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

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.

Combining abdominal and cosmetic breast surgery does not increase short-term complication rates: a comparison of each individual procedure and pretreatment risk stratification tool.

PubMed

Khavanin, Nima; Jordan, Sumanas W; Vieira, Brittany L; Hume, Keith M; Mlodinow, Alexei S; Simmons, Christopher J; Murphy, Robert X; Gutowski, Karol A; Kim, John Y S

2015-11-01

Combined abdominal and breast surgery presents a convenient and relatively cost-effective approach for accomplishing both procedures. This study is the largest to date assessing the safety of combined procedures, and it aims to develop a simple pretreatment risk stratification method for patients who desire a combined procedure. All women undergoing abdominoplasty, panniculectomy, augmentation mammaplasty, and/or mastopexy in the TOPS database were identified. Demographics and outcomes for combined procedures were compared to individual procedures using χ(2) and Student's t-tests. Multiple logistic regression provided adjusted odds ratios for the effect of a combined procedure on 30-day complications. Among combined procedures, a logistic regression model determined point values for pretreatment risk factors including diabetes (1 point), age over 53 (1), obesity (2), and 3+ ASA status (3), creating a 7-point pretreatment risk stratification tool. A total of 58,756 cases met inclusion criteria. Complication rates among combined procedures (9.40%) were greater than those of aesthetic breast surgery (2.66%; P < .001) but did not significantly differ from abdominal procedures (9.75%; P = .530). Nearly 77% of combined cases were classified as low-risk (0 points total) with a 9.78% complication rates. Medium-risk patients (1 to 3 points) had a 16.63% complication rate, and high-risk (4 to 7 points) 38.46%. Combining abdominal and breast procedures is safe in the majority of patients and does not increase 30-day complications rates. The risk stratification tool can continue to ensure favorable outcomes for patients who may desire a combined surgery. 4 Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

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.

A novel metric that quantifies risk stratification for evaluating diagnostic tests: The example of evaluating cervical-cancer screening tests across populations.

PubMed

Katki, Hormuzd A; Schiffman, Mark

2018-05-01

Our work involves assessing whether new biomarkers might be useful for cervical-cancer screening across populations with different disease prevalences and biomarker distributions. When comparing across populations, we show that standard diagnostic accuracy statistics (predictive values, risk-differences, Youden's index and Area Under the Curve (AUC)) can easily be misinterpreted. We introduce an intuitively simple statistic for a 2 × 2 table, Mean Risk Stratification (MRS): the average change in risk (pre-test vs. post-test) revealed for tested individuals. High MRS implies better risk separation achieved by testing. MRS has 3 key advantages for comparing test performance across populations with different disease prevalences and biomarker distributions. First, MRS demonstrates that conventional predictive values and the risk-difference do not measure risk-stratification because they do not account for test-positivity rates. Second, Youden's index and AUC measure only multiplicative relative gains in risk-stratification: AUC = 0.6 achieves only 20% of maximum risk-stratification (AUC = 0.9 achieves 80%). Third, large relative gains in risk-stratification might not imply large absolute gains if disease is rare, demonstrating a "high-bar" to justify population-based screening for rare diseases such as cancer. We illustrate MRS by our experience comparing the performance of cervical-cancer screening tests in China vs. the USA. The test with the worst AUC = 0.72 in China (visual inspection with acetic acid) provides twice the risk-stratification (i.e. MRS) of the test with best AUC = 0.83 in the USA (human papillomavirus and Pap cotesting) because China has three times more cervical precancer/cancer. MRS could be routinely calculated to better understand the clinical/public-health implications of standard diagnostic accuracy statistics. Published by Elsevier Inc.

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

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.

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.

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

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

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.

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

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

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.

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

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.

The Auckland Cataract Study II: Reducing Complications by Preoperative Risk Stratification and Case Allocation in a Teaching Hospital.

PubMed

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

2017-09-01

To assess the effect of preoperative risk stratification for phacoemulsification surgery on intraoperative complications in a teaching hospital. Prospective cohort study. Prospective assessment of consecutive phacoemulsification cases (N = 500) enabled calculation of a risk score (M-score of 0-8) using a risk stratification system. M-scores of >3 were allocated to senior surgeons. All surgeries were performed in a public teaching hospital setting, Auckland, New Zealand, in early 2016. Postoperatively, data were reviewed for complications and corrected distance visual acuity (CDVA). Results were compared to a prospective study (N = 500, phase 1) performed prior to formal introduction of risk stratification. Intraoperative complications increased with increasing M-scores (P = .044). Median M-score for complicated cases was higher (P = .022). Odds ratio (OR) for a complication increased 1.269 per unit increase in M-score (95% confidence interval [CI] 1.007-1.599, P = .043). Overall rate of any intraoperative complication was 5.0%. Intraoperative complication rates decreased from 8.4% to 5.0% (OR = 0.576, P = .043) comparing phase 1 and phase 2 (formal introduction of risk stratification). The severity of complications also reduced. A significant decrease in complications for M = 0 (ie, minimal risk cases) was also identified comparing the current study (3.1%) to phase 1 (7.2%), P = .034. There was no change in postoperative complication risks (OR 0.812, P = .434) or in mean postoperative CDVA (20/30, P = .484) comparing current with phase 1 outcomes. A simple preoperative risk stratification system, based on standard patient information gathered at preoperative consultation, appears to reduce intraoperative complications and support safer surgical training by appropriate allocation of higher-risk cases. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

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

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.

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.

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

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.

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

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

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

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.

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

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.

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

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.

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.

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

From Statistical Significance to Clinical Relevance: A Simple Algorithm to Integrate BNP and the Seattle Heart Failure Model for Risk Stratification in Heart Failure

PubMed Central

AbouEzzeddine, Omar F.; French, Benjamin; Mirzoyev, Sultan A.; Jaffe, Allan S; Levy, Wayne C.; Fang, James C.; Sweitzer, Nancy K.; Cappola, Thomas P.; Redfield, Margaret M.

2016-01-01

Background Heart failure (HF) guidelines recommend brain natriuretic peptide (BNP) and multivariable risk-scores such as the Seattle HF Model (SHFM) to predict risk in HF with reduced ejection fraction (HFrEF). A practical way to integrate information from these two prognostic tools is lacking. We sought to establish a SHFM+BNP risk-stratification algorithm. Methods The retrospective derivation cohort included consecutive patients with HFrEF at Mayo. One-year outcome (death, transplantation or ventricular assist device) was assessed. The SHFM+BNP algorithm was derived by stratifying patients within SHFM-predicted risk categories (≤2.5%, 2.6–≤10%, >10%) according to BNP above or below 700 pg/mL and comparing SHFM-predicted and observed event rates within each SHFM+BNP category. The algorithm was validated in a prospective, multicenter HFrEF registry (Penn HF Study). Results Derivation (n=441; one-year event rate 17%) and validation (n=1513; one-year event rate 12%) cohorts differed with the former being older and more likely ischemic with worse symptoms, lower EF, worse renal function, higher BNP and SHFM scores. In both cohorts, across the three SHFM-predicted risk strata, a BNP>700 pg/ml consistently identified patients with approximately three-fold the risk that the SHFM would have otherwise estimated regardless stage of HF, intensity and duration of HF-therapy, and comorbidities. Conversely, the SHFM was appropriately calibrated in patients with a BNP<700 pg/ml. Conclusion The simple SHFM+BNP algorithm displays stable performance across diverse HFrEF cohorts and may enhance risk stratification to enable appropriate decisions regarding HF therapeutic or palliative strategies. PMID:27021278

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 scoring models for predicting peri-operative morbidity and mortality in people with fragility hip fractures: Qualitative systematic review.

PubMed

Marufu, Takawira C; Mannings, Alexa; Moppett, Iain K

2015-12-01

Accurate peri-operative risk prediction is an essential element of clinical practice. Various risk stratification tools for assessing patients' risk of mortality or morbidity have been developed and applied in clinical practice over the years. This review aims to outline essential characteristics (predictive accuracy, objectivity, clinical utility) of currently available risk scoring tools for hip fracture patients. We searched eight databases; AMED, CINHAL, Clinical Trials.gov, Cochrane, DARE, EMBASE, MEDLINE and Web of Science for all relevant studies published until April 2015. We included published English language observational studies that considered the predictive accuracy of risk stratification tools for patients with fragility hip fracture. After removal of duplicates, 15,620 studies were screened. Twenty-nine papers met the inclusion criteria, evaluating 25 risk stratification tools. Risk stratification tools considered in more than two studies were; ASA, CCI, E-PASS, NHFS and O-POSSUM. All tools were moderately accurate and validated in multiple studies; however there are some limitations to consider. The E-PASS and O-POSSUM are comprehensive but complex, and require intraoperative data making them a challenge for use on patient bedside. The ASA, CCI and NHFS are simple, easy and inexpensive using routinely available preoperative data. Contrary to the ASA and CCI which has subjective variables in addition to other limitations, the NHFS variables are all objective. In the search for a simple and inexpensive, easy to calculate, objective and accurate tool, the NHFS may be the most appropriate of the currently available scores for hip fracture patients. However more studies need to be undertaken before it becomes a national hip fracture risk stratification or audit tool of choice. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

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.

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.

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.

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.

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

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

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

[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.

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

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

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.

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.

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.

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.

BAYESIAN BICLUSTERING FOR PATIENT STRATIFICATION.

PubMed

Khakabimamaghani, Sahand; Ester, Martin

2016-01-01

The move from Empirical Medicine towards Personalized Medicine has attracted attention to Stratified Medicine (SM). Some methods are provided in the literature for patient stratification, which is the central task of SM, however, there are still significant open issues. First, it is still unclear if integrating different datatypes will help in detecting disease subtypes more accurately, and, if not, which datatype(s) are most useful for this task. Second, it is not clear how we can compare different methods of patient stratification. Third, as most of the proposed stratification methods are deterministic, there is a need for investigating the potential benefits of applying probabilistic methods. To address these issues, we introduce a novel integrative Bayesian biclustering method, called B2PS, for patient stratification and propose methods for evaluating the results. Our experimental results demonstrate the superiority of B2PS over a popular state-of-the-art method and the benefits of Bayesian approaches. Our results agree with the intuition that transcriptomic data forms a better basis for patient stratification than genomic data.

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.

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 Central

Cavalcanti, Paulo Ernando Ferraz; Sá, Michel Pompeu Barros de Oliveira; dos Santos, Cecília Andrade; Esmeraldo, Isaac Melo; Chaves, Mariana Leal; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

2015-01-01

Objective 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. Methods 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. Results 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. Conclusion 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. PMID:26107445

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.

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

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

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.

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.

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/.

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.

Effect of sample stratification on dairy GWAS results

PubMed Central

2012-01-01

Background Artificial insemination and genetic selection are major factors contributing to population stratification in dairy cattle. In this study, we analyzed the effect of sample stratification and the effect of stratification correction on results of a dairy genome-wide association study (GWAS). Three methods for stratification correction were used: the efficient mixed-model association expedited (EMMAX) method accounting for correlation among all individuals, a generalized least squares (GLS) method based on half-sib intraclass correlation, and a principal component analysis (PCA) approach. Results Historical pedigree data revealed that the 1,654 contemporary cows in the GWAS were all related when traced through approximately 10–15 generations of ancestors. Genome and phenotype stratifications had a striking overlap with the half-sib structure. A large elite half-sib family of cows contributed to the detection of favorable alleles that had low frequencies in the general population and high frequencies in the elite cows and contributed to the detection of X chromosome effects. All three methods for stratification correction reduced the number of significant effects. EMMAX method had the most severe reduction in the number of significant effects, and the PCA method using 20 principal components and GLS had similar significance levels. Removal of the elite cows from the analysis without using stratification correction removed many effects that were also removed by the three methods for stratification correction, indicating that stratification correction could have removed some true effects due to the elite cows. SNP effects with good consensus between different methods and effect size distributions from USDA’s Holstein genomic evaluation included the DGAT1-NIBP region of BTA14 for production traits, a SNP 45kb upstream from PIGY on BTA6 and two SNPs in NIBP on BTA14 for protein percentage. However, most of these consensus effects had similar frequencies in the elite and average cows. Conclusions Genetic selection and extensive use of artificial insemination contributed to overlapped genome, pedigree and phenotype stratifications. The presence of an elite cluster of cows was related to the detection of rare favorable alleles that had high frequencies in the elite cluster and low frequencies in the remaining cows. Methods for stratification correction could have removed some true effects associated with genetic selection. PMID:23039970

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.

Modern risk stratification in coronary heart disease.

PubMed

Ginghina, C; Bejan, I; Ceck, C D

2011-11-14

The prevalence and impact of cardiovascular diseases in the world are growing. There are 2 million deaths due to cardiovascular disease each year in the European Union; the main cause of death being the coronary heart disease responsible for 16% of deaths in men and 15% in women. Prevalence of cardiovascular disease in Romania is estimated at 7 million people, of which 2.8 million have ischemic heart disease. In this epidemiological context, risk stratification is required for individualization of therapeutic strategies for each patient. The continuing evolution of the diagnosis and treatment techniques combines personalized medicine with the trend of therapeutic management leveling, based on guidelines and consensus, which are in constant update. The guidelines used in clinical practice have involved risk stratification and identification of patient groups in whom the risk-benefit ratio of using new diagnostic and therapeutic techniques has a positive value. Presence of several risk factors may indicate a more important total risk than the presence / significant increase from normal values of a single risk factor. Modern trends in risk stratification of patients with coronary heart disease are polarized between the use of simple data versus complex scores, traditional data versus new risk factors, generally valid scores versus personalized scores, depending on patient characteristics, type of coronary artery disease, with impact on the suggested therapy. All known information and techniques can be integrated in a complex system of risk assessment. The current trend in risk assessment is to identify coronary artery disease in early forms, before clinical manifestation, and to guide therapy, particularly in patients with intermediate risk, which can be classified in another class of risk based on new obtained information.

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.

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.

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.

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

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.

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

Introducing the reporting system for thyroid fine-needle aspiration cytology according to the new guidelines of the Japan Thyroid Association.

PubMed

Kakudo, Kennichi; Kameyama, Kaori; Miyauchi, Akira; Nakamura, Hirotoshi

2014-01-01

The Japan Thyroid Association (JTA) recently published new guidelines for clinical management of thyroid nodules. This paper introduces their diagnostic system for reporting thyroid fine-needle aspiration cytology. There are two points where the new reporting system that differs from existing internationally-accepted ones. The first is the subclassification of the so-called indeterminate category, which is divided into 'follicular neoplasm' and 'others'. The second is the subclassification of follicular neoplasm into 'favor benign', 'borderline' and 'favor malignant'. It is characterized by self-explanatory terminologies as to histological type and probability of malignancy to establish further risk stratification as well as to facilitate communication between clinicians and cytopathologists. The different treatment strategies adopted for thyroid nodules is deeply influenced by the particular diagnostic system used for thyroid cytology. In Western countries all patients with follicular neoplasms are advised to have immediate diagnostic surgery while patients in Japan often undergo further risk stratification without immediate surgery. The JTA diagnostic system of reporting thyroid cytology is designed for further risk stratification of patients with indeterminate cytology. If a surgeon applies diagnostic lobectomy to all patients with follicular neoplasm unselectively, this subclassification of follicular neoplasm has no practical meaning and is unnecessary. Cytological risk stratification of follicular neoplasms is optional and cytopathologists can choose either a simple 6-tier system without stratification of follicular neoplasm or a complicated 8-tier system depending on their experience in thyroid cytology and clinical management.

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 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

A Model-Free Machine Learning Method for Risk Classification and Survival Probability Prediction.

PubMed

Geng, Yuan; Lu, Wenbin; Zhang, Hao Helen

2014-01-01

Risk classification and survival probability prediction are two major goals in survival data analysis since they play an important role in patients' risk stratification, long-term diagnosis, and treatment selection. In this article, we propose a new model-free machine learning framework for risk classification and survival probability prediction based on weighted support vector machines. The new procedure does not require any specific parametric or semiparametric model assumption on data, and is therefore capable of capturing nonlinear covariate effects. We use numerous simulation examples to demonstrate finite sample performance of the proposed method under various settings. Applications to a glioma tumor data and a breast cancer gene expression survival data are shown to illustrate the new methodology in real data analysis.

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

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.

How-to-Do-It: A Practical Method for Teaching Seed Stratification.

ERIC Educational Resources Information Center

Englert, Karen M.; Shontz, Nancy N.

1989-01-01

Described is a laboratory procedure for teaching seed stratification. Materials, methods, results, and applicability of the experiment are explained. Diagrams showing the percent of total germination as a function of stratification time and the germination rate of stratified seeds are included. (RT)

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

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

Epidemiologic methods in clinical trials.

PubMed

Rothman, K J

1977-04-01

Epidemiologic methods developed to control confounding in non-experimental studies are equally applicable for experiments. In experiments, most confounding is usually controlled by random allocation of subjects to treatment groups, but randomization does not preclude confounding except for extremely large studies, the degree of confounding expected being inversely related to the size of the treatment groups. In experiments, as in non-experimental studies, the extent of confounding for each risk indicator should be assessed, and if sufficiently large, controlled. Confounding is properly assessed by comparing the unconfounded effect estimate to the crude effect estimate; a common error is to assess confounding by statistical tests of significance. Assessment of confounding involves its control as a prerequisite. Control is most readily and cogently achieved by stratification of the data, though with many factors to control simultaneously, multivariate analysis or a combination of multivariate analysis and stratification might be necessary.

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

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.

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.

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

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

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

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.

Identifying High-Risk Patients without Labeled Training Data: Anomaly Detection Methodologies to Predict Adverse Outcomes

PubMed Central

Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan

2010-01-01

For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083

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.

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.

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.

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.

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.

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.

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

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.

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.

Predicting the Presence of Clinically Significant Prostate Cancer using Multiparametric MRI and MR-US Fusion Biopsy | Division of Cancer Prevention

Cancer.gov

Prostate cancer is the second leading cause of cancer death in American men, accounting for 26% of new cancer diagnoses and 9% of cancer deaths in men. Active surveillance, radical prostatectomy and radiotherapy are commonly used treatments for clinically localized prostate cancer. However, current risk stratification methods cannot be used effectively to avoid subjecting

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

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.

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

[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.

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.

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.

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.

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.

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.

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.

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.

Prognostic value of predischarge electrocardiographic measurement of infarct size after thrombolysis: insights from GUSTO I Economics and Quality of Life substudy.

PubMed

Barbagelata, Alejandro; Califf, Robert M; Sgarbossa, Elena B; Knight, David; Mark, Daniel B; Granger, Christopher B; Armstrong, Paul W; Elizari, Marcelo; Birnbaum, Yochai; Grinfeld, Liliana R; Ohman, E Magnus; Wagner, Galen S

2004-11-01

Current methods for risk stratification after acute myocardial infarction (MI) include several noninvasive studies. In this cost-containment era, the development of low-cost means should be encouraged. We assessed the ability of an electrocardiogram (ECG) MI-sizing score to predict outcomes in patients enrolled in the Economics and Quality of Life (EQOL) sub study of the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries -I (GUSTO-I) trial. We classified patients by electrocardiographic Selvester QRS score at hospital discharge: those with a score 0-9 versus > or =10. Endpoints were 30-day and 1-year mortality, resource use, and quality-of-life measures. Patients with a QRS score <10 were well-matched with those with QRS score > or =10 with the exception of a trend to more anterior MI in the higher scored group. Patients with QRS score > or =10 had increased risk of death at 30-days (8.9% vs. 2.9% P < .001), and this difference persisted at 1 year (12.6% vs. 5.4%, P = .001). Recurrent chest pain, use of angiography, and angioplasty were similar during follow-up. However, there was a trend toward less coronary bypass surgery in patients with a QRS score > or =10. Readmission rates were higher at 30 days but similar at 1 year. Stratification of patients after acute MI by a simple measure of MI size identifies populations with different long-term prognoses; patients with a QRS score > or =10 (approximately 30% of the left ventricle infarcted) at discharge have poorer outcomes in both the short- and long-term. The standard 12-lead ECG provides a simple, economical means of risk stratification at discharge.

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.

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.

