone. Our objective was to define the pattern of internal oxidative changes in pomegranate seeds as dormancy was being broken by warm + cold stratification and by cold stratification alone. Embryos isolated from seeds after 1–42 days of warm stratification, after 56 days of warm stratification + 7, 28 or 56 days of cold stratification, and after 1–84 days of cold stratification alone, were used in biochemical tests. Hydrogen peroxide (H2O2), nitric oxide (NO), proline, lipid peroxidation, protein carbonylation, and activities of the scavenging enzymes superoxide dismutase (SOD), hydrogen peroxide enzyme and peroxidase in the embryos were assessed by colorimetric methods. Our results indicated that warm + cold stratification had a stronger dormancy-breaking effect than cold stratification (85% versus 50% germination), which may be attributed to a higher yield of H2O2, NO, lipid peroxidation and protein carbonylation in warm + cold stratification. Furthermore, warm + cold stratification-induced H2O2 change led to greater changes (elevation followed by attenuation) in activities of the scavenging enzymes than that induced by cold stratification alone. These results indicated that restriction of the level of reactive oxygen species change within a positive and safe range by such enzymes promoted seed germination. In addition, a relatively strong elevation of proline during warm + cold stratification also contributed to dormancy breakage and subsequent germination. In conclusion, the strong dormancy alleviating effect of warm + cold stratification on pomegranate seeds may be attributed to the corresponding active oxidative change via H2O2, NO, proline, malondialdehyde, protein carbonylation and scavenging enzymes. PMID:27154624

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

PubMed

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

Salinity stratification of the Mediterranean Sea during the Messinian crisis: A first model analysis

NASA Astrophysics Data System (ADS)

Simon, Dirk; Meijer, Paul Th.

2017-12-01

In the late Miocene, a thick and complex sequence of evaporites was deposited in the Mediterranean Sea during an interruption of normal marine sedimentation known as the Messinian Salinity Crisis. Because the related deposits are mostly hidden from scrutiny in the deep basin, correlation between onshore and offshore sediments is difficult, hampering the development of a comprehensive stratigraphic model. Since the various facies correspond to different salinities of the basin waters, it would help to have physics-based understanding of the spatial distribution of salt concentration. Here, we focus on modelling salinity as a function of depth, i.e., on the stratification of the water column. A box model is set up that includes a simple representation of a haline overturning circulation and of mixing. It is forced by Atlantic exchange and evaporative loss and is used to systematically explore the degree of stratification that results under a wide range of combinations of parameter values. The model demonstrates counterintuitive behaviour close to the saturation of halite. For parameter values that may well be realistic for the Messinian, we show that a significantly stratified Mediterranean water column can be established. In this case, Atlantic connectivity is limited but may be closer to modern magnitudes than previously thought. In addition, a slowing of Mediterranean overturning and a larger deep-water formation region (both in comparison to the present day) are required. Under these conditions, we would expect a longer duration of halite deposition than currently considered in the MSC stratigraphic consensus model.

Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-analysis.

PubMed

Carpenter, Christopher R; Shelton, Erica; Fowler, Susan; Suffoletto, Brian; Platts-Mills, Timothy F; Rothman, Richard E; Hogan, Teresita M

