Is risk stratification ever the same as 'profiling'?
Braithwaite, R Scott; Stevens, Elizabeth R; Caplan, Arthur
2016-05-01
Physicians engage in risk stratification as a normative part of their professional duties. Risk stratification has the potential to be beneficial in many ways, and implicit recognition of this potential benefit underlies its acceptance as a cornerstone of the medical profession. However, risk stratification also has the potential to be harmful. We argue that 'profiling' is a term that corresponds to risk stratification strategies in which there is concern that ethical harms exceed likely or proven benefits. In the case of risk stratification for health goals, this would occur most frequently if benefits were obtained by threats to justice, autonomy or privacy. We discuss implications of the potential overlap between risk stratification and profiling for researchers and for clinicians, and we consider whether there are salient characteristics that make a particular risk stratification algorithm more or less likely to overlap with profiling, such as whether the risk stratification algorithm is based on voluntary versus non-voluntary characteristics, based on causal versus non-causal characteristics, or based on signifiers of historical disadvantage. We also discuss the ethical challenges created when a risk stratification scheme helps all subgroups but some more than others, or when risk stratification harms some subgroups but benefits the aggregate group. 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/
A probabilistic topic model for clinical risk stratification from electronic health records.
Huang, Zhengxing; Dong, Wei; Duan, Huilong
2015-12-01
Risk stratification aims to provide physicians with the accurate assessment of a patient's clinical risk such that an individualized prevention or management strategy can be developed and delivered. Existing risk stratification techniques mainly focus on predicting the overall risk of an individual patient in a supervised manner, and, at the cohort level, often offer little insight beyond a flat score-based segmentation from the labeled clinical dataset. To this end, in this paper, we propose a new approach for risk stratification by exploring a large volume of electronic health records (EHRs) in an unsupervised fashion. Along this line, this paper proposes a novel probabilistic topic modeling framework called probabilistic risk stratification model (PRSM) based on Latent Dirichlet Allocation (LDA). The proposed PRSM recognizes a patient clinical state as a probabilistic combination of latent sub-profiles, and generates sub-profile-specific risk tiers of patients from their EHRs in a fully unsupervised fashion. The achieved stratification results can be easily recognized as high-, medium- and low-risk, respectively. In addition, we present an extension of PRSM, called weakly supervised PRSM (WS-PRSM) by incorporating minimum prior information into the model, in order to improve the risk stratification accuracy, and to make our models highly portable to risk stratification tasks of various diseases. We verify the effectiveness of the proposed approach on a clinical dataset containing 3463 coronary heart disease (CHD) patient instances. Both PRSM and WS-PRSM were compared with two established supervised risk stratification algorithms, i.e., logistic regression and support vector machine, and showed the effectiveness of our models in risk stratification of CHD in terms of the Area Under the receiver operating characteristic Curve (AUC) analysis. As well, in comparison with PRSM, WS-PRSM has over 2% performance gain, on the experimental dataset, demonstrating that incorporating risk scoring knowledge as prior information can improve the performance in risk stratification. Experimental results reveal that our models achieve competitive performance in risk stratification in comparison with existing supervised approaches. In addition, the unsupervised nature of our models makes them highly portable to the risk stratification tasks of various diseases. Moreover, patient sub-profiles and sub-profile-specific risk tiers generated by our models are coherent and informative, and provide significant potential to be explored for the further tasks, such as patient cohort analysis. We hypothesize that the proposed framework can readily meet the demand for risk stratification from a large volume of EHRs in an open-ended fashion. Copyright © 2015 Elsevier Inc. All rights reserved.
Gagnon, J.; Lévesque, E.; Borduas, F.; Chiquette, J.; Diorio, C.; Duchesne, N.; Dumais, M.; Eloy, L.; Foulkes, W.; Gervais, N.; Lalonde, L.; L’Espérance, B.; Meterissian, S.; Provencher, L.; Richard, J.; Savard, C.; Trop, I.; Wong, N.; Knoppers, B.M.; Simard, J.
2016-01-01
In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international perspective project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification—unlike those for population screening programs, which are currently well regulated—are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of perspective. Here, we describe the risk stratification process that was devised in the context of perspective, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies. PMID:28050152
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
Avram, Anca M; Esfandiari, Nazanene H; Wong, Ka Kit
2015-05-01
The use of preablation diagnostic radioiodine scans for risk stratification and radioiodine therapy planning for differentiated thyroid cancer (DTC) remains controversial. The objective was to assess the contribution of preablation diagnostic 131-I scans with SPECT/CT (Dx 131-I scan) to (1) the risk stratification and (2) the postoperative management of DTC. The study was designed as a prospective sequential patient series. The study was conducted at a University hospital. Three hundred twenty patients (pts) with DTC (219F; 101M, mean age 47.3 ± 16.4 y, range 10-90) were studied. Using clinical and histopathology information an endocrinologist performed risk stratification and determined postoperative management with respect to radioiodine therapy (RAI) planning. The decision to withhold or to administer RAI, and the recommended low, medium or high therapeutic 131-I activity were recorded. Dx 131-I scans were performed and interpreted by two nuclear medicine physicians as showing thyroid remnant, cervical nodal, or distant metastases. The endocrinologist then reperformed risk stratification and reformulated management after consideration of Dx 131-I scans and stimulated thyroglobulin (Tg) information. Main outcome measures were changes in risk stratification and management after Dx 131-I scans. Detection of unsuspected nodal and distant metastases and elevated stimulated Tg levels resulted in a change in the estimated risk of recurrence in 15% of patients, and management in 31% of patients, as compared to initial risk stratification and management based on histopathology alone. Both imaging data and stimulated thyroglobulin levels acquired at the time of Dx 131-I scans are consequential for 131-I therapy planning, providing information that changes risk stratification in 15% of patients as compared to recurrence risk estimation based on histopathology alone. Dx 131-I scans contribute to risk stratification by defining residual nodal and distant metastatic disease, changing clinical management in 29.4% of patients.
Avital, Itzhak; Langan, Russell C.; Summers, Thomas A.; Steele, Scott R.; Waldman, Scott A.; Backman, Vadim; Yee, Judy; Nissan, Aviram; Young, Patrick; Womeldorph, Craig; Mancusco, Paul; Mueller, Renee; Noto, Khristian; Grundfest, Warren; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Eberhardt, John; Man, Yan Gao; Brücher, Björn LDM; Stojadinovic, Alexander
2013-01-01
Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U.S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. PMID:23459409
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.
Huckel Schneider, Carmen; Gillespie, James A; Wilson, Andrew
2017-05-01
Risk stratification has become a widely used tool for linking people identified at risk of health deterioration to the most appropriate evidence-based care. This article systematically reviews recent literature to determine key factors that have been identified as critical enablers and/or barriers to successful implementation of risk stratification tools at a system level. A systematic search found 23 articles and four promising protocols for inclusion in the review, covering the use to 20 different risk stratification tools. These articles reported on only a small fraction of the risk stratification tools used in health systems; suggesting that while the development and statistical validation of risk stratification algorithms is widely reported, there has been little published evaluation of how they are implemented in real-world settings. Controlled studies provided some evidence that the use of risk stratification tools in combination with a care management plan offer patient benefits and that the use of a risk stratification tool to determine components of a care management plan may contribute to reductions in hospital readmissions, patient satisfaction and improved patient outcomes. Studies with the strongest focus on implementation used qualitative and case study methods. Among these, the literature converged on four key areas of implementation that were found to be critical for overcoming barriers to success: the engagement of clinicians and safeguarding equity, both of which address barriers of acceptance; the health system context to address administrative, political and system design barriers; and data management and integration to address logistical barriers.
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.
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.
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.
A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning
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
New Methods for the Analysis of Heartbeat Behavior in Risk Stratification
Glass, Leon; Lerma, Claudia; Shrier, Alvin
2011-01-01
Developing better methods for risk stratification for tachyarrhythmic sudden cardiac remains a major challenge for physicians and scientists. Since the transition from sinus rhythm to ventricular tachycardia/fibrillation happens by different mechanisms in different people, it is unrealistic to think that a single measure will be adequate to provide a good index for risk stratification. We analyze the dynamical properties of ventricular premature complexes over 24 h in an effort to understand the underlying mechanisms of ventricular arrhythmias and to better understand the arrhythmias that occur in individual patients. Two dimensional density plots, called heartprints, correlate characteristic features of the dynamics of premature ventricular complexes and the sinus rate. Heartprints show distinctive characteristics in individual patients. Based on a better understanding of the natures of transitions from sinus rhythm to sudden cardiac and the mechanisms of arrhythmia prior to cardiac arrest, it should be possible to develop better methods for risk stratification. PMID:22144963
Prospective Validation of ATA and ETA Sonographic Pattern Risk of Thyroid Nodules Selected for FNAC.
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.
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.
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.
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.
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.
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.
Modern risk stratification in coronary heart disease.
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.
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.
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
Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy.
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.
Proposals for enhanced health risk assessment and stratification in an integrated care scenario
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
Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions.
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.
Accurate Diabetes Risk Stratification Using Machine Learning: Role of Missing Value and Outliers.
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.
Salselas, Ana; Pestana, Inês; Bischoff, Francisco; Guimarães, Mariana; Andrade, Joaquim Aguiar
2015-01-01
Pregnant women with thromboembolic diseases, previous thrombotic episodes or thrombophilia family history were supervised in a multidisciplinary Obstetrics/ Hematology consultation in Centro Hospitalar São João EPE, Porto, Portugal. For the evaluation and medication of these women, a risk stratification scale was used. The aim of this study was to validate a Risk Stratification Scale and thromboprophylaxis protocol by means of comparing it with a similar scale, developed and published by Sarig. We have compared: The distribution, by risk groups, obtained through the application of the two scales on pregnant women followed at Centro Hospitalar São João, Porto, Portugal, consultation; the sensibility and specificity for each one of the scales (DeLong scale, applied to Receiver Operating Characteristic) curves; the outcomes in pregnancies followed in Hospital São João, Porto, PortugalResults: According to our Hema-Obs risk stratification scale, 29% were allocated to low-risk, 47% to high-risk and 24% to very-high-risk groups. According to Galit Sarig risk stratification scale, 24% were considered low-risk, 53% moderate, 16% high-risk and 7% as very high-risk group. In our study we observed 9% of spontaneous abortions, in comparison with 18% in the Galit Sarig cohort. From the application of Receiver Operating Characteristic curve to both risk stratification scales, the results of the calculated areas were 58,8% to our Hema-Obs risk stratification scale and 38,7% to Galit Sarig risk stratification scale, with a Delong test significancie of p = 0.0006. We concluded that Hema-Obs risk stratification scale is an effective support for clinical monitoring of therapeutic strategies.
Predicting the risk of sudden cardiac death.
Lerma, Claudia; Glass, Leon
2016-05-01
Sudden cardiac death (SCD) is the result of a change of cardiac activity from normal (typically sinus) rhythm to a rhythm that does not pump adequate blood to the brain. The most common rhythms leading to SCD are ventricular tachycardia (VT) or ventricular fibrillation (VF). These result from an accelerated ventricular pacemaker or ventricular reentrant waves. Despite significant efforts to develop accurate predictors for the risk of SCD, current methods for risk stratification still need to be improved. In this article we briefly review current approaches to risk stratification. Then we discuss the mathematical basis for dynamical transitions (called bifurcations) that may lead to VT and VF. One mechanism for transition to VT or VF involves a perturbation by a premature ventricular complex (PVC) during sinus rhythm. We describe the main mechanisms of PVCs (reentry, independent pacemakers and abnormal depolarizations). An emerging approach to risk stratification for SCD involves the development of individualized dynamical models of a patient based on measured anatomy and physiology. Careful analysis and modelling of dynamics of ventricular arrhythmia on an individual basis will be essential in order to improve risk stratification for SCD and to lay a foundation for personalized (precision) medicine in cardiology. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
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.
Proposals for enhanced health risk assessment and stratification in an integrated care scenario.
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/
Cardiac risk stratification in cardiac rehabilitation programs: a review of protocols
da Silva, Anne Kastelianne França; Barbosa, Marianne Penachini da Costa de Rezende; Bernardo, Aline Fernanda Barbosa; Vanderlei, Franciele Marques; Pacagnelli, Francis Lopes; Vanderlei, Luiz Carlos Marques
2014-01-01
Objective Gather and describe general characteristics of different protocols of risk stratification for cardiac patients undergoing exercise. Methods We conducted searches in LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO electronic databases, using the following descriptors: Cardiovascular Disease, Rehabilitation Centers, Practice Guideline, Exercise and Risk Stratification in the past 20 years. Results Were selected eight studies addressing methods of risk stratification in patients undergoing exercise. Conclusion None of the methods described could cover every situation the patient can be subjected to; however, they are essential to exercise prescription. PMID:25140477
The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy.
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.
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.
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
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
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
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.
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.
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.
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.
A three-gene expression signature model for risk stratification of patients with neuroblastoma.
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
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
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.
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.
Gong, Yi; Chen, Rui; Zhang, Xi; Zou, Zhong Min; Chen, Xing Hua
2017-07-01
To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Significant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum β2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index (IPI), revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Hong, Chae Moon; Lee, Won Kee; Jeong, Shin Young; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae
2014-11-01
The aim of this study was to validate the effectiveness of delayed risk stratification (DRS) in predicting structural progression and compare the predictive value of American Thyroid Association (ATA) risk stratification with that of DRS in patients with differentiated thyroid cancer (DTC). A total of 398 patients with DTC who underwent surgery followed by radioactive iodine ablation were enrolled. Patients were categorized as having excellent response, acceptable response, biochemical incomplete response, or structural incomplete response at 8-15 months' evaluation after radioactive iodine ablation for DRS. Effectiveness of DRS was evaluated according to structural progression-free survival (PFS; median follow-up, 10.7 years). A total of 229 patients (57.5%) were classified as having excellent response, 78 (19.6%) as having acceptable response, 62 (15.6%) as having biochemical incomplete response, and 29 patients (7.3%) as having structural incomplete response. After DRS, 60.2% of intermediate-risk patients and 20.5% of high-risk patients were shifted to the excellent response category. Sixty-nine patients (17.3%) showed structural progression. DRS showed statistical difference in PFS (hazard ratio, 4.268; 95% confidence interval, 3.258-5.477; P<0.001). In multivariate analysis of ATA risk stratification and DRS, DRS was significantly associated with PFS (hazard ratio, 4.383; 95% confidence interval, 3.250-5.912; P<0.001), but ATA risk stratification was not. There was no significant difference in deviances between the use of DRS alone and the use of both DRS and ATA risk stratification (χ=0.103, d.f.=1, P=0.748). DRS is superior to ATA risk stratification in predicting structural disease progression for DTC patients.
Quantitative risk stratification in Markov chains with limiting conditional distributions.
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.
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.
Cardiovascular risk assessment: addition of CKD and race to the Framingham equation
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
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
Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer
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
Cardiac risk stratification: Role of the coronary calcium score
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
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.
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.
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
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting
Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.« less
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
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.
Risk stratification in myelodysplastic syndromes: is there a role for gene expression profiling?
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.
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.
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
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.
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
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.
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.
Reddy, Ashok; Sessums, Laura; Gupta, Reshma; Jin, Janel; Day, Tim; Finke, Bruce; Bitton, Asaf
2017-09-01
Risk-stratified care management is essential to improving population health in primary care settings, but evidence is limited on the type of risk stratification method and its association with care management services. We describe risk stratification patterns and association with care management services for primary care practices in the Comprehensive Primary Care (CPC) initiative. We undertook a qualitative approach to categorize risk stratification methods being used by CPC practices and tested whether these stratification methods were associated with delivery of care management services. CPC practices reported using 4 primary methods to stratify risk for their patient populations: a practice-developed algorithm (n = 215), the American Academy of Family Physicians' clinical algorithm (n = 155), payer claims and electronic health records (n = 62), and clinical intuition (n = 52). CPC practices using practice-developed algorithm identified the most number of high-risk patients per primary care physician (282 patients, P = .006). CPC practices using clinical intuition had the most high-risk patients in care management and a greater proportion of high-risk patients receiving care management per primary care physician (91 patients and 48%, P =.036 and P =.128, respectively). CPC practices used 4 primary methods to identify high-risk patients. Although practices that developed their own algorithm identified the greatest number of high-risk patients, practices that used clinical intuition connected the greatest proportion of patients to care management services. © 2017 Annals of Family Medicine, Inc.
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.
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
Huebner, Thomas; Goernig, Matthias; Schuepbach, Michael; Sanz, Ernst; Pilgram, Roland; Seeck, Andrea; Voss, Andreas
2010-01-01
Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient-assisted living support the electrocardiological monitoring of at-risk patients. Conclusions: There are many promising methods for the exercise-free, non-invasive detection of CAD and myocardial ischemia in the stable and acute phases. In the coming years, these new methods will help enhance state-of-the-art procedures in routine diagnostics. The future can expect that equally novel methods for risk stratification and telemedicine will transition into clinical routine. PMID:21063467
Risk assessment and clinical decision making for colorectal cancer screening.
Schroy, Paul C; Caron, Sarah E; Sherman, Bonnie J; Heeren, Timothy C; Battaglia, Tracy A
2015-10-01
Shared decision making (SDM) related to test preference has been advocated as a potentially effective strategy for increasing adherence to colorectal cancer (CRC) screening, yet primary care providers (PCPs) are often reluctant to comply with patient preferences if they differ from their own. Risk stratification advanced colorectal neoplasia (ACN) provides a rational strategy for reconciling these differences. To assess the importance of risk stratification in PCP decision making related to test preference for average-risk patients and receptivity to use of an electronic risk assessment tool for ACN to facilitate SDM. Mixed methods, including qualitative key informant interviews and a cross-sectional survey. PCPs at an urban, academic safety-net institution. Screening preferences, factors influencing patient recommendations and receptivity to use of a risk stratification tool. Nine PCPs participated in interviews and 57 completed the survey. Despite an overwhelming preference for colonoscopy by 95% of respondents, patient risk (67%) and patient preferences (63%) were more influential in their decision making than patient comorbidities (31%; P < 0.001). Age was the single most influential risk factor (excluding family history), with <20% of respondents choosing factors other than age. Most respondents reported that they would be likely to use a risk stratification tool in their practice either 'often' (43%) or sometimes (53%). Risk stratification was perceived to be important in clinical decision making, yet few providers considered risk factors other than age for average-risk patients. Providers were receptive to the use of a risk assessment tool for ACN when recommending an appropriate screening test for select patients. © 2013 John Wiley & Sons Ltd.