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

Marginal Mean Weighting through Stratification: Adjustment for Selection Bias in Multilevel Data

ERIC Educational Resources Information Center

Hong, Guanglei

2010-01-01

Defining causal effects as comparisons between marginal population means, this article introduces marginal mean weighting through stratification (MMW-S) to adjust for selection bias in multilevel educational data. The article formally shows the inherent connections among the MMW-S method, propensity score stratification, and…

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

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

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.

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

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.

Stratified Sampling Design Based on Data Mining

PubMed Central

Kim, Yeonkook J.; Oh, Yoonhwan; Park, Sunghoon; Cho, Sungzoon

2013-01-01

Objectives To explore classification rules based on data mining methodologies which are to be used in defining strata in stratified sampling of healthcare providers with improved sampling efficiency. Methods We performed k-means clustering to group providers with similar characteristics, then, constructed decision trees on cluster labels to generate stratification rules. We assessed the variance explained by the stratification proposed in this study and by conventional stratification to evaluate the performance of the sampling design. We constructed a study database from health insurance claims data and providers' profile data made available to this study by the Health Insurance Review and Assessment Service of South Korea, and population data from Statistics Korea. From our database, we used the data for single specialty clinics or hospitals in two specialties, general surgery and ophthalmology, for the year 2011 in this study. Results Data mining resulted in five strata in general surgery with two stratification variables, the number of inpatients per specialist and population density of provider location, and five strata in ophthalmology with two stratification variables, the number of inpatients per specialist and number of beds. The percentages of variance in annual changes in the productivity of specialists explained by the stratification in general surgery and ophthalmology were 22% and 8%, respectively, whereas conventional stratification by the type of provider location and number of beds explained 2% and 0.2% of variance, respectively. Conclusions This study demonstrated that data mining methods can be used in designing efficient stratified sampling with variables readily available to the insurer and government; it offers an alternative to the existing stratification method that is widely used in healthcare provider surveys in South Korea. PMID:24175117

A three-gene expression signature model for risk stratification of patients with neuroblastoma.

PubMed

Garcia, Idoia; Mayol, Gemma; Ríos, José; Domenech, Gema; Cheung, Nai-Kong V; Oberthuer, André; Fischer, Matthias; Maris, John M; Brodeur, Garrett M; Hero, Barbara; Rodríguez, Eva; Suñol, Mariona; Galvan, Patricia; de Torres, Carmen; Mora, Jaume; Lavarino, Cinzia

2012-04-01

Neuroblastoma is an embryonal tumor with contrasting clinical courses. Despite elaborate stratification strategies, precise clinical risk assessment still remains a challenge. The purpose of this study was to develop a PCR-based predictor model to improve clinical risk assessment of patients with neuroblastoma. The model was developed using real-time PCR gene expression data from 96 samples and tested on separate expression data sets obtained from real-time PCR and microarray studies comprising 362 patients. On the basis of our prior study of differentially expressed genes in favorable and unfavorable neuroblastoma subgroups, we identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. The expression pattern of these genes was used to develop a PCR-based single-score predictor model. The model discriminated patients into two groups with significantly different clinical outcome [set 1: 5-year overall survival (OS): 0.93 ± 0.03 vs. 0.53 ± 0.06, 5-year event-free survival (EFS): 0.85 ± 0.04 vs. 0.042 ± 0.06, both P < 0.001; set 2 OS: 0.97 ± 0.02 vs. 0.61 ± 0.1, P = 0.005, EFS: 0.91 ± 0.8 vs. 0.56 ± 0.1, P = 0.005; and set 3 OS: 0.99 ± 0.01 vs. 0.56 ± 0.06, EFS: 0.96 ± 0.02 vs. 0.43 ± 0.05, both P < 0.001]. Multivariate analysis showed that the model was an independent marker for survival (P < 0.001, for all). In comparison with accepted risk stratification systems, the model robustly classified patients in the total cohort and in different clinically relevant risk subgroups. We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems. ©2012 AACR.

A Three-Gene Expression Signature Model for Risk Stratification of Patients with Neuroblastoma

PubMed Central

Garcia, Idoia; Mayol, Gemma; Ríos, José; Domenech, Gema; Cheung, Nai-Kong V.; Oberthuer, André; Fischer, Matthias; Maris, John M.; Brodeur, Garrett M.; Hero, Barbara; Rodríguez, Eva; Suñol, Mariona; Galvan, Patricia; de Torres, Carmen; Mora, Jaume; Lavarino, Cinzia

2014-01-01

Purpose Neuroblastoma is an embryonal tumor with contrasting clinical courses. Despite elaborate stratification strategies, precise clinical risk assessment still remains a challenge. The purpose of this study was to develop a PCR-based predictor model to improve clinical risk assessment of patients with neuroblastoma. Experimental Design The model was developed using real-time PCR gene expression data from 96 samples and tested on separate expression data sets obtained from real-time PCR and microarray studies comprising 362 patients. Results On the basis of our prior study of differentially expressed genes in favorable and unfavorable neuroblastoma subgroups, we identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. The expression pattern of these genes was used to develop a PCR-based single-score predictor model. The model discriminated patients into two groups with significantly different clinical outcome [set 1: 5-year overall survival (OS): 0.93 ± 0.03 vs. 0.53 ± 0.06, 5-year event-free survival (EFS): 0.85 ± 0.04 vs. 0.042 ± 0.06, both P < 0.001; set 2 OS: 0.97 ± 0.02 vs. 0.61 ± 0.1, P = 0.005, EFS: 0.91 ± 0.8 vs. 0.56 ± 0.1, P = 0.005; and set 3 OS: 0.99 ± 0.01 vs. 0.56 ± 0.06, EFS: 0.96 ± 0.02 vs. 0.43 ± 0.05, both P < 0.001]. Multivariate analysis showed that the model was an independent marker for survival (P < 0.001, for all). In comparison with accepted risk stratification systems, the model robustly classified patients in the total cohort and in different clinically relevant risk subgroups. Conclusion We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems. PMID:22328561

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.

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

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

Revealing the timing of ocean stratification using remotely sensed ocean fronts

NASA Astrophysics Data System (ADS)

Miller, Peter I.; Loveday, Benjamin R.

2017-10-01

Stratification is of critical importance to the circulation, mixing and productivity of the ocean, and is expected to be modified by climate change. Stratification is also understood to affect the surface aggregation of pelagic fish and hence the foraging behaviour and distribution of their predators such as seabirds and cetaceans. Hence it would be prudent to monitor the stratification of the global ocean, though this is currently only possible using in situ sampling, profiling buoys or underwater autonomous vehicles. Earth observation (EO) 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 paper describes a novel algorithm that accumulates evidence for stratification from a sequence of oceanic front maps, and discusses preliminary results in comparison with in situ data and simulations from 3D hydrodynamic models. In certain regions, this method can reveal the timing of the seasonal onset and breakdown of stratification.

The influence of atmospheric stratification on scatterometer data

NASA Technical Reports Server (NTRS)

Louis, Jean-Francois; Hoffman, Ross N.

1989-01-01

The effects of atmospheric stratification and the stability of the atmospheric stratification on the scatterometer data measuring surface winds over the ocean were investigated using the boundary layer model developed by Louis (1979). A variational analysis method is proposed, which allows direct assimilation of scatterometer data. It is shown that the effect of the stability of atmospheric stratification on the wind increment is relatively small. However, it is a systematic effect, and neglecting it would consistently underestimate the winds in stable regions.

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.

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

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.

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.

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.

Barrett's oesophagus: how should we manage it?

PubMed Central

Old, O J; Almond, L M; Barr, H

2015-01-01

Endoscopic surveillance remains the core management of non-dysplastic Barrett's oesophagus, although questions regarding its efficacy in reducing mortality from oesophageal adenocarcinoma have yet to be definitively answered, and randomised trial data are awaited. One of the main goals of current research is to achieve risk stratification, identifying those at high risk of progression. The recent British Society of Gastroenterology (BSG) guidelines on surveillance have taken a step in this direction with interval stratification on clinicopathological grounds. The majority of Barrett's oesophagus remains undiagnosed, and this has led to investigation of methods of screening for Barrett's oesophagus, ideally non-endoscopic methods capable of reliably identifying dysplasia. Chemoprevention to prevent progression is currently under investigation, and may become a key component of future treatment. The availability of effective endotherapy means that accurate identification of dysplasia is more important than ever. There is now evidence to support intervention with radiofrequency ablation (RFA) for low-grade dysplasia (LGD), but recent data have emphasised the need for consensus pathology for LGD. Ablative treatment has become well established for high-grade dysplasia, and should be employed for flat lesions where there is no visible abnormality. Of the ablative modalities, RFA has the strongest evidence base. Endoscopic resection should be performed for all visible lesions, and is now the treatment of choice for T1a tumours. Targeting those with high-risk disease will, hopefully, lead to efficacious and cost-effective surveillance, and the trend towards earlier intervention to halt progression gives cause for optimism that this will ultimately result in fewer deaths from oesophageal adenocarcinoma. PMID:28839797

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

Impact on Water Heater Performance of Heating Methods that Promote Tank Temperature Stratification

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

Gluesenkamp, Kyle R; BushPE, John D

2016-01-01

During heating of a water heater tank, the vertical temperature stratification of the water can be increased or decreased, depending on the method of heating. Methods that increase stratification during heating include (1) removing cold water from the tank bottom, heating it, and re-introducing it to the tank top at relatively low flow rate, (2) using a heat exchanger wrapped around the tank, through which heating fluid (with finite specific heat) flows from top to bottom, and (3) using an immersed heat element that is relatively high in the tank. Using such methods allows for improved heat pump water heatermore » (HPWH) cycle efficiencies when the heat pump can take advantage of the lower temperatures that exist lower in the tank, and accommodate the resulting glide. Transcritical cycles are especially well-suited to capitalize on this opportunity, and other HPWH configurations (that have been proposed elsewhere) may benefit as well. This work provides several stratification categories of heat pump water heater tank configurations relevant to their stratification potential. To illustrate key differences among categories, it also compiles available experimental data for (a) single pass pumped flow, (b) multi-pass pumped flow, and (c) top-down wrapped tank with transcritical refrigerant.« less

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.

Computer-aided diagnosis of psoriasis skin images with HOS, texture and color features: A first comparative study of its kind.

PubMed

Shrivastava, Vimal K; Londhe, Narendra D; Sonawane, Rajendra S; Suri, Jasjit S

2016-04-01

Psoriasis is an autoimmune skin disease with red and scaly plaques on skin and affecting about 125 million people worldwide. Currently, dermatologist use visual and haptic methods for diagnosis the disease severity. This does not help them in stratification and risk assessment of the lesion stage and grade. Further, current methods add complexity during monitoring and follow-up phase. The current diagnostic tools lead to subjectivity in decision making and are unreliable and laborious. This paper presents a first comparative performance study of its kind using principal component analysis (PCA) based CADx system for psoriasis risk stratification and image classification utilizing: (i) 11 higher order spectra (HOS) features, (ii) 60 texture features, and (iii) 86 color feature sets and their seven combinations. Aggregate 540 image samples (270 healthy and 270 diseased) from 30 psoriasis patients of Indian ethnic origin are used in our database. Machine learning using PCA is used for dominant feature selection which is then fed to support vector machine classifier (SVM) to obtain optimized performance. Three different protocols are implemented using three kinds of feature sets. Reliability index of the CADx is computed. Among all feature combinations, the CADx system shows optimal performance of 100% accuracy, 100% sensitivity and specificity, when all three sets of feature are combined. Further, our experimental result with increasing data size shows that all feature combinations yield high reliability index throughout the PCA-cutoffs except color feature set and combination of color and texture feature sets. HOS features are powerful in psoriasis disease classification and stratification. Even though, independently, all three set of features HOS, texture, and color perform competitively, but when combined, the machine learning system performs the best. The system is fully automated, reliable and accurate. Copyright © 2016 Elsevier Ireland Ltd. 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 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

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

Specific expression of novel long non-coding RNAs in high-hyperdiploid childhood acute lymphoblastic leukemia

PubMed Central

Drouin, Simon; Caron, Maxime; St-Onge, Pascal; Gioia, Romain; Richer, Chantal; Oualkacha, Karim; Droit, Arnaud; Sinnett, Daniel

2017-01-01

Pre-B cell childhood acute lymphoblastic leukemia (pre-B cALL) is a heterogeneous disease involving many subtypes typically stratified using a combination of cytogenetic and molecular-based assays. These methods, although widely used, rely on the presence of known chromosomal translocations, which is a limiting factor. There is therefore a need for robust, sensitive, and specific molecular biomarkers unaffected by such limitations that would allow better risk stratification and consequently better clinical outcome. In this study we performed a transcriptome analysis of 56 pre-B cALL patients to identify expression signatures in different subtypes. In both protein-coding and long non-coding RNAs (lncRNA), we identified subtype-specific gene signatures distinguishing pre-B cALL subtypes, particularly in t(12;21) and hyperdiploid cases. The genes up-regulated in pre-B cALL subtypes were enriched in bivalent chromatin marks in their promoters. LncRNAs is a new and under-studied class of transcripts. The subtype-specific nature of lncRNAs suggests they may be suitable clinical biomarkers to guide risk stratification and targeted therapies in pre-B cALL patients. PMID:28346506

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

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.

Ultrasound Imaging for Risk Assessment in Atherosclerosis

PubMed Central

Steinl, David C.; Kaufmann, Beat A.

2015-01-01

Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging. PMID:25938969

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.

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.

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/

Delirium, Frailty, and Fast-Track Surgery in Oncogeriatrics: Is There a Link?

PubMed Central

Monacelli, Fiammetta; Signori, Alessio; Prefumo, Matteo; Giannotti, Chiara; Nencioni, Alessio; Romairone, Emanuele; Scabini, Stefano; Odetti, Patrizio

2018-01-01

Background/Aims Postoperative delirium (POD) is more frequent in elderly patients undergoing major cancer surgery. The interplay between individual clinical vulnerability and a series of perioperative factors seems to play a relevant role. Surgery is the first-line treatment option for cancer, and fast-track surgery (FTS) has been documented to decrease postoperative complications. The study sought to assess, after comprehensive geriatric assessment (CGA) and frailty stratification (Rockwood 40 items index), which perioperative parameters were predictive of POD development in elderly patients undergoing FTS for colorectal cancer. Methods A total of 107 consecutive subjects admitted for elective colorectal FTS were enrolled. All patients underwent CGA, frailly stratification, Timed up & go (TUG) test, 4AT test for delirium screening, anesthesiologists physical status classification, and Dindo-Clavien classification. Results The incidence of POD was 12.3%. Patients’ prevalent clinical phenotype was pre-frail. The multivariate analysis indicated physical performance (TUG in seconds) as the most significant predictor of POD for each second of increase. Conclusions Only few procedure-specific studies have examined the impact of FTS for colorectal cancer on POD. This is the first study to investigate the risk factors for POD, in a vulnerable octogenarian oncogeriatric population submitted to FTS surgery and frailty stratification. PMID:29515621

Frailty and Organization of Health and Social Care.

PubMed

Clegg, Andrew; Young, John

2015-01-01

In this chapter, we consider how health and social care can best be organized for older people with frailty. We will consider the merits of routine frailty identification, including risk stratification methods, to inform the provision of evidence-based treatment and holistic, goal-oriented care. We will also consider how best to place older people with frailty at the heart of health and social care systems so that the complex challenges associated with this vulnerable group are addressed. 2015 S. Karger AG, Basel.

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

Stratified sampling design based on data mining.

PubMed

Kim, Yeonkook J; Oh, Yoonhwan; Park, Sunghoon; Cho, Sungzoon; Park, Hayoung

2013-09-01

To explore classification rules based on data mining methodologies which are to be used in defining strata in stratified sampling of healthcare providers with improved sampling efficiency. We performed k-means clustering to group providers with similar characteristics, then, constructed decision trees on cluster labels to generate stratification rules. We assessed the variance explained by the stratification proposed in this study and by conventional stratification to evaluate the performance of the sampling design. We constructed a study database from health insurance claims data and providers' profile data made available to this study by the Health Insurance Review and Assessment Service of South Korea, and population data from Statistics Korea. From our database, we used the data for single specialty clinics or hospitals in two specialties, general surgery and ophthalmology, for the year 2011 in this study. Data mining resulted in five strata in general surgery with two stratification variables, the number of inpatients per specialist and population density of provider location, and five strata in ophthalmology with two stratification variables, the number of inpatients per specialist and number of beds. The percentages of variance in annual changes in the productivity of specialists explained by the stratification in general surgery and ophthalmology were 22% and 8%, respectively, whereas conventional stratification by the type of provider location and number of beds explained 2% and 0.2% of variance, respectively. This study demonstrated that data mining methods can be used in designing efficient stratified sampling with variables readily available to the insurer and government; it offers an alternative to the existing stratification method that is widely used in healthcare provider surveys in South Korea.

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.

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.

Urban noise functional stratification for estimating average annual sound level.

PubMed

Rey Gozalo, Guillermo; Barrigón Morillas, Juan Miguel; Prieto Gajardo, Carlos

2015-06-01

Road traffic noise causes many health problems and the deterioration of the quality of urban life; thus, adequate spatial noise and temporal assessment methods are required. Different methods have been proposed for the spatial evaluation of noise in cities, including the categorization method. Until now, this method has only been applied for the study of spatial variability with measurements taken over a week. In this work, continuous measurements of 1 year carried out in 21 different locations in Madrid (Spain), which has more than three million inhabitants, were analyzed. The annual average sound levels and the temporal variability were studied in the proposed categories. The results show that the three proposed categories highlight the spatial noise stratification of the studied city in each period of the day (day, evening, and night) and in the overall indicators (L(And), L(Aden), and L(A24)). Also, significant differences between the diurnal and nocturnal sound levels show functional stratification in these categories. Therefore, this functional stratification offers advantages from both spatial and temporal perspectives by reducing the sampling points and the measurement time.

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

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

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

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.

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.

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

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.

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.

Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

NASA Astrophysics Data System (ADS)

Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

2017-02-01

The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

[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.

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.

Quantifying the predictive accuracy of time-to-event models in the presence of competing risks.

PubMed

Schoop, Rotraut; Beyersmann, Jan; Schumacher, Martin; Binder, Harald

2011-02-01

Prognostic models for time-to-event data play a prominent role in therapy assignment, risk stratification and inter-hospital quality assurance. The assessment of their prognostic value is vital not only for responsible resource allocation, but also for their widespread acceptance. The additional presence of competing risks to the event of interest requires proper handling not only on the model building side, but also during assessment. Research into methods for the evaluation of the prognostic potential of models accounting for competing risks is still needed, as most proposed methods measure either their discrimination or calibration, but do not examine both simultaneously. We adapt the prediction error proposal of Graf et al. (Statistics in Medicine 1999, 18, 2529–2545) and Gerds and Schumacher (Biometrical Journal 2006, 48, 1029–1040) to handle models with competing risks, i.e. more than one possible event type, and introduce a consistent estimator. A simulation study investigating the behaviour of the estimator in small sample size situations and for different levels of censoring together with a real data application follows.

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

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.

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.

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.

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

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.

An efficient modeling method for thermal stratification simulation in a BWR suppression pool

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

Haihua Zhao; Ling Zou; Hongbin Zhang

2012-09-01

The suppression pool in a BWR plant not only is the major heat sink within the containment system, but also provides major emergency cooling water for the reactor core. In several accident scenarios, such as LOCA and extended station blackout, thermal stratification tends to form in the pool after the initial rapid venting stage. Accurately predicting the pool stratification phenomenon is important because it affects the peak containment pressure; and the pool temperature distribution also affects the NPSHa (Available Net Positive Suction Head) and therefore the performance of the pump which draws cooling water back to the core. Current safetymore » analysis codes use 0-D lumped parameter methods to calculate the energy and mass balance in the pool and therefore have large uncertainty in prediction of scenarios in which stratification and mixing are important. While 3-D CFD methods can be used to analyze realistic 3D configurations, these methods normally require very fine grid resolution to resolve thin substructures such as jets and wall boundaries, therefore long simulation time. For mixing in stably stratified large enclosures, the BMIX++ code has been developed to implement a highly efficient analysis method for stratification where the ambient fluid volume is represented by 1-D transient partial differential equations and substructures such as free or wall jets are modeled with 1-D integral models. This allows very large reductions in computational effort compared to 3-D CFD modeling. The POOLEX experiments at Finland, which was designed to study phenomena relevant to Nordic design BWR suppression pool including thermal stratification and mixing, are used for validation. GOTHIC lumped parameter models are used to obtain boundary conditions for BMIX++ code and CFD simulations. Comparison between the BMIX++, GOTHIC, and CFD calculations against the POOLEX experimental data is discussed in detail.« less

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.