2015-01-01

A significant proportion of geriatric patients experience suboptimal outcomes following episodes of emergency department (ED) care. Risk stratification screening instruments exist to distinguish vulnerable subsets, but their prognostic accuracy varies. This systematic review quantifies the prognostic accuracy of individual risk factors and ED-validated screening instruments to distinguish patients more or less likely to experience short-term adverse outcomes like unanticipated ED returns, hospital readmissions, functional decline, or death. A medical librarian and two emergency physicians conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and ClinicalTrials.gov using numerous combinations of search terms, including emergency medical services, risk stratification, geriatric, and multiple related MeSH terms in hundreds of combinations. Two authors hand-searched relevant specialty society research abstracts. Two physicians independently reviewed all abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies instrument to assess individual study quality. When two or more qualitatively similar studies were identified, meta-analysis was conducted using Meta-DiSc software. Primary outcomes were sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment threshold analysis was constructed based on the meta-analytic summary estimate of prognostic accuracy for one outcome. A total of 7,940 unique citations were identified yielding 34 studies for inclusion in this systematic review. Studies were significantly heterogeneous in terms of country, outcomes assessed, and the timing of post-ED outcome assessments. All studies occurred in ED settings and none used published clinical decision rule derivation methodology. Individual risk factors assessed included dementia, delirium, age, dependency, malnutrition, pressure sore risk, and self-rated health. None of these risk factors significantly increased the risk of adverse outcome (LR+ range = 0.78 to 2.84). The absence of dependency reduces the risk of 1-year mortality (LR- = 0.27) and nursing home placement (LR- = 0.27). Five constructs of frailty were evaluated, but none increased or decreased the risk of adverse outcome. Three instruments were evaluated in the meta-analysis: Identification of Seniors at Risk, Triage Risk Screening Tool, and Variables Indicative of Placement Risk. None of these instruments significantly increased (LR+ range for various outcomes = 0.98 to 1.40) or decreased (LR- range = 0.53 to 1.11) the risk of adverse outcomes. The test threshold for 3-month functional decline based on the most accurate instrument was 42%, and the treatment threshold was 61%. Risk stratification of geriatric adults following ED care is limited by the lack of pragmatic, accurate, and reliable instruments. Although absence of dependency reduces the risk of 1-year mortality, no individual risk factor, frailty construct, or risk assessment instrument accurately predicts risk of adverse outcomes in older ED patients. Existing instruments designed to risk stratify older ED patients do not accurately distinguish high- or low-risk subsets. Clinicians, educators, and policy-makers should not use these instruments as valid predictors of post-ED adverse outcomes. Future research to derive and validate feasible ED instruments to distinguish vulnerable elders should employ published decision instrument methods and examine the contributions of alternative variables, such as health literacy and dementia, which often remain clinically occult. © 2014 by the Society for Academic Emergency Medicine.

Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

PubMed Central

Giessen, C; Fischer von Weikersthal, L; Laubender, R P; Stintzing, S; Modest, D P; Schalhorn, A; Schulz, C; Heinemann, V

2013-01-01

Background: Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients. Patients and Methods: A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients. Results: Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome. Conclusion: Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD. PMID:23963138

Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PubMed

Hemmati, Philipp G; Vuong, Lam G; Terwey, Theis H; Jehn, Christian F; le Coutre, Philipp; Penack, Olaf; Na, Il-Kang; Dörken, Bernd; Arnold, Renate

2017-02-01

The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microvolt T-Wave Alternans

PubMed Central

Verrier, Richard L.; Klingenheben, Thomas; Malik, Marek; El-Sherif, Nabil; Exner, Derek V.; Hohnloser, Stefan H.; Ikeda, Takanori; Martínez, Juan Pablo; Narayan, Sanjiv M.; Nieminen, Tuomo; Rosenbaum, David S.

2014-01-01

This consensus guideline was prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and is cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society. It discusses the electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the morphology and amplitude of the ST- segment or T-wave). This statement focuses on its physiological basis and measurement technologies and its clinical utility in stratifying risk for life-threatening ventricular arrhythmias. Signal processing techniques including the frequency-domain Spectral Method and the time-domain Modified Moving Average method have demonstrated the utility of TWA in arrhythmia risk stratification in prospective studies in >12,000 patients. The majority of exercise-based studies using both methods have reported high relative risks for cardiovascular mortality and for sudden cardiac death in patients with preserved as well as depressed left ventricular ejection fraction. Studies with ambulatory electrocardiogram-based TWA analysis with Modified Moving Average method have yielded significant predictive capacity. However, negative studies with the Spectral Method have also appeared, including 2 interventional studies in patients with implantable defibrillators. Meta-analyses have been performed to gain insights into this issue. Frontiers of TWA research include use in arrhythmia risk stratification of individuals with preserved ejection fraction, improvements in predictivity with quantitative analysis, and utility in guiding medical as well as device-based therapy. Overall, although TWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy. PMID:21920259

Best practice in the use of natalizumab in multiple sclerosis

PubMed Central

2013-01-01

Natalizumab is approved for the treatment of patients with relapsing–remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use. PMID:23483450

Emergency department management of syncope: need for standardization and improved risk stratification.

PubMed

Thiruganasambandamoorthy, Venkatesh; Taljaard, Monica; Stiell, Ian G; Sivilotti, Marco L A; Murray, Heather; Vaidyanathan, Aparna; Rowe, Brian H; Calder, Lisa A; Lang, Eddy; McRae, Andrew; Sheldon, Robert; Wells, George A