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.
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 Associated with Pulse Pressure on Out-of-Office Blood Pressure Measurement
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
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.
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.
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.
External validation of scoring systems in risk stratification of upper gastrointestinal bleeding.
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.
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.
Deep Vein Thrombosis Prophylaxis: State of the Art.
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.
Accurate and robust genomic prediction of celiac disease using statistical learning.
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.
Predictors of Post-discharge Mortality Among Patients Hospitalized for Acute Heart Failure
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
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.
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
Segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.
Voss, A; Fischer, C; Schroeder, R; Figulla, H R; Goernig, M
2010-01-01
The prognostic value of heart rate variability in patients with dilated cardiomyopathy (DCM) is limited and does not contribute to risk stratification although the dynamics of ventricular repolarization differs considerably between DCM patients and healthy subjects. Neither linear nor nonlinear methods of heart rate variability analysis could discriminate between patients at high and low risk for sudden cardiac death. The aim of this study was to analyze the suitability of the new developed segmented Poincaré plot analysis (SPPA) to enhance risk stratification in DCM. In contrast to the usual applied Poincaré plot analysis the SPPA retains nonlinear features from investigated beat-to-beat interval time series. Main features of SPPA are the rotation of cloud of points and their succeeded variability depended segmentation. Significant row and column probabilities were calculated from the segments and led to discrimination (up to p<0.005) between low and high risk in DCM patients. For the first time an index from Poincaré plot analysis of heart rate variability was able to contribute to risk stratification in patients suffering from DCM.
Clinical Risk Stratification for Primary Prevention Implantable Cardioverter Defibrillators
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
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.
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.
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
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.
Classification of drugs with different risk profiles.
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.
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.
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
Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification.
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.
Barrett’s oesophagus: Current controversies
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.
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.
Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification
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
An Interoperable System toward Cardiac Risk Stratification from ECG Monitoring
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
Prediction of Breast Cancer Risk by Aberrant Methylation in Mammary Duct Lavage
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
All men with vasculogenic erectile dysfunction require a cardiovascular workup.
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.
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.
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.
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.
Syncope: risk stratification and clinical decision making.
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.
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
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.
Predicting Geriatric Falls Following an Episode of Emergency Department Care: A Systematic Review
Carpenter, Christopher R.; Avidan, Michael S.; Wildes, Tanya; Stark, Susan; Fowler, Susan A.; Lo, Alexander X.
2015-01-01
Background Falls are the leading cause of traumatic mortality in geriatric adults. Despite recent multispecialty guideline recommendations that advocate for proactive fall prevention protocols in the emergency department (ED), the ability of risk factors or risk stratification instruments to identify subsets of geriatric patients at increased risk for short-term falls is largely unexplored. Objectives This was a systematic review and meta-analysis of ED-based history, physical examination, and fall risk stratification instruments with the primary objective of providing a quantitative estimate for each risk factor’s accuracy to predict future falls. A secondary objective was to quantify ED fall risk assessment test and treatment thresholds using derived estimates of sensitivity and specificity. Methods A medical librarian and two emergency physicians (EPs) conducted a medical literature search of PUBMED, EMBASE, CINAHL, CENTRAL, DARE, the Cochrane Registry, and Clinical Trials. Unpublished research was located by a hand search of emergency medicine (EM) research abstracts from national meetings. Inclusion criteria for original studies included ED-based assessment of pre-ED or post-ED fall risk in patients 65 years and older with sufficient detail to reproduce contingency tables for meta-analysis. Original study authors were contacted for additional details when necessary. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used to assess individual study quality for those studies that met inclusion criteria. When more than one qualitatively similar study assessed the same risk factor for falls at the same interval following an ED evaluation, then meta-analysis was performed using Meta-DiSc software. The primary outcomes were sensitivity, specificity, and likelihood ratios for fall risk factors or risk stratification instruments. Secondary outcomes included estimates of test and treatment thresholds using the Pauker method based on accuracy, screening risk, and the projected benefits or harms of fall prevention interventions in the ED. Results A total of 608 unique and potentially relevant studies were identified, but only three met our inclusion criteria. Two studies that included 660 patients assessed 29 risk factors and two risk stratification instruments for falls in geriatric patients in the 6 months following an ED evaluation, while one study of 107 patients assessed the risk of falls in the preceding 12 months. A self-report of depression was associated with the highest positive likelihood ratio (LR) of 6.55 (95% confidence interval [CI] = 1.41 to 30.48). Six fall predictors were identified in more than one study (past falls, living alone, use of walking aid, depression, cognitive deficit, and more than six medications) and meta-analysis was performed for these risk factors. One screening instrument was sufficiently accurate to identify a subset of geriatric ED patients at low risk for falls with a negative LR of 0.11 (95% CI = 0.06 to 0.20). The test threshold was 6.6% and the treatment threshold was 27.5%. Conclusions This study demonstrates the paucity of evidence in the literature regarding ED-based screening for risk of future falls among older adults. The screening tools and individual characteristics identified in this study provide an evidentiary basis on which to develop screening protocols for geriatrics adults in the ED to reduce fall risk PMID:25293956
Predicting geriatric falls following an episode of emergency department care: a systematic review.
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.
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.
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.
Correction of Population Stratification in Large Multi-Ethnic Association Studies
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
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
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.
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
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.
Prostate cancer: predicting high-risk prostate cancer-a novel stratification tool.
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.
Saba, Luca; Jain, Pankaj K; Suri, Harman S; Ikeda, Nobutaka; Araki, Tadashi; Singh, Bikesh K; Nicolaides, Andrew; Shafique, Shoaib; Gupta, Ajay; Laird, John R; Suri, Jasjit S
2017-06-01
Severe atherosclerosis disease in carotid arteries causes stenosis which in turn leads to stroke. Machine learning systems have been previously developed for plaque wall risk assessment using morphology-based characterization. The fundamental assumption in such systems is the extraction of the grayscale features of the plaque region. Even though these systems have the ability to perform risk stratification, they lack the ability to achieve higher performance due their inability to select and retain dominant features. This paper introduces a polling-based principal component analysis (PCA) strategy embedded in the machine learning framework to select and retain dominant features, resulting in superior performance. This leads to more stability and reliability. The automated system uses offline image data along with the ground truth labels to generate the parameters, which are then used to transform the online grayscale features to predict the risk of stroke. A set of sixteen grayscale plaque features is computed. Utilizing the cross-validation protocol (K = 10), and the PCA cutoff of 0.995, the machine learning system is able to achieve an accuracy of 98.55 and 98.83%corresponding to the carotidfar wall and near wall plaques, respectively. The corresponding reliability of the system was 94.56 and 95.63%, respectively. The automated system was validated against the manual risk assessment system and the precision of merit for same cross-validation settings and PCA cutoffs are 98.28 and 93.92%for the far and the near wall, respectively.PCA-embedded morphology-based plaque characterization shows a powerful strategy for risk assessment and can be adapted in clinical settings.
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.
Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention.
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.
Role of imaging in evaluation of sudden cardiac death risk in hypertrophic cardiomyopathy.
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.
Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient
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
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/.
Utility of the exercise electrocardiogram testing in sudden cardiac death risk stratification.
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.
Combining risk markers improves cardiovascular risk prediction in women.
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.
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
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
Hann, Katie E J; Fraser, Lindsay; Side, Lucy; Gessler, Sue; Waller, Jo; Sanderson, Saskia C; Freeman, Madeleine; Jacobs, Ian; Lanceley, Anne
2017-12-16
Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non-genetic information including epidemiological information is rolled out on a population basis, training will be needed for HCPs in primary care to enable them to provide appropriate support to women at each stage of the process.
Prediction of breast cancer risk based on profiling with common genetic variants.
Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; Dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Figueroa, Jonine; Chanock, Stephen J; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J; Olson, Janet E; Vachon, Celine; Pankratz, Vernon S; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M; Hunter, David J; Lindstrom, Sara; Tamimi, Rulla M; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J; Doody, Michele M; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G; Milne, Roger L; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Koppert, Linetta B; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Eccles, Diana M; Tapper, William J; Rafiq, Sajjad; John, Esther M; Whittemore, Alice S; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E; Yao, Song; Zheng, Wei; Halverson, Sandra L; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Simard, Jacques; Hall, Per; Easton, Douglas F; Garcia-Closas, Montserrat
2015-05-01
Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © The Author 2015. Published by Oxford University Press.
Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
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
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.
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
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.
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.
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.
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.
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).
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
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.
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.
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.
Santos, Ana A. S.; Silva, Anne K. F.; Vanderlei, Franciele M.; Christofaro, Diego G. D.; Gonçalves, Aline F. L.; Vanderlei, Luiz C. M.
2016-01-01
ABSTRACT Background Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. Objective To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. Method The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Société Française de Cardiologie, and the Sociedad Española de Cardiología. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. Results Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. Conclusion The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID:27556385
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
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.
Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case-control study.
Zhu, Yanping; Liu, Kuo; Tang, Xun; Wang, Jinwei; Yu, Zhiping; Wu, Yiqun; Chen, Dafang; Wang, Xueyin; Fang, Kai; Li, Na; Huang, Shaoping; Hu, Yonghua
2014-11-01
Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene-environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95% CI 1.04-3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95% CI 1.06-6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95% CI 1.54-8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.
Tissue-based biomarkers in prostate cancer
Clinton, Timothy N.; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Raj, Ganesh V; Woldu, Solomon L
2017-01-01
Introduction Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert Commentary Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques. PMID:29226251
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.
Dynamic TIMI Risk Score for STEMI
Amin, Sameer T.; Morrow, David A.; Braunwald, Eugene; Sloan, Sarah; Contant, Charles; Murphy, Sabina; Antman, Elliott M.
2013-01-01
Background Although there are multiple methods of risk stratification for ST‐elevation myocardial infarction (STEMI), this study presents a prospectively validated method for reclassification of patients based on in‐hospital events. A dynamic risk score provides an initial risk stratification and reassessment at discharge. Methods and Results The dynamic TIMI risk score for STEMI was derived in ExTRACT‐TIMI 25 and validated in TRITON‐TIMI 38. Baseline variables were from the original TIMI risk score for STEMI. New variables were major clinical events occurring during the index hospitalization. Each variable was tested individually in a univariate Cox proportional hazards regression. Variables with P<0.05 were incorporated into a full multivariable Cox model to assess the risk of death at 1 year. Each variable was assigned an integer value based on the odds ratio, and the final score was the sum of these values. The dynamic score included the development of in‐hospital MI, arrhythmia, major bleed, stroke, congestive heart failure, recurrent ischemia, and renal failure. The C‐statistic produced by the dynamic score in the derivation database was 0.76, with a net reclassification improvement (NRI) of 0.33 (P<0.0001) from the inclusion of dynamic events to the original TIMI risk score. In the validation database, the C‐statistic was 0.81, with a NRI of 0.35 (P=0.01). Conclusions This score is a prospectively derived, validated means of estimating 1‐year mortality of STEMI at hospital discharge and can serve as a clinically useful tool. By incorporating events during the index hospitalization, it can better define risk and help to guide treatment decisions. PMID:23525425
Dynamic TIMI risk score for STEMI.
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 assessment and management of chest pain in primary care: A focus on acute coronary syndrome
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.
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.
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
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.
Mortality risk stratification in severely anaemic Jehovah's Witness patients.
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.
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.
Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.
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
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
Advantages of early diagnosis of diabetic neuropathy in the prevention of diabetic foot ulcers.
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.
Neuroblastoma: clinical and biological approach to risk stratification and treatment.
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.
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
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.
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.
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
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.
Standardized reporting guidelines for emergency department syncope risk-stratification research.
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.
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
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.
Modelling the distribution of chickens, ducks, and geese in China
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
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
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
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.
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.
Applicability of an established management algorithm for colon injuries following blunt trauma.
Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Fabian, Timothy C; Croce, Martin A
2013-02-01
Operative management at our institution for all colon injuries have followed a defined algorithm (ALG) based on risk factors originally identified for penetrating injuries. The purpose of this study was to evaluate the applicability of the ALG to blunt colon injuries. Patients with blunt colon injuries during 13 years were identified. As per the ALG, nondestructive (ND) injuries are treated with primary repair. Patients with destructive wounds (serosal tear of ≥50% colon circumference, mesenteric devascularization, and perforations) and concomitant risk factors (transfusion of >6 U packed red blood cells and/or presence of significant comorbidities) are diverted, while patients with no risk factors undergo resection plus anastomosis (RA). Outcomes included suture line failure (SLF), abscess, and mortality. Stratification analysis was performed to determine additional risk factors in the management of blunt colon injuries. A total 151 patients were identified: 76 with destructive injuries and 75 with ND injuries. Of those with destructive injuries, 44 (59%) underwent RA and 29 (39%) underwent diversion. All ND injuries underwent primary repair. Adherence to the ALG was 95%: three patients with destructive injuries underwent primary repair, and five patients with risk factors underwent RA. There were three SLFs (2%) (one involved deviation from the ALG) and eight abscesses (5%). Colon-related mortality was 2.1%. Stratification analysis based on mesenteric involvement, degree of shock, and need for abbreviated laparotomy failed to identify additional risk factors for SLF following RA for blunt colon injuries. Adherence to an ALG, originally defined for penetrating colon injuries, simplified the management of blunt colon injuries. ND injuries should be primarily repaired. For destructive wounds, management based on a defined ALG achieves an acceptably low morbidity and mortality rate. Prognostic/epidemiologic study, level III; therapeutic study, level IV.
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.
CoAIMs: A Cost-Effective Panel of Ancestry Informative Markers for Determining Continental Origins
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
The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report
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
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.
Hydra: A web-based system for cardiovascular analysis, diagnosis and treatment.
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.
Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention
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
Stratification of breast cancer risk in women with atypia: a Mayo cohort study.
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.
Brun, Francesca; Groeneweg, Judith A.; Gear, Kathleen; Sinagra, Gianfranco; van der Heijden, Jeroen; Mestroni, Luisa; Hauer, Richard N.; Borgstrom, Mark; Marcus, Frank I.; Hughes, Trina
2016-01-01
Objectives The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). Background There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. Methods This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. Results Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. Conclusion These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death. PMID:27790640
A new risk stratification algorithm for the management of patients with adrenal incidentalomas.
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.
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.
Cytogenetic prognostication within medulloblastoma subgroups.
Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D
2014-03-20
Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.
Cytogenetic Prognostication Within Medulloblastoma Subgroups
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
Development of a Bayesian Classifier for Breast Cancer Risk Stratification: A Feasibility Study
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
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
Patel, Archana; Prakash, Amber Abhijeet; Pusdekar, Yamini V; Kulkarni, Hemant; Hibberd, Patricia
2017-09-19
Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB. Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community health workers actively monitored these women from 24 to 36 weeks of gestation for these signs or symptoms. If they were present (HRPB positive) the identified women were brought to government health facilities for assessment and management. HRPB positive could also be determined by the provider if the woman presented directly to the facility. Risk stratification was based on the number of signs or symptoms present. The outcome of preterm birth was based on the clinical assessment of gestational age < 37 weeks at delivery or a birth weight of <2000 g. Between July 1, 2012 and 30 November, 2013, 686 of 7050 (9.7%) pregnant women studied, delivered preterm. 732 (10.4%) women were HRPB positive, of whom 333 (45.5%) delivered preterm. Of the remaining 6318(89.6%) HRPB negative women 353 (5.6%) delivered preterm. The likelihood ratio (LR) of a preterm birth in the HRPB positives was 8.14 (95% confidence interval 7.16-9.26). The LR of a preterm birth increased in women who had more signs or symptoms of HRBP (p < 0.00001). More signs or symptoms of HRPB were also associated with a shorter time to delivery, lower birth weight and higher rates of stillbirths, neonatal deaths and postnatal complications. Addition of risk stratification improved the prediction of preterm delivery (Integrated Discrimination Improvement 17% (95% CI 15-19%)). The package for detection of signs and symptoms of HRPB is feasible, promising and likely to improve management of preterm labor. NCT01073475 on February 21, 2010 and NCT01084096 on March 9, 2010.
Recent Advances in the Biology and Treatment of T Cell Acute Lymphoblastic Leukemia.
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.
Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors.
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.
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.
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.
A new stratification of mourning dove call-count routes
Blankenship, L.H.; Humphrey, A.B.; MacDonald, D.
1971-01-01
The mourning dove (Zenaidura macroura) call-count survey is a nationwide audio-census of breeding mourning doves. Recent analyses of the call-count routes have utilized a stratification based upon physiographic regions of the United States. An analysis of 5 years of call-count data, based upon stratification using potential natural vegetation, has demonstrated that this uew stratification results in strata with greater homogeneity than the physiographic strata, provides lower error variance, and hence generates greatet precision in the analysis without an increase in call-count routes. Error variance was reduced approximately 30 percent for the contiguous United States. This indicates that future analysis based upon the new stratification will result in an increased ability to detect significant year-to-year changes.
Progress towards personalized therapeutics: biologic- and risk-directed therapy for neuroblastoma.
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.
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
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.
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
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.
Hudson, Jessica L; Bell, Jennifer M; Crabtree, Traves D; Kreisel, Daniel; Patterson, G Alexander; Meyers, Bryan F; Puri, Varun
2018-01-01
Formal pulmonary function testing with laboratory spirometry (LS) is the standard of care for risk stratification before lung resection. LS and handheld office spirometry (OS) are clinically comparable for forced expiratory volume in 1 second and forced vital capacity. We investigated the safety of preoperative risk stratification based solely on OS. Patients at low-risk for cardiopulmonary complications were enrolled in a single-center prospective study and underwent preoperative OS. Formal LS was not performed when forced expiratory volume in 1 second was more than 60% by OS. Propensity score matching was used to compare patients in the OS group to low-risk institutional database patients (2008 to 2015) who underwent LS and lung resection. Standardized mean differences determined model covariate balance. The McNemar test and log-rank test were performed, respectively, for categorical and continuous paired outcome data. There were 66 prospectively enrolled patients who received OS and underwent pulmonary resection, and 1,290 patients received preoperative LS, resulting in 52 propensity score-matched pairs (83%). There were no deaths and two 30-day readmissions per group. The major morbidity risk was similar in each group (7.7%). All analyses of discordant pair morbidity had p exceeding 0.56. There was no association between length of stay and exposure to OS vs LS (p = 0.31). The estimated annual institutional cost savings from performing OS only and avoiding LS was $38,000. Low-risk patients undergoing lung resection can be adequately and safely assessed using OS without formal LS, with significant cost savings. With upcoming bundled care reimbursement paradigms, such safe and effective strategies are likely to be more widely used. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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.