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 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

A Matter of Classes: Stratifying Health Care Populations to Produce Better Estimates of Inpatient Costs

PubMed Central

Rein, David B

2005-01-01

Objective To stratify traditional risk-adjustment models by health severity classes in a way that is empirically based, is accessible to policy makers, and improves predictions of inpatient costs. Data Sources Secondary data created from the administrative claims from all 829,356 children aged 21 years and under enrolled in Georgia Medicaid in 1999. Study Design A finite mixture model was used to assign child Medicaid patients to health severity classes. These class assignments were then used to stratify both portions of a traditional two-part risk-adjustment model predicting inpatient Medicaid expenditures. Traditional model results were compared with the stratified model using actuarial statistics. Principal Findings The finite mixture model identified four classes of children: a majority healthy class and three illness classes with increasing levels of severity. Stratifying the traditional two-part risk-adjustment model by health severity classes improved its R2 from 0.17 to 0.25. The majority of additional predictive power resulted from stratifying the second part of the two-part model. Further, the preference for the stratified model was unaffected by months of patient enrollment time. Conclusions Stratifying health care populations based on measures of health severity is a powerful method to achieve more accurate cost predictions. Insurers who ignore the predictive advances of sample stratification in setting risk-adjusted premiums may create strong financial incentives for adverse selection. Finite mixture models provide an empirically based, replicable methodology for stratification that should be accessible to most health care financial managers. PMID:16033501

A statistically valid method for using FIA plots to guide spectral class rejection in producing stratification maps

Treesearch

Michael L. Hoppus; Andrew J. Lister

2002-01-01

A Landsat TM classification method (iterative guided spectral class rejection) produced a forest cover map of southern West Virginia that provided the stratification layer for producing estimates of timberland area from Forest Service FIA ground plots using a stratified sampling technique. These same high quality and expensive FIA ground plots provided ground reference...

Does quantifying epicardial and intrathoracic fat with noncontrast computed tomography improve risk stratification beyond calcium scoring alone?

PubMed

Forouzandeh, Farshad; Chang, Su Min; Muhyieddeen, Kamil; Zaid, Rashid R; Trevino, Alejandro R; Xu, Jiaqiong; Nabi, Faisal; Mahmarian, John J

2013-01-01

Noncontrast cardiac computed tomography allows calculation of coronary artery calcium score (CACS) and measurement of epicardial adipose tissue (EATv) and intrathoracic fat (ITFv) volumes. It is unclear whether fat volume information contributes to risk stratification. Cardiac computed tomography was performed in 760 consecutive patients with acute chest pain admitted thorough the emergency department. None had prior coronary artery disease. CACS was calculated using the Agatston method. EATv and ITFv were semiautomatically calculated. Median patient follow-up was 3.3 years. Mean patient age was 54.4±13.7 years and Framingham risk score 8.2±8.2. The 45 patients (5.9%) with major acute cardiac events (MACE) were older (64.8±13.9 versus 53.7±13.4 years), more frequently male (60% versus 40%), and had a higher median Framingham risk score (16 versus 4) and CACS (268 versus 0) versus those without events (all P<0.01). The MACE group had a higher median of EATv (154 versus 116 mL) and ITFv (330 versus 223 mL), and a higher prevalence of EATv >125 mL (67% versus 44%) and ITFv >250 mL (64% versus 42%) (all P<0.01). CACS, EATv, and ITFv were all independently associated with MACE. CACS was associated with MACE after adjustment for fat volumes (P<0.0001), whereas EATv and ITFv improved the risk model only in patients with CACS >400. CACS and fat volumes are independently associated with MACE in acute chest pain patients and beyond that provided by clinical information alone. Although fat volumes may add prognostic value in patients with CACS >400, CACS is most strongly correlated with outcome.

Risk stratification of patients with severe heart failure awaiting heart transplantation-prospective national registry POLKARD HF.

PubMed

Zieliński, T; Browarek, A; Zembala, M; Sadowski, J; Zakliczyński, M; Przybylowski, P; Roguski, K; Kosakowska, A B; Korewicki, J

2009-10-01

Most methods used in the risk assessment of heart transplant candidates do not include new biomarkers. The aim of the study was to examine the value of NTproBNP and hsCRP and their combined use together with HFSS score in the risk assessment of patients with heart failure enlisted for heart transplantation. Data of 658 patients enlisted for heart transplantation in all active transplantation centers were stored in a prospective registry. The composite end point-death or urgent transplantation was recorded during the follow-up. Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%) patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for risk of death or urgent transplantation where highly significant when pts were stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to the hsCRP level on admission (P < .002). In the multivariate Cox proportional hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P < .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the area under the curve (AUC) values were considered, AUC area was for HFSS - 0.645, for NTproBNP - 0.653 and for hsCRP - 0.566. When all those variables were included together in the model, the AUC value rose to 0.6943. Based on those results a weighted risk model with all three parameters was proposed. HFSS, NTproBNP and hsCRP levels are independent stratification variables of survival or need for urgent heart transplantation. Their predictive value is moderately increased when they are analyzed together.

Estimating the heterogeneous relationship between peer drinking and youth alcohol consumption in Chile using propensity score stratification.

PubMed

Han, Yoonsun; Grogan-Kaylor, Andrew; Delva, Jorge; Xie, Yu

2014-11-17

When estimating the association between peer and youth alcohol consumption, it is critical to account for possible differential levels of response to peer socialization processes across youth, in addition to variability in individual, family, and social factors. Failure to account for intrinsic differences in youth's response to peers may pose a threat of selection bias. To address this issue, we used a propensity score stratification method to examine whether the size of the association between peer and youth drinking is contingent upon differential predicted probabilities of associating with alcohol-consuming friends. Analyzing a Chilean youth sample (N = 914) of substance use, we found that youths are susceptible to the detrimental role of peer drinkers, but the harmful relationship with one's own drinking behavior may be exacerbated among youth who already have a high probability of socializing with peers who drink. In other words, computing a single weighted-average estimate for peer drinking would have underestimated the detrimental role of peers, particularly among at-risk youths, and overestimated the role of drinking peers among youths who are less susceptible to peer socialization processes. Heterogeneous patterns in the association between peer and youth drinking may shed light on social policies that target at-risk youths.

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.

A comparison of five methods of measuring mammographic density: a case-control study.

PubMed

Astley, Susan M; Harkness, Elaine F; Sergeant, Jamie C; Warwick, Jane; Stavrinos, Paula; Warren, Ruth; Wilson, Mary; Beetles, Ursula; Gadde, Soujanya; Lim, Yit; Jain, Anil; Bundred, Sara; Barr, Nicola; Reece, Valerie; Brentnall, Adam R; Cuzick, Jack; Howell, Tony; Evans, D Gareth

2018-02-05

High mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening. Women participating in the "Predicting Risk Of Cancer At Screening" (PROCAS) study, a study of cancer risk, completed questionnaires to provide personal information to enable computation of the Tyrer-Cuzick risk score. Mammographic density was assessed by visual analogue scale (VAS), thresholding (Cumulus) and fully-automated methods (Densitas, Quantra, Volpara) in contralateral breasts of 366 women with unilateral breast cancer (cases) detected at screening on entry to the study (Cumulus 311/366) and in 338 women with cancer detected subsequently. Three controls per case were matched using age, body mass index category, hormone replacement therapy use and menopausal status. Odds ratios (OR) between the highest and lowest quintile, based on the density distribution in controls, for each density measure were estimated by conditional logistic regression, adjusting for classic risk factors. The strongest predictor of screen-detected cancer at study entry was VAS, OR 4.37 (95% CI 2.72-7.03) in the highest vs lowest quintile of percent density after adjustment for classical risk factors. Volpara, Densitas and Cumulus gave ORs for the highest vs lowest quintile of 2.42 (95% CI 1.56-3.78), 2.17 (95% CI 1.41-3.33) and 2.12 (95% CI 1.30-3.45), respectively. Quantra was not significantly associated with breast cancer (OR 1.02, 95% CI 0.67-1.54). Similar results were found for subsequent cancers, with ORs of 4.48 (95% CI 2.79-7.18), 2.87 (95% CI 1.77-4.64) and 2.34 (95% CI 1.50-3.68) in highest vs lowest quintiles of VAS, Volpara and Densitas, respectively. Quantra gave an OR in the highest vs lowest quintile of 1.32 (95% CI 0.85-2.05). Visual density assessment demonstrated a strong relationship with cancer, despite known inter-observer variability; however, it is impractical for population-based screening. Percentage density measured by Volpara and Densitas also had a strong association with breast cancer risk, amongst the automated measures evaluated, providing practical automated methods for risk stratification.

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.

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 (

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

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

PubMed

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

2017-06-01

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

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.

Psychiatric Disorders, High-Risk Behaviors, and Chronicity of Episodes Among Predominantly African American Homeless Chicago Youth

PubMed Central

Castro, Anne L.; Gustafson, Erika L.; Ford, Ashley E.; Edidin, Jennifer P.; Smith, Dale L.; Hunter, Scott J.; Karnik, Niranjan S.

2014-01-01

Objective This cross-sectional study investigated the relationships between psychiatric and substance-related disorders, high-risk behaviors, and the onset, duration, and frequency of homelessness among homeless youth in Chicago. Methods Sixty-six homeless youth were recruited from two shelters in Chicago. Demographic characteristics, psychopathology, substance use, and risk behaviors were assessed for each participant. Results Increased frequency and duration of homeless episodes were positively correlated with higher rates of psychiatric diagnoses. Increased number of psychiatric diagnoses was positively correlated with increased high-risk behaviors. Participants with diagnoses of Current Suicidality, Manic Episodes, Obsessive Compulsive Disorder, Substance Abuse, and Psychotic Disorder had a higher chronicity of homelessness than those without diagnoses. Conclusions Significant differences were evident between the three time parameters, suggesting that stratification of data by different time variables may benefit homelessness research by identifying meaningful subgroups who may benefit from individualized interventions. PMID:25130234

Postoperative urinary retention after inguinal hernia repair: a single institution experience.

PubMed

Blair, A B; Dwarakanath, A; Mehta, A; Liang, H; Hui, X; Wyman, C; Ouanes, J P P; Nguyen, H T

2017-12-01

Inguinal hernia repair is a common general surgery procedure with low morbidity. However, postoperative urinary retention (PUR) occurs in up to 22% of patients, resulting in further extraneous treatments.This single institution series investigates whether patient comorbidities, surgical approaches, and anesthesia methods are associated with developing PUR after inguinal hernia repairs. This is a single institution retrospective review of inguinal hernia from 2012 to 2015. PUR was defined as patients without a postoperative urinary catheter who subsequently required bladder decompression due to an inability to void. Univariate and multivariate logistic regressions were performed to quantify the associations between patient, surgical, and anesthetic factors with PUR. Stratification analysis was conducted at age of 50 years. 445 patients were included (42.9% laparoscopic and 57.1% open). Overall rate of PUR was 11.2% (12% laparoscopic, 10.6% open, and p = 0.64). In univariate analysis, PUR was significantly associated with patient age >50 and history of benign prostatic hyperplasia (BPH). Risk stratification for age >50 revealed in this cohort a 2.49 times increased PUR risk with lack of intraoperative bladder decompression (p = 0.013). At our institution, we found that patient age, history of BPH, and bilateral repair were associated with PUR after inguinal hernia repair. No association was found with PUR and laparoscopic vs open approach. Older males may be at higher risk without intraoperative bladder decompression, and therefore, catheter placement should be considered in this population, regardless of surgical approach.

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

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

Computer-Aided Nodule Assessment and Risk Yield Risk Management of Adenocarcinoma: The Future of Imaging?

PubMed

Foley, Finbar; Rajagopalan, Srinivasan; Raghunath, Sushravya M; Boland, Jennifer M; Karwoski, Ronald A; Maldonado, Fabien; Bartholmai, Brian J; Peikert, Tobias

2016-01-01

Increased clinical use of chest high-resolution computed tomography results in increased identification of lung adenocarcinomas and persistent subsolid opacities. However, these lesions range from very indolent to extremely aggressive tumors. Clinically relevant diagnostic tools to noninvasively risk stratify and guide individualized management of these lesions are lacking. Research efforts investigating semiquantitative measures to decrease interrater and intrarater variability are emerging, and in some cases steps have been taken to automate this process. However, many such methods currently are still suboptimal, require validation and are not yet clinically applicable. The computer-aided nodule assessment and risk yield software application represents a validated tool for the automated, quantitative, and noninvasive tool for risk stratification of adenocarcinoma lung nodules. Computer-aided nodule assessment and risk yield correlates well with consensus histology and postsurgical patient outcomes, and therefore may help to guide individualized patient management, for example, in identification of nodules amenable to radiological surveillance, or in need of adjunctive therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Properties of the endogenous post-stratified estimator using a random forests model

Treesearch

John Tipton; Jean Opsomer; Gretchen G. Moisen

2012-01-01

Post-stratification is used in survey statistics as a method to improve variance estimates. In traditional post-stratification methods, the variable on which the data is being stratified must be known at the population level. In many cases this is not possible, but it is possible to use a model to predict values using covariates, and then stratify on these predicted...

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

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

Multiscale analysis of heart rate dynamics: entropy and time irreversibility measures.

PubMed

Costa, Madalena D; Peng, Chung-Kang; Goldberger, Ary L

2008-06-01

Cardiovascular signals are largely analyzed using traditional time and frequency domain measures. However, such measures fail to account for important properties related to multiscale organization and non-equilibrium dynamics. The complementary role of conventional signal analysis methods and emerging multiscale techniques, is, therefore, an important frontier area of investigation. The key finding of this presentation is that two recently developed multiscale computational tools--multiscale entropy and multiscale time irreversibility--are able to extract information from cardiac interbeat interval time series not contained in traditional methods based on mean, variance or Fourier spectrum (two-point correlation) techniques. These new methods, with careful attention to their limitations, may be useful in diagnostics, risk stratification and detection of toxicity of cardiac drugs.

Multiscale Analysis of Heart Rate Dynamics: Entropy and Time Irreversibility Measures

PubMed Central

Peng, Chung-Kang; Goldberger, Ary L.

2016-01-01

Cardiovascular signals are largely analyzed using traditional time and frequency domain measures. However, such measures fail to account for important properties related to multiscale organization and nonequilibrium dynamics. The complementary role of conventional signal analysis methods and emerging multiscale techniques, is, therefore, an important frontier area of investigation. The key finding of this presentation is that two recently developed multiscale computational tools— multiscale entropy and multiscale time irreversibility—are able to extract information from cardiac interbeat interval time series not contained in traditional methods based on mean, variance or Fourier spectrum (two-point correlation) techniques. These new methods, with careful attention to their limitations, may be useful in diagnostics, risk stratification and detection of toxicity of cardiac drugs. PMID:18172763

Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis

PubMed Central

Asayama, Kei; Thijs, Lutgarde; Brguljan-Hitij, Jana; Niiranen, Teemu J.; Hozawa, Atsushi; Boggia, José; Aparicio, Lucas S.; Hara, Azusa; Johansson, Jouni K.; Ohkubo, Takayoshi; Tzourio, Christophe; Stergiou, George S.; Sandoya, Edgardo; Tsuji, Ichiro; Jula, Antti M.; Imai, Yutaka; Staessen, Jan A.

2014-01-01

Background The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP). Methods and Findings This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100. Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries. Conclusions HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings. Please see later in the article for the Editors' Summary PMID:24465187

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.

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

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.

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

Predictor characteristics necessary for building a clinically useful risk prediction model: a simulation study.

PubMed

Schummers, Laura; Himes, Katherine P; Bodnar, Lisa M; Hutcheon, Jennifer A

2016-09-21

Compelled by the intuitive appeal of predicting each individual patient's risk of an outcome, there is a growing interest in risk prediction models. While the statistical methods used to build prediction models are increasingly well understood, the literature offers little insight to researchers seeking to gauge a priori whether a prediction model is likely to perform well for their particular research question. The objective of this study was to inform the development of new risk prediction models by evaluating model performance under a wide range of predictor characteristics. Data from all births to overweight or obese women in British Columbia, Canada from 2004 to 2012 (n = 75,225) were used to build a risk prediction model for preeclampsia. The data were then augmented with simulated predictors of the outcome with pre-set prevalence values and univariable odds ratios. We built 120 risk prediction models that included known demographic and clinical predictors, and one, three, or five of the simulated variables. Finally, we evaluated standard model performance criteria (discrimination, risk stratification capacity, calibration, and Nagelkerke's r 2 ) for each model. Findings from our models built with simulated predictors demonstrated the predictor characteristics required for a risk prediction model to adequately discriminate cases from non-cases and to adequately classify patients into clinically distinct risk groups. Several predictor characteristics can yield well performing risk prediction models; however, these characteristics are not typical of predictor-outcome relationships in many population-based or clinical data sets. Novel predictors must be both strongly associated with the outcome and prevalent in the population to be useful for clinical prediction modeling (e.g., one predictor with prevalence ≥20 % and odds ratio ≥8, or 3 predictors with prevalence ≥10 % and odds ratios ≥4). Area under the receiver operating characteristic curve values of >0.8 were necessary to achieve reasonable risk stratification capacity. Our findings provide a guide for researchers to estimate the expected performance of a prediction model before a model has been built based on the characteristics of available predictors.

Eigenmode resonance in a two-layer stratification

NASA Astrophysics Data System (ADS)

Kanda, Isao; Linden, P. F.

2002-06-01

In this paper, we study the velocity field at the density interface of a two-layer stratification system when the flow is forced at the mid-depth of the lower layer by the source sink forcing method. It is known that, in a sufficiently strong linear stratification, the source sink forcing in certain configurations produces a single-vortex pattern which corresponds to the lowest eigenmode of the Helmholtz equation (Kanda & Linden 2001). Two types of forcing configuration are used for the two-layer experiments: one that leads to a steady single-vortex pattern in a linear stratification, and one that results in an unsteady irregular state. Strong single-vortex patterns appear intermittently for the former configurations despite the absence of stratification at the forcing height. When the single-vortex pattern occurs at the density interface, a similar flow field extends down to the forcing height. The behaviour is explained as the coupling of the resonant eigenmode at the interface with the horizontal component of the forcing jets. The results show that stratification can organise a flow, even though it is forced by an apparently random three-dimensional forcing.

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

NASA Technical Reports Server (NTRS)

Hohnloser, Stefan H.; Klingenheben, Thomas; Bloomfield, Daniel; Dabbous, Omar; Cohen, Richard J.

2003-01-01

OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.

Malaria Risk Mapping for Control in the Republic of Sudan

PubMed Central

Noor, Abdisalan M.; ElMardi, Khalid A.; Abdelgader, Tarig M.; Patil, Anand P.; Amine, Ahmed A. A.; Bakhiet, Sahar; Mukhtar, Maowia M.; Snow, Robert W.