2015-08-01

Variations in emergency department (ED) syncope management have not been well studied. The goals of this study were to assess variations in management, and emergency physicians' risk perception and disposition decision making. We conducted a prospective study of adults with syncope in six EDs in four cities over 32 months. We collected patient characteristics, ED management, disposition, physicians' prediction probabilities at index presentation and followed patients for 30 days for serious outcomes: death, myocardial infarction (MI), arrhythmia, structural heart disease, pulmonary embolism, significant hemorrhage, or procedural interventions. We used descriptive statistics, ROC curves, and regression analyses. We enrolled 3662 patients: mean age 54.3 years, and 12.9 % were hospitalized. Follow-up data were available for 3365 patients (91.9 %) and 345 patients (10.3 %) suffered serious outcomes: 120 (3.6 %) after ED disposition including 48 patients outside the hospital. After accounting for differences in patient case mix, the rates of ED investigations and disposition were significantly different (p < 0.0001) across the four study cities; as were the rates of 30-day serious outcomes (p < 0.0001) and serious outcomes after ED disposition (p = 0.0227). There was poor agreement between physician risk perception and both observed event rates and referral patterns (p < 0.0001). Only 76.7 % (95 % CI 68.1-83.6) of patients with serious outcomes were appropriately referred. There are large and unexplained differences in ED syncope management. Moreover, there is poor agreement between physician risk perception, disposition decision making, and serious outcomes after ED disposition. A valid risk-stratification tool might help standardize ED management and improve disposition decision making.

Acute colonic diverticulitis: modern understanding of pathomechanisms, risk factors, disease burden and severity.

PubMed

Søreide, Kjetil; Boermeester, Marja A; Humes, David J; Velmahos, George C

2016-12-01

Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed. Literature search of risk factors, pathophysiology, epidemiology and disease burden/severity reported over the last decade. Acute diverticulitis is a common disease and has a high disease burden. Incidence of hospital admissions is reported around 71 per 100,000 population, with reported increase in several subpopulations over the last decades. The incidence is likely to increase further with the aging populations. Risk factors for left-sided acute diverticulitis include dietary, anthropometric and lifestyle factors. Disease mechanisms are still poorly understood, but a distinction between inflammation and infection is emerging. The integrative and complex role of the gut microbiota has become an interesting factor for both understanding the disease as well as a potential target for intervention using probiotics. Mild, self-limiting events are increasingly reported from studies of successful non-antibiotic management in a considerable number of cases. Risk markers of progression to or presence of severe, complicated disease are needed for better disease stratification. Current risk stratification by clinical, imaging or endoscopic means is imperfect and needs validation. Long-term results from minimal-invasive and comparative surgical trials may better help inform clinicians and patients. Over- and under-treatment as well as over- and under-diagnosis of severity is likely to continue in clinical practice due to lack of reliable, robust and universal severity and classification systems. Better understanding of pathophysiology is needed.

Risk Stratification of Stress Fractures and Prediction of Return-to-Duty

DTIC Science & Technology

2016-12-01

African-American) and 20 male; [month 7-28] Done 4) Perform standard whole bone finite element analysis [month 7-28]. Done 5) Perform data cleaning and...NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kristin Popp M Mary Betty Diamond 5d. PROJECT NUMBER Mary Bouxsein 5e. TASK NUMBER E-Mail: kpopp

A case of long QT syndrome: challenges on a bumpy road.

PubMed

Magnusson, Peter; Gustafsson, Per-Erik

2017-06-01

Beta-agonist treatment during pregnancy may unmask the diagnosis of long QT syndrome. The QT prolongation can result in functional AV block. A history of seizure and/or sudden death in a family member should raise suspicion of ventricular tachycardia. More than one mutation may coexist. Refusal of beta-blocker therapy complicates risk stratification.

Prostate cancer mortality risk in relation to working underground in the Wismut cohort study of German uranium miners, 1970-2003.

PubMed

Walsh, Linda; Dufey, Florian; Tschense, Annemarie; Schnelzer, Maria; Sogl, Marion; Kreuzer, Michaela

2012-01-01

A recent study and comprehensive literature review has indicated that mining could be protective against prostate cancer. This indication has been explored further here by analysing prostate cancer mortality in the German 'Wismut' uranium miner cohort, which has detailed information on the number of days worked underground. An historical cohort study of 58 987 male mine workers with retrospective follow-up before 1999 and prospective follow-up since 1999. Uranium mine workers employed during the period 1970-1990 in the regions of Saxony and Thuringia, Germany, contributing 1.42 million person-years of follow-up ending in 2003. Simple standardised mortality ratio (SMR) analyses were applied to assess differences between the national and cohort prostate cancer mortality rates and complemented by refined analyses done entirely within the cohort. The internal comparisons applied Poisson regression excess relative prostate cancer mortality risk model with background stratification by age and calendar year and a whole range of possible explanatory covariables that included days worked underground and years worked at high physical activity with γ radiation treated as a confounder. The analysis is based on miner data for 263 prostate cancer deaths. The overall SMR was 0.85 (95% CI 0.75 to 0.95). A linear excess relative risk model with the number of years worked at high physical activity and the number of days worked underground as explanatory covariables provided a statistically significant fit when compared with the background model (p=0.039). Results (with 95% CIs) for the excess relative risk per day worked underground indicated a statistically significant (p=0.0096) small protective effect of -5.59 (-9.81 to -1.36) ×10(-5). Evidence is provided from the German Wismut cohort in support of a protective effect from working underground on prostate cancer mortality risk.

CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.

PubMed

Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B

2016-01-01

Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.

Clinical guidelines and practice: in search of the truth.

PubMed

Kereiakes, Dean J; Antman, Elliott M

2006-09-19

Data from randomized clinical trials, non-randomized studies, and registries, as well as expert panel consensus are appropriately weighted and woven into the context of clinical practice guidelines. Recent guidelines for the care of patients with ischemic heart disease have emphasized both risk stratification and early coronary angiography with revascularization of patients with high-risk indicators. Advances in our understanding of the pathogenesis of acute coronary syndromes and the dynamics of therapeutic innovation (improvement in catheter-based technologies and adjunctive pharmacotherapy) mandate the timely update and revision of practice guidelines. We believe that the weight of evidence remains clearly in support of an early invasive treatment strategy based on risk stratification. Arguments regarding treatment strategy (invasive vs. conservative) are misguided, and greater focus should be placed on improving the treatment-risk paradox demonstrated in clinical practice as well as on strategies to enhance current guideline compliance and utilization. Interest exists in establishing regional centers of excellence for care of patients with acute ischemic heart disease, analogous to the regionalized approach already established for patients with trauma or stroke. This approach is supported by data that demonstrate an inverse relationship between both institutional and operator procedural volumes and mortality, as well as by existing constraints in resources such as specialized nurses and subspecialty-trained physicians. It is appropriate at this time to briefly review specific aspects of the American College of Cardiology/American Heart Association practice guidelines and the current process of care for acute ischemic heart disease.

Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

PubMed

Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

2017-09-06

The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P < 0.001). The SMFS nomogram had significantly higher c-index values in the training and validation sets than the TNM staging system (P < 0.001 and P = 0.005, respectively). Three proposed risk stratification groups were created using the nomograms, and enabled significant discrimination of SMFS for each risk group. The prognostic nomograms established in this study enable accurate stratification of distinct risk groups for skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

Role of central obesity in risk stratification after an acute coronary event: does central obesity add prognostic value to the Global Registry of Acute Coronary Events (GRACE) risk score in patients with acute coronary syndrome?

PubMed

Martins, Albino; Ribeiro, Sílvia; Gonçalves, Pierre; Correia, Adelino

2013-10-01

Accurate risk stratification is an important step in the initial management of acute coronary syndrome (ACS), and current guidelines recommend the use of risk scores, such as the Global Registry of Acute Coronary Events risk score (GRACE RS). Recent studies have suggested that abdominal obesity is associated with cardiovascular events in patients with ACS. However, little is known about the additional value of abdominal obesity beyond risk scores. The aim of our study was thus to assess whether waist circumference, a surrogate of abdominal adiposity, adds prognostic information to the GRACE RS. This was a retrospective cohort study of ACS patients admitted consecutively to a cardiac care unit between June 2009 and July 2010. The composite of all-cause mortality or myocardial reinfarction within six months of index hospitalization was used as the endpoint for the analysis. A total of 285 patients were studied, 96.1% admitted for myocardial infarction (with or without ST elevation) and 3.9% for unstable angina. At the end of the follow-up period, 10 patients had died and the composite endpoint had been reached in 27 patients (9.5%). More than 70% of the study population were obese or overweight, and abdominal obesity was present in 44.6%. The GRACE RS showed poor predictive accuracy (area under the curve 0.60), and most of the GRACE variables did not reach statistical significance in multivariate analysis. The addition of waist circumference to the GRACE RS did not improve its discriminatory performance. Abdominal obesity does not add prognostic information to the GRACE RS to predict six-month mortality or myocardial reinfarction.

Current treatment trends and the need for better predictive tools in the management of ductal carcinoma in situ of the breast.