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
Alexander, L M
1998-01-01
The Joint National Committee's report on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure was released in November 1997. With its release, an increased emphasis on "treating the patient, not just the number" has taken place. The report provides a comprehensive review of recent clinical evidence that helps guide clinical decision making in the care of the hypertensive patient. A new disease classification system entitled "risk stratification" is introduced and takes into account comorbid conditions that are present for many hypertensive individuals. This risk stratification is then linked to treatment strategies and provides a concise decision analysis framework to aid in clinical decision making. Community-based prevention strategies are also highlighted and should raise the awareness of clinicians to adopt these recommendations and integrate them more aggressively into daily practice. Increased emphasis on patient compliance to improve overall hypertension control rates is also presented. Maximum efficacy through once-daily dosing and fixed-dose combinations are reviewed in the report. The JNC report is a comprehensive resource for clinicians in primary care practice. Its evidenced-based approach is a wonderful teaching tool for those clinicians who also serve as clinical educators in primary care.
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.
Clinical guidelines and practice: in search of the truth.
Kereiakes, Dean J; Antman, Elliott M
2006-09-19
Data from randomized clinical trials, non-randomized studies, and registries, as well as expert panel consensus are appropriately weighted and woven into the context of clinical practice guidelines. Recent guidelines for the care of patients with ischemic heart disease have emphasized both risk stratification and early coronary angiography with revascularization of patients with high-risk indicators. Advances in our understanding of the pathogenesis of acute coronary syndromes and the dynamics of therapeutic innovation (improvement in catheter-based technologies and adjunctive pharmacotherapy) mandate the timely update and revision of practice guidelines. We believe that the weight of evidence remains clearly in support of an early invasive treatment strategy based on risk stratification. Arguments regarding treatment strategy (invasive vs. conservative) are misguided, and greater focus should be placed on improving the treatment-risk paradox demonstrated in clinical practice as well as on strategies to enhance current guideline compliance and utilization. Interest exists in establishing regional centers of excellence for care of patients with acute ischemic heart disease, analogous to the regionalized approach already established for patients with trauma or stroke. This approach is supported by data that demonstrate an inverse relationship between both institutional and operator procedural volumes and mortality, as well as by existing constraints in resources such as specialized nurses and subspecialty-trained physicians. It is appropriate at this time to briefly review specific aspects of the American College of Cardiology/American Heart Association practice guidelines and the current process of care for acute ischemic heart disease.
Overview and recent advances in the treatment of neuroblastoma.
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.
Clinical neurocardiology defining the value of neuroscience‐based cardiovascular therapeutics
Ajijola, Olujimi A.; Anand, Inder; Armour, J. Andrew; Chen, Peng‐Sheng; Esler, Murray; De Ferrari, Gaetano M.; Fishbein, Michael C.; Goldberger, Jeffrey J.; Harper, Ronald M.; Joyner, Michael J.; Khalsa, Sahib S.; Kumar, Rajesh; Lane, Richard; Mahajan, Aman; Po, Sunny; Schwartz, Peter J.; Somers, Virend K.; Valderrabano, Miguel; Vaseghi, Marmar; Zipes, Douglas P.
2016-01-01
Abstract The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. PMID:27114333
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.
A Personalized Risk Stratification Platform for Population Lifetime Healthcare.
Daowd, Ali; Abidi, Samina Raza; Abusharekh, Ashraf; Abidi, Syed Sibte Raza
2018-01-01
Chronic diseases are the leading cause of death worldwide. It is well understood that if modifiable risk factors are targeted, most chronic diseases can be prevented. Lifetime health is an emerging health paradigm that aims to assist individuals to achieve desired health targets, and avoid harmful lifecycle choices to mitigate the risk of chronic diseases. Early risk identification is central to lifetime health. In this paper, we present a digital health-based platform (PRISM) that leverages artificial intelligence, data visualization and mobile health technologies to empower citizens to self-assess, self-monitor and self-manage their overall risk of major chronic diseases and pursue personalized chronic disease prevention programs. PRISM offers risk assessment tools for 5 chronic conditions, 2 psychiatric disorders and 8 different cancers.
Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder
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
Parkinson, Craig; Foley, Kieran; Whybra, Philip; Hills, Robert; Roberts, Ashley; Marshall, Chris; Staffurth, John; Spezi, Emiliano
2018-04-11
Prognosis in oesophageal cancer (OC) is poor. The 5-year overall survival (OS) rate is approximately 15%. Personalised medicine is hoped to increase the 5- and 10-year OS rates. Quantitative analysis of PET is gaining substantial interest in prognostic research but requires the accurate definition of the metabolic tumour volume. This study compares prognostic models developed in the same patient cohort using individual PET segmentation algorithms and assesses the impact on patient risk stratification. Consecutive patients (n = 427) with biopsy-proven OC were included in final analysis. All patients were staged with PET/CT between September 2010 and July 2016. Nine automatic PET segmentation methods were studied. All tumour contours were subjectively analysed for accuracy, and segmentation methods with < 90% accuracy were excluded. Standardised image features were calculated, and a series of prognostic models were developed using identical clinical data. The proportion of patients changing risk classification group were calculated. Out of nine PET segmentation methods studied, clustering means (KM2), general clustering means (GCM3), adaptive thresholding (AT) and watershed thresholding (WT) methods were included for analysis. Known clinical prognostic factors (age, treatment and staging) were significant in all of the developed prognostic models. AT and KM2 segmentation methods developed identical prognostic models. Patient risk stratification was dependent on the segmentation method used to develop the prognostic model with up to 73 patients (17.1%) changing risk stratification group. Prognostic models incorporating quantitative image features are dependent on the method used to delineate the primary tumour. This has a subsequent effect on risk stratification, with patients changing groups depending on the image segmentation method used.
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.
Ledesma-Gumba, M A; Danguilan, R A; Casasola, C C; Ona, E T
2008-09-01
To evaluate the efficacy of tailored immunosuppressive regimens prescribed according to a risk stratification scoring system based on the number of HLA mismatches, donor source, panel-reactive antibodies (PRA), and repeat transplant. Patients in a retrospective cohort of 329 kidney transplantations performed from October 2004 to December 2005 were assigned scores of 0, 2, 4, or 6 with higher scores for > or =1 HLA mismatches, PRA > 10%, repeat transplant, and unrelated or deceased donor. Added scores of < or =4 comprised the low-risk group who received a Calcineurin inhibitor (CNI)-based regimen without induction, whereas a score > or = 6 denoted high risk including a CNI-based regimen with an interleukin-2 receptor antibody. The efficacy analysis compared the incidences of biopsy-proven acute rejection episodes (BPAR) at 1 year. Only 227 (69%) of 329 patients had a complete data set and 84 were excluded because they did not follow the prescribed protocol, yielding 113 low- and 30 high-risk patients in the final population. Low-risk patients had a mean PRA of 5.4%, living related donors in 68%, and primary transplants. High-risk patients had a mean PRA of 18.8% (range = 10%-97%), living nonrelated donors in 84%, four deceased donors, and four repeat transplants. The overall 1-year incidence of BPAR was 5.7%. No significant difference (P = .081) was observed in 1-year BPAR between the low- (4.5%) and high-risk (9.8%) groups. Likewise, no significant difference in the 1-year mean serum creatinine was observed according to the CNI. The mean creatinine was 1.12 for cyclosporine and 1.38 for tacrolimus treatment (P = .06) in the low-risk group and 1.08 for cyclosporine and 1.2 for tacrolimus (P = .61) in the high-risk cohort. There was no significant difference in acute rejection rates between the immunologically low- or high-risk patients using tailored immunosuppression, which was effective to minimize its occurrence with good renal function at 1 year.
External Validation of the HERNIAscore: An Observational Study.
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.
The Cost-Effective Evaluation of Syncope.
Angus, Steven
2016-09-01
Syncope is a common clinical problem that carries a high socioeconomic burden. A structured approach in the evaluation of syncope with special emphasis on a detailed history, comprehensive physical examination that includes orthostatic vital signs, and an electrocardiogram, proves to be the most cost-effective approach. The need for additional testing and hospital admission should be based on the results of the initial evaluation and use of risk-stratification tools that help identify those syncope patients at highest risk for poor outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Benndorf, Matthias; Waibel, Lorenz; Krönig, Malte; Jilg, Cordula Annette; Langer, Mathias; Krauss, Tobias
2018-02-01
To validate the risk stratification algorithm of the Prostate Imaging Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2 category 3) in the peripheral zone based on focal contrast enhancement and to compare cancer rates in category 3, upgraded category 4 and category 4 based on markedly low ADC value. We retrospectively analyze 172 consecutive patients undergoing prostate MRI with 315 histopathologically verified lesions. We select all lesions either assigned category 3 or category 4 in the peripheral zone for further analysis. We compare cancer rates with the two-sided chi-squared test. To determine inter-observer agreement about contrast enhancement two blinded radiologists evaluate the subset of category 3 lesions based on the diffusion weighted sequence. The frequency of peripheral PI-RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only) in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P < 0.01. Inter-observer agreement is moderate for evaluation of contrast enhancement with kappa values between 0.46 and 0.5. We demonstrate a trend of increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to category 4 based on markedly low ADC value. Peripheral lesions of intermediary risk in the diffusion weighted sequence account for 21.6% of all prostate lesions encountered. Since it is likely that patient management recommendations will be linked to assessment categories in future versions of PI-RADS, cancer rates in upgraded category 4 and category 4 based on markedly low ADC values should be in a similar range. We conclude that in future studies of PI-RADSv2 upgraded category 4 and category 4 based on markedly low ADC value should be reported separately to generate a database for meta-analysis of cancer rates. Copyright © 2017 Elsevier B.V. All rights reserved.
Improving risk-stratification of Diabetes complications using temporal data mining.
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.
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.
The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.
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.
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.
Advanced colorectal neoplasia risk stratification by penalized logistic regression.
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.
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.
Biomarker discovery and development in pediatric critical care medicine
Kaplan, Jennifer M.; Wong, Hector R.
2010-01-01
Objective To frame the general process of biomarker discovery and development, and to describe a proposal for the development of a multi-biomarker based risk model for pediatric septic shock. Data Source Narrative literature review and author generated data. Main Results Biomarkers can be grouped into four broad classes, based on the intended function: diagnostic, monitoring, surrogate, and stratification. Biomarker discovery and development requires a rigorous process, which is frequently not well followed in the critical care medicine literature. Very few biomarkers have successfully transitioned from the candidate stage to the true biomarker stage. There is great interest in developing diagnostic and stratification biomarkers for sepsis. Procalcitonin is currently the most promising diagnostic biomarker for sepsis. Recent evidence suggests that interleukin-8 can be used to stratify children with septic shock having a high likelihood of survival with standard care. Currently, there is a multi-institutional effort to develop a multi-biomarker based sepsis risk model intended to predict outcome and illness severity for individual children with septic shock. Conclusions Biomarker discovery and development is an important portion of the pediatric critical care medicine translational research agenda. This effort will require collaboration across multiple institutions and investigators. Rigorous conduct of biomarker-focused research holds the promise of transforming our ability to care for individual patients and our ability to conduct clinical trials in a more effective manner. PMID:20473243
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
Amsbaugh, Mark J; Yusuf, Mehran; Cash, Elizabeth; Silverman, Craig; Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin; Perez, Cesar; Bert, Robert; Redman, Rebecca; Dunlap, Neal
2016-10-01
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. 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(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), 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. 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. Copyright © 2016 Elsevier Inc. All rights reserved.
Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A
2016-04-01
Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97% (sensitivity 98% and specificity 88%). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75%, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team.
Stratification of the Risk of Sudden Death in Nonischemic Heart Failure
Pimentel, Maurício; Zimerman, Leandro Ioschpe; Rohde, Luis Eduardo
2014-01-01
Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure. PMID:25352509
Coronary heart disease risk stratification: pitfalls and possibilities.
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.
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.
Martínez-Terroba, Elena; Behrens, Carmen; de Miguel, Fernando J; Agorreta, Jackeline; Monsó, Eduard; Millares, Laura; Sainz, Cristina; Mesa-Guzman, Miguel; Pérez-Gracia, Jose Luis; Lozano, María Dolores; Zulueta, Javier J; Pio, Ruben; Wistuba, Ignacio I; Montuenga, Luis M; Pajares, María J
2018-05-13
Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer patients are classified conceals hidden biological heterogeneity, manifested in heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers to assess individual patient risk is an unmet medical need. Here we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI and SLC2A1) to stratify early lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8 th edition, 2018). A test cohort (n=239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression following stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). The model resulted in a highly significant predictor of five-year outcome for disease-free survival (P<0.001) and overall survival (P<0.001). The prognostic ability of the model was externally validated in an independent multi-institutional cohort of patients (n=114, P=0.021). We also demonstrated that this molecular classifier adds relevant information to the gold standard TNM-based pathological staging with a highly significant improvement of likelihood ratio. We subsequently developed a combined prognostic index (CPI) including both the molecular and the pathological data which improved the risk stratification in both cohorts (P≤0.001). Moreover, the signature may help to select stage I-IIA patients who might benefit from adjuvant chemotherapy. In summary, this protein-based signature accurately identifies those patients with high risk of recurrence and death, and adds further prognostic information to the TNM-based clinical staging, even applying the new IASLC 8 th edition staging criteria. More importantly, it may be a valuable tool for selecting patients for adjuvant therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Contemporary approach to essential thrombocythemia and polycythemia vera.
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
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
A new gender-specific model for skin autofluorescence risk stratification
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.
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.
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.
Voss, Andreas; Fischer, Claudia; Schroeder, Rico; Figulla, Hans R; Goernig, Matthias
2012-07-01
The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.
Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer.
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
Current approaches for risk stratification of infectious complications in pediatric oncology.
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.
Risk stratification and management of acute pulmonary embolism.
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.
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.
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.
Nanchen, David; Raggi, Paolo
2017-11-01
Atherosclerosis imaging has been the focus of intense debate and research for several decades. Among its primary applications are risk stratification of asymptomatic individuals and follow-up of atherosclerosis progression under a variety of treatments designed to retard or regress the development of arterial disease. Although endorsed and supported by many, this approach has been fiercely opposed by several key opinion leaders over the years. Similarly, regulatory agencies have raised a number of objections to resist the approval of new drugs and devices based on surrogate imaging markers. However, there is a large body of evidence in the medical literature that shows that risk stratification is improved with implementation of atherosclerosis imaging. Additionally, numerous lipid-modifying agents have been tested as far as their ability to affect progression of atherosclerosis, and in many cases the information obtained with imaging was in line with the outcome of subsequent clinical trials. This pros-and-cons debate was staged to bring up in a fun and provoking way the main arguments in favour or against the application of atherosclerosis imaging in the main settings described above. Copyright © 2017 Elsevier B.V. All rights reserved.
Earthquake Hoax in Ghana: Exploration of the Cry Wolf Hypothesis
Aikins, Moses; Binka, Fred
2012-01-01
This paper investigated the belief of the news of impending earthquake from any source in the context of the Cry Wolf hypothesis as well as the belief of the news of any other imminent disaster from any source. We were also interested in the correlation between preparedness, risk perception and antecedents. This explorative study consisted of interviews, literature and Internet reviews. Sampling was of a simple random nature. Stratification was carried out by sex and residence type. The sample size of (N=400), consisted of 195 males and 205 Females. Further stratification was based on residential classification used by the municipalities. The study revealed that a person would believe news of an impending earthquake from any source, (64.4%) and a model significance of (P=0.000). It also showed that a person would believe news of any other impending disaster from any source, (73.1%) and a significance of (P=0.003). There is association between background, risk perception and preparedness. Emergency preparedness is weak. Earthquake awareness needs to be re-enforced. There is a critical need for public education of earthquake preparedness. The authors recommend developing emergency response program for earthquakes, standard operating procedures for a national risk communication through all media including instant bulk messaging. PMID:28299086
Left main coronary artery disease: pathophysiology, diagnosis, and treatment.
Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W
2018-06-01
The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.
[Screening for atherosclerosis to prevent cardiovascular risk : a pro-contra debate].
Nanchen, David; Genest, Jacques
2018-02-28
Detecting atherosclerosis using imaging techniques is the subject of intense debate in the scientific community. Among the arguments in favor of screening, a better identification or better stratification of cardiovascular risk is mentioned, compared to cardiovascular risk scores based solely on traditional risk factors, such as blood pressure or cholesterol levels. Imaging techniques are also used to monitor the progression of atherosclerosis among patients using lipid-lowering or antihypertensive drugs in primary prevention. However, several experts in recent years have challenged the clinical utility of these imaging techniques in asymptomatic adults. This article proposes a debate « for or against » to describe the main arguments for or against the use of imaging for screening for atherosclerosis.
A Model-Free Machine Learning Method for Risk Classification and Survival Probability Prediction.
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.
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.
Pérez-Fernández, Guillermo Alberto; Grau-Abalo, Ricardo
2012-01-01
There are many risk factors for developing hypertension. In the XXI century, smarter ways to investigate are needed, so preventing the turning of an adolescent into a hypertensive adult must be a priority. The aim of this paper is to predict the risk of hypertension onset in adulthood, from cardiovascular tension and risk stratification since adolescence. A representative sample of 125 adolescents from the project "Pesquisaje Escolar en la Adolescencia de Hipertensión Arterial" (PESESCAD-HTA) was studied. They were diagnosed with prehypertension in 2001, and were followed for eight years (96 months) until January 2009. Two predictive indexes were obtained. The first, based on the total cardiovascular risk and the second from the multiplication of these risks with an accuracy index for each of 61.6% and 70.4%, respectively. The index based on the multiplication of cardiovascular risk can predict, with adequate accuracy, the turning of a prehypertensive adolescent into hypertensive once he/she reaches adulthood.
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
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.