2012-01-01

Evidence shows that malaria risk maps are rarely tailored to address national control program ambitions. Here, we generate a malaria risk map adapted for malaria control in Sudan. Community Plasmodium falciparum parasite rate (PfPR) data from 2000 to 2010 were assembled and were standardized to 2–10 years of age (PfPR2–10). Space-time Bayesian geostatistical methods were used to generate a map of malaria risk for 2010. Surfaces of aridity, urbanization, irrigation schemes, and refugee camps were combined with the PfPR2–10 map to tailor the epidemiological stratification for appropriate intervention design. In 2010, a majority of the geographical area of the Sudan had risk of < 1% PfPR2–10. Areas of meso- and hyperendemic risk were located in the south. About 80% of Sudan's population in 2011 was in the areas in the desert, urban centers, or where risk was < 1% PfPR2–10. Aggregated data suggest reducing risks in some high transmission areas since the 1960s. PMID:23033400

Chemotherapy Response Assessment by FDG-PET-CT in Early-stage Classical Hodgkin Lymphoma: Moving Beyond the Five-Point Deauville Score

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

Milgrom, Sarah A., E-mail: samilgrom@mdanderson.org; Dong, Wenli; Akhtari, Mani

Purpose: In early-stage classical Hodgkin lymphoma, fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans are performed routinely after chemotherapy, and the 5-point Deauville score is used to report the disease response. We hypothesized that other PET-CT parameters, considered in combination with Deauville score, would improve risk stratification. Methods and Materials: Patients treated for stage I to II Hodgkin lymphoma from 2003 to 2013, who were aged ≥18 years and had analyzable PET-CT scans performed before and after chemotherapy, were eligible. The soft tissue volume (STV), maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were recorded from the PET-CTmore » scans before and after chemotherapy. Reductions were defined as 1 − (final PET-CT value)/(corresponding initial PET-CT value). The primary endpoint was freedom from progression (FFP). Results: For 202 patients treated with chemotherapy with or without radiation therapy, the 5-year FFP was 89% (95% confidence interval 85%-93%). All PET-CT parameters were strongly associated with the Deauville score (P<.001) and FFP (P<.0001) on univariate analysis. The Deauville score was highly predictive of FFP (C-index 0.89) but was less discriminating in the Deauville 1 to 4 subset (C-index 0.67). Therefore, we aimed to identify PET-CT parameters that would improve risk stratification for this subgroup (n=187). STV reduction was predictive of outcome (C-index 0.71) and was dichotomized with an optimal cutoff of 0.65 (65% reduction in STV). A model incorporating the Deauville score and STV reduction predicted FFP more accurately than either measurement alone in the Deauville 1 to 4 subset (C-index 0.83). The improvement in predictive accuracy of this composite measure compared with the Deauville score alone met statistical significance (P=.045). Conclusions: The relative reduction in tumor size is an independent predictor of outcome. Combined with the Deauville score, it might improve risk stratification and contribute to response-adapted individualization of therapy.« less

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.

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

[Genetic testing in polygenic diseases : Atrial fibrillation, arterial hypertension and coronary artery disease].

PubMed

Trenkwalder, T; Kessler, T; Schunkert, H

2017-08-01

Genetic testing plays an increasing role in cardiovascular medicine. Advances in technology and the development of novel and more affordable (high throughput) methods have led to the identification of genetic risk factors in research and clinical practice. Also, this progress has simplified the screening of patients and individuals at risk. In case of rare monogenic diseases, diagnostics, risk stratification, and, in some cases, treatment decisions have become easier. For common, polygenic cardiovascular diseases, the situation is more complex due to interaction of modifiable external risk factors and nonmodifiable factors like genetic predisposition. Over the last few years, it has been shown that multiple genes are involved in the pathophysiology of these cardiovascular diseases rather than one single gene. In the following article, we give an overview of the genetic risk factors in polygenic cardiovascular diseases as atrial fibrillation, arterial hypertension and coronary artery disease. Furthermore, we aim to illustrate in which cases genetic testing is recommended in these diseases.

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.

Predictive risk stratification model: a progressive cluster-randomised trial in chronic conditions management (PRISMATIC) research protocol

PubMed Central

2013-01-01

Background An ageing population increases demand on health and social care. New approaches are needed to shift care from hospital to community and general practice. A predictive risk stratification tool (Prism) has been developed for general practice that estimates risk of an emergency hospital admission in the following year. We present a protocol for the evaluation of Prism. Methods/Design We will undertake a mixed methods progressive cluster-randomised trial. Practices begin as controls, delivering usual care without Prism. Practices will receive Prism and training randomly, and thereafter be able to use Prism with clinical and technical support. We will compare costs, processes of care, satisfaction and patient outcomes at baseline, 6 and 18 months, using routine data and postal questionnaires. We will assess technical performance by comparing predicted against actual emergency admissions. Focus groups and interviews will be undertaken to understand how Prism is perceived and adopted by practitioners and policy makers. We will model data using generalised linear models and survival analysis techniques to determine whether any differences exist between intervention and control groups. We will take account of covariates and explanatory factors. In the economic evaluation we will carry out a cost-effectiveness analysis to examine incremental cost per emergency admission to hospital avoided and will examine costs versus changes in primary and secondary outcomes in a cost-consequence analysis. We will also examine changes in quality of life of patients across the risk spectrum. We will record and transcribe focus groups and interviews and analyse them thematically. We have received full ethical and R&D approvals for the study and Information Governance Review Panel (IGRP) permission for the use of routine data. We will comply with the CONSORT guidelines and will disseminate the findings at national and international conferences and in peer-reviewed journals. Discussion The proposed study will provide information on costs and effects of Prism; how it is used in practice, barriers and facilitators to its implementation; and its perceived value in supporting the management of patients with and at risk of developing chronic conditions. Trial registration Controlled Clinical Trials ISRCTN no. ISRCTN55538212. PMID:24330749

Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications

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

Waxweiler, Timothy V., E-mail: timothy.waxweiler@ucdenver.edu; Rusthoven, Chad G.; Proper, Michelle S.

Purpose: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. Methods and Materials: From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex,more » year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. Results: A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P<.001). Conclusions: The current COG risk group stratification for children with NRSTS has been validated with a large number of children in the SEER database.« less

Assessment of left atrial appendage function by transthoracic pulsed Doppler echocardiography: Comparing against transesophageal interrogation and predicting echocardiographic risk factors for stroke.

PubMed

Wai, Shin Hnin; Kyu, Kyu; Galupo, Mary Joyce; Songco, Geronica G; Kong, William K F; Lee, Chi Hang; Yeo, Tiong Cheng; Poh, Kian Keong

2017-10-01

Transesophageal echocardiographic (TEE) findings of left atrial appendage (LAA) thrombus, spontaneous echo contrast (SEC), and LAA dysfunction are established risk factors of cardioembolic stroke. The semi-invasive nature of TEE limits its utility as a routine risk stratification tool. We aim to correlate TEE and transthoracic echocardiography (TTE) pulsed Doppler measurements of LAA flow velocities and use TTE measurements to predict TEE findings. We prospectively measured pulsed Doppler LAA flow velocities in 103 consecutive patients on TEE and TTE. There was a strong correlation between TEE and TTE LAA emptying velocity (LAA E) (r = .88, P < .001) and a moderate correlation between LAA filling velocities (r = .50, P < .001). TTE LAA E predicted the presence of thrombus or SEC independent of atrial fibrillation (AF). To predict the presence of thrombus or SEC, the optimal TTE LAA E cutoff was ≤30 cm/s in all patients (75% sensitive, 90% specific) and ≤31 cm/s in AF patients (80% sensitive, 79% specific). To predict LAA dysfunction (TEE E ≤ 20 cm/s), the optimal TTE LAA E cutoff was ≤27 cm/s (100% sensitive, 89% specific in all patients and 100% sensitive, 74% specific in AF patients). TTE assessment of LAA function is feasible and correlates well with the more invasive TEE method. It predicts the presence of thrombus, SEC, and LAA dysfunction on TEE. TTE LAA assessment has incremental value in thromboembolic risk stratification and should be utilized more frequently. © 2017, Wiley Periodicals, Inc.

Metabolic Profiles Predict Adverse Events Following Coronary Artery Bypass Grafting

PubMed Central

Shah, Asad A.; Craig, Damian M.; Sebek, Jacqueline K.; Haynes, Carol; Stevens, Robert C.; Muehlbauer, Michael J.; Granger, Christopher B.; Hauser, Elizabeth R.; Newby, L. Kristin; Newgard, Christopher B.; Kraus, William E.; Hughes, G. Chad; Shah, Svati H.

2012-01-01

Objectives Clinical models incompletely predict outcomes following coronary artery bypass grafting. Novel molecular technologies may identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. Methods The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected prior to surgery. Principal-components analysis and Cox proportional hazards regression modeling were used to assess the relation between metabolite factor levels and a composite outcome of post-coronary artery bypass grafting myocardial infarction, need for percutaneous coronary intervention, repeat coronary artery bypass grafting, or death. Results Over a mean follow-up of 4.3 ± 2.4 years, 126 subjects (26.4%) suffered an adverse event. Three principal-components analysis-derived factors were significantly associated with adverse outcome in univariable analysis: short-chain dicarboxylacylcarnitines (factor 2, P=0.001); ketone-related metabolites (factor 5, P=0.02); and short-chain acylcarnitines (factor 6, P=0.004). These three factors remained independently predictive of adverse outcome after multivariable adjustment: factor 2 (adjusted hazard ratio 1.23; 95% confidence interval [1.10-1.38]; P<0.001), factor 5 (1.17 [1.01-1.37], P=0.04), and factor 6 (1.14 [1.02-1.27], P=0.03). Conclusions Metabolic profiles are independently associated with adverse outcomes following coronary artery bypass grafting. These profiles may represent novel biomarkers of risk that augment existing tools for risk stratification of coronary artery bypass grafting patients and may elucidate novel biochemical pathways that mediate risk. PMID:22306227

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.

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.

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.

Obesity as a risk factor for developing functional limitation among older adults: A conditional inference tree analysis.

PubMed

Cheng, Feon W; Gao, Xiang; Bao, Le; Mitchell, Diane C; Wood, Craig; Sliwinski, Martin J; Smiciklas-Wright, Helen; Still, Christopher D; Rolston, David D K; Jensen, Gordon L

2017-07-01

To examine the risk factors of developing functional decline and make probabilistic predictions by using a tree-based method that allows higher order polynomials and interactions of the risk factors. The conditional inference tree analysis, a data mining approach, was used to construct a risk stratification algorithm for developing functional limitation based on BMI and other potential risk factors for disability in 1,951 older adults without functional limitations at baseline (baseline age 73.1 ± 4.2 y). We also analyzed the data with multivariate stepwise logistic regression and compared the two approaches (e.g., cross-validation). Over a mean of 9.2 ± 1.7 years of follow-up, 221 individuals developed functional limitation. Higher BMI, age, and comorbidity were consistently identified as significant risk factors for functional decline using both methods. Based on these factors, individuals were stratified into four risk groups via the conditional inference tree analysis. Compared to the low-risk group, all other groups had a significantly higher risk of developing functional limitation. The odds ratio comparing two extreme categories was 9.09 (95% confidence interval: 4.68, 17.6). Higher BMI, age, and comorbid disease were consistently identified as significant risk factors for functional decline among older individuals across all approaches and analyses. © 2017 The Obesity Society.

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.

Outpatient management of community-acquired pneumonia.

PubMed

Froes, Filipe; Pereira, João Gonçalves; Póvoa, Pedro

2018-04-01

The first guidelines on community-acquired pneumonia (CAP) were published in 1993, but since then many of the challenges regarding the outpatient management of CAP persist. These include the difficulty in establishing the initial clinical diagnosis, its risk stratification, which will dictate the place of treatment, the empirical choice of antibiotics, the relative scarcity of novel antibiotics and the importance of knowing local microbiological susceptibility patterns. New molecular biology methods have changed the etiologic perspective of CAP, especially the contribution of virus. Lung ultrasound and biomarkers might aid diagnosis and severity stratification in the outpatient setting. Antibiotic resistance is a growing problem that reinforces the importance of novel antibiotics. And finally, prevention and the use of anti-pneumococcal vaccine are instrumental in reducing the burden of disease. Most of CAP cases are managed in the community; however, most research comes from hospitalized severe patients. New and awaited advances might contribute to aid diagnosis, cause and assessment of patients with CAP in the community. This knowledge might prove decisive in the execution of stewardship programmes that maintain current antibiotics, safeguard future ones and reinforce prevention.

Distinctive clinical course and pattern of relapse in adolescents with medulloblastoma

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

Tabori, Uri; Sung, Lillian; Hukin, Juliette

2006-02-01

Purpose: To report the clinical course of adolescents with medulloblastoma, with specific emphasis on prognosis and pattern of relapse. Methods and Materials: We retrospectively studied the clinical course and outcomes of children aged 10-20 years with medulloblastoma, treated at centers throughout Canada between 1986 and 2003. To better assess time to relapse, a cohort of patients aged 3-20 years at diagnosis was generated. Results: A total of 72 adolescents were analyzed. Five-year overall survival and event-free survival rates were 78.3% {+-} 5.4% and 68.0% {+-} 6.2%, respectively. Late relapses occurred at a median of 3.0 years (range, 0.3-6.8 years). Inmore » univariate analysis, conventional risk stratification and the addition of chemotherapy to craniospinal radiation did not have prognostic significance. Female patients had improved overall survival (p = 0.007). Time to relapse increased with age in a linear fashion. After relapse, patients faired poorly regardless of treatment modality. Patients who did not receive chemotherapy initially had improved progression-free survival at relapse (p 0.05). Conclusions: Our study suggests that adolescents with medulloblastoma might have a unique prognosis and pattern of relapse, dissimilar to those in younger children. They might benefit from different risk stratifications and prolonged follow-up. These issues should be addressed in future prospective trials.« less

The Molecular Classification of Medulloblastoma: Driving the next generation clinical trials

PubMed Central

Leary, Sarah E. S.; Olson, James M.

2012-01-01

Purpose of Review Most children diagnosed with cancer today are expected to be cured. Medulloblastoma, the most common pediatric malignant brain tumor, is an example of a disease that has benefitted from advances in diagnostic imaging, surgical techniques, radiation therapy and combination chemotherapy over the past decades. An incurable disease 50 years ago, approximately 70% of children with medulloblastoma are now cured of their disease. However, the pace of increasing the cure rate has slowed over the past two decades, and we have likely reached the maximal benefit that can be achieved with cytotoxic therapy and clinical risk stratification. Long-term toxicity of therapy also remains significant. To increase cure rates and decrease long-term toxicity, there is great interest in incorporating biologic “targeted” therapy into treatment of medulloblastoma, but this will require a paradigm shift in how we classify and study disease. Recent Findings Using genome-based high-throughput analytic techniques, several groups have independently reported methods of molecular classification of medulloblastoma within the past year. This has resulted in a working consensus to view medulloblastoma as four molecular subtypes including WNT pathway subtype, SHH pathway subtype, and two less well-defined subtypes, Group C and Group D. Summary Novel classification and risk stratification based on biologic subtypes of disease will form the basis of further study in medulloblastoma, and identify specific subtypes which warrant greater research focus. PMID:22189395

Do Risky Friends Change the Efficacy of a Primary Care Brief Intervention for Adolescent Alcohol Use?

PubMed Central

Louis-Jacques, Jennifer; Knight, John R; Sherritt, Lon; Van Hook, Shari; Harris, Sion K

2013-01-01

Purpose To determine if peer risk (having friends who drink or approve of drinking) modifies the effects of a computer-facilitated Screening and provider Brief Advice (cSBA) intervention on adolescent alcohol use. Methods We assessed intervention effect using logistic regression modeling with generalized estimating equations on a sample of 2092 adolescents. Effect modification by peer risk was analyzed separately for alcohol initiation (drinking at follow-up in baseline non-drinkers) and cessation (no drinking at follow-up in baseline drinkers) by testing an interaction term (treatment condition by peer risk). Interpretation of the interaction effect was further clarified by subsequent stratification by peer risk. Results The intervention effect on alcohol cessation was significantly greater among those with peer risk (aRRR: Risk 1.44, 1.18–1.76 vs. No Risk 0.98, 0.41–2.36) at 3 months follow-up. There was no such finding for alcohol initiation. Conclusions Alcohol screening and brief provider counseling may differentially benefit adolescent drinkers with drinking friends. PMID:24216313

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.

Development and Validation of a Deep Neural Network Model for Prediction of Postoperative In-hospital Mortality.

PubMed

Lee, Christine K; Hofer, Ira; Gabel, Eilon; Baldi, Pierre; Cannesson, Maxime

2018-04-17

The authors tested the hypothesis that deep neural networks trained on intraoperative features can predict postoperative in-hospital mortality. The data used to train and validate the algorithm consists of 59,985 patients with 87 features extracted at the end of surgery. Feed-forward networks with a logistic output were trained using stochastic gradient descent with momentum. The deep neural networks were trained on 80% of the data, with 20% reserved for testing. The authors assessed improvement of the deep neural network by adding American Society of Anesthesiologists (ASA) Physical Status Classification and robustness of the deep neural network to a reduced feature set. The networks were then compared to ASA Physical Status, logistic regression, and other published clinical scores including the Surgical Apgar, Preoperative Score to Predict Postoperative Mortality, Risk Quantification Index, and the Risk Stratification Index. In-hospital mortality in the training and test sets were 0.81% and 0.73%. The deep neural network with a reduced feature set and ASA Physical Status classification had the highest area under the receiver operating characteristics curve, 0.91 (95% CI, 0.88 to 0.93). The highest logistic regression area under the curve was found with a reduced feature set and ASA Physical Status (0.90, 95% CI, 0.87 to 0.93). The Risk Stratification Index had the highest area under the receiver operating characteristics curve, at 0.97 (95% CI, 0.94 to 0.99). Deep neural networks can predict in-hospital mortality based on automatically extractable intraoperative data, but are not (yet) superior to existing methods.

Prevalence and predictors of pathological gambling: results from the St. Louis personality, health and lifestyle (SLPHL) study

PubMed Central

Cunningham-Williams, Renee M.; Grucza, Richard A.; Cottler, Linda B.; Womack, Sharon B.; Books, Samantha J.; Przybeck, Thomas R.; Spitznagel, Edward L.; Cloninger, C. Robert

2006-01-01

Objectives We report the prevalence of and risk and protective factors for DSM-IV sub-threshold gambling (1–4 criteria) and pathological gambling disorder (PGD; 5–10 criteria) in a non-clinical household sample of St. Louis area gamblers. Methods Of the 7689 individuals contacted via Random Digit Dialing, 3292 were screened eligible. Of these, 1142 from households in 6 contiguous regions in Missouri and Illinois consented to participate and were mailed a St. Louis Area Personality, Health, and Lifestyle (SLPHL) Survey. Results Post-stratification weighted data (n = 913) indicate lifetime prevalence rates of 12.4% sub-threshold and 2.5% PGD (conditional prevalence = 21.5% and 4.3% respectively). Risk and protective factors for gambling severity varied in the sample. Conclusions Targeted prevention messages are warranted specifically for gamblers of varying risk for PGD. PMID:15804388

Development of an Echocardiographic Risk-Stratification Index to Predict Heart Failure in Patients With Stable Coronary Artery Disease

PubMed Central

Stevens, Steven M.; Farzaneh-Far, Ramin; Na, Beeya; Whooley, Mary A.; Schiller, Nelson B.