PubMed

Martínez-Pérez, Carlos; Turnbull, Arran K; Ekatah, Gregory E; Arthur, Laura M; Sims, Andrew H; Thomas, Jeremy S; Dixon, J Michael

2017-04-01

Ductal carcinoma in situ (DCIS) of the breast represents a group of heterogeneous non-invasive lesions the incidence of which has risen dramatically since the advent of mammography screening. In this review we summarise current treatment trends and up-to-date results from clinical trials studying surgery and adjuvant therapy alternatives, including the recent consensus on excision margin width and its role in decision-making for post-excision radiotherapy. The main challenge in the clinical management of DCIS continues to be the tailoring of treatment to individual risk, in order to avoid the over-treatment of low-risk lesions or under-treatment of DCIS with higher risk of recurring or progressing into invasion. While studies estimate that only about 40% of DCIS would become invasive if untreated, heterogeneity and complex natural history have prevented adequate identification of these higher-risk lesions. Here we discuss attempts to develop prognostic tools for the risk stratification of DCIS lesions and their limitations. Early results of a UK-wide audit of DCIS management (the Sloane Project) have also demonstrated a lack of consistency in treatment. In this review we offer up-to-date perspectives on current treatment and prediction of DCIS, highlighting the pressing clinical need for better prognostic indices. Tools integrating both clinical and histopathological factors together with molecular biomarkers may hold potential for adequate stratification of DCIS according to risk. This could help develop standardised practices for optimal management of patients with DCIS, improving clinical outcomes while providing only the amount of therapy required for each individual patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applicability of an established management algorithm for colon injuries following blunt trauma.

PubMed

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Fabian, Timothy C; Croce, Martin A

2013-02-01

Operative management at our institution for all colon injuries have followed a defined algorithm (ALG) based on risk factors originally identified for penetrating injuries. The purpose of this study was to evaluate the applicability of the ALG to blunt colon injuries. Patients with blunt colon injuries during 13 years were identified. As per the ALG, nondestructive (ND) injuries are treated with primary repair. Patients with destructive wounds (serosal tear of ≥50% colon circumference, mesenteric devascularization, and perforations) and concomitant risk factors (transfusion of >6 U packed red blood cells and/or presence of significant comorbidities) are diverted, while patients with no risk factors undergo resection plus anastomosis (RA). Outcomes included suture line failure (SLF), abscess, and mortality. Stratification analysis was performed to determine additional risk factors in the management of blunt colon injuries. A total 151 patients were identified: 76 with destructive injuries and 75 with ND injuries. Of those with destructive injuries, 44 (59%) underwent RA and 29 (39%) underwent diversion. All ND injuries underwent primary repair. Adherence to the ALG was 95%: three patients with destructive injuries underwent primary repair, and five patients with risk factors underwent RA. There were three SLFs (2%) (one involved deviation from the ALG) and eight abscesses (5%). Colon-related mortality was 2.1%. Stratification analysis based on mesenteric involvement, degree of shock, and need for abbreviated laparotomy failed to identify additional risk factors for SLF following RA for blunt colon injuries. Adherence to an ALG, originally defined for penetrating colon injuries, simplified the management of blunt colon injuries. ND injuries should be primarily repaired. For destructive wounds, management based on a defined ALG achieves an acceptably low morbidity and mortality rate. Prognostic/epidemiologic study, level III; therapeutic study, level IV.

Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

PubMed

Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

2017-07-01

Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy. Copyright© 2017 Ferrata Storti Foundation.

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

External Validation of European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) for Risk Prioritization in an Iranian Population

PubMed Central

Atashi, Alireza; Amini, Shahram; Tashnizi, Mohammad Abbasi; Moeinipour, Ali Asghar; Aazami, Mathias Hossain; Tohidnezhad, Fariba; Ghasemi, Erfan; Eslami, Saeid

2018-01-01

Introduction The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is a prediction model which maps 18 predictors to a 30-day post-operative risk of death concentrating on accurate stratification of candidate patients for cardiac surgery. Objective The objective of this study was to determine the performance of the EuroSCORE II risk-analysis predictions among patients who underwent heart surgeries in one area of Iran. Methods A retrospective cohort study was conducted to collect the required variables for all consecutive patients who underwent heart surgeries at Emam Reza hospital, Northeast Iran between 2014 and 2015. Univariate and multivariate analysis were performed to identify covariates which significantly contribute to higher EuroSCORE II in our population. External validation was performed by comparing the real and expected mortality using area under the receiver operating characteristic curve (AUC) for discrimination assessment. Also, Brier Score and Hosmer-Lemeshow goodness-of-fit test were used to show the overall performance and calibration level, respectively. Results Two thousand five hundred eight one (59.6% males) were included. The observed mortality rate was 3.3%, but EuroSCORE II had a prediction of 4.7%. Although the overall performance was acceptable (Brier score=0.047), the model showed poor discriminatory power by AUC=0.667 (sensitivity=61.90, and specificity=66.24) and calibration (Hosmer-Lemeshow test, P<0.01). Conclusion Our study showed that the EuroSCORE II discrimination power is less than optimal for outcome prediction and less accurate for resource allocation programs. It highlights the need for recalibration of this risk stratification tool aiming to improve post cardiac surgery outcome predictions in Iran. PMID:29617500

Derivation and Validation of a Renal Risk Score for People With Type 2 Diabetes

PubMed Central

Elley, C. Raina; Robinson, Tom; Moyes, Simon A.; Kenealy, Tim; Collins, John; Robinson, Elizabeth; Orr-Walker, Brandon; Drury, Paul L.