NASA Astrophysics Data System (ADS)
Moodie, A. J.; Nittrouer, J. A.; Ma, H.; Lamb, M. P.; Carlson, B.; Kineke, G. C.; Parker, G.
2017-12-01
High concentrations of suspended sediment in channelized fluid flow produces density stratification that can alter the turbulent flow structure, thus limiting fluid momentum redistribution and affecting sediment transport capacity. A low channel-bed slope and large flow depth are hypothesized to be additional important factors contributing to density stratification. However, there are limited observations of density stratification in large rivers, especially those that carry significant fluxes of mud, and so the conditions leading to the development of density stratification are poorly constrained. The Yellow River, China, is a fine-grained and low-sloping river that maintains some of the highest suspended sediment concentrations in large rivers worldwide, making it an ideal natural laboratory for studying density stratification and its impact on sediment transport. Suspended sediment samples from the lower Yellow River, collected over a range of discharge conditions, produced sediment concentration profiles that are used in conjunction with velocity profiles to determine the threshold shear velocity for density stratification effects to develop. Comparing measured and predicted concentration and velocity profiles demonstrates that, there is no significant density stratification for base flow conditions; however, above a shear velocity value of 0.05 m/s, there is a progressive offset between the measured and predicted profiles, indicating that density stratification is increasingly important with higher shear stress values. The analyses further indicate that sediment entrainment from the bed and sediment diffusivity within the water column are significantly impacted by density stratification, suggesting that shear stress and sediment transport rates are inhibited by the development of density stratification. Near-bed concentration measurements are used to assess a stress-to-entrainment relationship, accounting for density stratification. These measurements are being used to refine relations for sediment entrainment and sediment flux in sandy and muddy, lowland rivers and deltas.
Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury
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
Admission glucose does not improve GRACE score at 6 months and 5 years after myocardial infarction.
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.
Preventing Contrast-induced Renal Failure: A Guide.
Faggioni, Michela; Mehran, Roxana
2016-10-01
Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid deterioration of renal function within a few days of parenteral administration of contrast media (CM) in the absence of alternative causes. CI-AKI is the most common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 % in patients undergoing percutaneous coronary intervention. Although usually self-resolving, in patients with pre-existing chronic kidney disease (CKD) or concomitant risk factors for renal damage, CI-AKI is associated with increased short-and long-term morbidity and mortality. Therefore, risk stratification based on clinical and peri-procedural characteristics is crucial in selecting patients at risk of CI-AKI who would benefit the most from implementation of preventive measures.
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.
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.
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
Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.
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.
Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian
2018-06-07
The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.
Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y.-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian
2018-01-01
Abstract The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians. PMID:29850820
Stratification of Recanalization for Patients with Endovascular Treatment of Intracranial Aneurysms
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
Mills, Joseph L; Conte, Michael S; Armstrong, David G; Pomposelli, Frank B; Schanzer, Andres; Sidawy, Anton N; Andros, George
2014-01-01
Critical limb ischemia, first defined in 1982, was intended to delineate a subgroup of patients with a threatened lower extremity primarily because of chronic ischemia. It was the intent of the original authors that patients with diabetes be excluded or analyzed separately. The Fontaine and Rutherford Systems have been used to classify risk of amputation and likelihood of benefit from revascularization by subcategorizing patients into two groups: ischemic rest pain and tissue loss. Due to demographic shifts over the last 40 years, especially a dramatic rise in the incidence of diabetes mellitus and rapidly expanding techniques of revascularization, it has become increasingly difficult to perform meaningful outcomes analysis for patients with threatened limbs using these existing classification systems. Particularly in patients with diabetes, limb threat is part of a broad disease spectrum. Perfusion is only one determinant of outcome; wound extent and the presence and severity of infection also greatly impact the threat to a limb. Therefore, the Society for Vascular Surgery Lower Extremity Guidelines Committee undertook the task of creating a new classification of the threatened lower extremity that reflects these important considerations. We term this new framework, the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. Risk stratification is based on three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). The implementation of this classification system is intended to permit more meaningful analysis of outcomes for various forms of therapy in this challenging, but heterogeneous population. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Wang, Hung-Ming; Cheng, Nai-Ming; Lee, Li-Yu; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Liao, Chun-Ta; Yang, Lan-Yan; Yen, Tzu-Chen
2016-02-01
The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC. © 2015 UICC.
A Review on Automatic Mammographic Density and Parenchymal Segmentation
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
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
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.
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.
On Stratification in Changing Higher Education: The "Analysis of Status" Revisited
ERIC Educational Resources Information Center
Bloch, Roland; Mitterle, Alexander
2017-01-01
This article seeks to shed light on current dynamics of stratification in changing higher education and proposes an analytical perspective to account for these dynamics based on Martin Trow's work on "the analysis of status." In research on higher education, the term "stratification" is generally understood as a metaphor that…
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.
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
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
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.
Lebentrau, S; May, M; Weckermann, D; Speck, T; Wick, A-K; Mathew, M; Schostak, M
2017-02-01
The adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) is based on the individual risk profile (RP) and its sufficient transfer from the clinic to the doctor's office. The objectives of our study were to verify the importance and degree of transfer of RP and recommendation for risk-adapted adjuvant treatment (RAAT) in patients with NMIBC as well as to develop appropriate tools for this purpose, if necessary. An email-based survey distributed to urologists in Brandenburg, Berlin, Bavaria and Lower Saxony explored the questions mentioned above. In addition, a tool for risk stratification and information transfer for patients with NMIBC was developed and validated. From a total of 134 questionnaires analyzed, 55 were from clinic urologists (CUs) and 79 were from ambulant urologists (AUs). Although 9 out of 10 urologists considered the RP of importance, only 29 % of CUs and 24 % of AUs (p = 0.553) confirmed that the RP was always mentioned in medical reports. The recommendation for RAAT was confirmed from 62 % of CUs and 20 % of AUs (p < 0.001). A recommendation for RAAT in the medical report was requested by 86 % of AUs. The risk calculator presented here - to our knowledge the first with integration of the 2004 WHO grading - is delivered in all mathematically possible constellations a RP, according to guideline recommendations. Urologists in the clinic and doctor's office both attach considerable importance to the determination and transfer of RP and the recommendation for RAAT. There was evidence to suggest an overestimation of the quality of medical reports by the CU. The risk calculator provides an easy and cost-neutral option to improve risk stratification and information transfer from the clinic to the doctor's office.
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.
Stapleton, Tadhg; Connolly, Deirdre; O'Neill, Desmond
2015-01-01
While a clinical pre-selection screening process for a stroke patient's suitability for driving has been acknowledged, little is known about the factors or processes influencing this screening typically conducted by clinicians practicing at a generalist level. This study explored this clinical stratification process through the use of semi-structured interviews with senior occupational therapists (n = 17) and stroke physicians (n = 7) using qualitative description methodology. The findings revealed a trichotomy stratification of stroke patients for driving in the clinical setting; those who are fit to drive, unfit to drive, and a "maybe" group who need more detailed assessment and observation. Factors that had a major influence on this clinical-based stratification of driving suitability were client's levels of awareness, insight, and impulsivity. A period of prolonged contact with the client was preferential to guide the stratification decision in order for clinicians to build a comprehensive picture of the person. A mix of assessment approaches including standardized assessment but with increased emphasis on naturalistic observation of functional performance underpinned the clinical stratification process. This study uncovers some of the factors and processes influencing the early clinical-based stratification of driving suitability after stroke, and highlights the contribution of the generalist practitioner in the assessment of fitness to drive continuum.
[Syncope and work: role of the occupational physician and global risk stratification].
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.
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.
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
Contemporary post surgical management of differentiated thyroid carcinoma.
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.
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.
Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients.
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.
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.
Foster, Meredith C; Rawlings, Andreea M; Marrett, Elizabeth; Neff, David; Grams, Morgan E; Kasiske, Bertram L; Willis, Kerry; Inker, Lesley A; Coresh, Josef; Selvin, Elizabeth
2014-05-01
Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. Nationally representative cross-sectional study. 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. CKD and LDL cholesterol defined using a single laboratory value. Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
The Molecular Classification of Medulloblastoma: Driving the next generation clinical trials
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
Wood, M E; Flynn, B S; Stockdale, A
2013-01-01
Risk stratification based on family history is a feature of screening guidelines for a number of cancers and referral guidelines for genetic counseling/testing for cancer risk. Our aim was to describe primary care physician perceptions of their role in managing cancer risk based on family history. Structured interviews were conducted by a medical anthropologist with primary care physicians in 3 settings in 2 north-eastern states. Transcripts were systematically analyzed by a research team to identify major themes expressed by participants. Forty interviews were conducted from May 2003 through May 2006. Physicians provided a diversity of views on roles in management of cancer risk based on family history, management practices and patient responses to risk information. They also provided a wide range of perspectives on criteria used for referral to specialists, types of specialists referred to and expected management roles for referred patients. Some primary care physicians appeared to make effective use of family history information for cancer risk management, but many in this sample did not. Increased focus on efficient assessment tools based on recognized guidelines, accessible guides to management options, and patient education and decision aids may be useful directions to facilitate broader use of family history information for cancer risk management. Copyright © 2013 S. Karger AG, Basel.
Cucchi, David G J; Denys, Barbara; Kaspers, Gertjan J L; Janssen, Jeroen J W M; Ossenkoppele, Gert J; de Haas, Valérie; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M; Philippé, Jan; Csikós, Tamás; Kwidama, Zinia; de Moerloose, Barbara; de Bont, Eveline S J M; Lissenberg-Witte, Birgit I; Zweegman, Sonja; Verwer, Femke; Vandepoele, Karl; Schuurhuis, Gerrit Jan; Sonneveld, Edwin; Cloos, Jacqueline
2018-05-31
Controversy exists whether internal tandem duplication of FMS-like tyrosine kinase 3 ( FLT3- internal tandem duplication [ITD]) allelic ratio (AR) and/or length of the ITD should be taken into account for risk stratification of pediatric acute myeloid leukemia (AML) and whether it should be measured on RNA or DNA. Moreover, the ITD status may be of relevance for selecting patients eligible for FLT3 inhibitors. Here, we included 172 pediatric AML patients, of whom 36 (21%) harbored FLT3 -ITD as determined on both RNA and DNA. Although there was a good correlation between both parameters AR spearman = 0.62 (95% confidence interval, 0.22-0.87) and ITDlength spearman = 0.98 (95% confidence interval, 0.90-1.00), only AR ≥ 0.5 and length ≥48 base pairs (bps) based on RNA measurements were significantly associated with overall survival (AR: P logrank = .008; ITDlength: P logrank = .011). In large ITDs (>156 bp on DNA) a remarkable 90-bp difference exists between DNA and RNA, including intron 14, which is spliced out in RNA. Ex vivo exposure (n = 30) to FLT3 inhibitors, in particular to the FLT3-specific inhibitor gilteritinib, showed that colony-forming capacity was significantly more reduced in FLT3 -ITD-AR ≥ 0.5 compared with ITD-AR-low and ITD - patient samples ( P < .001). RNA-based FLT3 -ITD measurements are recommended for risk stratification, and the relevance of AR regarding eligibility for FLT3-targeted therapy warrants further study. © 2018 by The American Society of Hematology.
The Effect of Barotropic and Baroclinic Tides on Coastal Stratification and Mixing
NASA Astrophysics Data System (ADS)
Suanda, S. H.; Feddersen, F.; Kumar, N.
2017-12-01
The effects of barotropic and baroclinic tides on subtidal stratification and vertical mixing are examined with high-resolution, three-dimensional numerical simulations of the Central Californian coastal upwelling region. A base simulation with realistic atmospheric and regional-scale boundary forcing but no tides (NT) is compared to two simulations with the addition of predominantly barotropic local tides (LT) and with combined barotropic and remotely generated, baroclinic tides (WT) with ≈ 100 W m-1 onshore baroclinic energy flux. During a 10 day period of coastal upwelling when the domain volume-averaged temperature is similar in all three simulations, LT has little difference in subtidal temperature and stratification compared to NT. In contrast, the addition of remote baroclinic tides (WT) reduces the subtidal continental shelf stratification up to 50% relative to NT. Idealized simulations to isolate barotropic and baroclinic effects demonstrate that within a parameter space of typical U.S. West Coast continental shelf slopes, barotropic tidal currents, incident energy flux, and subtidal stratification, the dissipating baroclinic tide destroys stratification an order of magnitude faster than barotropic tides. In WT, the modeled vertical temperature diffusivity at the top (base) of the bottom (surface) boundary layer is increased up to 20 times relative to NT. Therefore, the width of the inner-shelf (region of surface and bottom boundary layer overlap) is increased approximately 4 times relative to NT. The change in stratification due to dissipating baroclinic tides is comparable to the magnitude of the observed seasonal cycle of stratification.
Colvin, Loretta J; Collop, Nancy A
2016-01-01
No regulatory mandate exists in the United States (U.S.) for comprehensive obstructive sleep apnea (OSA) risk assessment and stratification for commercial motor vehicle (CMV) drivers. Current Federal Motor Carrier Safety Administration (FMCSA) requirements are outdated and depend largely on subjective report, a less reliable strategy in an occupational setting. Without FMCSA standards, sleep specialists, occupational medical examiners and employers rely on a collection of medical consensus recommendations to establish standards of care. These recommendations advise OSA risk assessment through a combination of focused medical history, physical examination, questionnaires, and accident history, which increase OSA detection compared to current FMCSA standards. For those diagnosed with OSA, consensus-based risk stratification helps identify CMV drivers who may benefit from OSA treatment and establish minimum standards for assessing treatment efficacy and adherence. Unfortunately no consolidated recommendation exists; rather, publications span medical and governmental literature in a patchwork fashion that no longer fully reflect current practice due to subsequent advances in OSA diagnosis, treatment, and technology. Based on searches of medical literature, internet materials, and reference lists from existing publications, an overview and discussion of key published recommendations regarding OSA assessment and treatment in CMV operators is provided. Suggestions for incorporating these recommendations into clinical sleep medicine practice in the U.S. are presented. The challenge for sleep specialists is maintaining the delicate balance between recommendations impacting standard of care and associated medico-legal impact with stakeholder interests from medical, regulatory, industry and public perspectives while providing high quality and efficient care. © 2016 American Academy of Sleep Medicine.
Recent advances in understanding idiopathic pulmonary fibrosis
Daccord, Cécile; Maher, Toby M.
2016-01-01
Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645
Pedersen, N E; Oestergaard, D; Lippert, A
2016-05-01
When investigating early warning scores and similar physiology-based risk stratification tools, death, cardiac arrest and intensive care unit admission are traditionally used as end points. A large proportion of the patients identified by these end points cannot be saved, even with optimal treatment. This could pose a limitation to studies using these end points. We studied current expert opinion on end points for validating tools for the identification of patients in hospital wards at risk of imminent critical illness. The Delphi consensus methodology was used. We identified 22 experts based on objective criteria; 17 participated in the study. Each expert panel member's suggestions for end points were collected and distributed to the entire expert panel in anonymised form. The experts reviewed, rated and commented the suggested end points through the rounds in the Delphi process, and the experts' combined rating of the usefulness of each suggestion was established. A gross list of 86 suggestions for end points, relating to 13 themes, was produced. No items were uniformly recognised as ideal. The themes cardiac arrest, death, and level of care contained the items receiving highest ratings. End points relating to death, cardiac arrest and intensive care unit admission currently comprise the most obvious compromises for investigating early warning scores and similar risk stratification tools. Additional end points from the gross list of suggested end points could become feasible with the increased availability of large data sets with a multitude of recorded parameters. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Perlis, Roy H
2013-07-01
Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches--a naïve Bayes classifier and a support vector machine, and a random forest model--was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Lip, Gregory Y H; Hansen, Morten Lock; Hansen, Peter Riis; Tolstrup, Janne Schurmann; Lindhardsen, Jesper; Selmer, Christian; Ahlehoff, Ole; Olsen, Anne-Marie Schjerning; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian
2011-01-01
Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. Design Registry based cohort study. Setting Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. Main outcome measures Stroke and thromboembolism. Results Of 121 280 patients with non-valvular atrial fibrillation, 73 538 (60.6%) fulfilled the study inclusion criteria. In patients at “low risk” (score=0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS2 and 0.78 (0.58 to 1.04) with CHA2DS2-VASc at one year’s follow-up. In patients at “intermediate risk” (score=1), this rate was 4.75 (4.45 to 5.07) with CHADS2 and 2.01 (1.70 to 2.36) with CHA2DS2-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years’ follow-up were 0.812 (0.796 to 0.827) with CHADS2 and 0.888 (0.875 to 0.900) with CHA2DS2-VASc. Conclusions The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA2DS2-VASc performed better than CHADS2 in predicting patients at high risk, and those categorised as low risk by CHA2DS2-VASc were truly at low risk for thromboembolism. PMID:21282258
Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know.
Rose, Trevor A; Choi, Jung W
2015-09-01
Intravenous contrast is commonly used in noninvasive imaging procedures such as magnetic resonance imaging and computed tomography and can evaluate blood vessels and better characterize soft-tissue lesions. Although the incidence of adverse events after administration of contrast is low, it is important that clinicians and radiologists minimize risks and respond quickly and effectively when reactions occur. We will discuss a range of adverse events to iodinated and gadolinium-based contrast agents, including allergic-like reactions, nephrotoxicity, extravasation, and nephrogenic systemic fibrosis. We will review risk stratification for patients, as well as premedication and treatment of adverse events. Copyright © 2015 Elsevier Inc. All rights reserved.
Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J
2017-10-01
To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.
Prevention of Cardiovascular Disease in Women.
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.
Holmes, Ann M; Ackermann, Ronald T; Katz, Barry P; Downs, Stephen M; Inui, Thomas S
2010-12-01
Capacity constraints and efficiency considerations require that disease management programs identify patients most likely to benefit from intervention. Predictive modeling with available administrative data has been used as a strategy to match patients with appropriate interventions. Administrative data, however, can be plagued by problems of incompleteness and delays in processing. In this article, we examine the effects of these problems on the effectiveness of using administrative data to identify suitable candidates for disease management, and we evaluate various proposed solutions. We build prospective models using regression analysis and evaluate the resulting stratification algorithms using R² statistics, areas under receiver operator characteristic curves, and cost concentration ratios. We find delays in receipt of data reduce the effectiveness of the stratification algorithm, but the degree of compromise depends on what proportion of the population is targeted for intervention. Surprisingly, we find that supplementing partial data with a longer panel of more outdated data produces algorithms that are inferior to algorithms based on a shorter window of more recent data. Demographic data add little to algorithms that include prior claims data, and are an inadequate substitute when claims data are unavailable. Supplementing demographic data with additional information on self-reported health status improves the stratification performance only slightly and only when disease management is targeted to the highest risk patients. We conclude that the extra costs associated with surveying patients for health status information or retrieving older claims data cannot be justified given the lack of evidence that either improves the effectiveness of the stratification algorithm.