2009-01-01

OBJECTIVES We sought to determine which transthoracic echocardiographic (TTE) measurements most strongly predict heart failure (HF) and to develop an index for risk stratification in outpatients with coronary artery disease (CAD). BACKGROUND Many TTE measurements have been shown to be predictive of HF, and they might be useful if aggregated into a risk-prediction index. METHODS We performed TTE in 1,024 outpatients with stable CAD enrolled in the Heart and Soul study and followed them for 4.4 years. With Cox proportional hazard models, we evaluated the association of 15 TTE measurements with subsequent HF hospital stay. Those measurements that independently predicted HF were combined into an index. Variables were defined as normal or abnormal on the basis of dichotomous cutoffs determined from the American Society of Echocardiography. Abnormal variables in each measurement were assigned points on the basis of strength of association with HF. RESULTS Of the 15 variables, 5 measurements were independent predictors of HF: left ventricular mass index (LVMI), left atrial volume index (LAVI), mitral regurgitation (MR), left ventricular outflow tract velocity-time integral (VTILVOT), and diastolic dysfunction (DD). In multivariate analysis, each of the 5 measurements independently predicted HF: LVMI >90 g/m2 (hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.3 to 7.2, p < 0.0001); pseudo-normal or restrictive DD (HR: 2.9; 95% CI: 1.8 to 4.5, p < 0.0001); VTILVOT <22 mm (HR: 2.2; 95% CI: 1.4 to 3.5, p = 0.0004); mild, moderate, or severe MR (HR: 1.8; 95% CI: 1.2 to 2.8, p = 0.009); and LAVI >29 ml/m2 (HR: 1.6; 95% CI: 1.0 to 2.5, p = 0.06). Combining these measurements, the Heart Failure Index ranged from 0 to 8, representing risk as follows: 3 points for LVMI, 2 points for DD, and 1 point for VTILVOT, MR, and LAVI. Among participants with 0 to 2 points: 4% had HF hospital stays (reference); 3 to 4 points: 10% (HR: 2.4; 95% CI: 1.3 to 4.4, p = 0.003); 5 to 6 points: 24% (HR: 6.2; 95% CI: 3.6 to 10.6, p < 0.0001); 7 to 8 points: 48% (HR: 13.7; 95% CI: 7.2 to 25.9, p < 0.0001). CONCLUSIONS We identified 5 TTE measurements that independently predict HF in patients with stable CAD and combined them as an index that might be useful for risk stratification and serial observations. PMID:19356527

An Interoperable System toward Cardiac Risk Stratification from ECG Monitoring

PubMed Central

Mora-Jiménez, Inmaculada; Ramos-López, Javier; Quintanilla Fernández, Teresa; García-García, Antonio; Díez-Mazuela, Daniel; García-Alberola, Arcadi

2018-01-01

Many indices have been proposed for cardiovascular risk stratification from electrocardiogram signal processing, still with limited use in clinical practice. We created a system integrating the clinical definition of cardiac risk subdomains from ECGs and the use of diverse signal processing techniques. Three subdomains were defined from the joint analysis of the technical and clinical viewpoints. One subdomain was devoted to demographic and clinical data. The other two subdomains were intended to obtain widely defined risk indices from ECG monitoring: a simple-domain (heart rate turbulence (HRT)), and a complex-domain (heart rate variability (HRV)). Data provided by the three subdomains allowed for the generation of alerts with different intensity and nature, as well as for the grouping and scrutinization of patients according to the established processing and risk-thresholding criteria. The implemented system was tested by connecting data from real-world in-hospital electronic health records and ECG monitoring by considering standards for syntactic (HL7 messages) and semantic interoperability (archetypes based on CEN/ISO EN13606 and SNOMED-CT). The system was able to provide risk indices and to generate alerts in the health records to support decision-making. Overall, the system allows for the agile interaction of research and clinical practice in the Holter-ECG-based cardiac risk domain. PMID:29494497

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.

USA Stratified Monopoly: A Simulation Game about Social Class Stratification

ERIC Educational Resources Information Center

Fisher, Edith M.

2008-01-01

Effectively teaching college students about social class stratification is a difficult challenge. Explanations for this difficulty tend to focus on the students who often react with resistance, paralysis, or rage. Sociologists have been using games and simulations as alternative methods for several decades to teach about these sensitive subjects.…

Properties of Endogenous Post-Stratified Estimation using remote sensing data

Treesearch

John Tipton; Jean Opsomer; Gretchen Moisen

2013-01-01

Post-stratification is commonly used to improve the precision of survey estimates. In traditional poststratification methods, the stratification variable must be known at the population level. When suitable covariates are available at the population level, an alternative approach consists of fitting a model on the covariates, making predictions for the population and...

Structural Analysis of a Consumption-Based Stratification Indicator: Relational Proximity of Household Expenditures

ERIC Educational Resources Information Center

Katz-Gerro, Tally; Talmud, Ilan

2005-01-01

This paper proposes a new analysis of consumption inequality using relational methods, derived from network images of social structure. We combine structural analysis with theoretical concerns in consumer research to propose a relational theory of consumption space, to construct a stratification indicator, and to demonstrate its analytical…

Quantitative description of the effect of stratification on dormancy release of grape seeds in response to various temperatures and water contents

PubMed Central

Wang, W. Q.; Song, S. Q.; Li, S. H.; Gan, Y. Y.; Wu, J. H.; Cheng, H. Y.

2009-01-01

The effect of stratification on dormancy release of grape seeds crossing from the sub- to the supraoptimal range of temperatures and water contents was analysed by modified threshold models. The stratification impacted on dormancy release in three different ways: (i) dormancy was consistently released with prolonged stratification time when stratified at temperatures of <15 °C; (ii) at 15 °C and 20 °C, the stratification effect initially increased, and then decreased with extended time; and (iii) stratification at 25 °C only reduced germinable seeds. These behaviours indicated that stratification could not only release primary dormancy but also induce secondary dormancy in grape seed. The rate of dormancy release changed linearly in two phases, while induction increased exponentially with increasing temperature. The thermal time approaches effectively quantified dormancy release only at suboptimal temperature, but a quantitative method to integrate the occurrence of dormancy release and induction at the same time could describe it well at either sub- or supraoptimal temperatures. The regression with the percentage of germinable seeds versus stratification temperature or water content within both the sub- and supraoptimal range revealed how the optimal temperature (Tso) and water content (Wso) for stratification changed. The Tso moved from 10.6 °C to 5.3 °C with prolonged time, while Wso declined from >0.40 g H2O g DW−1 at 5 °C to ∼0.23 g H2O g DW−1 at 30 °C. Dormancy release in grape seeds can occur across a very wide range of conditions, which has important implications for their ability to adapt to a changeable environment in the wild. PMID:19491305

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.

Medical Conditions in the First Years of Life Associated with Future Diagnosis of ASD in Children.

PubMed

Alexeeff, Stacey E; Yau, Vincent; Qian, Yinge; Davignon, Meghan; Lynch, Frances; Crawford, Phillip; Davis, Robert; Croen, Lisa A

2017-07-01

This study examines medical conditions diagnosed prior to the diagnosis of autism spectrum disorder (ASD). Using a matched case control design with 3911 ASD cases and 38,609 controls, we found that 38 out of 79 medical conditions were associated with increased ASD risk. Developmental delay, mental health, and neurology conditions had the strongest associations (ORs 2.0-23.3). Moderately strong associations were observed for nutrition, genetic, ear nose and throat, and sleep conditions (ORs 2.1-3.2). Using machine learning methods, we clustered children based on their medical conditions prior to ASD diagnosis and demonstrated ASD risk stratification. Our findings provide new evidence indicating that children with ASD have a disproportionate burden of certain medical conditions preceding ASD diagnosis.

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.

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.

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.

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.

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

PubMed

Wentzensen, Nicolas; Wacholder, Sholom

2013-02-01

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

Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

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

Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu; Yusuf, Mehran; Cash, Elizabeth

Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016),more » and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant.« less

B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

PubMed Central

Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

2014-01-01

Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

Covariance of biophysical data with digital topograpic and land use maps over the FIFE site

NASA Technical Reports Server (NTRS)

Davis, F. W.; Schimel, D. S.; Friedl, M. A.; Michaelsen, J. C.; Kittel, T. G. F.; Dubayah, R.; Dozier, J.

1992-01-01

This paper discusses the biophysical stratification of the FIFE site, implementation of the stratification utilizing geographic information system methods, and validation of the stratification with respect to field measurements of biomass, Bowen ratio, soil moisture, and the greenness vegetation index (GVI) derived from TM satellite data. Maps of burning and topographic position were significantly associated with variation in GVI, biomass, and Bowen ratio. The stratified design did not significantly alter the estimated site-wide means for surface climate parameters but accounted for between 25 and 45 percent of the sample variance depending on the variable.

CANARY Risk Management of Adenocarcinoma: The Future of Imaging?

PubMed Central

Foley, Finbar; Rajagopalan, Srinivasan; Raghunath, Sushravya M; Boland, Jennifer M; Karwoski, Ronald A.; Maldonado, Fabien; Bartholmai, Brian J; Peikert, Tobias

2016-01-01

Increased clinical utilization of chest high resolution computed tomography results in increased identification of lung adenocarcinomas and persistent sub-solid opacities. However, these lesions range from very indolent to extremely aggressive tumors. Clinically relevant diagnostic tools to non-invasively risk stratify and guide individualized management of these lesions are lacking. Research efforts investigating semi-quantitative measures to decrease inter- and intra-rater variability are emerging, and in some cases steps have been taken to automate this process. However, many such methods currently are still sub-optimal, require validation and are not yet clinically applicable. The Computer-Aided Nodule Assessment and Risk Yield (CANARY) software application represents a validated tool for the automated, quantitative, non-invasive tool for risk stratification of adenocarcinoma lung nodules. CANARY correlates well with consensus histology and post-surgical patient outcomes and therefore may help to guide individualized patient management e.g. in identification of nodules amenable to radiological surveillance, or in need of adjunctive therapy. PMID:27568149

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.

The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy.

PubMed

Fernandes Serôdio, João; Martins Oliveira, Mário; Matoso Laranjo, Sérgio; Tavares, Cristiano; Silva Cunha, Pedro; Abreu, Ana; Branco, Luísa; Alves, Sandra; Rocha, Isabel; Cruz Ferreira, Rui

2016-06-01

Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

The Children's Hepatic tumors International Collaboration (CHIC): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model

PubMed Central

Czauderna, Piotr; Haeberle, Beate; Hiyama, Eiso; Rangaswami, Arun; Krailo, Mark; Maibach, Rudolf; Rinaldi, Eugenia; Feng, Yurong; Aronson, Daniel; Malogolowkin, Marcio; Yoshimura, Kenichi; Leuschner, Ivo; Lopez-Terrada, Dolores; Hishiki, Tomoro; Perilongo, Giorgio; von Schweinitz, Dietrich; Schmid, Irene; Watanabe, Kenichiro; Derosa, Marisa; Meyers, Rebecka

2016-01-01

Introduction Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge. Methods Four multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined. Results Significantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome. Conclusion We have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases. PMID:26655560

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

PubMed Central

Chen, Ya-Fang; Chen, Wan-Jin; Lin, Xiao-Zhen; Zhang, Qi-Jie; Cai, Jiang-Ping; Liou, Chia-Wei; Wang, Ning

2015-01-01

Background: Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods: Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population. Results: Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082–0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030–0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112–11.523, P = 0.033), other haplogroups also did not show significant differences in the group. Conclusions: Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese. PMID:26112715

The research on endothelial function in women and men at risk for cardiovascular disease (REWARD) study: methodology

PubMed Central

2011-01-01

Background Endothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD) in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR) test (a proxy measure of endothelial function) for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1) endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2) endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men. Methods/Design A total of 1972 patients (812 men and 1160 women) undergoing a dipyridamole stress testing were recruited. Medical history, CVD risk factors, health behaviours, psychological status, and gender identity were assessed via structured interview or self-report questionnaires at baseline. In addition, FHR was assessed, as well as levels of sex hormones via blood draw. Patients will be followed for 5 years to assess major CVD events (cardiac mortality, non-fatal MI, revascularization procedures, and cerebrovascular events). Discussion This is the first study to determine the extent and nature of any sex differences in the ability of endothelial function to predict CVD events. We believe the results of this study will provide data that will better inform the choice of diagnostic tests in men and women and bring the quality of risk stratification in women on par with that of men. PMID:21831309

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

Zauls, A. Jason, E-mail: zauls@musc.edu; Watkins, John M.; Wahlquist, Amy E.

Purpose: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups. Methods: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) {<=}3 cm, and {<=}3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS),more » time to local failure (TTLF), and tumor bed failure (TBF). Results: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06). Conclusions: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.« less

Investigation of Methods to Predict Thermal Stratification and Its Effect on Solar Energy System Performance.

DTIC Science & Technology

1980-05-01

International Conference, Vol 1, Dhahran, Saudi Arabia (November 1975), pp 508-510. + C. W. J. Van Koppen, L. S. Fischer, and A. Dijkmans ...S. Fischer, and A. Dijkmans , "Stratification Effects in te Short and Long Term Storage of Solar Heat," Proceed- ings, 1978 meeting of Amercan Sec

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.

Entropy-based consensus clustering for patient stratification.

PubMed

Liu, Hongfu; Zhao, Rui; Fang, Hongsheng; Cheng, Feixiong; Fu, Yun; Liu, Yang-Yu

2017-09-01

Patient stratification or disease subtyping is crucial for precision medicine and personalized treatment of complex diseases. The increasing availability of high-throughput molecular data provides a great opportunity for patient stratification. Many clustering methods have been employed to tackle this problem in a purely data-driven manner. Yet, existing methods leveraging high-throughput molecular data often suffers from various limitations, e.g. noise, data heterogeneity, high dimensionality or poor interpretability. Here we introduced an Entropy-based Consensus Clustering (ECC) method that overcomes those limitations all together. Our ECC method employs an entropy-based utility function to fuse many basic partitions to a consensus one that agrees with the basic ones as much as possible. Maximizing the utility function in ECC has a much more meaningful interpretation than any other consensus clustering methods. Moreover, we exactly map the complex utility maximization problem to the classic K -means clustering problem, which can then be efficiently solved with linear time and space complexity. Our ECC method can also naturally integrate multiple molecular data types measured from the same set of subjects, and easily handle missing values without any imputation. We applied ECC to 110 synthetic and 48 real datasets, including 35 cancer gene expression benchmark datasets and 13 cancer types with four molecular data types from The Cancer Genome Atlas. We found that ECC shows superior performance against existing clustering methods. Our results clearly demonstrate the power of ECC in clinically relevant patient stratification. The Matlab package is available at http://scholar.harvard.edu/yyl/ecc . yunfu@ece.neu.edu or yyl@channing.harvard.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

PubMed

Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

2016-03-01

Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Fine-scale patterns of population stratification confound rare variant association tests.

PubMed

O'Connor, Timothy D; Kiezun, Adam; Bamshad, Michael; Rich, Stephen S; Smith, Joshua D; Turner, Emily; Leal, Suzanne M; Akey, Joshua M

2013-01-01

Advances in next-generation sequencing technology have enabled systematic exploration of the contribution of rare variation to Mendelian and complex diseases. Although it is well known that population stratification can generate spurious associations with common alleles, its impact on rare variant association methods remains poorly understood. Here, we performed exhaustive coalescent simulations with demographic parameters calibrated from exome sequence data to evaluate the performance of nine rare variant association methods in the presence of fine-scale population structure. We find that all methods have an inflated spurious association rate for parameter values that are consistent with levels of differentiation typical of European populations. For example, at a nominal significance level of 5%, some test statistics have a spurious association rate as high as 40%. Finally, we empirically assess the impact of population stratification in a large data set of 4,298 European American exomes. Our results have important implications for the design, analysis, and interpretation of rare variant genome-wide association studies.

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.

Utilising monitoring and modelling of estuarine environments to investigate catchment conditions responsible for stratification events in a typically well-mixed urbanised estuary

NASA Astrophysics Data System (ADS)

Lee, Serena B.; Birch, Gavin F.

2012-10-01

Estuarine health is affected by contamination from stormwater, particularly in highly-urbanised environments. For systems where catchment monitoring is insufficient, novel techniques must be employed to determine the impact of urban runoff on receiving water bodies. In the present work, estuarine monitoring and modelling were successfully employed to determine stormwater runoff volumes and establish an appropriate rainfall/runoff relationship capable of replicating fresh-water discharge due to the full range of precipitation conditions in the Sydney Estuary, Australia. Using estuary response to determine relationships between catchment rainfall and runoff is a widely applicable method and may be of assistance in the study of waterways where monitoring fluvial discharges is not practical or is beyond the capacity of management authorities. For the Sydney Estuary, the SCS-CN method replicated rainfall/runoff and was applied in numerical modelling experiments investigating the hydrodynamic characteristics affecting stratification and estuary recovery following high precipitation. Numerical modelling showed stratification in the Sydney Estuary was dominated by fresh-water discharge. Spring tides and up-estuary winds contributed to mixing and neap tides and down-estuary winds enhanced stratification.

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.

Finite element solution to passive scalar transport behind line sources under neutral and unstable stratification

NASA Astrophysics Data System (ADS)

Liu, Chun-Ho; Leung, Dennis Y. C.

2006-02-01

This study employed a direct numerical simulation (DNS) technique to contrast the plume behaviours and mixing of passive scalar emitted from line sources (aligned with the spanwise direction) in neutrally and unstably stratified open-channel flows. The DNS model was developed using the Galerkin finite element method (FEM) employing trilinear brick elements with equal-order interpolating polynomials that solved the momentum and continuity equations, together with conservation of energy and mass equations in incompressible flow. The second-order accurate fractional-step method was used to handle the implicit velocity-pressure coupling in incompressible flow. It also segregated the solution to the advection and diffusion terms, which were then integrated in time, respectively, by the explicit third-order accurate Runge-Kutta method and the implicit second-order accurate Crank-Nicolson method. The buoyancy term under unstable stratification was integrated in time explicitly by the first-order accurate Euler method. The DNS FEM model calculated the scalar-plume development and the mean plume path. In particular, it calculated the plume meandering in the wall-normal direction under unstable stratification that agreed well with the laboratory and field measurements, as well as previous modelling results available in literature.

[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.

Comparison of different risk stratification systems in predicting short-term serious outcome of syncope patients

PubMed Central

Safari, Saeed; Baratloo, Alireza; Hashemi, Behrooz; Rahmati, Farhad; Forouzanfar, Mohammad Mehdi; Motamedi, Maryam; Mirmohseni, Ladan

2016-01-01

Background: Determining etiologic causes and prognosis can significantly improve management of syncope patients. The present study aimed to compare the values of San Francisco, Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL), Boston, and Risk Stratification of Syncope in the Emergency Department (ROSE) score clinical decision rules in predicting the short-term serious outcome of syncope patients. Materials and Methods: The present diagnostic accuracy study with 1-week follow-up was designed to evaluate the predictive values of the four mentioned clinical decision rules. Screening performance characteristics of each model in predicting mortality, myocardial infarction (MI), and cerebrovascular accidents (CVAs) were calculated and compared. To evaluate the value of each aforementioned model in predicting the outcome, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated and receiver-operating curve (ROC) curve analysis was done. Results: A total of 187 patients (mean age: 64.2 ± 17.2 years) were enrolled in the study. Mortality, MI, and CVA were seen in 19 (10.2%), 12 (6.4%), and 36 (19.2%) patients, respectively. Area under the ROC curve for OESIL, San Francisco, Boston, and ROSE models in prediction the risk of 1-week mortality, MI, and CVA was in the 30–70% range, with no significant difference among models (P > 0.05). The pooled model did not show higher accuracy in prediction of mortality, MI, and CVA compared to others (P > 0.05). Conclusion: This study revealed the weakness of all four evaluated models in predicting short-term serious outcome of syncope patients referred to the emergency department without any significant advantage for one among others. PMID:27904602

Pulmonary emphysema is a predictor of pneumothorax after CT-guided transthoracic pulmonary biopsies of pulmonary nodules

PubMed Central

Lendeckel, Derik; Kromrey, Marie-Luise; Ittermann, Till; Schäfer, Sophia; Mensel, Birger; Kühn, Jens-Peter

2017-01-01

Purpose Pneumothoraces are the most frequently occurring complications of CT-guided percutaneous transthoracic pulmonary biopsies (PTPB). The aim of this study was to evaluate the influence of pre-diagnostic lung emphysema on the incidence and extent of pneumothoraces and to establish a risk stratification for the evaluation of the pre-procedure complication probability. Material and methods CT-guided PTPB of 100 pre-selected patients (mean age 67.1±12.8 years) were retrospectively enrolled from a single center database of 235 PTPB performed between 2012–2014. Patients were grouped according to pneumothorax appearance directly after PTPB (group I: without pneumothorax, n = 50; group II: with pneumothorax, n = 50). Group II was further divided according to post-interventional treatment (group IIa: chest tube placement, n = 24; group IIb: conservative therapy, n = 26). For each patient pre-diagnostic percentage of emphysema was quantified using CT density analysis. Emphysema stages were compared between groups using bivariate analyses and multinomial logistic regression analyses. Results Emphysema percentage was significantly associated with the occurrence of post-interventional pneumothorax (p = 0.006). Adjusted for potential confounders (age, gender, lesion size and length of interventional pathway) the study yielded an OR of 1.07 (p = 0.042). Absolute risk of pneumothorax increased from 43.4% at an emphysema rate of 5% to 73.8% at 25%. No differences could be seen in patients with pneumothorax between percentage of emphysema and mode of therapy (p = 0.721). Conclusion The rate of lung emphysema is proportionally related to the incidence of pneumothorax after CT-guided PTPB and allows pre-interventional risk stratification. There is no association between stage of emphysema and post-interventional requirement of chest tube placement. PMID:28574995

TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia

PubMed Central

Chagtai, Tasnim; Popov, Sergey D.; Sebire, Neil J.; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R.; Grundy, Paul; Dome, Jeffrey S.; Pritchard-Jones, Kathy

2014-01-01

Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. PMID:25313908

Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features

PubMed Central

Tamayo, Pablo; Cho, Yoon-Jae; Tsherniak, Aviad; Greulich, Heidi; Ambrogio, Lauren; Schouten-van Meeteren, Netteke; Zhou, Tianni; Buxton, Allen; Kool, Marcel; Meyerson, Matthew; Pomeroy, Scott L.; Mesirov, Jill P.