2013-01-01

OBJECTIVE Diabetes has become the leading cause of end-stage renal disease (ESRD). Renal risk stratification could assist in earlier identification and targeted prevention. This study aimed to derive risk models to predict ESRD events in type 2 diabetes in primary care. RESEARCH DESIGN AND METHODS The nationwide derivation cohort included adults with type 2 diabetes from the New Zealand Diabetes Cohort Study initially assessed during 2000–2006 and followed until December 2010, excluding those with pre-existing ESRD. The outcome was fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death from ESRD). Risk models were developed using Cox proportional hazards models, and their performance was assessed in a separate validation cohort. RESULTS The derivation cohort included 25,736 individuals followed for up to 11 years (180,497 person-years; 86% followed for ≥5 years). At baseline, mean age was 62 years, median diabetes duration 5 years, and median HbA1c 7.2% (55 mmol/mol); 37% had albuminuria; and median estimated glomerular filtration rate (eGFR) was 77 mL/min/1.73 m2. There were 637 ESRD events (2.5%) during follow-up. Models that included sex, ethnicity, age, diabetes duration, albuminuria, serum creatinine, systolic blood pressure, HbA1c, smoking status, and previous cardiovascular disease status performed well with good discrimination and calibration in the derivation cohort and the validation cohort (n = 5,877) (C-statistics 0.89–0.92), improving predictive performance compared with previous models. CONCLUSIONS These 5-year renal risk models performed very well in two large primary care populations with type 2 diabetes. More accurate risk stratification could facilitate earlier intervention than using eGFR and/or albuminuria alone. PMID:23801726

Cardiac troponin I: prothrombotic risk marker in non-valvular atrial fibrillation.

PubMed

Providência, Rui; Paiva, Luís; Faustino, Ana; Botelho, Ana; Trigo, Joana; Casalta-Lopes, João; Nascimento, José; Leitão-Marques, António Manuel

2013-08-10

Evidence of a link between small rises in cardiac troponin I (cTnI) and an increased risk of thromboembolic events (TE) in atrial fibrillation (AF) is currently scarce. We aimed to assess the relation between cTnI and findings of an increased thromboembolic risk in patients with non-valvular AF using transesophageal echocardiography. We have included 245 patients performing transthoracic and transesophageal echocardiogram, alongside with laboratory assessment (including cTnI) in a cross-sectional survey. Changes associated to TE were sought on transesophageal echocardiogram: left atrial or left atrial appendage thrombus, dense spontaneous echocardiographic contrast, low flow velocities in the left atrial appendage and protuberant aortic plaques. Comparisons were performed according to the baseline concentration of cTnI, regarding the prevalence of these changes. We have added cTnI to CHADS2 and CHA2DS2-VASc scores in order to assess its capability to refine risk stratification using transesophageal markers as surrogate endpoints and assessed it by means of ROC-curve analysis and Net Reclassification Improvement (NRI). A direct relation between rising concentrations of cTnI and a higher prevalence of transesophageal echocardiogram changes was found. Furthermore, the addition of cTnI to CHADS2 and CHA2DS2-VASc scores improved their ability to predict changes associated to TE on transesophageal echocardiography both through ROC-curve analysis and NRI. cTnI seems to be associated to thromboembolic risk in patients with AF. The possible role of cTnI in the refinement of risk stratification schemes needs to be tested in further prospective studies using clinical endpoints. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Superior survival of unmanipulated haploidentical hematopoietic stem cell transplantation compared with chemotherapy alone used as post-remission therapy in adults with standard-risk acute lymphoblastic leukemia in first complete remission.