Quantifying risk and assessing outcome in cardiac surgery.
Higgins, T L
1998-06-01
Quality improvement, research, and reporting of outcome results can be stratified by preoperative risk by using a logistic regression equation or scores to correct for multiple risk factors. The more than 30-fold mortality differences between lowest and highest risk patients make it critical to stratify outcome results by patient severity. Probabilities are not predictions, however, and caution must be exercised when applying scores to individuals. Outcome assessment will grow in its importance to professionals, initially in the guise of quality reporting and improvement, but increasingly as a tool for risk assessment, patient counseling, and directing therapeutic decisions based on more complete information about patient subgroups. Physicians may be called on for recommendations in choosing systems for their hospitals and communities. Therefore, it is important to have an understanding of how such systems are developed, what factors indicate adequate performance of a system, and how such systems of risk stratification should be applied in practice.
Gimeno-Blanes, Francisco J.; Blanco-Velasco, Manuel; Barquero-Pérez, Óscar; García-Alberola, Arcadi; Rojo-Álvarez, José L.
2016-01-01
Great effort has been devoted in recent years to the development of sudden cardiac risk predictors as a function of electric cardiac signals, mainly obtained from the electrocardiogram (ECG) analysis. But these prediction techniques are still seldom used in clinical practice, partly due to its limited diagnostic accuracy and to the lack of consensus about the appropriate computational signal processing implementation. This paper addresses a three-fold approach, based on ECG indices, to structure this review on sudden cardiac risk stratification. First, throughout the computational techniques that had been widely proposed for obtaining these indices in technical literature. Second, over the scientific evidence, that although is supported by observational clinical studies, they are not always representative enough. And third, via the limited technology transfer of academy-accepted algorithms, requiring further meditation for future systems. We focus on three families of ECG derived indices which are tackled from the aforementioned viewpoints, namely, heart rate turbulence (HRT), heart rate variability (HRV), and T-wave alternans. In terms of computational algorithms, we still need clearer scientific evidence, standardizing, and benchmarking, siting on advanced algorithms applied over large and representative datasets. New scenarios like electronic health recordings, big data, long-term monitoring, and cloud databases, will eventually open new frameworks to foresee suitable new paradigms in the near future. PMID:27014083
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.
Update on risk stratification and treatment of newly diagnosed multiple myeloma.
Kapoor, Prashant; Rajkumar, S Vincent
2011-10-01
Multiple myeloma is the second most common hematologic malignancy. Chromosomal aberrations are important prognostic determinants that influence the clinical decision-making in newly-diagnosed multiple myeloma (NDMM). Patients are considered high-risk if any of the following features are detected: hypodiploidy, deletion 13 by cytogenetics, t(4;14), t(14;16), t(14;20) and/or 17 p deletion. In the absence of these features patients are considered standard risk. Outside of trials, risk-adapted therapy in the transplant-eligible high-risk patients advocates use of bortezomib-based induction therapy followed by autologous stem cell transplantation (ASCT) and bortezomib-based maintenance therapy. High-risk, transplant-ineligible patients should also utilize bortezomib as initial therapy since it is known to overcome the poor prognosis associated with some high-risk features. The goal of therapy in high-risk patients is to attain and maintain a state of complete remission as much as possible. In contrast, the standard-risk, transplant-eligible patients may be treated with either lenalidomide-dexamethasone or bortezomib-based therapy followed by ASCT. In such patients, ASCT can also be deferred until first relapse if the patients are tolerating initial therapy well. Lenalidomide maintenance therapy in the post-transplant setting in standard-risk patients is controversial and not recommended routinely. For transplant-ineligible standard-risk patients, multiple options exist, although in the absence direct comparisons, we prefer lenalidomide plus low-dose dexamethasone over melphalan-based combinations. This review outlines evidence-based management approaches in NDMM, with a focus on risk-adapted therapy.
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
Kato, Tomoko S; Stevens, Gerin R; Jiang, Jeffrey; Schulze, P Christian; Gukasyan, Natalie; Lippel, Matthew; Levin, Alison; Homma, Shunichi; Mancini, Donna; Farr, Maryjane
2013-03-01
Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)<14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS <4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors. We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation. Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI<5gm-m(2)/beat (OR 6.70, p < 0.01), PCWP>20 mm Hg (OR 5.48, p < 0.01), MELD-A>14 (OR 3.72, p< 0.01) and peak VO(2)<14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A>14 and peak VO(2)<14-1 point each; and PCWP>20 and RVSWI<5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events. Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Peeters, Patrick; Van Biesen, Wim; Veys, Nic; Lemahieu, Wim; De Moor, Bart; De Meester, Johan
2016-04-07
Shared decision making is nowadays acknowledged as an essential step when deciding on starting renal replacement therapy. Valid risk stratification of prognosis is, besides discussing quality of life, crucial in this regard. We intended to validate a recently published risk stratification model in a large cohort of incident patients starting renal replacement therapy in Flanders. During 3 years (2001-2003), the data set collected for the Nederlandstalige Belgische Vereniging voor Nefrologie (NBVN) registry was expanded with parameters of comorbidity. For all incident patients, the abbreviated REIN score(aREIN), being the REIN score without the parameter "mobility", was calculated, and prognostication of mortality at 3, 6 and 12 month after start of renal replacement therapy (RRT) was evaluated. Three thousand four hundred seventy-two patients started RRT in Flanders during the observation period (mean age 67.6 ± 14.3, 56.7 % men, 33.6 % diabetes). The mean aREIN score was 4.1 ± 2.8, and 56.8, 23.1, 12.6 and 7.4 % of patients had a score of ≤4, 5-6, 7-8 or ≥9 respectively. Mortality at 3, 6 and 12 months was 8.6, 14.1 and 19.6 % in the overall and 13.2, 21.5 and 31.9 % in the group with age >75 respectively. In RoC analysis, the aREIN score had an AUC of 0.74 for prediction of survival at 3, 6 and 12 months. There was an incremental increase in mortality with the aREIN score from 5.6 to 45.8 % mortality at 6 months for those with a score ≤4 or ≥9 respectively. The aREIN score is a useful tool to predict short term prognosis of patients starting renal replacement therapy as based on comorbidity and age, and delivers meaningful discrimination between low and high risk populations. As such, it can be a useful instrument to be incorporated in shared decision making on whether or not start of dialysis is worthwhile.
Risk stratification of gallbladder polyps (1-2 cm) for surgical intervention with 18F-FDG PET/CT.
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 (
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.
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
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.
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.
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.
Porter, Jeremy C; Lusk, Heather M; Katz, Alan R
2014-08-01
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. 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. 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). 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.
Diagnostic performance of an acoustic-based system for coronary artery disease risk stratification.
Winther, Simon; Nissen, Louise; Schmidt, Samuel Emil; Westra, Jelmer Sybren; Rasmussen, Laust Dupont; Knudsen, Lars Lyhne; Madsen, Lene Helleskov; Kirk Johansen, Jane; Larsen, Bjarke Skogstad; Struijk, Johannes Jan; Frost, Lars; Holm, Niels Ramsing; Christiansen, Evald Høj; Botker, Hans Erik; Bøttcher, Morten
2018-06-01
Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD. We included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20. Haemodynamically significant CAD assessed from FFR was present in 145 (10.0%) patients. In the entire cohort, the predefined CAD-score had a sensitivity of 63% and a specificity of 44%. In total, 50% had an updated CAD-score value ≤20. At this cut-off, sensitivity was 81% (95% CI 73% to 87%), specificity 53% (95% CI 50% to 56%), positive predictive value 16% (95% CI 13% to 18%) and negative predictive value 96% (95% CI 95% to 98%) for diagnosing haemodynamically significant CAD. Sound-based detection of CAD enables risk stratification superior to clinical risk scores. With a negative predictive value of 96%, this new acoustic rule-out system could potentially supplement clinical assessment to guide decisions on the need for further diagnostic investigation. ClinicalTrials.gov identifier NCT02264717; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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
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
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. 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. 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. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.
Frailty and Organization of Health and Social Care.
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.
Stratified sampling design based on data mining.
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.
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.
Imaging, Health Record, and Artificial Intelligence: Hype or Hope?
Mazzanti, Marco; Shirka, Ervina; Gjergo, Hortensia; Hasimi, Endri
2018-05-10
The review is focused on "digital health", which means advanced analytics based on multi-modal data. The "Health Care Internet of Things", which uses sensors, apps, and remote monitoring could provide continuous clinical information in the cloud that enables clinicians to access the information they need to care for patients everywhere. Greater standardization of acquisition protocols will be needed to maximize the potential gains from automation and machine learning. Recent artificial intelligence applications on cardiac imaging will not be diagnosing patients and replacing doctors but will be augmenting their ability to find key relevant data they need to care for a patient and present it in a concise, easily digestible format. Risk stratification will transition from oversimplified population-based risk scores to machine learning-based metrics incorporating a large number of patient-specific clinical and imaging variables in real-time beyond the limits of human cognition. This will deliver highly accurate and individual personalized risk assessments and facilitate tailored management plans.
On the role of modeling choices in estimation of cerebral aneurysm wall tension.
Ramachandran, Manasi; Laakso, Aki; Harbaugh, Robert E; Raghavan, Madhavan L
2012-11-15
To assess various approaches to estimating pressure-induced wall tension in intracranial aneurysms (IA) and their effect on the stratification of subjects in a study population. Three-dimensional models of 26 IAs (9 ruptured and 17 unruptured) were segmented from Computed Tomography Angiography (CTA) images. Wall tension distributions in these patient-specific geometric models were estimated based on various approaches such as differences in morphological detail utilized or modeling choices made. For all subjects in the study population, the peak wall tension was estimated using all investigated approaches and were compared to a reference approach-nonlinear finite element (FE) analysis using the Fung anisotropic model with regionally varying material fiber directions. Comparisons between approaches were focused toward assessing the similarity in stratification of IAs within the population based on peak wall tension. The stratification of IAs tension deviated to some extent from the reference approach as less geometric detail was incorporated. Interestingly, the size of the cerebral aneurysm as captured by a single size measure was the predominant determinant of peak wall tension-based stratification. Within FE approaches, simplifications to isotropy, material linearity and geometric linearity caused a gradual deviation from the reference estimates, but it was minimal and resulted in little to no impact on stratifications of IAs. Differences in modeling choices made without patient-specificity in parameters of such models had little impact on tension-based IA stratification in this population. Increasing morphological detail did impact the estimated peak wall tension, but size was the predominant determinant. Copyright © 2012 Elsevier Ltd. All rights reserved.
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
Primary thrombocytosis in children
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
Rational use of drug-eluting stents: a comparison of different policies.
Remmel, Marko; Hartmann, Franz; Harland, Lars C; Schunkert, Heribert; Radke, Peter W
2007-06-01
Long-term results of recent landmark trials document both benefits and risks of drug-eluting stents (DES) for coronary revascularization. Interestingly, the conclusions drawn from these data vary widely since significant differences in DES penetration rates become obvious when the utilization of this technology is compared between hospitals or even countries. Based on the recommendations of the European Society of Cardiology, the FDA as well as data derived from the BASKET-LATE study, we propose that a maximum penetration rate of 50% for DES seems appropriate at present. Analysis of the length/diameter distribution combined with the use of validated restenosis reference charts allows identification of high-risk patients regarding restenosis risk and modeling the use of DES depending on financial resources and clinical indication. Such algorithm provides the rational for preprocedural risk stratification and efficient use of resources.
Bleeker, Jonathan S.; Hogan, William J.
2011-01-01
Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665
Heart rate variability as predictive factor for sudden cardiac death.
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.
Yan, Chen-Hua; Jiang, Qian; Wang, Jing; Xu, Lan-Ping; Liu, Dai-Hong; Jiang, Hao; Chen, Huan; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun
2014-09-01
We wanted to compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with chemotherapy alone in adults with standard-risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1). One hundred thirty-eight consecutive adult patients with standard-risk ALL in CR1 were retrospectively investigated. Of these patients, 59 received chemotherapy alone (group A) and 79 received unmanipulated haploidentical HSCT (group B). Cumulative incidence of relapse at 5 years in group A was significantly higher than that in group B (66.3% versus 29.9%, P < .0001). Overall and disease-free survival in group A were significantly inferior to group B (P < .0001). Moreover, multivariate analyses demonstrated that central nervous system leukemia (P = .002), T cell immunophenotype (P = .044), expression of E2A-PBX1 (P = .007), and positive minimal residual disease after the first cycle of consolidation (P = .004) were correlated with relapse. Patients with 1 of 4 risk factors were assigned to the high-risk group. Otherwise, patients without risk factors were assigned to the low-risk group. In the high-risk group, HSCT had lower relapse rates and superior DFS compared with chemotherapy (P < .05), but in the low-risk group, there were no differences between HSCT and chemotherapy (P > .05). This study is the first to demonstrate that compared with chemotherapy alone, haploidentical HSCT is a better postremission therapy in adults with standard-risk ALL in CR1. Moreover, based on the 4 risk factors, the establishment of risk stratification could identify the subgroup of patients with a higher risk of relapse in adults with standard-risk ALL in CR1. Furthermore, risk stratification-directed postremission therapies using haploidentical HSCT or chemotherapy alone not only reduce relapse rate but also avoid unnecessary treatment-related mortality and improve survival. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Chromosome 9p21 In Ischemic Stroke: Population Structure and Meta-Analysis
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
Molecular reclassification of Crohn's disease: a cautionary note on population stratification.
Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel
2013-01-01
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals.
Molecular Reclassification of Crohn’s Disease: A Cautionary Note on Population Stratification
Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M.; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel
2013-01-01
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn’s disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn’s disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. PMID:24147066
Lauer, Michael S; Pothier, Claire E; Magid, David J; Smith, S Scott; Kattan, Michael W
2007-12-18
The exercise treadmill test is recommended for risk stratification among patients with intermediate to high pretest probability of coronary artery disease. Posttest risk stratification is based on the Duke treadmill score, which includes only functional capacity and measures of ischemia. To develop and externally validate a post-treadmill test, multivariable mortality prediction rule for adults with suspected coronary artery disease and normal electrocardiograms. Prospective cohort study conducted from September 1990 to May 2004. Exercise treadmill laboratories in a major medical center (derivation set) and a separate HMO (validation set). 33,268 patients in the derivation set and 5821 in the validation set. All patients had normal electrocardiograms and were referred for evaluation of suspected coronary artery disease. The derivation set patients were followed for a median of 6.2 years. A nomogram-illustrated model was derived on the basis of variables easily obtained in the stress laboratory, including age; sex; history of smoking, hypertension, diabetes, or typical angina; and exercise findings of functional capacity, ST-segment changes, symptoms, heart rate recovery, and frequent ventricular ectopy in recovery. The derivation data set included 1619 deaths. Although both the Duke treadmill score and our nomogram-illustrated model were significantly associated with death (P < 0.001), the nomogram was better at discrimination (concordance index for right-censored data, 0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate- to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The model also predicted 3-year mortality rates well in the validation set: Based on an optimal cut-point for a negative predictive value of 0.97, derivation and validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25% and 29% above the cut-point. Blood test-based measures or left ventricular ejection fraction were not included. The nomogram can be applied only to patients with a normal electrocardiogram. Clinical utility remains to be tested. A simple nomogram based on easily obtained pretest and exercise test variables predicted all-cause mortality in adults with suspected coronary artery disease and normal electrocardiograms.
Association between gastric cancer and the Kyoto classification of gastritis.
Shichijo, Satoki; Hirata, Yoshihiro; Niikura, Ryota; Hayakawa, Yoku; Yamada, Atsuo; Koike, Kazuhiko
2017-09-01
Histological gastritis is associated with gastric cancer, but its diagnosis requires biopsy. Many classifications of endoscopic gastritis are available, but not all are useful for risk stratification of gastric cancer. The Kyoto Classification of Gastritis was proposed at the 85th Congress of the Japan Gastroenterological Endoscopy Society. This cross-sectional study evaluated the usefulness of the Kyoto Classification of Gastritis for risk stratification of gastric cancer. From August 2013 to September 2014, esophagogastroduodenoscopy was performed and the gastric findings evaluated according to the Kyoto Classification of Gastritis in a total of 4062 patients. The following five endoscopic findings were selected based on previous reports: atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. A total of 3392 patients (1746 [51%] men and 1646 [49%] women) were analyzed. Among them, 107 gastric cancers were diagnosed. Atrophy was found in 2585 (78%) and intestinal metaplasia in 924 (27%). Enlarged folds, nodularity, and diffuse redness were found in 197 (5.8%), 22 (0.6%), and 573 (17%), respectively. In univariate analyses, the severity of atrophy, intestinal metaplasia, diffuse redness, age, and male sex were associated with gastric cancer. In a multivariate analysis, atrophy and male sex were found to be independent risk factors. Younger age and severe atrophy were determined to be associated with diffuse-type gastric cancer. Endoscopic detection of atrophy was associated with the risk of gastric cancer. Thus, patients with severe atrophy should be examined carefully and may require intensive follow-up. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Automation to improve efficiency of field expedient injury prediction screening.