2011-01-01

Purpose Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. Patients and Methods A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78). Results On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse. Conclusion The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification. PMID:21357789

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

PubMed Central

Vasuri, Francesco; Malvi, Deborah; Rosini, Francesca; Baldin, Pamela; Fiorentino, Michelangelo; Paccapelo, Alexandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Golfieri, Rita; Morselli-Labate, Antonio Maria; Grigioni, Walter Franco; D’Errico-Grigioni, Antonia

2014-01-01

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT). PMID:25309084

Efficient and sparse feature selection for biomedical text classification via the elastic net: Application to ICU risk stratification from nursing notes.

PubMed

Marafino, Ben J; Boscardin, W John; Dudley, R Adams

2015-04-01

Sparsity is often a desirable property of statistical models, and various feature selection methods exist so as to yield sparser and interpretable models. However, their application to biomedical text classification, particularly to mortality risk stratification among intensive care unit (ICU) patients, has not been thoroughly studied. To develop and characterize sparse classifiers based on the free text of nursing notes in order to predict ICU mortality risk and to discover text features most strongly associated with mortality. We selected nursing notes from the first 24h of ICU admission for 25,826 adult ICU patients from the MIMIC-II database. We then developed a pair of stochastic gradient descent-based classifiers with elastic-net regularization. We also studied the performance-sparsity tradeoffs of both classifiers as their regularization parameters were varied. The best-performing classifier achieved a 10-fold cross-validated AUC of 0.897 under the log loss function and full L2 regularization, while full L1 regularization used just 0.00025% of candidate input features and resulted in an AUC of 0.889. Using the log loss (range of AUCs 0.889-0.897) yielded better performance compared to the hinge loss (0.850-0.876), but the latter yielded even sparser models. Most features selected by both classifiers appear clinically relevant and correspond to predictors already present in existing ICU mortality models. The sparser classifiers were also able to discover a number of informative - albeit nonclinical - features. The elastic-net-regularized classifiers perform reasonably well and are capable of reducing the number of features required by over a thousandfold, with only a modest impact on performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

PubMed Central

Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

Emergency Physicians’ Perceptions and Decision-making Processes Regarding Patients Presenting with Palpitations

PubMed Central

Probst, Marc A.; Kanzaria, Hemal K.; Hoffman, Jerome R.; Mower, William R.; Moheimani, Roya S.; Sun, Benjamin C.; Quigley, Denise D.

2015-01-01

Background Palpitations are a common emergency department (ED) complaint, yet relatively little research exists on this topic from an emergency care perspective. Objectives We sought to describe the perceptions and clinical decision-making processes of emergency physicians (EP) surrounding patients with palpitations. Methods We conducted 21 semistructured interviews with a convenience sample of EPs. We recruited participants from academic and community practice settings from four regions of the US. The transcribed interviews were analyzed using a combination of structural coding and grounded theory approaches with ATLAS.ti, a qualitative data analysis software program. Results EPs perceive palpitations to be a common but generally benign chief complaint. EPs' clinical approach to palpitations, with regards to testing, treatment and ED management, can be classified as relating to one or more of the following themes: (1) risk-stratification, (2) diagnostic categorization, (3) algorithmic management, and (4) case-specific gestalt. With regard to disposition decisions, four main themes emerged: (1) presence of a serious diagnosis, (2) perceived need for further cardiac testing/monitoring, (3) presence of key associated symptoms, (4) request of other physician or patient desire. The inter-rater reliability exercise yielded a Fleiss' kappa measure of 0.69, indicating substantial agreement between coders. Conclusion EPs perceive palpitations to be a common but generally benign chief complaint. EPs rely on one, or more, of four main clinical approaches to manage these patients. These findings could help guide future efforts at developing risk-stratification tools and clinical algorithms for patients with palpitations. PMID:25943288

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.

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

Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool.

PubMed

Veeravagu, Anand; Li, Amy; Swinney, Christian; Tian, Lu; Moraff, Adrienne; Azad, Tej D; Cheng, Ivan; Alamin, Todd; Hu, Serena S; Anderson, Robert L; Shuer, Lawrence; Desai, Atman; Park, Jon; Olshen, Richard A; Ratliff, John K

2017-07-01

OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery. RESULTS The authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

Deconstructing Pretest Risk Enrichment to Optimize Prediction of Psychosis in Individuals at Clinical High Risk.

PubMed

Fusar-Poli, Paolo; Rutigliano, Grazia; Stahl, Daniel; Schmidt, André; Ramella-Cravaro, Valentina; Hitesh, Shetty; McGuire, Philip

2016-12-01

Pretest risk estimation is routinely used in clinical medicine to inform further diagnostic testing in individuals with suspected diseases. To our knowledge, the overall characteristics and specific determinants of pretest risk of psychosis onset in individuals undergoing clinical high risk (CHR) assessment are unknown. To investigate the characteristics and determinants of pretest risk of psychosis onset in individuals undergoing CHR assessment and to develop and externally validate a pretest risk stratification model. Clinical register-based cohort study. Individuals were drawn from electronic, real-world, real-time clinical records relating to routine mental health care of CHR services in South London and the Maudsley National Health Service Trust in London, United Kingdom. The study included nonpsychotic individuals referred on suspicion of psychosis risk and assessed by the Outreach and Support in South London CHR service from 2002 to 2015. Model development and validation was performed with machine-learning methods based on Least Absolute Shrinkage and Selection Operator for Cox proportional hazards model. Pretest risk of psychosis onset in individuals undergoing CHR assessment. Predictors included age, sex, age × sex interaction, race/ethnicity, socioeconomic status, marital status, referral source, and referral year. A total of 710 nonpsychotic individuals undergoing CHR assessment were included. The mean age was 23 years. Three hundred ninety-nine individuals were men (56%), their race/ethnicity was heterogenous, and they were referred from a variety of sources. The cumulative 6-year pretest risk of psychosis was 14.55% (95% CI, 11.71% to 17.99%), confirming substantial pretest risk enrichment during the recruitment of individuals undergoing CHR assessment. Race/ethnicity and source of referral were associated with pretest risk enrichment. The predictive model based on these factors was externally validated, showing moderately good discrimination and sufficient calibration. It was used to stratify individuals undergoing CHR assessment into 4 classes of pretest risk (6-year): low, 3.39% (95% CI, 0.96% to 11.56%); moderately low, 11.58% (95% CI, 8.10% to 16.40%); moderately high, 23.69% (95% CI, 16.58% to 33.20%); and high, 53.65% (95% CI, 36.78% to 72.46%). Significant risk enrichment occurs before individuals are assessed for a suspected CHR state. Race/ethnicity and source of referral are associated with pretest risk enrichment in individuals undergoing CHR assessment. A stratification model can identify individuals at differential pretest risk of psychosis. Identification of these subgroups may inform outreach campaigns and subsequent testing and eventually optimize psychosis prediction.

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.

Ancestry estimation and control of population stratification for sequence-based association studies.

PubMed

Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Stambolian, Dwight; Chew, Emily Y; Branham, Kari E; Heckenlively, John; Fulton, Robert; Wilson, Richard K; Mardis, Elaine R; Lin, Xihong; Swaroop, Anand; Zöllner, Sebastian; Abecasis, Gonçalo R

2014-04-01

Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification

PubMed Central

Uellendahl, Marly; de Siqueira, Maria Eduarda Menezes; Calado, Eveline Barros; Kalil-Filho, Roberto; Sobral, Dário; Ribeiro, Clébia; Oliveira, Wilson; Martins, Silvia; Narula, Jagat; Rochitte, Carlos Eduardo

2016-01-01

Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD. PMID:27982271

Genetic Heterogeneity of Self-Reported Ancestry Groups in an Admixed Brazilian Population

PubMed Central

Lins, Tulio C; Vieira, Rodrigo G; Abreu, Breno S; Gentil, Paulo; Moreno-Lima, Ricardo; Oliveira, Ricardo J; Pereira, Rinaldo W

2011-01-01

Background Population stratification is the main source of spurious results and poor reproducibility in genetic association findings. Population heterogeneity can be controlled for by grouping individuals in ethnic clusters; however, in admixed populations, there is evidence that such proxies do not provide efficient stratification control. The aim of this study was to evaluate the relation of self-reported with genetic ancestry and the statistical risk of grouping an admixed sample based on self-reported ancestry. Methods A questionnaire that included an item on self-reported ancestry was completed by 189 female volunteers from an admixed Brazilian population. Individual genetic ancestry was then determined by genotyping ancestry informative markers. Results Self-reported ancestry was classified as white, intermediate, and black. The mean difference among self-reported groups was significant for European and African, but not Amerindian, genetic ancestry. Pairwise fixation index analysis revealed a significant difference among groups. However, the increase in the chance of type 1 error was estimated to be 14%. Conclusions Self-reporting of ancestry was not an appropriate methodology to cluster groups in a Brazilian population, due to high variance at the individual level. Ancestry informative markers are more useful for quantitative measurement of biological ancestry. PMID:21498954

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.

The Aristotle method: a new concept to evaluate quality of care based on complexity.

PubMed

Lacour-Gayet, François; Clarke, David R

2005-06-01

Evaluation of quality of care is a duty of the modern medical practice. A reliable method of quality evaluation able to compare fairly institutions and inform a patient and his family of the potential risk of a procedure is clearly needed. It is now well recognized that any method that purports to evaluate quality of care should include a case mix/risk stratification method. No valuable method was available until recently in pediatric cardiac surgery. The Aristotle method is a new concept of evaluation of quality of care in congenital heart surgery based on the complexity of the surgical procedures. Involving a panel of expert surgeons, the project started in 1999 and included 50 pediatric surgeons from 23 countries. The basic score adjusts the complexity of a given procedure and is calculated as the sum of potential for mortality, potential for morbidity and anticipated technical difficulty. The Comprehensive Score further adjusts the complexity according to the specific patient characteristics (anatomy, associated procedures, co-morbidity, etc.). The Aristotle method is original as it introduces several new concepts: the calculated complexity is a constant for a given patient all over the world; complexity is an independent value and risk is a variable depending on the performance; and Performance = Complexity x Outcome. The Aristotle score is a good vector of communication between patients, doctors and insurance companies and may stimulate the quality and the organization of heath care in our field and in others.

High efficiency stratification of apple cultivar Ligol seed dormancy by phytohormones, heat shock and pulsed radio frequency.

PubMed

Grzesik, Mieczysław; Górnik, Krzysztof; Janas, Regina; Lewandowki, Mariusz; Romanowska-Duda, Zdzislawa; Duijn, Bert van

2017-12-01

The aim of the study was to improve the effect of stratification of apple "Ligol" seeds by application of selected compounds, phytohormones, and physical methods For this purpose the seeds were stratified at 3°C in distilled water or in the presence of potassium nitrate (KNO 3 ), ethephon (ET), carbon monoxide (CO), hydrogen peroxide (H 2 O 2 ), a mixture of KNO 3 , ET, CO, H 2 O 2 , gibberellins (GA 3 ), 6-benzylaminopurine (BAP), jasmonic acid (JA), salicylic acid (SA) and a mixture of SA, GA 3 , BAP, JA, nitric oxide (NO), hydrogen chloride (HCL). Arranged protocols included various durations and combinations of selected compounds and phytohormones as well as laser and red light, heat shock - 2h heat shock (45°C) and Pulsed Radio Frequency (PRF) were investigated by germination tests and the activity of selected enzymes, gas exchange and index of chlorophyll in leaves. The obtained results showed the possibility to shorten more effectively the time of the apple 'Ligol' dormancy removal by treatments of the stratified seeds at 3°C with different biological and physical methods Selected compounds and phytohormones acted collectively as a regulatory complex controlling the course of release from dormancy. Physical methods (PRF and heat shock) additionally contributed to dormancy breakage. Duration of phytohormones or compounds impacts during stratification should be prolonged to minimum 7days to assure more balanced conditions of the regulatory complex for the acceleration of dormancy a removal. The most beneficial results were obtained after seed stratification for 7days on filter paper moistened in KNO 3 +Etephon+CO+H 2 O 2 at 3°C, and then on filter paper moistened in phytohormones (GA 3 +BAP+JA) till the end of seed germination (3°C). The application of this protocol could be a very useful tool in a shortening the apple breeding cycle since the period of removing dormancy was reduced by 38days in comparison to stratified in water. PRF has also the additive role in breaking dormancy of apple 'Ligol' seed. Positive effects of compounds and phytohormones applied during stratification remarkably accelerated the growth of developed from them seedlings. Further research is needed to optimize stratification methods with appropriate contents and concentrations of compounds and phytohormones combined with PRF exposure. Copyright © 2017 Elsevier GmbH. All rights reserved.

Efficiency and precision for estimating timber and non-timber attributes using Landsat-based stratification methods in two-phase sampling in northwest California

Treesearch

Antti T. Kaartinen; Jeremy S. Fried; Paul A. Dunham

2002-01-01

Three Landsat TM-based GIS layers were evaluated as alternatives to conventional, photointerpretation-based stratification of FIA field plots. Estimates for timberland area, timber volume, and volume of down wood were calculated for California's North Coast Survey Unit of 2.5 million hectares. The estimates were compared on the basis of standard errors,...

Development of techniques for producing static strata maps and development of photointerpretive methods based on multitemporal LANDSAT data

NASA Technical Reports Server (NTRS)

Colwell, R. N. (Principal Investigator); Hay, C. M.; Thomas, R. W.; Benson, A. S.

1977-01-01

Progress in the evaluation of the static stratification procedure and the development of alternative photointerpretive techniques to the present LACIE procedure for the identification of training fields is reported. Statistically significant signature controlling variables were defined for use in refining the stratification procedure. A subset of the 1973-74 Kansas LACIE segments for wheat was analyzed.

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.

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.

Analysis of blood pressure signal in patients with different ventricular ejection fraction using linear and non-linear methods.

PubMed

Arcentales, Andres; Rivera, Patricio; Caminal, Pere; Voss, Andreas; Bayes-Genis, Antonio; Giraldo, Beatriz F

2016-08-01

Changes in the left ventricle function produce alternans in the hemodynamic and electric behavior of the cardiovascular system. A total of 49 cardiomyopathy patients have been studied based on the blood pressure signal (BP), and were classified according to the left ventricular ejection fraction (LVEF) in low risk (LR: LVEF>35%, 17 patients) and high risk (HR: LVEF≤35, 32 patients) groups. We propose to characterize these patients using a linear and a nonlinear methods, based on the spectral estimation and the recurrence plot, respectively. From BP signal, we extracted each systolic time interval (STI), upward systolic slope (BPsl), and the difference between systolic and diastolic BP, defined as pulse pressure (PP). After, the best subset of parameters were obtained through the sequential feature selection (SFS) method. According to the results, the best classification was obtained using a combination of linear and nonlinear features from STI and PP parameters. For STI, the best combination was obtained considering the frequency peak and the diagonal structures of RP, with an area under the curve (AUC) of 79%. The same results were obtained when comparing PP values. Consequently, the use of combined linear and nonlinear parameters could improve the risk stratification of cardiomyopathy patients.

Understanding PSA and its derivatives in prediction of tumor volume: addressing health disparities in prostate cancer risk stratification

PubMed Central

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-01-01

Objectives To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Results Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). Materials and Methods We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Conclusions Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer. PMID:28160549

Repeatability of Central and Peripheral Pulse Wave Velocity Measures: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Tanaka, Hirofumi; Palta, Priya; Patel, Mehul D.; Camplain, Ricky; Couper, David; Cheng, Susan; Al Qunaibet, Ada; Poon, Anna K.; Heiss, Gerardo

2016-01-01

BACKGROUND Arterial stiffness measures are emerging tools for risk assessment and stratification for hypertension and cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (cfPWV) is an established measure of central arterial stiffness. Other measures of PWV include femoral-ankle (faPWV), a measure of peripheral stiffness, and brachial-ankle PWV (baPWV), a composite measure of central and peripheral stiffness. Repeatability of central, peripheral, and composite PWV measures has not been adequately examined or compared. METHODS Participants (n = 79; mean age 75.7 years; USA) from a repeatability study nested within the Atherosclerosis Risk in Communities (ARIC) Study visit 5 (2011–2013) underwent 2 standardized visits, 4–8 weeks apart. Trained technicians obtained 2 PWV measurements at each visit using the VP-1000 Plus system. We calculated the intraclass correlation coefficient (ICC), SE of measurement, and minimal detectable change (MDC95; 95% confidence interval) and difference (MDD). RESULTS The ICCs and 95% confidence intervals (95% CIs) were 0.70 (0.59, 0.81) for cfPWV, 0.84 (0.78, 0.90) for baPWV, and 0.69 (0.59, 0.79) for faPWV. The MDC95 between repeat measures within an individual was 411.0cm/s for cfPWV, 370.6cm/s for baPWV, and 301.4cm/s for faPWV. The MDD for 2 independent samples of 100 per group was 139.3cm/s for cfPWV, 172.3cm/s for baPWV, and 100.4cm/s for faPWV. CONCLUSIONS Repeatability was acceptable for all PWV measures in a multicenter, population-based study of older adults and supports its use in epidemiologic studies. Quantifying PWV measurement variation is critical for applications to risk assessment and stratification and eventual translation to clinical practice. PMID:26232036

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.

A feasibility study of cell phone and landline phone interviews for monitoring of risk and protection factors for chronic diseases in Brazil.

PubMed

Moura, Erly Catarina; Claro, Rafael Moreira; Bernal, Regina; Ribeiro, Juliano; Malta, Deborah Carvalho; Morais Neto, Otaliba

2011-02-01

The study objective was to evaluate the feasibility of interviews by cell phone as a complement to interviews by landline to estimate risk and protection factors for chronic non-communicable diseases. Adult cell phone users were evaluated by random digit dialing. Questions asked were: age, sex, education, race, marital status, ownership of landline and cell phones, health condition, weight and height, medical diagnosis of hypertension and diabetes, physical activity, diet, binge drinking and smoking. The estimates were calculated using post-stratification weights. The cell phone interview system showed a reduced capacity to reach elderly and low educated populations. The estimates of the risk and protection factors for chronic non-communicable diseases in cell phone interviews were equal to the estimates obtained by landline phone. Eligibility, success and refusal rates using the cell phone system were lower than those of the landline system, but loss and cost were much higher, suggesting it is unsatisfactory as a complementary method in such a context.

Prevention of Contrast-Induced Nephropathy (CIN) in Interventional Radiology Practice

PubMed Central

Gupta, Rajan K.; Bang, Tami J.