PubMed

Yan, Chen-Hua; Jiang, Qian; Wang, Jing; Xu, Lan-Ping; Liu, Dai-Hong; Jiang, Hao; Chen, Huan; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun

2014-09-01

We wanted to compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with chemotherapy alone in adults with standard-risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1). One hundred thirty-eight consecutive adult patients with standard-risk ALL in CR1 were retrospectively investigated. Of these patients, 59 received chemotherapy alone (group A) and 79 received unmanipulated haploidentical HSCT (group B). Cumulative incidence of relapse at 5 years in group A was significantly higher than that in group B (66.3% versus 29.9%, P < .0001). Overall and disease-free survival in group A were significantly inferior to group B (P < .0001). Moreover, multivariate analyses demonstrated that central nervous system leukemia (P = .002), T cell immunophenotype (P = .044), expression of E2A-PBX1 (P = .007), and positive minimal residual disease after the first cycle of consolidation (P = .004) were correlated with relapse. Patients with 1 of 4 risk factors were assigned to the high-risk group. Otherwise, patients without risk factors were assigned to the low-risk group. In the high-risk group, HSCT had lower relapse rates and superior DFS compared with chemotherapy (P < .05), but in the low-risk group, there were no differences between HSCT and chemotherapy (P > .05). This study is the first to demonstrate that compared with chemotherapy alone, haploidentical HSCT is a better postremission therapy in adults with standard-risk ALL in CR1. Moreover, based on the 4 risk factors, the establishment of risk stratification could identify the subgroup of patients with a higher risk of relapse in adults with standard-risk ALL in CR1. Furthermore, risk stratification-directed postremission therapies using haploidentical HSCT or chemotherapy alone not only reduce relapse rate but also avoid unnecessary treatment-related mortality and improve survival. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score.

PubMed

Cavalcanti, Paulo Ernando Ferraz; Sá, Michel Pompeu Barros de Oliveira; Santos, Cecília Andrade dos; Esmeraldo, Isaac Melo; Chaves, Mariana Leal; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

2015-01-01

To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality. Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed. 360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766. The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality.

Case finding with incomplete administrative data: observations on playing with less than a full deck.

PubMed

Holmes, Ann M; Ackermann, Ronald T; Katz, Barry P; Downs, Stephen M; Inui, Thomas S

2010-12-01

Capacity constraints and efficiency considerations require that disease management programs identify patients most likely to benefit from intervention. Predictive modeling with available administrative data has been used as a strategy to match patients with appropriate interventions. Administrative data, however, can be plagued by problems of incompleteness and delays in processing. In this article, we examine the effects of these problems on the effectiveness of using administrative data to identify suitable candidates for disease management, and we evaluate various proposed solutions. We build prospective models using regression analysis and evaluate the resulting stratification algorithms using R² statistics, areas under receiver operator characteristic curves, and cost concentration ratios. We find delays in receipt of data reduce the effectiveness of the stratification algorithm, but the degree of compromise depends on what proportion of the population is targeted for intervention. Surprisingly, we find that supplementing partial data with a longer panel of more outdated data produces algorithms that are inferior to algorithms based on a shorter window of more recent data. Demographic data add little to algorithms that include prior claims data, and are an inadequate substitute when claims data are unavailable. Supplementing demographic data with additional information on self-reported health status improves the stratification performance only slightly and only when disease management is targeted to the highest risk patients. We conclude that the extra costs associated with surveying patients for health status information or retrieving older claims data cannot be justified given the lack of evidence that either improves the effectiveness of the stratification algorithm.

Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk

This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.

High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome

PubMed Central

Miller-Hodges, Eve; Anand, Atul; Shah, Anoop S.V.; Chapman, Andrew R.; Gallacher, Peter; Lee, Kuan Ken; Farrah, Tariq; Halbesma, Nynke; Blackmur, James P.; Newby, David E.; Mills, Nicholas L.