Teyhen, Deydre S; Shaffer, Scott W; Umlauf, Jon A; Akerman, Raymond J; Canada, John B; Butler, Robert J; Goffar, Stephen L; Walker, Michael J; Kiesel, Kyle B; Plisky, Phillip J
2012-07-01
Musculoskeletal injuries are a primary source of disability in the U.S. Military. Physical training and sports-related activities account for up to 90% of all injuries, and 80% of these injuries are considered overuse in nature. As a result, there is a need to develop an evidence-based musculoskeletal screen that can assist with injury prevention. The purpose of this study was to assess the capability of an automated system to improve the efficiency of field expedient tests that may help predict injury risk and provide corrective strategies for deficits identified. The field expedient tests include survey questions and measures of movement quality, balance, trunk stability, power, mobility, and foot structure and mobility. Data entry for these tests was automated using handheld computers, barcode scanning, and netbook computers. An automated algorithm for injury risk stratification and mitigation techniques was run on a server computer. Without automation support, subjects were assessed in 84.5 ± 9.1 minutes per subject compared with 66.8 ± 6.1 minutes per subject with automation and 47.1 ± 5.2 minutes per subject with automation and process improvement measures (p < 0.001). The average time to manually enter the data was 22.2 ± 7.4 minutes per subject. An additional 11.5 ± 2.5 minutes per subject was required to manually assign an intervention strategy. Automation of this injury prevention screening protocol using handheld devices and netbook computers allowed for real-time data entry and enhanced the efficiency of injury screening, risk stratification, and prescription of a risk mitigation strategy.
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.
Martin, Shelby; Wagner, Jesse; Lupulescu-Mann, Nicoleta; Ramsey, Katrina; Cohen, Aaron; Graven, Peter; Weiskopf, Nicole G; Dorr, David A
2017-08-02
To measure variation among four different Electronic Health Record (EHR) system documentation locations versus 'gold standard' manual chart review for risk stratification in patients with multiple chronic illnesses. Adults seen in primary care with EHR evidence of at least one of 13 conditions were included. EHRs were manually reviewed to determine presence of active diagnoses, and risk scores were calculated using three different methodologies and five EHR documentation locations. Claims data were used to assess cost and utilization for the following year. Descriptive and diagnostic statistics were calculated for each EHR location. Criterion validity testing compared the gold standard verified diagnoses versus other EHR locations and risk scores in predicting future cost and utilization. Nine hundred patients had 2,179 probable diagnoses. About 70% of the diagnoses from the EHR were verified by gold standard. For a subset of patients having baseline and prediction year data (n=750), modeling showed that the gold standard was the best predictor of outcomes on average for a subset of patients that had these data. However, combining all data sources together had nearly equivalent performance for prediction as the gold standard. EHR data locations were inaccurate 30% of the time, leading to improvement in overall modeling from a gold standard from chart review for individual diagnoses. However, the impact on identification of the highest risk patients was minor, and combining data from different EHR locations was equivalent to gold standard performance. The reviewer's ability to identify a diagnosis as correct was influenced by a variety of factors, including completeness, temporality, and perceived accuracy of chart data.
Clinical risk management approach for long-duration space missions.
Gray, Gary W; Sargsyan, Ashot E; Davis, Jeffrey R
2010-12-01
In the process of crewmember evaluation and certification for long-duration orbital missions, the International Space Station (ISS) Multilateral Space Medicine Board (MSMB) encounters a surprisingly wide spectrum of clinical problems. Some of these conditions are identified within the ISS Medical Standards as requiring special consideration, or as falling outside the consensus Medical Standards promulgated for the ISS program. To assess the suitability for long-duration missions on ISS for individuals with medical problems that fall outside of standards or are otherwise of significant concern, the MSMB has developed a risk matrix approach to assess the risks to the individual, the mission, and the program. The goal of this risk assessment is to provide a more objective, evidence- and risk-based approach for aeromedical disposition. Using a 4 x 4 risk matrix, the probability of an event is plotted against the potential impact. Event probability is derived from a detailed review of clinical and aerospace literature, and based on the best available evidence. The event impact (consequences) is assessed and assigned within the matrix. The result has been a refinement of MSMB case assessment based on evidence-based data incorporated into a risk stratification process. This has encouraged an objective assessment of risk and, in some cases, has resulted in recertification of crewmembers with medical conditions which hitherto would likely have been disqualifying. This paper describes a risk matrix approach developed for MSMB disposition decisions. Such an approach promotes objective, evidence-based decision-making and is broadly applicable within the aerospace medicine community.
Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.G.; Jutabha, Rome; Ghassemi, Kevin; Dulai, Gareth S.; Machicado, Gustavo A.
2015-01-01
BACKGROUND AND AIMS Few prospective reports describe the short term natural history of colon diverticular hemorrhage based upon stigmata of recent hemorrhage and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes are to report the 30 day natural history of definitive diverticular hemorrhage based upon stigmata and to describe Doppler probe blood flow detection and as a guide to definitive hemostasis. METHODS Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30 day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. Natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after washing away clots are reported. Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis is also reported in a recent cohort. RESULTS For natural history patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. Doppler probe detected arterial blood flow in 92% of major stigmata, none after hemostasis and no one rebled. CONCLUSIONS 1. Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. 2. Patients with clean diverticula or only flat spots had no rebleeding. 3. High rates of arterial blood flow were detected under major stigmata with Doppler probe but with obliteration by hemostasis no rebleeding occurred. PMID:26227931
Patient Stratification Using Electronic Health Records from a Chronic Disease Management Program.
Chen, Robert; Sun, Jimeng; Dittus, Robert S; Fabbri, Daniel; Kirby, Jacqueline; Laffer, Cheryl L; McNaughton, Candace D; Malin, Bradley
2016-01-04
The goal of this study is to devise a machine learning framework to assist care coordination programs in prognostic stratification to design and deliver personalized care plans and to allocate financial and medical resources effectively. This study is based on a de-identified cohort of 2,521 hypertension patients from a chronic care coordination program at the Vanderbilt University Medical Center. Patients were modeled as vectors of features derived from electronic health records (EHRs) over a six-year period. We applied a stepwise regression to identify risk factors associated with a decrease in mean arterial pressure of at least 2 mmHg after program enrollment. The resulting features were subsequently validated via a logistic regression classifier. Finally, risk factors were applied to group the patients through model-based clustering. We identified a set of predictive features that consisted of a mix of demographic, medication, and diagnostic concepts. Logistic regression over these features yielded an area under the ROC curve (AUC) of 0.71 (95% CI: [0.67, 0.76]). Based on these features, four clinically meaningful groups are identified through clustering - two of which represented patients with more severe disease profiles, while the remaining represented patients with mild disease profiles. Patients with hypertension can exhibit significant variation in their blood pressure control status and responsiveness to therapy. Yet this work shows that a clustering analysis can generate more homogeneous patient groups, which may aid clinicians in designing and implementing customized care programs. The study shows that predictive modeling and clustering using EHR data can be beneficial for providing a systematic, generalized approach for care providers to tailor their management approach based upon patient-level factors.
Chen, F; He, B-C; Yan, L-J; Qiu, Y; Lin, L-S; Cai, L
2017-04-01
We know of only limited data about the role of oral hygiene and the risk of oral cancer with different standards of education. The aim of this study was to assess the association between oral hygiene and risk of oral cancer, with stratification by standard of education, in Chinese women. We organised a case-control study with 250 women with oral cancer and 996 age-matched controls in Fujian, China. Data were collected by personal interview using a structured questionnaire. We used unconditional logistic regression with stratification by educational standard to estimate the odds ratios (OR) and 95% CI. Tooth-brushing twice a day or more was inversely related to the risk of oral cancer in women with high school education or above (OR 0.50; 95% CI 0.25 to 0.98), but not in those who were illiterate or had primary-middle school education. Wearing dentures showed an increased risk only in less well-educated women: the OR were 2.23 (95% CI 1.14 to 4.34) for the illiterate and 1.68 (95% CI 1.08 to 2.62) for the primary-middle school group. The loss of more than five teeth and oral ulceration were associated with increased risks of oral cancer in all three groups. There was also a multiplicative interaction between oral hygiene and standard of education for risk of oral cancer (p=0.001). Our results suggest that oral hygiene seems to have a critical role in the risk of oral cancer in Chinese women, but this effect may be modified by their educational standard. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Colvin, Loretta J.; Collop, Nancy A.
2016-01-01
No regulatory mandate exists in the United States (U.S.) for comprehensive obstructive sleep apnea (OSA) risk assessment and stratification for commercial motor vehicle (CMV) drivers. Current Federal Motor Carrier Safety Administration (FMCSA) requirements are outdated and depend largely on subjective report, a less reliable strategy in an occupational setting. Without FMCSA standards, sleep specialists, occupational medical examiners and employers rely on a collection of medical consensus recommendations to establish standards of care. These recommendations advise OSA risk assessment through a combination of focused medical history, physical examination, questionnaires, and accident history, which increase OSA detection compared to current FMCSA standards. For those diagnosed with OSA, consensus-based risk stratification helps identify CMV drivers who may benefit from OSA treatment and establish minimum standards for assessing treatment efficacy and adherence. Unfortunately no consolidated recommendation exists; rather, publications span medical and governmental literature in a patchwork fashion that no longer fully reflect current practice due to subsequent advances in OSA diagnosis, treatment, and technology. Based on searches of medical literature, internet materials, and reference lists from existing publications, an overview and discussion of key published recommendations regarding OSA assessment and treatment in CMV operators is provided. Suggestions for incorporating these recommendations into clinical sleep medicine practice in the U.S. are presented. The challenge for sleep specialists is maintaining the delicate balance between recommendations impacting standard of care and associated medico-legal impact with stakeholder interests from medical, regulatory, industry and public perspectives while providing high quality and efficient care. Citation: Colvin LJ, Collop NA. Commercial motor vehicle driver obstructive sleep apnea screening and treatment in the United States: an update and recommendation overview. J Clin Sleep Med 2016;12(1):113–125. PMID:26094916
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.
Stratified Sampling Design Based on Data Mining
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
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.
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,...
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.
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.
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.
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
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
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
Peri-procedural risk stratification and management of patients with Williams syndrome.
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.
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.
A score model to predict risk of events in patients with Brugada Syndrome.
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.
Mavrogeni, Sophie I; Sfikakis, Petros P; Dimitroulas, Theodoros; Koutsogeorgopoulou, Loukia; Katsifis, Gikas; Markousis-Mavrogenis, George; Kolovou, Genovefa; Kitas, George D
2018-06-01
Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.
Stratification of habitats for identifying habitat selection by Merriam's turkeys
Mark A. Rumble; Stanley H. Anderson
1992-01-01
Habitat selection patterns of Merriamâs Turkeys were compared in hierarchical analyses of three levels of habitat stratification. Habitat descriptions in first-level analyses were based on dominant species of vegetation. Habitat descriptions in second-level analyses were based on dominant species of vegetation and overstory canopy cover. Habitat descriptions in third-...
Baugh, Christopher W; Greenberg, Jeffrey O; Mahler, Simon A; Kosowsky, Joshua M; Schuur, Jeremiah D; Parmar, Siddharth; Ciociolo, George R; Carr, Christina W; Ghazinouri, Roya; Scirica, Benjamin M
2016-12-01
Chest pain is a common complaint in the emergency department, and a small but important minority represents an acute coronary syndrome (ACS). Variation in diagnostic workup, risk stratification, and management may result in underuse, misuse, and/or overuse of resources. From July to October 2014, we conducted a prospective cohort study in an academic medical center by implementing a Standardized Clinical Assessment and Management Plan (SCAMP) for chest pain based on the HEART score. In addition to capturing adherence to the SCAMP algorithm and reasons for any deviations, we measured troponin sample timing; rates of stress test utilization; length of stay (LOS); and 30-day rates of revascularization, ACS, and death. We identified 239 patients during the enrollment period who were eligible to enter the SCAMP, of whom 97 patients were entered into the pathway. Patients were risk stratified into one of 3 risk tiers: high (n = 3), intermediate (n = 40), and low (n = 54). Among low-risk patients, recommendations for troponin testing were not followed in 56%, and 11% received stress tests contrary to the SCAMP recommendation. None of the low-risk patients had elevated troponin measurements, and none had an abnormal stress test. Mean LOS in low-risk patients managed with discordant plans was 22:26 h/min, compared with 9:13 h/min in concordant patients (P < 0.001). Mean LOS in intermediate-risk patients with stress testing was 25:53 h/min, compared with 7:55 h/min for those without (P < 0.001). At 30 days, 10% of intermediate-risk patients and 0% of low-risk patients experienced an ACS event (risk difference 10% [0.7%-19%]); none experienced revascularization or death. The most frequently cited reason for deviation from the SCAMP was lack of confidence in the tool. Compliance with SCAMP recommendations for low- and intermediate-risk patients was poor, largely due to lack of confidence in the tool. However, in our study population, outcomes suggest that deviation from the SCAMP yielded no additional clinical benefit while significantly prolonging emergency department LOS.
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.
Validation of a risk stratification tool for fall-related injury in a state-wide cohort.
McCoy, Thomas H; Castro, Victor M; Cagan, Andrew; Roberson, Ashlee M; Perlis, Roy H
2017-02-06
A major preventable contributor to healthcare costs among older individuals is fall-related injury. We sought to validate a tool to stratify such risk based on readily available clinical data, including projected medication adverse effects, using state-wide medical claims data. Sociodemographic and clinical features were drawn from health claims paid in the state of Massachusetts for individuals aged 35-65 with a hospital admission for a period spanning January-December 2012. Previously developed logistic regression models of hospital readmission for fall-related injury were refit in a testing set including a randomly selected 70% of individuals, and examined in a training set comprised of the remaining 30%. Medications at admission were summarised based on reported adverse effect frequencies in published medication labelling. The Massachusetts health system. A total of 68 764 hospitalised individuals aged 35-65 years. Hospital readmission for fall-related injury defined by claims code. A total of 2052 individuals (3.0%) were hospitalised for fall-related injury within 90 days of discharge, and 3391 (4.9%) within 180 days. After recalibrating the model in a training data set comprised of 48 136 individuals (70%), model discrimination in the remaining 30% test set yielded an area under the receiver operating characteristic curve (AUC) of 0.74 (95% CI 0.72 to 0.76). AUCs were similar across age decades (0.71 to 0.78) and sex (0.72 male, 0.76 female), and across most common diagnostic categories other than psychiatry. For individuals in the highest risk quartile, 11.4% experienced fall within 180 days versus 1.2% in the lowest risk quartile; 57.6% of falls occurred in the highest risk quartile. This analysis of state-wide claims data demonstrates the feasibility of predicting fall-related injury requiring hospitalisation using readily available sociodemographic and clinical details. This translatable approach to stratification allows for identification of high-risk individuals in whom interventions are likely to be cost-effective. 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/.
pyNBS: A Python implementation for network-based stratification of tumor mutations.
Huang, Justin K; Jia, Tongqiu; Carlin, Daniel E; Ideker, Trey
2018-03-28
We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes. In addition to release of the software, we benchmark its key parameters and provide a compact cancer reference network that increases the significance of tumor stratification using the NBS algorithm. The structure of the code exposes key steps of the algorithm to foster further collaborative development. The package, along with examples and data, can be downloaded and installed from the URL http://www.github.com/huangger/pyNBS/. jkh013@ucsd.edu.
Advances in the management of PML: focus on natalizumab.
Fox, Robert
2011-11-01
Progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the central nervous system, occurs mainly in the setting of broad-based and selective immunosuppression. The immunomodulatory agent most often implicated in the development of PML is the monoclonal antibody natalizumab. Management of PML begins with risk stratification. Factors that predict the risk of PML are JC virus (JCV) antibody status, history of chemotherapy use, and cumulative exposure to natalizumab. The risk of natalizumab-related PML increases up to a duration of 36 months of therapy, after which the risk appears to level off. If suspicious for PML, the use of a sensitive JCV polymerase chain reaction assay permits early diagnosis. Immune reconstitution represents the mainstay of treatment for PML. With rapid reversal of immunosuppression followed by immunologic recovery, almost all patients suffer clinical deterioration termed immune reconstitution inflammatory syndrome (IRIS). High-dose corticosteroids are often recommended if a clinical and imaging syndrome resembling IRIS develops after immune restoration.
Wassink, Annemarie M; van der Graaf, Yolanda; Janssen, Kristel J; Cook, Nancy R; Visseren, Frank L
2012-12-01
Although the overall average 10-year cardiovascular risk for patients with manifest atherosclerosis is considered to be more than 20%, actual risk for individual patients ranges from much lower to much higher. We investigated whether information on metabolic syndrome (MetS) or its individual components improves cardiovascular risk stratification in these patients. We conducted a prospective cohort study in 3679 patients with clinical manifest atherosclerosis from the Secondary Manifestations of ARTerial disease (SMART) study. Primary outcome was defined as any cardiovascular event (cardiovascular death, ischemic stroke or myocardial infarction). Three pre-specified prediction models were derived, all including information on established MetS components. The association between outcome and predictors was quantified using a Cox proportional hazard analysis. Model performance was assessed using global goodness-of-fit fit (χ(2)), discrimination (C-index) and ability to improve risk stratification. A total of 417 cardiovascular events occurred among 3679 patients with 15,102 person-years of follow-up (median follow-up 3.7 years, range 1.6-6.4 years). Compared to a model with age and gender only, all MetS-based models performed slightly better in terms of global model fit (χ(2)) but not C-index. The Net Reclassification Index associated with the addition of MetS (yes/no), the dichotomous MetS-components or the continuous MetS-components on top of age and gender was 2.1% (p = 0.29), 2.3% (p = 0.31) and 7.5% (p = 0.01), respectively. Prediction models incorporating age, gender and MetS can discriminate between patients with clinical manifest atherosclerosis at the highest vascular risk and those at lower risk. The addition of MetS components to a model with age and gender correctly reclassifies only a small proportion of patients into higher- and lower-risk categories. The clinical utility of a prediction model with MetS is therefore limited.