2010-01-01

Contrast-induced nephropathy (CIN) is a widely recognized and clinically significant problem in patients undergoing an increasing number of minimally invasive procedures that require contrast administration. Contrast-induced nephropathy is the third most common cause of hospital-acquired renal failure and has significant prognostic implications on patient outcomes. Interventional practitioners are faced with challenging decisions regarding prophylaxis and patient management. The major risk factor for developing CIN is preexisting renal dysfunction, particularly in association with diabetes. Patients are considered to be at risk when estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCCr) is less than 60. The cornerstone of prevention of CIN is appropriate risk stratification, intravenous hydration with normal saline or sodium bicarbonate, appropriate withholding of nephrotoxic medications, use of low or iso-osmolar contrast media, and various intraprocedural methods for iodinated contrast dose reduction. Although N-acetylcysteine administration is popular, it remains unproven. Practitioners must be familiar with prevention strategies and diagnosis of CIN to minimize its clinical impact. PMID:22550376

The effect of different methods to compute N on estimates of mixing in stratified flows

NASA Astrophysics Data System (ADS)

Fringer, Oliver; Arthur, Robert; Venayagamoorthy, Subhas; Koseff, Jeffrey

2017-11-01

The background stratification is typically well defined in idealized numerical models of stratified flows, although it is more difficult to define in observations. This may have important ramifications for estimates of mixing which rely on knowledge of the background stratification against which turbulence must work to mix the density field. Using direct numerical simulation data of breaking internal waves on slopes, we demonstrate a discrepancy in ocean mixing estimates depending on the method in which the background stratification is computed. Two common methods are employed to calculate the buoyancy frequency N, namely a three-dimensionally resorted density field (often used in numerical models) and a locally-resorted vertical density profile (often used in the field). We show that how N is calculated has a significant effect on the flux Richardson number Rf, which is often used to parameterize turbulent mixing, and the turbulence activity number Gi, which leads to errors when estimating the mixing efficiency using Gi-based parameterizations. Supported by ONR Grant N00014-08-1-0904 and LLNL Contract DE-AC52-07NA27344.

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

Glaucoma and quality of life: fall and driving risk.

PubMed

Montana, Cynthia L; Bhorade, Anjali M

2018-03-01

Numerous population-based studies suggest that glaucoma is an independent risk factor for falling and motor vehicle collisions, particularly for older adults. These adverse events lead to increased healthcare expenditures and decreased quality of life. Current research priorities, therefore, include identifying factors that predispose glaucoma patients to falling and unsafe driving, and developing screening strategies and targeted rehabilitation. The purpose of this article is to review recent studies that address these priorities. Studies continue to support that glaucoma patients, particularly those with advanced disease, have an increased risk of falling or unsafe driving. Risk factors, however, remain variable and include severity and location of visual field defects, contrast sensitivity, and performance on divided attention tasks. Such variability is likely because of the multifactorial nature of ambulating and driving and compensatory strategies used by patients. Falls and unsafe driving remain a serious public health issue for older adults with glaucoma. Ambulation and driving are complex tasks and there is no consensus yet, regarding the best methods for risk stratification and targeted interventions to increase safety. Therefore, comprehensive and individualized assessments are recommended to most effectively evaluate a patient's risk for falling or unsafe driving.

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

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

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

A Review on Automatic Mammographic Density and Parenchymal Segmentation

PubMed Central

He, Wenda; Juette, Arne; Denton, Erika R. E.; Oliver, Arnau

2015-01-01

Breast cancer is the most frequently diagnosed cancer in women. However, the exact cause(s) of breast cancer still remains unknown. Early detection, precise identification of women at risk, and application of appropriate disease prevention measures are by far the most effective way to tackle breast cancer. There are more than 70 common genetic susceptibility factors included in the current non-image-based risk prediction models (e.g., the Gail and the Tyrer-Cuzick models). Image-based risk factors, such as mammographic densities and parenchymal patterns, have been established as biomarkers but have not been fully incorporated in the risk prediction models used for risk stratification in screening and/or measuring responsiveness to preventive approaches. Within computer aided mammography, automatic mammographic tissue segmentation methods have been developed for estimation of breast tissue composition to facilitate mammographic risk assessment. This paper presents a comprehensive review of automatic mammographic tissue segmentation methodologies developed over the past two decades and the evidence for risk assessment/density classification using segmentation. The aim of this review is to analyse how engineering advances have progressed and the impact automatic mammographic tissue segmentation has in a clinical environment, as well as to understand the current research gaps with respect to the incorporation of image-based risk factors in non-image-based risk prediction models. PMID:26171249

Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.

PubMed

Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan

2017-09-01

Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.

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.

Calculation of Local Stress and Fatigue Resistance due to Thermal Stratification on Pressurized Surge Line Pipe

NASA Astrophysics Data System (ADS)

Bandriyana, B.; Utaja

2010-06-01

Thermal stratification introduces thermal shock effect which results in local stress and fatique problems that must be considered in the design of nuclear power plant components. Local stress and fatique calculation were performed on the Pressurize Surge Line piping system of the Pressurize Water Reactor of the Nuclear Power Plant. Analysis was done on the operating temperature between 177 to 343° C and the operating pressure of 16 MPa (160 Bar). The stagnant and transient condition with two kinds of stratification model has been evaluated by the two dimensional finite elements method using the ANSYS program. Evaluation of fatigue resistance is developed based on the maximum local stress using the ASME standard Code formula. Maximum stress of 427 MPa occurred at the upper side of the top half of hot fluid pipe stratification model in the transient case condition. The evaluation of the fatigue resistance is performed on 500 operating cycles in the life time of 40 years and giving the usage value of 0,64 which met to the design requirement for class 1 of nuclear component. The out surge transient were the most significant case in the localized effects due to thermal stratification.

Noninvasive assessment of arterial function in children: clinical applications

PubMed Central

Aggoun, Y; Beghetti, M

2002-01-01

Non invasive methods to assess arterial function are widely used in adults. The development and progression of arterial vascular disease is a multifactorial process that can start early in life, thus even in a pediatric population. Risk factors for cardiovascular disease mediate their effects by altering the structure, properties and function of wall and endothelial components of the arterial blood vessels. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression. Measurements that provide more direct information in relation to changes in arterial wall integrity clearly hold predictive and therapeutic potential. The aim of this current review will be to describe the non-invasive procedure used in children to investigate the mechanical properties of a great elastic artery, the common carotid, and the endothelial function of the brachial artery. The accuracy of recording noninvasively the blood pressure wave contour along the arterial tree has been improved by the technique of applanation tonometry. The results obtained with these methods in previous studies are described. PMID:22368620

A Predictive Score for Thrombosis Associated with Breast, Colorectal, Lung, or Ovarian Cancer: The Prospective COMPASS-Cancer-Associated Thrombosis Study.

PubMed

Gerotziafas, Grigoris T; Taher, Ali; Abdel-Razeq, Hikmat; AboElnazar, Essam; Spyropoulos, Alex C; El Shemmari, Salem; Larsen, Annette K; Elalamy, Ismail

2017-10-01

The stratification of outpatients on chemotherapy for breast, colorectal, lung, and ovarian cancers at risk of venous thromboembolism (VTE) remains an unmet clinical need. The derivation of a risk assessment model (RAM) for VTE in these patients was the aim of the study "Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis" (COMPASS-CAT). The derivation cohort consisted of 1,023 outpatients. Patients on low molecular weight heparin (LMWH) thromboprophylaxis were excluded. Documented symptomatic VTE was the endpoint of the study. Patients had breast (61%), colorectal (17%), lung (13%), or ovarian cancer (8.6%) at localized (30%) or advanced stage (70%). In 64% of patients, cancer was diagnosed within the last 6 months prior to inclusion. Most of them were on chemotherapy when assessed. Symptomatic VTE occurred in 8.5% of patients. The COMPASS-CAT RAM includes the following variables: (a) anthracycline or anti - hormonal therapy, (b) time since cancer diagnosis, (c) central venous catheter, (d) stage of cancer, (e) presence of cardiovascular risk factors, (f) recent hospitalization for acute medical illness, (g) personal history of VTE, and (h) platelet count. At 6 months, patients stratified at low/intermediate and high-risk groups had VTE rates of 1.7% and 13.3%, respectively. The area under the curve of receiver operating characteristics analysis was 0.85. The sensitivity and specificity of the RAM were 88% and 52%, respectively. The negative and positive predictive values of the RAM were 98% and 13%, respectively. The COMPASS-CAT RAM includes reliable and easily collected VTE risk predictors and, in contrast to the Khorana score, it is applicable after the initiation of anticancer treatment in patients with common solid tumors. Its robustness for stratification of patients at high and low/intermediate VTE risk needs to be externally validated. The Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis (COMPASS-CAT) study provides a new risk assessment model (RAM) for venous thromboembolism (VTE) applicable in outpatients with breast, colorectal, lung or ovarian cancer. The COMPASS-CAT RAM is robust, applicable during chemotherapy and determines the need for VTE prévention by including reliable and easily collected VTE predictors associated with cancer status, its treatment as well as with patients' characteristics and comorbidities. An independent external validation of the RAM is indicated before its use in clinical practice. © 2017 The Authors The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Risk-Stratified Imputation in Survival Analysis

PubMed Central

Kennedy, Richard E.; Adragni, Kofi P.; Tiwari, Hemant K.; Voeks, Jenifer H.; Brott, Thomas G.; Howard, George

2013-01-01

Background Censoring that is dependent on covariates associated with survival can arise in randomized trials due to changes in recruitment and eligibility criteria to minimize withdrawals, potentially leading to biased treatment effect estimates. Imputation approaches have been proposed to address censoring in survival analysis; and while these approaches may provide unbiased estimates of treatment effects, imputation of a large number of outcomes may over- or underestimate the associated variance based on the imputation pool selected. Purpose We propose an improved method, risk-stratified imputation, as an alternative to address withdrawal related to the risk of events in the context of time-to-event analyses. Methods Our algorithm performs imputation from a pool of replacement subjects with similar values of both treatment and covariate(s) of interest, that is, from a risk-stratified sample. This stratification prior to imputation addresses the requirement of time-to-event analysis that censored observations are representative of all other observations in the risk group with similar exposure variables. We compared our risk-stratified imputation to case deletion and bootstrap imputation in a simulated dataset in which the covariate of interest (study withdrawal) was related to treatment. A motivating example from a recent clinical trial is also presented to demonstrate the utility of our method. Results In our simulations, risk-stratified imputation gives estimates of treatment effect comparable to bootstrap and auxiliary variable imputation while avoiding inaccuracies of the latter two in estimating the associated variance. Similar results were obtained in analysis of clinical trial data. Limitations Risk-stratified imputation has little advantage over other imputation methods when covariates of interest are not related to treatment, although its performance is superior when covariates are related to treatment. Risk-stratified imputation is intended for categorical covariates, and may be sensitive to the width of the matching window if continuous covariates are used. Conclusions The use of the risk-stratified imputation should facilitate the analysis of many clinical trials, in which one group has a higher withdrawal rate that is related to treatment. PMID:23818434

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.

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.

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.

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 consideration of atmospheric stability within wind farm AEP calculations

NASA Astrophysics Data System (ADS)

Schmidt, Jonas; Chang, Chi-Yao; Dörenkämper, Martin; Salimi, Milad; Teichmann, Tim; Stoevesandt, Bernhard

2016-09-01

The annual energy production of an existing wind farm including thermal stratification is calculated with two different methods and compared to the average of three years of SCADA data. The first method is based on steady state computational fluid dynamics simulations and the assumption of Reynolds-similarity at hub height. The second method is a wake modelling calculation, where a new stratification transformation model was imposed on the Jensen an Ainslie wake models. The inflow states for both approaches were obtained from one year WRF simulation data of the site. Although all models underestimate the mean wind speed and wake effects, the results from the phenomenological wake transformation are compatible with high-fidelity simulation results.

Highly Sensitive Troponin I Followed by Advanced Coronary Artery Disease Assessment Using Computed Tomography Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-up in Acute Chest Pain Patients: Results from ROMICAT II Trial

PubMed Central

Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Maurovich-Horvat, Pal; Pope, J. Hector; Truong, Quynh A.; Udelson, James E.; Peacock, W. Frank; White, Charles S.; Woodard, Pamela K.; Fleg, Jerome L.; Nagurney, John T.; Januzzi, James L.; Hoffmann, Udo

2015-01-01

Objectives We compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization. Background HsTn I and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department (ED) evaluation of patients with suspected ACS. Methods We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II trial and randomized to coronary CTA who also had hsTn I measurement at the time of the ED presentation. We assessed coronary CTA for traditional (no CAD, non-obstructive CAD, ≥50% stenosis) and advanced features of CAD (≥50% stenosis, high-risk plaque features: positive remodeling, low <30 Hounsfield Units plaque, napkin ring sign, spotty calcium). Results Of 160 patients (mean age: 53±8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with HsTn I below the limit of detection (n=9, 5.6%), intermediate (n=139, 86.9%), and above the 99th percentile (n=12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of ≥50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTn I (n=87, 54.4%; ACS rate 0%), while patients with both ≥50% stenosis and high-risk plaque were at high risk (n=13, 8.1%; ACS rate 69.2%) and patients with either ≥50% stenosis or high-risk plaque were at intermediate risk for ACS (n=39, 24.4%; ACS rate 7.7%). HsTn I/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (AUC 0.84, 95%CI 0.80-0.88 vs. 0.74, 95%CI 0.70-0.78; p<0.001). Conclusions HsTn I at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (Multicenter Study to Rule Out Myocardial Infarction/Ischemia by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239) PMID:26476506

Current Management Strategy for Active Surveillance in Prostate Cancer.

PubMed

Syed, Jamil S; Javier-Desloges, Juan; Tatzel, Stephanie; Bhagat, Ansh; Nguyen, Kevin A; Hwang, Kevin; Kim, Sarah; Sprenkle, Preston C

2017-02-01

Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

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.

Taxonomy of Caribbean Tourism Alcohol Venues: Implications for HIV Transmission*

PubMed Central

GUILAMO-RAMOS, Vincent; JACCARD, James; MCCARTHY, Katharine; QUIÑONES, Zahira; LUSHIN, Viktor; SKINNER-DAY, Molly; PADILLA, Mark; MEISTERLIN, Leah

2013-01-01

Background Tourism areas represent ecologies of heightened HIV vulnerability characterized by a disproportionate concentration of alcohol venues. Limited research has explored how alcohol venues facilitate HIV transmission. Methods We spatially mapped locations of alcohol venues in a Dominican tourism town and conducted a venue-based survey of key informants (n=135) focused on three facets of alcohol venues: structural features, type of patrons, and HIV risk behaviors. Using latent class analysis, we identified evidence-based typologies of alcohol venues for each of the three facets. Focused contrasts identified the co-occurrence of classes of structural features, classes of types of patrons, and classes of HIV risk behavior, thus elaborating the nature of high risk venues. Results We identified three categories of venue structural features, three for venue patrons, and five for HIV risk behaviors. Analysis revealed that alcohol venues with the greatest structural risks (e.g., sex work on site with lack of HIV prevention services) were most likely frequented by the venue patron category characterized by high population-mixing between locals and foreign tourists, who were in turn most likely to engage in the riskiest behaviors. Conclusion Our results highlight the stratification of venue patrons into groups who engage in behaviors of varying risk in structural settings that vary in risk. The convergence of high-risk patron groups in alcohol venues with the greatest structural risk suggests these locations have potential for HIV transmission. Policymakers and prevention scientists can use these methods and data to target HIV prevention resources to identified priority areas. PMID:23478154

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.

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.

TU-D-207B-03: Early Assessment of Response to Chemoradiotherapy Based On Textural Analysis of Pre and Mid-Treatment FDG-PET Image in Locally Advanced Head and Neck Cancer

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

Cui, Y; Pollom, E; Loo, B

Purpose: To evaluate whether tumor textural features extracted from both pre- and mid-treatment FDG-PET images predict early response to chemoradiotherapy in locally advanced head and neck cancer, and investigate whether they provide complementary value to conventional volume-based measurements. Methods: Ninety-four patients with locally advanced head and neck cancers were retrospectively studied. All patients received definitive chemoradiotherapy and underwent FDG-PET planning scans both before and during treatment. Within the primary tumor we extracted 6 textural features based on gray-level co-occurrence matrices (GLCM): entropy, dissimilarity, contrast, correlation, energy, and homogeneity. These image features were evaluated for their predictive power of treatment responsemore » to chemoradiotherapy in terms of local recurrence free survival (LRFS) and progression free survival (PFS). Logrank test were used to assess the statistical significance of the stratification between low- and high-risk groups. P-values were adjusted for multiple comparisons by the false discovery rate (FDR) method. Results: All six textural features extracted from pre-treatment PET images significantly differentiated low- and high-risk patient groups for LRFS (P=0.011–0.038) and PFS (P=0.029–0.034). On the other hand, none of the textural features on mid-treatment PET images was statistically significant in stratifying LRFS (P=0.212–0.445) or PFS (P=0.168–0.299). An imaging signature that combines textural feature (GLCM homogeneity) and metabolic tumor volume showed an improved performance for predicting LRFS (hazard ratio: 22.8, P<0.0001) and PFS (hazard ratio: 13.9, P=0.0005) in leave-one-out cross validation. Intra-tumor heterogeneity measured by textural features was significantly lower in mid-treatment PET images than in pre-treatment PET images (T-test: P<1.4e-6). Conclusion: Tumor textural features on pretreatment FDG-PET images are predictive for response to chemoradiotherapy in locally advanced head and neck cancer. The complementary information offered by textural features improves patient stratification and may potentially aid in personalized risk-adaptive therapy.« less

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.

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.

Observations of Tidal Straining Within Two Different Ocean Environments in the East China Sea: Stratification and Near-Bottom Turbulence

NASA Astrophysics Data System (ADS)

Yang, Wei; Wei, Hao; Zhao, Liang

2017-11-01

Tidal straining describes the straining effect induced by the vertical shear of oscillatory tidal currents that act on horizontal density gradients. It tends to create tidal periodic stratification and modulate the turbulence in the bottom boundary layer (BBL). Here, we present observations of current, hydrology and turbulence obtained at two mooring stations that are characterized by two typical hydrological environments in the East China Sea (ECS). One is located adjacent to the Changjiang River's mouth, and the other is located over a sloping shelf which is far from the freshwater sources. Tidal straining induces a semidiurnal switching between stable and unstable stratification at both stations. Near-bottom high-frequency velocity measurements further reveal that the dissipation rate of turbulent kinetic energy (TKE) is highly elevated during periods when unstable stratification occurs. A comparison between the TKE dissipation rate (ɛ) and the shear production (P) further reveals that the near-bottom mixing is locally shear-induced most of the time except during the unstable stratification period. Within this period, the magnitude of dissipation exceeds the expected value based on the law of the wall by an order of magnitude. The buoyancy flux that calculated by the balance method is too small to compensate for the existing discrepancy between the dissipation and shear production. Another plausible candidate is the advection of TKE, which may play an important role in the TKE budget during the unstable stratification period.

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

PubMed Central

2009-01-01

Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients. PMID:20028510

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.

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.

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.

Implementing risk-stratified screening for common cancers: a review of potential ethical, legal and social issues

PubMed Central

Hall, A.E.; Chowdhury, S.; Hallowell, N.; Pashayan, N.; Dent, T.; Pharoah, P.; Burton, H.

2014-01-01

Background The identification of common genetic variants associated with common cancers including breast, prostate and ovarian cancers would allow population stratification by genotype to effectively target screening and treatment. As scientific, clinical and economic evidence mounts there will be increasing pressure for risk-stratified screening programmes to be implemented. Methods This paper reviews some of the main ethical, legal and social issues (ELSI) raised by the introduction of genotyping into risk-stratified screening programmes, in terms of Beauchamp and Childress's four principles of biomedical ethics—respect for autonomy, non-maleficence, beneficence and justice. Two alternative approaches to data collection, storage, communication and consent are used to exemplify the ELSI issues that are likely to be raised. Results Ultimately, the provision of risk-stratified screening using genotyping raises fundamental questions about respective roles of individuals, healthcare providers and the state in organizing or mandating such programmes, and the principles, which underpin their provision, particularly the requirement for distributive justice. Conclusions The scope and breadth of these issues suggest that ELSI relating to risk-stratified screening will become increasingly important for policy-makers, healthcare professionals and a wide diversity of stakeholders. PMID:23986542

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

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.

Paradigm of pretest risk stratification before coronary computed tomography.