2018-01-01

Background: High-sensitivity cardiac troponin testing may improve the risk stratification and diagnosis of myocardial infarction, but concentrations can be challenging to interpret in patients with renal impairment, and the effectiveness of testing in this group is uncertain. Methods: In a prospective multicenter study of consecutive patients with suspected acute coronary syndrome, we evaluated the performance of high-sensitivity cardiac troponin I in those with and without renal impairment (estimated glomerular filtration rate <60mL/min/1.73m2). The negative predictive value and sensitivity of troponin concentrations below the risk stratification threshold (5 ng/L) at presentation were reported for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. The positive predictive value and specificity at the 99th centile diagnostic threshold (16 ng/L in women, 34 ng/L in men) was determined for index type 1 myocardial infarction. Subsequent type 1 myocardial infarction and cardiac death were reported at 1 year. Results: Of 4726 patients identified, 904 (19%) had renal impairment. Troponin concentrations <5 ng/L at presentation identified 17% of patients with renal impairment as low risk for the primary outcome (negative predictive value, 98.4%; 95% confidence interval [CI], 96.0%–99.7%; sensitivity 98.9%; 95%CI, 97.5%–99.9%), in comparison with 56% without renal impairment (P<0.001) with similar performance (negative predictive value, 99.7%; 95% CI, 99.4%–99.9%; sensitivity 98.4%; 95% CI, 97.2%–99.4%). The positive predictive value and specificity at the 99th centile were lower in patients with renal impairment at 50.0% (95% CI, 45.2%–54.8%) and 70.9% (95% CI, 67.5%–74.2%), respectively, in comparison with 62.4% (95% CI, 58.8%–65.9%) and 92.1% (95% CI, 91.2%–93.0%) in those without. At 1 year, patients with troponin concentrations >99th centile and renal impairment were at greater risk of subsequent myocardial infarction or cardiac death than those with normal renal function (24% versus 10%; adjusted hazard ratio, 2.19; 95% CI, 1.54–3.11). Conclusions: In suspected acute coronary syndrome, high-sensitivity cardiac troponin identified fewer patients with renal impairment as low risk and more as high risk, but with lower specificity for type 1 myocardial infarction. Irrespective of diagnosis, patients with renal impairment and elevated cardiac troponin concentrations had a 2-fold greater risk of a major cardiac event than those with normal renal function, and should be considered for further investigation and treatment. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123. PMID:28978551

Revealing the timing of ocean stratification using remotely-sensed ocean fronts: links with marine predators

NASA Astrophysics Data System (ADS)

Miller, P. I.; Loveday, B. R.

2016-02-01

Stratification is of critical importance to the mixing and productivity of the ocean, though currently it can only be measured using in situ sampling, profiling buoys or underwater autonomous vehicles. Stratification is understood to affect the surface aggregation of pelagic fish and hence the foraging behaviour and distribution of their predators such as seabirds and cetaceans. Satellite Earth observation sensors cannot directly detect stratification, but can observe surface features related to the presence of stratification, for example shelf-sea fronts that separate tidally-mixed water from seasonally stratified water. This presentation describes a novel algorithm that accumulates evidence for stratification from a sequence of oceanic front maps, and in certain regions can reveal the timing of the seasonal onset and breakdown of stratification. Initial comparisons will be made with seabird locations acquired through GPS tagging. If successful, a remotely-sensed stratification timing index would augment the ocean front metrics already developed at PML, that have been applied in over 20 journal articles relating marine predators to ocean fronts. The figure below shows a preliminary remotely-sensed 'stratification' index, for 25-31 Jul. 2010, where red indicates water with stronger evidence for stratification.

Prediction of Febrile Neutropenia after Chemotherapy Based on Pretreatment Risk Factors among Cancer Patients

PubMed Central

Aagaard, Theis; Roen, Ashley; Daugaard, Gedske; Brown, Peter; Sengeløv, Henrik; Mocroft, Amanda; Lundgren, Jens; Helleberg, Marie

2017-01-01

Abstract Background Febrile neutropenia (FN) is a common complication to chemotherapy associated with a high burden of morbidity and mortality. Reliable prediction of individual risk based on pretreatment risk factors allows for stratification of preventive interventions. We aimed to develop such a risk stratification model to predict FN in the 30 days after initiation of chemotherapy. Methods We included consecutive treatment-naïve patients with solid cancers and diffuse large B-cell lymphomas at Copenhagen University Hospital, 2010–2015. Data were obtained from the PERSIMUNE repository of electronic health records. FN was defined as neutrophils ≤0.5 × 10E9/L ​at the time of either a blood culture sample or death. Time from initiation of chemotherapy to FN was analyzed using Fine-Gray models with death as a competing event. Risk factors investigated were: age, sex, body surface area, haemoglobin, albumin, neutrophil-to-lymphocyte ratio, Charlson Comorbidity Index (CCI) and chemotherapy drugs. Parameter estimates were scaled and summed to create the risk score. The scores were grouped into four: low, intermediate, high and very high risk. Results Among 8,585 patients, 467 experienced FN, incidence rate/30 person-days 0.05 (95% CI, 0.05–0.06). Age (1 point if > 65 years), albumin (1 point if < 39 g/L), CCI (1 point if > 2) and chemotherapy (range -5 to 6 points/drug) predicted FN. Median score at inclusion was 2 points (range –5 to 9). The cumulative incidence and the incidence rates and hazard ratios of FN are shown in Figure 1 and Table 1, respectively. Conclusion We developed a risk score to predict FN the first month after initiation of chemotherapy. The score is easy to use and provides good differentiation of risk groups; the score needs independent validation before routine use. Disclosures All authors: No reported disclosures.