PubMed

Jensen, Jesper Møller; Ovrehus, Kristian A; Nielsen, Lene H; Jensen, Jesper K; Larsen, Henrik M; Nørgaard, Bjarne L

2009-01-01

The optimal method of determining the pretest risk of coronary artery disease as a patient selection tool before coronary multidetector computed tomography (MDCT) is unknown. We investigated the ability of 3 different clinical risk scores to predict the outcome of coronary MDCT. This was a retrospective study of 551 patients consecutively referred for coronary MDCT on a suspicion of coronary artery disease. Diamond-Forrester, Duke, and Morise risk models were used to predict coronary artery stenosis (>50%) as assessed by coronary MDCT. The models were compared by receiver operating characteristic analysis. The distribution of low-, intermediate-, and high-risk persons, respectively, was established and compared for each of the 3 risk models. Overall, all risk prediction models performed equally well. However, the Duke risk model classified the low-risk patients more correctly than did the other models (P < 0.01). In patients without coronary artery calcification (CAC), the predictive value of the Duke risk model was superior to the other risk models (P < 0.05). Currently available risk prediction models seem to perform better in patients without CAC. Between the risk prediction models, there was a significant discrepancy in the distribution of patients at low, intermediate, or high risk (P < 0.01). The 3 risk prediction models perform equally well, although the Duke risk score may have advantages in subsets of patients. The choice of risk prediction model affects the referral pattern to MDCT. Copyright (c) 2009 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. 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.

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.

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

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.

Adherence to physical activity recommendations and physical and mental health risk in people with severe mental illness in Uganda.

PubMed

Vancampfort, Davy; Probst, Michel; Basangwa, David; De Hert, Marc; Myin-Germeys, Inez; van Winkel, Ruud; Ward, Philip B; Rosenbaum, Simon; Mugisha, James

2017-11-29

This study investigated cardio-metabolic risk factors among patients with severe mental illness who do or do not meet the recommendations of 150min per week of physical activity. A secondary aim was to assess whether those that do meet the recommendations report lower levels of mental health symptoms. 107 (60♀) Ugandan in- and outpatients (mean age=34.4 ± 9.7 years) with severe mental illness (depression=7, bipolar disorder=55, schizophrenia=45) completed the Physical Activity Vital Sign (PAVS) method and Brief Symptoms Inventory -18. Participants were also screened for abdominal obesity (waist circumference>90cm), overweight (body mass index≥25) and hypertension (systolic pressure≥140mmHg and/or diastolic pressure≥90mmHg).48.6% (n = 52) of patients met the physical activity recommendations as assessed by the PAVS method. 41.1% (n = 44) were overweight, 40.2% (n = 43) had abdominal obesity and 23.4% (n = 25) had hypertension. Those who did not meet the physical activity recommendations were significantly older, had a higher BSI-18 somatisation score, and had a higher risk of overweight [relative risk (RR) = 2.88, 95% confidence interval (CI) = 1.59-4.99], abdominal obesity (RR = 1.82, 95%CI = 1.13-2.93), and hypertension (RR = 2.16, 95%CI = 0.99-4.73). The PAVS is a feasible method of assessing physical activity among patients with severe mental illness in a low resource setting. The PAVS may have clinical utility for physical and mental health risk stratification. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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…

Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children’s Hepatic tumors International Collaboration

PubMed Central

Meyers, Rebecka L; Maibach, Rudolf; Hiyama, Eiso; Häberle, Beate; Krailo, Mark; Rangaswami, Arun; Aronson, Daniel C; Malogolowkin, Marcio H; Perilongo, Giorgio; von Schweinitz, Dietrich; Ansari, Marc; Lopez-Terrada, Dolores; Tanaka, Yukichi; Alaggio, Rita; Leuschner, Ivo; Hishiki, Tomoro; Schmid, Irene; Watanabe, Kenichiro; Yoshimura, Kenichi; Feng, Yurong; Rinaldi, Eugenia; Saraceno, Davide; Derosa, Marisa; Czauderna, Piotr

2017-01-01

Summary Background Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children’s Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. Methods The CHIC steering committee—consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children’s Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)—created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3–7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101–1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. Findings Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. Interpretation We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). Funding European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children’s Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant. PMID:27884679

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.

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.

Intrabreed Stratification Related to Divergent Selection Regimes in Purebred Dogs May Affect the Interpretation of Genetic Association Studies

PubMed Central

Chang, Melanie L.; Yokoyama, Jennifer S.; Branson, Nick; Dyer, Donna J.; Hitte, Christophe; Overall, Karen L.

2009-01-01

Until recently, canine genetic research has not focused on population structure within breeds, which may confound the results of case–control studies by introducing spurious correlations between phenotype and genotype that reflect population history. Intrabreed structure may exist when geographical origin or divergent selection regimes influence the choices of potential mates for breeding dogs. We present evidence for intrabreed stratification from a genome-wide marker survey in a sample of unrelated dogs. We genotyped 76 Border Collies, 49 Australian Shepherds, 17 German Shepherd Dogs, and 17 Portuguese Water Dogs for our primary analyses using Affymetrix Canine v2.0 single-nucleotide polymorphism (SNP) arrays. Subsets of autosomal markers were examined using clustering algorithms to facilitate assignment of individuals to populations and estimation of the number of populations represented in the sample. SNPs passing stringent quality control filters were employed for explicitly phylogenetic analyses reconstructing relationships between individuals using maximum parsimony and Bayesian methods. We used simulation studies to explore the possible effects of intrabreed stratification on genome-wide association studies. These analyses demonstrate significant stratification in at least one of our primary breeds of interest, the Border Collie. Demographic and pedigree data suggest that this population substructure may result from geographic isolation or divergent selection regimes practiced by breeders with different breeding program goals. Simulation studies indicate that such stratification could result in false discovery rates significant enough to confound genome-wide association analyses. Intrabreed stratification should be accounted for when designing and interpreting the results of case–control association studies using purebred dogs.

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.

Incorporating genomics into breast and prostate cancer screening: assessing the implications

PubMed Central

Chowdhury, Susmita; Dent, Tom; Pashayan, Nora; Hall, Alison; Lyratzopoulos, Georgios; Hallowell, Nina; Hall, Per; Pharoah, Paul; Burton, Hilary

2013-01-01

Individual risk prediction and stratification based on polygenic profiling may be useful in disease prevention. Risk-stratified population screening based on multiple factors including a polygenic risk profile has the potential to be more efficient than age-stratified screening. In this article, we summarize the implications of personalized screening for breast and prostate cancers. We report the opinions of multidisciplinary international experts who have explored the scientific, ethical, and logistical aspects of stratified screening. We have identified (i) the need to recognize the benefits and harms of personalized screening as compared with existing screening methods, (ii) that the use of genetic data highlights complex ethical issues including discrimination against high-risk individuals by insurers and employers and patient autonomy in relation to genetic testing of minors, (iii) the need for transparency and clear communication about risk scores, about harms and benefits, and about reasons for inclusion and exclusion from the risk-based screening process, and (iv) the need to develop new professional competences and to assess cost-effectiveness and acceptability of stratified screening programs before implementation. We conclude that health professionals and stakeholders need to consider the implications of incorporating genetic information in intervention strategies for health-care planning in the future. Genet Med 2013:15(6):423–432 PMID:23412607

Prevalence of HCV Infection Among Clients in Community-Based Health Settings in Hawaii, 2002–2010: Assessing Risk Factors

PubMed Central

Porter, Jeremy C.; Lusk, Heather M.

2014-01-01

Objectives. We sought to determine the prevalence of HCV infection and identify risk factors associated with HCV infection among at-risk clients presenting to community-based health settings in Hawaii. Methods. Clients from 23 community-based sites were administered risk factor questionnaires and screened for HCV antibodies from December 2002 through May 2010. We performed univariate and multivariate logistic regression analyses. Results. Of 3306 participants included in the analysis, 390 (11.8%) tested antibody positive for HCV. Highest HCV antibody prevalence (17.0%) was in persons 45 to 64 years old compared with all other age groups. Significant independent risk factors were current or prior injection drug use (P < .001), blood transfusion prior to July 1992 (P = .002), and having an HCV-infected sex partner (P = .03). Stratification by gender revealed sexual exposure to be significant for males (P = .001). Conclusions. Despite Hawaii’s ethnic diversity, high hepatocellular carcinoma incidence, and a statewide syringe exchange program in place since the early 1990s, our HCV prevalence and risk factor findings are remarkably consistent with those reported from the mainland United States. Hence, effective interventions identified from US mainland population studies should be generalizable to Hawaii. PMID:24028267

Thermal stratification potential in rocket engine coolant channels

NASA Technical Reports Server (NTRS)

Kacynski, Kenneth J.

1992-01-01

The potential for rocket engine coolant channel flow stratification was computationally studied. A conjugate, 3-D, conduction/advection analysis code (SINDA/FLUINT) was used. Core fluid temperatures were predicted to vary by over 360 K across the coolant channel, at the throat section, indicating that the conventional assumption of a fully mixed fluid may be extremely inaccurate. Because of the thermal stratification of the fluid, the walls exposed to the rocket engine exhaust gases will be hotter than an assumption of full mixing would imply. In this analysis, wall temperatures were 160 K hotter in the turbulent mixing case than in the full mixing case. The discrepancy between the full mixing and turbulent mixing analyses increased with increasing heat transfer. Both analysis methods predicted identical channel resistances at the coolant inlet, but in the stratified analysis the thermal resistance was negligible. The implications are significant. Neglect of thermal stratification could lead to underpredictions in nozzle wall temperatures. Even worse, testing at subscale conditions may be inadequate for modeling conditions that would exist in a full scale engine.

Temperature Stratification in a Cryogenic Fuel Tank

NASA Technical Reports Server (NTRS)

Daigle, Matthew John; Smelyanskiy, Vadim; Boschee, Jacob; Foygel, Michael Gregory

2013-01-01

A reduced dynamical model describing temperature stratification effects driven by natural convection in a liquid hydrogen cryogenic fuel tank has been developed. It accounts for cryogenic propellant loading, storage, and unloading in the conditions of normal, increased, and micro- gravity. The model involves multiple horizontal control volumes in both liquid and ullage spaces. Temperature and velocity boundary layers at the tank walls are taken into account by using correlation relations. Heat exchange involving the tank wall is considered by means of the lumped-parameter method. By employing basic conservation laws, the model takes into consideration the major multi-phase mass and energy exchange processes involved, such as condensation-evaporation of the hydrogen, as well as flows of hydrogen liquid and vapor in the presence of pressurizing helium gas. The model involves a liquid hydrogen feed line and a tank ullage vent valve for pressure control. The temperature stratification effects are investigated, including in the presence of vent valve oscillations. A simulation of temperature stratification effects in a generic cryogenic tank has been implemented in Matlab and results are presented for various tank conditions.

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.

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PubMed

Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

2015-03-01

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Hemodynamic Based Coronary Artery Aneurysm Thrombosis Risk Stratification in Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Mathew, M.; McCrindle, B.; Kahn, A.; Burns, J.; Marsden, A.

2017-11-01

Coronary artery aneurysms (CAA) as a result of Kawasaki Disease (KD) put patients at risk for thrombosis and myocardial infarction. Current AHA guidelines recommend CAA diameter >8 mm or Z-score >10 as the criterion for initiating systemic anticoagulation. Our hypothesis is that hemodynamic data derived from computational blood flow simulations is a better predictor of thrombosis than aneurysm diameter alone. Patient-specific coronary models were constructed from CMRI for a cohort of 10 KD patients (5 confirmed thrombosis cases) and simulations with fluid structure interaction were performed using the stabilized finite element Navier-Stokes solver available in SimVascular. We used a closed-loop lumped parameter network (LPN) to model the heart and vascular boundary conditions coupled numerically to the flow solver. An automated parameter estimation method was used to match LPN values to clinical data for each patient. Hemodynamic data analysis resulted in low correlation between Wall Shear Stress (WSS)/ Particle Residence Time (PRT) and CAA diameter but demonstrates the positive correlation between hemodynamics and adverse patient outcomes. Our results suggest that quantifying WSS and PRT should enable identification of regions at higher risk of thrombosis. We propose a quantitative method to non-invasively assess the abnormal flow in CAA following KD that could potentially improve clinical decision-making regarding anticoagulation therapy.

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.

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.

Microbial stratification structure within cathodic biofilm of the microbial fuel cell using the freezing microtome method.

PubMed

Li, Xiao; Lu, Yaobin; Luo, Haiping; Liu, Guangli; Zhang, Renduo

2017-10-01

The aim of this study was to investigate the microbial stratification structure within cathodic biofilm of the microbial fuel cell (MFC) using the freezing microtome method. Experiments were conducted in a single-chamber air-cathode MFC with 0.8g/L maltodextrin as substrate for ∼30d operation. The maximum power density was 945±10mW/m 2 in the MFC. Maltodextrin resulted in the relative abundance of Candidatus Saccharibacteria of 37.0% in the anodic biofilm. Different bacterial communities were identified in different layers within the cathodic biofilm. The relative abundance of Enterococcus was 3.7%, 10.5%, and 1.6% in the top (100-150μm), middle (50-100μm), and bottom (0-50μm) layers, respectively. Higher bacterial viability was observed within the top and bottom layers of the cathodic biofilm. Understanding the stratification of bacterial community in cathodic biofilm should be important to control the cathodic biofilm in the MFC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Residential exposure to pesticides as risk factor for childhood and young adult brain tumors: A systematic review and meta-analysis.

PubMed

Van Maele-Fabry, Geneviève; Gamet-Payrastre, Laurence; Lison, Dominique

2017-09-01

Accumulating evidence suggests a positive association between exposure to non-agricultural pesticides and childhood brain tumors (CBT). (1) To conduct a systematic review and meta-analysis of published studies on the association between residential/household/domestic exposure to pesticides and childhood brain tumors. (2) To clarify variables that could impact the results. Publications in English were identified from a MEDLINE search through 28 February 2017 and from the reference list of identified publications. Risk estimates were extracted from 18 case-control studies published between 1979 and 2016 and study quality assessments were performed. Summary odds ratios (mOR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study quality, critical exposure period, exposure location, specific exposures, pesticide category, application methods, type of pest treated, type of CBT, child's age at diagnosis and geographic location. Statistically significant associations were observed with CBT after combining all studies (mOR: 1.26; 95% CI: 1.13-1.40) without evidence of inconsistency between study results or publication bias. Specifically, increased risks were observed for several groupings and more particularly for gliomas and exposure involving insecticides. Statistical significance was also reached for high quality studies, for all exposure periods, for indoor exposure and, more particularly, during the prenatal period for all stratifications involving insecticides (except for outdoor use), for pet treatments, for flea/tick treatment, for studies from USA/Canada and studies from Europe (borderline) as well as for data from studies including children of up to 10years at diagnosis and of up to 15years. Our findings support an association between residential exposure to pesticides and childhood brain tumors. Although causality cannot be established, these results add to the evidence leading to recommend limiting residential use of pesticides and to support public health policies serving this objective. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Perception of earthquake risk in Taiwan: effects of gender and past earthquake experience.

PubMed

Kung, Yi-Wen; Chen, Sue-Huei

2012-09-01

This study explored how individuals in Taiwan perceive the risk of earthquake and the relationship of past earthquake experience and gender to risk perception. Participants (n= 1,405), including earthquake survivors and those in the general population without prior direct earthquake exposure, were selected and interviewed through a computer-assisted telephone interviewing procedure using a random sampling and stratification method covering all 24 regions of Taiwan. A factor analysis of the interview data yielded a two-factor structure of risk perception in regard to earthquake. The first factor, "personal impact," encompassed perception of threat and fear related to earthquakes. The second factor, "controllability," encompassed a sense of efficacy of self-protection in regard to earthquakes. The findings indicated prior earthquake survivors and females reported higher scores on the personal impact factor than males and those with no prior direct earthquake experience, although there were no group differences on the controllability factor. The findings support that risk perception has multiple components, and suggest that past experience (survivor status) and gender (female) affect the perception of risk. Exploration of potential contributions of other demographic factors such as age, education, and marital status to personal impact, especially for females and survivors, is discussed. Future research on and intervention program with regard to risk perception are suggested accordingly. © 2012 Society for Risk Analysis.

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.

Galectin 3 complements BNP in risk stratification in acute heart failure

PubMed Central

Fermann, Gregory J.; Lindsell, Christopher J.; Storrow, Alan B.; Hart, Kimberly; Sperling, Matthew; Roll, Susan; Weintraub, Neal L.; Miller, Karen F.; Maron, David J.; Naftilan, Allen J.; Mcpherson, John A.; Sawyer, Douglas B.; Christenson, Robert; Collins, Sean P.

2013-01-01

Background Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Methods Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Results Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. Conclusion In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events. PMID:22998064

Comparing the association of GFR estimated by the CKD-EPI and MDRD study equations and mortality: the third national health and nutrition examination survey (NHANES III)

PubMed Central

2012-01-01

Background The Chronic Kidney Disease Epidemiology Collaboration equation for estimation of glomerular filtration rate (eGFRCKD-EPI) improves GFR estimation compared with the Modification of Diet in Renal Disease Study equation (eGFRMDRD) but its association with mortality in a nationally representative population sample in the US has not been studied. Methods We examined the association between eGFR and mortality among 16,010 participants of the Third National Health and Nutrition Examination Survey (NHANES III). Primary predictors were eGFRCKD-EPI and eGFRMDRD. Outcomes of interest were all-cause and cardiovascular disease (CVD) mortality. Improvement in risk categorization with eGFRCKD-EPI was evaluated using adjusted relative hazard (HR) and Net Reclassification Improvement (NRI). Results Overall, 26.9% of the population was reclassified to higher eGFR categories and 2.2% to lower eGFR categories by eGFRCKD-EPI, reducing the proportion of prevalent CKD classified as stage 3–5 from 45.6% to 28.8%. There were 3,620 deaths (1,540 from CVD) during 215,082 person-years of follow-up (median, 14.3 years). Among those with eGFRMDRD 30–59 ml/min/1.73 m2, 19.4% were reclassified to eGFRCKD-EPI 60–89 ml/min/1.73 m2 and these individuals had a lower risk of all-cause mortality (adjusted HR, 0.53; 95% CI, 0.34-0.84) and CVD mortality (adjusted HR, 0.51; 95% CI, 0.27-0.96) compared with those not reclassified. Among those with eGFRMDRD >60 ml/min/1.73 m2, 0.5% were reclassified to lower eGFRCKD-EPI and these individuals had a higher risk of all-cause (adjusted HR, 1.31; 95% CI, 1.01-1.69) and CVD (adjusted HR, 1.42; 95% CI, 1.01-1.99) mortality compared with those not reclassified. Risk prediction improved with eGFRCKD-EPI; NRI was 0.21 for all-cause mortality (p < 0.001) and 0.22 for CVD mortality (p < 0.001). Conclusions eGFRCKD-EPI categories improve mortality risk stratification of individuals in the US population. If eGFRCKD-EPI replaces eGFRMDRD in the US, it will likely improve risk stratification. PMID:22702805

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.

In Vivo Biomarkers for Targeting Colorectal Neoplasms

PubMed Central

Hsiung, Pei-Lin; Wang, Thomas

2011-01-01

Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

‘Someday it will be the norm’: physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project

PubMed Central

Vassy, Jason L; Christensen, Kurt D; Slashinski, Melody J; Lautenbach, Denise M; Raghavan, Sridharan; Robinson, Jill Oliver; Blumenthal-Barby, Jennifer; Feuerman, Lindsay Zausmer; Lehmann, Lisa Soleymani; Murray, Michael F; Green, Robert C; McGuire, Amy L

2015-01-01

Aim To describe practicing physicians’ perceived clinical utility of genome sequencing. Materials & methods We conducted a mixed-methods analysis of data from 18 primary care physicians and cardiologists in a study of the clinical integration of whole-genome sequencing. Physicians underwent brief genomics continuing medical education before completing surveys and semi-structured interviews. Results Physicians described sequencing as currently lacking clinical utility because of its uncertain interpretation and limited impact on clinical decision-making, but they expressed the idea that its clinical integration was inevitable. Potential clinical uses for sequencing included complementing other clinical information, risk stratification, motivating patient behavior change and pharmacogenetics. Conclusion Physicians given genomics continuing medical education use the language of both evidence-based and personalized medicine in describing the utility of genome-wide testing in patient care. PMID:25642274