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
2016-10-01
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. 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. 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 HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). 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. 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/
Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study
Sporle, Andrew; Corbin, Marine; Cheng, Soo; Harawira, Pauline; Gray, Michelle; Whaanga, Tracey; Guilford, Parry; Koea, Jonathan; Pearce, Neil
2017-01-01
Māori, the indigenous people of New Zealand, experience disproportionate rates of stomach cancer, compared to non-Māori. The overall aim of the study was to better understand the reasons for the considerable excess of stomach cancer in Māori and to identify priorities for prevention. Māori stomach cancer cases from the New Zealand Cancer Registry between 1 February 2009 and 31 October 2013 and Māori controls, randomly selected from the New Zealand electoral roll were matched by 5-year age bands to cases. Logistic regression was used to estimate odd ratios (OR) and 95% confidence intervals (CI) between exposures and stomach cancer risk. Post-stratification weighting of controls was used to account for differential non-response by deprivation category. The study comprised 165 cases and 480 controls. Nearly half (47.9%) of cases were of the diffuse subtype. There were differences in the distribution of risk factors between cases and controls. Of interest were the strong relationships seen with increased stomach risk and having >2 people sharing a bedroom in childhood (OR 3.30, 95%CI 1.95–5.59), testing for H pylori (OR 12.17, 95%CI 6.15–24.08), being an ex-smoker (OR 2.26, 95%CI 1.44–3.54) and exposure to environmental tobacco smoke in adulthood (OR 3.29, 95%CI 1.94–5.59). Some results were attenuated following post-stratification weighting. This is the first national study of stomach cancer in any indigenous population and the first Māori-only population-based study of stomach cancer undertaken in New Zealand. We emphasize caution in interpreting the findings given the possibility of selection bias. Population-level strategies to reduce the incidence of stomach cancer in Māori include expanding measures to screen and treat those infected with H pylori and a continued policy focus on reducing tobacco consumption and uptake. PMID:28732086
Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A
2010-06-17
There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.
Incorporating genomics into breast and prostate cancer screening: assessing the implications
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
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
Challenges and opportunities for imaging journals: emerging from the shadows.
Kressel, Herbert Y
2011-09-01
In this article, we will discuss the challenges and opportunities for imaging journals in the next decades. These include: the importance of optimizing online communication to enhance exchange of ideas in the sciences and the necessity to facilitate the development of quantitative tools that will aid in risk stratification, diagnosis, monitoring of therapy, and disease surveillance in an era of "P4 medicine". Journals will also need to promote the evidence-based evaluation of promising technologies so that the resources expended in healthcare may be most effectively used.
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.
Collaborative Review: Risk-Based Prostate Cancer Screening
Zhu, Xiaoye; Albertsen, Peter C.; Andriole, Gerald L.; Roobol, Monique J.; Schröder, Fritz H.; Vickers, Andrew J.
2016-01-01
Context Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. Objective This review critically examines the current evidence regarding risk-based PCa screening. Evidence acquisition A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. Evidence synthesis Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. Conclusions PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages. PMID:22134009
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
Kistler, Andreas D.; Serra, Andreas L.; Siwy, Justyna; Poster, Diane; Krauer, Fabienne; Torres, Vicente E.; Mrug, Michal; Grantham, Jared J.; Bae, Kyongtae T.; Bost, James E.; Mullen, William; Wüthrich, Rudolf P.; Mischak, Harald; Chapman, Arlene B.
2013-01-01
Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI). The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV) based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001) with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD. PMID:23326375
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.
Malaria ecotypes and stratification.
Schapira, Allan; Boutsika, Konstantina
2012-01-01
To deal with the variability of malaria, control programmes need to stratify their malaria problem into a number of smaller units. Such stratification may be based on the epidemiology of malaria or on its determinants such as ecology. An ecotype classification was developed by the World Health Organization (WHO) around 1990, and it is time to assess its usefulness for current malaria control as well as for malaria modelling on the basis of published research. Journal and grey literature was searched for articles on malaria or Anopheles combined with ecology or stratification. It was found that all malaria in the world today could be assigned to one or more of the following ecotypes: savanna, plains and valleys; forest and forest fringe; foothill; mountain fringe and northern and southern fringes; desert fringe; coastal and urban. However, some areas are in transitional or mixed zones; furthermore, the implications of any ecotype depend on the biogeographical region, sometimes subregion, and finally, the knowledge on physiography needs to be supplemented by local information on natural, anthropic and health system processes including malaria control. Ecotyping can therefore not be seen as a shortcut to determine control interventions, but rather as a framework to supplement available epidemiological and entomological data so as to assess malaria situations at the local level, think through the particular risks and opportunities and reinforce intersectoral action. With these caveats, it does however emerge that several ecotypic distinctions are well defined and have relatively constant implications for control within certain biogeographic regions. Forest environments in the Indo-malay and the Neotropics are, with a few exceptions, associated with much higher malaria risk than in adjacent areas; the vectors are difficult to control, and the anthropic factors also often converge to impose constraints. Urban malaria in Africa is associated with lower risk than savanna malaria; larval control may be considered though its role is not so far well established. In contrast, urban malaria in the Indian subcontinent is associated with higher risks than most adjacent rural areas, and larval control has a definite, though not exclusive, role. Simulation modelling of cost-effectiveness of malaria control strategies in different scenarios should prioritize ecotypes where malaria control encounters serious technical problems. Further field research on malaria and ecology should be interdisciplinary, especially with geography, and pay more attention to juxtapositions and to anthropic elements, especially migration. Copyright © 2012 Elsevier Ltd. All rights reserved.
Deleger, Louise; Brodzinski, Holly; Zhai, Haijun; Li, Qi; Lingren, Todd; Kirkendall, Eric S; Alessandrini, Evaline; Solti, Imre
2013-12-01
To evaluate a proposed natural language processing (NLP) and machine-learning based automated method to risk stratify abdominal pain patients by analyzing the content of the electronic health record (EHR). We analyzed the EHRs of a random sample of 2100 pediatric emergency department (ED) patients with abdominal pain, including all with a final diagnosis of appendicitis. We developed an automated system to extract relevant elements from ED physician notes and lab values and to automatically assign a risk category for acute appendicitis (high, equivocal, or low), based on the Pediatric Appendicitis Score. We evaluated the performance of the system against a manually created gold standard (chart reviews by ED physicians) for recall, specificity, and precision. The system achieved an average F-measure of 0.867 (0.869 recall and 0.863 precision) for risk classification, which was comparable to physician experts. Recall/precision were 0.897/0.952 in the low-risk category, 0.855/0.886 in the high-risk category, and 0.854/0.766 in the equivocal-risk category. The information that the system required as input to achieve high F-measure was available within the first 4 h of the ED visit. Automated appendicitis risk categorization based on EHR content, including information from clinical notes, shows comparable performance to physician chart reviewers as measured by their inter-annotator agreement and represents a promising new approach for computerized decision support to promote application of evidence-based medicine at the point of care.
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.
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.
Liang, Yang; Yang, Lin-Hai; Jiang, Hui; Yuan, Xiao-Jun; Sun, Li-Rong; Wang, Ning-Ling; Tang, Jing-Yan
2015-04-01
This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates. © 2015 John Wiley & Sons Ltd.
Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E
2016-03-01
Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Metabolic Profiles Predict Adverse Events Following Coronary Artery Bypass Grafting
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
Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig; Hansen, Tine W; Rasmussen, Susanne; Wachtell, Kristian; Torp-Pedersen, Christian; Hildebrandt, Per R; Ibsen, Hans
2010-01-01
In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt-proBNP), related to hemodynamic cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), related to metabolic cardiovascular risk factors and urine albumin/creatinine ratio (UACR), related to hemodynamic as well as metabolic risk factors. In healthy subjects with a 10-year risk of cardiovascular death lower than 5% based on HeartScore and therefore not eligible for primary prevention, the actual 10-year risk of cardiovascular death exceeded 5% in a small subgroup of subjects with UACR higher than the 95-percentile of approximately 1.6 mg/mmol. Combined use of high UACR or high hsCRP identified a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup of 48% with extremely high cardiovascular risk who should be referred for specialist care to optimize treatment.
Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy.
Calkins, Hugh; Corrado, Domenico; Marcus, Frank
2017-11-21
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and an increased risk of sudden cardiac death. Although structural abnormalities of the right ventricle predominate, it is well recognized that left ventricular involvement is common, particularly in advanced disease, and that left-dominant forms occur. The pathological characteristic of ARVC is myocyte loss with fibrofatty replacement. Since the first detailed clinical description of the disorder in 1982, significant advances have been made in understanding this disease. Once the diagnosis of ARVC is established, the single most important clinical decision is whether a particular patient's sudden cardiac death risk is sufficient to justify placement of an implantable cardioverter-defibrillator. The importance of this decision reflects the fact that ARVC is a common cause of sudden death in young people and that sudden death may be the first manifestation of the disease. This decision is particularly important because these are often young patients who are expected to live for many years. Although an implantable cardioverter-defibrillator can save lives in individuals with this disease, it is also well recognized that implantable cardioverter-defibrillator therapy is associated with both short- and long-term complications. Decisions about the placement of an implantable cardioverter-defibrillator are based on an estimate of a patient's risk of sudden cardiac death, as well as their preferences and values. The primary purpose of this article is to provide a review of the literature that concerns risk stratification in patients with ARVC and to place this literature in the framework of the 3 authors' considerable lifetime experiences in caring for patients with ARVC. The most important parameters to consider when determining arrhythmic risk include electric instability, including the frequency of premature ventricular contractions and sustained ventricular arrhythmia; proband status; extent of structural disease; cardiac syncope; male sex; the presence of multiple mutations or a mutation in TMEM43; and the patient's willingness to restrict exercise and to eliminate participation in competitive or endurance exercise. © 2017 American Heart Association, Inc.
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.
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
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.
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.
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.
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?
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.
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.
de Mel, Sanjay; Chen, Yunxin; Gopalakrishnan, Sathish Kumar; Ooi, Melissa; Teo, Constance; Tan, Daryl; Teo, Min Li Claire; Tso, Allison CY; Lee, Lian King; Nagarajan, Chandramouli; Goh, Yeow Tee; Chng, Wee Joo
2017-01-01
Multiple myeloma (MM) is an incurable plasma cell neoplasm with an incidence of 100 patients per year in Singapore. Major advances have been made in the diagnosis, risk stratification and treatment of MM in the recent past. The reclassification of a subset of patients with smouldering MM, based on high-risk biomarkers, and the development of the revised international staging system are among the key new developments in diagnosis and staging. The use of novel agent-based treatment has resulted in significant improvements in the survival and quality of life of many patients with MM. Determining the optimal use of proteasome inhibitors, immunomodulators and, more recently, monoclonal antibodies is an area of ongoing investigation. In this guideline, we aim to provide an overview of the management of MM, incorporating the latest developments in diagnosis and treatment. PMID:27609508
CE: Preventing Contrast-Induced Acute Kidney Injury.
Gallegos, Yvonne; Taha, Asma Ali; Rutledge, Dana N
2016-12-01
: Diagnostic radiographic imaging scans using intravascular iodinated contrast media can lead to various complications. The most salient of these is contrast-induced acute kidney injury (CI-AKI) or contrast-induced nephropathy, a potentially costly and serious patient safety concern. Prevention strategies are the cornerstone of evidence-based clinical management for patients receiving contrast agents. These include preprocedure screening, stratification of patients based on risk factors, and protective interventions, the most important of which is hydration both before and after the radiographic imaging scan. There is a gap, however, between best evidence and clinical practice in terms of exact hydration protocols. Nurses play an important role in nephropathy prevention and need to be familiar with CI-AKI as a potential complication of radiographic imaging scans. In order to ensure safe, high-quality care, nurses must be involved in efforts to prevent CI-AKI as well as interventions that minimize patients' risk of kidney injury.
Progress in molecular-based management of differentiated thyroid cancer
Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin
2014-01-01
Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556
NASA Astrophysics Data System (ADS)
Seth, Sohan; Akram, Ahsan R.; McCool, Paul; Westerfeld, Jody; Wilson, David; McLaughlin, Stephen; Dhaliwal, Kevin; Williams, Christopher K. I.
2016-08-01
Solitary pulmonary nodules are common, often incidental findings on chest CT scans. The investigation of pulmonary nodules is time-consuming and often leads to protracted follow-up with ongoing radiological surveillance, however, clinical calculators that assess the risk of the nodule being malignant exist to help in the stratification of patients. Furthermore recent advances in interventional pulmonology include the ability to both navigate to nodules and also to perform autofluorescence endomicroscopy. In this study we assessed the efficacy of incorporating additional information from label-free fibre-based optical endomicrosopy of the nodule on assessing risk of malignancy. Using image analysis and machine learning approaches, we find that this information does not yield any gain in predictive performance in a cohort of patients. Further advances with pulmonary endomicroscopy will require the addition of molecular tracers to improve information from this procedure.
de Mel, Sanjay; Chen, Yunxin; Gopalakrishnan, Sathish Kumar; Ooi, Melissa; Teo, Constance; Tan, Daryl; Teo, Min Li Claire; Tso, Allison Cy; Lee, Lian King; Nagarajan, Chandramouli; Goh, Yeow Tee; Chng, Wee Joo
2017-02-01
Multiple myeloma (MM) is an incurable plasma cell neoplasm with an incidence of 100 patients per year in Singapore. Major advances have been made in the diagnosis, risk stratification and treatment of MM in the recent past. The reclassification of a subset of patients with smouldering MM, based on high-risk biomarkers, and the development of the revised international staging system are among the key new developments in diagnosis and staging. The use of novel agent-based treatment has resulted in significant improvements in the survival and quality of life of many patients with MM. Determining the optimal use of proteasome inhibitors, immunomodulators and, more recently, monoclonal antibodies is an area of ongoing investigation. In this guideline, we aim to provide an overview of the management of MM, incorporating the latest developments in diagnosis and treatment. Copyright: © Singapore Medical Association.
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,…
Chinain, Mireille; Darius, H Taiana; Ung, André; Fouc, Mote Tchou; Revel, Taina; Cruchet, Philippe; Pauillac, Serge; Laurent, Dominique
2010-10-01
Based on epidemiological data available through long-term monitoring surveys conducted by both the Public Health Directorate and the Louis Malardé Institute, ciguatera is highly endemic in French Polynesia, most notably in Raivavae (Australes) which appears as a hot spot of ciguatera with an average incidence rate of 140 cases/10,000 population for the period 2007-2008. In order to document the ciguatera risk associated with Raivavae lagoon, algal and toxin-based field monitoring programs were conducted in this island from April 2007 to May 2008. Practically, the distribution, abundance and toxicity of Gambierdiscus populations, along with the toxicity levels in 160 fish distributed within 25 distinct species, were assessed in various sampling locations. Herbivores such as Scarids (parrotfish) and Acanthurids (unicornfish) were rated as high-risk species based on receptor-binding assay toxicity data. A map of the risk stratification within the Raivavae lagoon was also produced, which indicates that locations where both natural and man-made disturbances have occurred remained the most susceptible to CFP incidents. Our findings also suggest that, locally, the traditional knowledge about ciguatera may not be scientifically complete but is functionally correct. Community education resulted in self-regulating behaviour towards avoidance of high-risk fish species and fishing locations. Copyright 2009 Elsevier Ltd. All rights reserved.
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.
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.
A national approach to diabetes foot risk stratification and foot care.
Leese, G P; Stang, D; Pearson, D W
2011-08-01
The Scottish Diabetes Foot Action Group (SDG) has developed and introduced a national strategy plan for diabetic foot care across Scotland. This has involved the implementation of an evidence-based national foot screening and risk stratification programme that has already covered 61% of the population in just the first two years. Nationally agreed patient information foot leaflets and professional education material have been introduced, and a consensus for antibiotic use in the diabetic foot has been published. Information on multidisciplinary specialist foot services has been collected, indicating that 58% of Health Board areas have consultants with dedicated sessions in their job plan to a foot clinic, and 42% had integrated orthotic involvement. The SDG aims to increase these figures. Work has been undertaken to support local podiatry networks and improve communication between the specialist centre and the community. At a national level the SDG is working with Foot in Diabetes UK (FDUK) to recognize key podiatry skills by developing core competencies and a competency framework for the diabetes podiatrist and diabetes orthotist. The annual Scottish Diabetes Survey indicates some improvement in amputation rates with prevalence decreasing from 0.8% to 0.5%, and improved recording of foot ulceration at a national level. This national strategy has helped highlight the importance and difficulties facing diabetes foot care and should help to continue to improve the quality of care of people with diabetes who have foot-related problems.
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.
Johnson, Tracy L; Brewer, Daniel; Estacio, Raymond; Vlasimsky, Tara; Durfee, Michael J; Thompson, Kathy R; Everhart, Rachel M; Rinehart, Deborath J; Batal, Holly
2015-01-01
The Center for Medicare and Medicaid Innovation (CMMI) awarded Denver Health's (DH) integrated, safety net health care system $19.8 million to implement a "population health" approach into the delivery of primary care. This major practice transformation builds on the Patient Centered Medical Home (PCMH) and Wagner's Chronic Care Model (CCM) to achieve the "Triple Aim": improved health for populations, care to individuals, and lower per capita costs. This paper presents a case study of how DH integrated published predictive models and front-line clinical judgment to implement a clinically actionable, risk stratification of patients. This population segmentation approach was used to deploy enhanced care team staff resources and to tailor care-management services to patient need, especially for patients at high risk of avoidable hospitalization. Developing, implementing, and gaining clinical acceptance of the Health Information Technology (HIT) solution for patient risk stratification was a major grant objective. In addition to describing the Information Technology (IT) solution itself, we focus on the leadership and organizational processes that facilitated its multidisciplinary development and ongoing iterative refinement, including the following: team composition, target population definition, algorithm rule development, performance assessment, and clinical-workflow optimization. We provide examples of how dynamic business intelligence tools facilitated clinical accessibility for program design decisions by enabling real-time data views from a population perspective down to patient-specific variables. We conclude that population segmentation approaches that integrate clinical perspectives with predictive modeling results can better identify high opportunity patients amenable to medical home-based, enhanced care team interventions.
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.
Agrawal, Hitesh; Molossi, Silvana; Alam, Mahboob; Sexson-Tejtel, S Kristen; Mery, Carlos M; McKenzie, E Dean; Fraser, Charles D; Qureshi, Athar M
2017-03-01
The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.
Barrett's oesophagus: how should we manage it?
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
Møller, M H; Engebjerg, M C; Adamsen, S; Bendix, J; Thomsen, R W
2012-05-01
Accurate and early identification of high-risk surgical patients with perforated peptic ulcer (PPU) is important for triage and risk stratification. The objective of the present study was to develop a new and improved clinical rule to predict mortality in patients following surgical treatment for PPU. nationwide cohort study based on prospectively collected data. thirty-five hospitals in Denmark. a total of 2668 patients surgically treated for gastric or duodenal PPU between 1 February 2003 and 31 August 2009. 30-day mortality. We derived a new clinical prediction rule for 30-day mortality and evaluated and compared its prognostic performance with the American Society of Anaesthesiologists (ASA) and Boey scores. A total of 708 patients (27%) died within 30 days of surgery. The Peptic Ulcer Perforation (PULP) score - comprised eight variables with an adjusted odds ratio of more than 1.28: 1) age > 65 years, 2) active malignant disease or AIDS, 3) liver cirrhosis, 4) steroid use, 5) time from perforation to admission > 24 h, 6) pre-operative shock, 7) serum creatinine > 130 μM, and 8) the four levels of the ASA score (from 2 to 5). The score predicted mortality well (area under receiver operating characteristics curve (AUC) 0.83). It performed considerably better than the Boey score (AUC 0.70) and better than the ASA score alone (AUC 0.78). The PULP score accurately predicts 30-day mortality in patients operated for PPU and can assist in risk stratification and triage. © 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.
Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M
2015-01-01
Objectives A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO2 would not provide accurate assessment of lung injury severity. Design A prospective, multicentre, observational study. Setting A network of teaching hospitals. Participants 478 patients with eligible criteria for moderate (100
Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M
2015-03-27
A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO₂/FiO₂) at ARDS onset. Since the proposal did not mandate PaO₂/FiO₂ calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO₂/FiOv would not provide accurate assessment of lung injury severity. A prospective, multicentre, observational study. A network of teaching hospitals. 478 patients with eligible criteria for moderate (100
NASA Astrophysics Data System (ADS)
Riethdorf, Jan-Rainer; Max, Lars; Nürnberg, Dirk; Lembke-Jene, Lester; Tiedemann, Ralf
2013-01-01
Based on models and proxy data, it has been proposed that salinity-driven stratification weakened in the subarctic North Pacific during the last deglaciation, which potentially contributed to the deglacial rise in atmospheric carbon dioxide. We present high-resolution subsurface temperature (TMg/Ca) and subsurface salinity-approximating (δ18Oivc-sw) records across the last 20,000 years from the subarctic North Pacific and its marginal seas, derived from combined stable oxygen isotopes and Mg/Ca ratios of the planktonic foraminiferal species Neogloboquadrina pachyderma (sin.). Our results indicate regionally differing changes of subsurface conditions. During the Heinrich Stadial 1 and the Younger Dryas cold phases, our sites were subject to reduced thermal stratification, brine rejection due to sea-ice formation, and increased advection of low-salinity water from the Alaskan Stream. In contrast, the Bølling-Allerød warm phase was characterized by strengthened thermal stratification, stronger sea-ice melting, and influence of surface waters that were less diluted by the Alaskan Stream. From direct comparison with alkenone-based sea surface temperature estimates (SSTUk'37), we suggest deglacial thermocline changes that were closely related to changes in seasonal contrasts and stratification of the mixed layer. The modern upper-ocean conditions seem to have developed only since the early Holocene.
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
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.
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.
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.
Near-Surface Effects of Free Atmosphere Stratification in Free Convection
NASA Astrophysics Data System (ADS)
Mellado, Juan Pedro; van Heerwaarden, Chiel C.; Garcia, Jade Rachele
2016-04-01
The effect of a linear stratification in the free atmosphere on near-surface properties in a free convective boundary layer (CBL) is investigated by means of direct numerical simulation. We consider two regimes: a neutral stratification regime, which represents a CBL that grows into a residual layer, and a strong stratification regime, which represents the equilibrium (quasi-steady) entrainment regime. We find that the mean buoyancy varies as z^{-1/3}, in agreement with classical similarity theory. However, the root-mean-square (r.m.s.) of the buoyancy fluctuation and the r.m.s. of the vertical velocity vary as z^{-0.45} and ln z, respectively, both in disagreement with theory. These scaling laws are independent of the stratification regime, but the depth over which they are valid depends on the stratification. In the strong stratification regime, this depth is about 20 to 25 % of the CBL depth instead of the commonly used 10 %, which we only observe under neutral conditions. In both regimes, the near-surface flow structure can be interpreted as a hierarchy of circulations attached to the surface. Based on this structure, we define a new near-surface layer in free convection, the plume-merging layer, that is conceptually different from the constant-flux layer. The varying depth of the plume-merging layer depending on the stratification accounts for the varying depth of validity of the scaling laws. These findings imply that the buoyancy transfer law needed in mixed-layer and single-column models is well described by the classical similarity theory, independent of the stratification in the free atmosphere, even though other near-surface properties, such as the r.m.s. of the buoyancy fluctuation and the r.m.s. of the vertical velocity, are inconsistent with that theory.
Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art.
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.
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.
Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann
2018-03-01
While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy.
Schlansky, Barry; Hwang, Joo Ha
2009-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and antiinflammatory properties, and aspirin is increasingly employed in the primary and secondary prevention of cardiovascular disease and ischemic stroke. Despite undisputed therapeutic efficacy for these indications, all NSAIDs impart a considerable risk of peptic ulcer disease and upper gastrointestinal hemorrhage. A growing body of evidence supports an association between non-aspirin NSAIDs and acute coronary syndromes, and an expanding understanding of the gastroduodenal effects of aspirin, COX-2 selective agents, clopidogrel, and Helicobacter pylori synergism fuel controversies in NSAID use. In this review, we discuss risk stratification of patients taking NSAIDs and the appropriate application of proven gastro-protective strategies to decrease the incidence of gastrointestinal hemorrhage based upon an individualized assessment of risk for potential toxicities. Prevention of NSAID-related gastropathy is an important clinical issue, and therapeutic strategies for both the primary and secondary prevention of adverse events are continually evolving.
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.
Risk Stratification of Stress Fractures and Prediction of Return to Duty
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
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
Lan, Chen-Chia; Tseng, Chun-Hung; Chen, Jiunn-Horng; Lan, Joung-Liang; Wang, Yu-Chiao; Tsay, Gregory J; Hsu, Chung-Yi
2016-11-01
An increased risk of suicide ideation and death has been reported in patients with fibromyalgia. This study aimed to evaluate the risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with comorbidities. We used the Longitudinal Health Insurance Database, a subset of the national insurance claim dataset, which enrolled 1 million Taiwanese people from 2000 to 2005, to identify 95,150 patients with incident fibromyalgia (ICD-9-CM 729.0-729.1) and 190,299 reference subjects matched by sex, age, and index date of diagnosis, with a mean of 8.46 ± 2.37 years of follow-up until 2011. The risk of a suicide event (ICD-9-CM, External-Cause Codes 950-959) was analyzed with a Cox proportional hazards model. Stratification analysis was performed by separating fibromyalgia patients and reference subjects with respect to each comorbidity to determine the risk of suicide in fibromyalgia patients with or without comorbidity relative to subjects who had neither fibromyalgia nor comorbidity. In this Taiwanese dataset, there were 347 suicide events in patients with fibromyalgia (4.16 per 10 person-years) and 424 in matched reference subjects (2.63 per 10 person-years) with a significant crude hazard ratio (HR) of 1.58 (95% confidence interval [CI] 1.38-1.83) and an adjusted HR of 1.38 (95% CI 1.17-1.71) for fibromyalgia patients relative to the matched reference subjects. According to the 2 × 2 stratification analysis, we found that fibromyalgia patients without comorbidity had an independent but mild risk of a suicide event with adjusted HRs ranging from 1.33 to 1.69 relative to subjects with neither fibromyalgia nor comorbidity. Meanwhile, fibromyalgia patients with comorbidity led to a markedly enhanced risk of a suicide event relative to the matched reference subjects, with adjusted HRs ranging from 1.51 to 8.23. Our analysis confirmed a mild-to-moderate risk of a suicide event in patients with primary fibromyalgia. Attention should be paid to the prevention of suicide in fibromyalgia patients with concomitant comorbidities.
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.
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.
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
Ko, Gary T; So, Wing-Yee; Tong, Peter C; Le Coguiec, Francois; Kerr, Debborah; Lyubomirsky, Greg; Tamesis, Beaver; Wolthers, Troels; Nan, Jennifer; Chan, Juliana
2010-05-13
The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care. The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose. The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions. The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes.
A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma
Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang
2015-01-01
Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236
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.
Chronic Kidney Disease in Pregnancy.
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.
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.
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
Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H
2012-08-01
With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.
Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H
2012-01-01
With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715
68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.
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.
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
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
A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer.
Salvucci, Manuela; Würstle, Maximilian L; Morgan, Clare; Curry, Sarah; Cremona, Mattia; Lindner, Andreas U; Bacon, Orna; Resler, Alexa J; Murphy, Áine C; O'Byrne, Robert; Flanagan, Lorna; Dasgupta, Sonali; Rice, Nadege; Pilati, Camilla; Zink, Elisabeth; Schöller, Lisa M; Toomey, Sinead; Lawler, Mark; Johnston, Patrick G; Wilson, Richard; Camilleri-Broët, Sophie; Salto-Tellez, Manuel; McNamara, Deborah A; Kay, Elaine W; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Hennessy, Bryan T; Longley, Daniel B; Rehm, Markus; Prehn, Jochen H M
2017-03-01
Purpose: Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. Experimental Design: Apoptosis competency of primary tumor samples from patients with stage III colorectal cancer ( n = 120) was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC, and XIAP. An enriched APOPTO-CELL signature (APOPTO-CELL-PC3) was synthesized to capture apoptosome-independent effects of Caspase-3. Furthermore, a machine learning Random Forest approach was applied to APOPTO-CELL-PC3 and available molecular and clinicopathologic data to identify a further enhanced signature. Association of the signature with prognosis was evaluated in an independent colon adenocarcinoma cohort (TCGA COAD, n = 136). Results: We identified 3 prognostic biomarkers ( P = 0.04, P = 0.006, and P = 0.0004 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively) with increasing stratification accuracy for patients with stage III colorectal cancer.The APOPTO-CELL-PC3 signature ranked highest among all features. The prognostic value of the signatures was independently validated in stage III TCGA COAD patients ( P = 0.01, P = 0.04, and P = 0.02 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively). The signatures provided further stratification for patients with CMS1-3 molecular subtype. Conclusions: The integration of a systems-biology-based biomarker for apoptosis competency with machine learning approaches is an appealing and innovative strategy toward refined patient stratification. The prognostic value of apoptosis competency is independent of other available clinicopathologic and molecular factors, with tangible potential of being introduced in the clinical management of patients with stage III colorectal cancer. Clin Cancer Res; 23(5); 1200-12. ©2016 AACR . ©2016 American Association for Cancer Research.
An efficient sampling strategy for selection of biobank samples using risk scores.
Björk, Jonas; Malmqvist, Ebba; Rylander, Lars; Rignell-Hydbom, Anna
2017-07-01
The aim of this study was to suggest a new sample-selection strategy based on risk scores in case-control studies with biobank data. An ongoing Swedish case-control study on fetal exposure to endocrine disruptors and overweight in early childhood was used as the empirical example. Cases were defined as children with a body mass index (BMI) ⩾18 kg/m 2 ( n=545) at four years of age, and controls as children with a BMI of ⩽17 kg/m 2 ( n=4472 available). The risk of being overweight was modelled using logistic regression based on available covariates from the health examination and prior to selecting samples from the biobank. A risk score was estimated for each child and categorised as low (0-5%), medium (6-13%) or high (⩾14%) risk of being overweight. The final risk-score model, with smoking during pregnancy ( p=0.001), birth weight ( p<0.001), BMI of both parents ( p<0.001 for both), type of residence ( p=0.04) and economic situation ( p=0.12), yielded an area under the receiver operating characteristic curve of 67% ( n=3945 with complete data). The case group ( n=416) had the following risk-score profile: low (12%), medium (46%) and high risk (43%). Twice as many controls were selected from each risk group, with further matching on sex. Computer simulations showed that the proposed selection strategy with stratification on risk scores yielded consistent improvements in statistical precision. Using risk scores based on available survey or register data as a basis for sample selection may improve possibilities to study heterogeneity of exposure effects in biobank-based studies.
Medical Conditions in the First Years of Life Associated with Future Diagnosis of ASD in Children.
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.
The Indiana Chronic Disease Management Program
Rosenman, Marc B; Holmes, Ann M; Ackermann, Ronald T; Murray, Michael D; Doebbeling, Caroline Carney; Katz, Barry; Li, Jingjin; Zillich, Alan; Prescott, Victoria M; Downs, Stephen M; Inui, Thomas S
2006-01-01
The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation. PMID:16529571
The Indiana Chronic Disease Management Program.
Rosenman, Marc B; Holmes, Ann M; Ackermann, Ronald T; Murray, Michael D; Doebbeling, Caroline Carney; Katz, Barry; Li, Jingjin; Zillich, Alan; Prescott, Victoria M; Downs, Stephen M; Inui, Thomas S
2006-01-01
The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation.
Kones, Richard
2010-01-01
The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization. PMID:20730020
Kones, Richard
2010-08-09
The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization.
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
Brito, Juan P; Ito, Yasuhiro; Miyauchi, Akira; Tuttle, R Michael
2016-01-01
The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States. A risk-stratified approach to the evaluation of patients with probable or proven PMC being considered for an active surveillance management approach requires an evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound characteristics (e.g., size of the primary tumor, the location of the tumor within the thyroid gland); (ii) patient characteristics (e.g., age, comorbidities, willingness to accept observation); and (iii) medical team characteristics (e.g., availability and experience of the multidisciplinary team). Based on an analysis of the critical factors within each of these domains, patients with probable or proven PTC can then be classified as ideal, appropriate, or inappropriate candidates for active surveillance. Risk stratification utilizing the proposed decision-making framework will improve the ability of clinicians to recognize individual patients with proven or probable PMC who are most likely to benefit from an active surveillance management option while at the same time identifying patients with proven or probable PMC that would be better served with an upfront biopsy and surgical management approach.
A comparison of five methods of measuring mammographic density: a case-control study.
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.
Hussen, Sophia A; Bowleg, Lisa; Sangaramoorthy, Thurka; Malebranche, David J
2012-01-01
Black men in the USA experience disproportionately high rates of HIV infection, particularly in the Southeastern part of the country. We conducted 90 qualitative in-depth interviews with Black men living in the state of Georgia and analysed the transcripts using Sexual Script Theory to: (1) characterise the sources and content of sexual scripts that Black men were exposed to during their childhood and adolescence and (2) describe the potential influence of formative scripts on adult HIV sexual risk behaviour. Our analyses highlighted salient sources of cultural scenarios (parents, peers, pornography, sexual education and television), interpersonal scripts (early sex- play, older female partners, experiences of child abuse) and intrapsychic scripts that participants described. Stratification of participant responses based on sexual-risk behaviour revealed that lower- and higher-risk men described exposure to similar scripts during their formative years; however, lower-risk men reported an ability to cognitively process and challenge the validity of risk-promoting scripts that they encountered. Implications for future research are discussed.
Gualtierotti, Roberta; Parisi, Marco; Ingegnoli, Francesca
2018-04-01
Patients with inflammatory rheumatic diseases often need orthopaedic surgery due to joint involvement. Total hip replacement and total knee replacement are frequent surgical procedures in these patients. Due to the complexity of the inflammatory rheumatic diseases, the perioperative management of these patients must envisage a multidisciplinary approach. The frequent association with extraarticular comorbidities must be considered when evaluating perioperative risk of the patient and should guide the clinician in the decision-making process. However, guidelines of different medical societies may vary and are sometimes contradictory. Orthopaedics should collaborate with rheumatologists, anaesthesiologists and, when needed, cardiologists and haematologists with the common aim of minimising perioperative risk in patients with inflammatory rheumatic diseases. The aim of this review is to provide the reader with simple practical recommendations regarding perioperative management of drugs such as disease-modifying anti-rheumatic drugs, corticosteroids, non-steroidal anti-inflammatory drugs and tools for a risk stratification for cardiovascular and thromboembolic risk based on current evidence for patients with inflammatory rheumatic diseases.
Landgren, Ola; Mateos, María-Victoria
2015-01-01
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder. SMM is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma (MM). There have been major advances in the diagnosis, prognosis, and management of SMM in the last few years. These include a revised disease definition, identification of several new prognostic factors, a classification based on underlying cytogenetic changes, and new treatment options. Importantly, a subset of patients previously considered SMM is now reclassified as MM on the basis of biomarkers identifying patients with an ≥80% risk of progression within 2 years. SMM has assumed greater significance on the basis of recent trials showing that early therapy can be potentially beneficial to patients. As a result, there is a need to accurately diagnose and risk-stratify patients with SMM, including routine incorporation of modern imaging and laboratory techniques. In this review, we outline current concepts in diagnosis and risk stratification of SMM, and provide specific recommendations on the management of SMM. PMID:25838344
Home telemonitoring of vital signs--technical challenges and future directions.
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.
Mortality following unemployment during an economic downturn: Swedish register-based cohort study.
Montgomery, Scott; Udumyan, Ruzan; Magnuson, Anders; Osika, Walter; Sundin, Per-Ola; Blane, David
2013-01-01
To investigate if unemployment during an economic downturn is associated with mortality, even among men with markers of better health (higher cognitive function scores and qualifications), and to assess whether the associations vary by age at unemployment. Longitudinal register-based cohort study. Study entry was in 1990 and 2001 when Sweden was entering periods of significant economic contraction. A representative sample of men from the general population (n=234 782) born between 1952 and 1956 who participated in military conscription examinations. Men in receipt of disability or sickness benefit at study entry were excluded. All-cause mortality. Unemployment compared with employment in 1991 (ages 34-38 years) produced adjusted HRs (with 95% CIs) for all-cause mortality (3651 deaths) during follow-up to 2001 and after stratification by education of 2.35 (1.99 to 2.76) for compulsory education, 2.25 (1.97 to 2.58) for up to 3 years postcompulsory education and 1.90 (1.40 to 2.57) for more than 3 years postcompulsory education. When unemployment was compared with employment in 2001 (ages 45-49 years) with follow-up to 2010, the pattern of mortality risk (4271 deaths) stratified by education was reversed, producing adjusted HRs of 2.81 (2.47 to 3.21) for compulsory education, 2.87 (2.58 to 3.19) for up to 3 years postcompulsory education and 3.44 (2.78 to 4.25) for more than 3 years postcompulsory education. Interaction testing confirmed effect modification by age/period (p=0.003). The degree of gradient reversal was slightly less pronounced after stratification by cognitive function but produced a similar pattern of results (p=0.004). Unemployment at older ages is associated with greater mortality risk than at younger ages, with the greatest relative increase in risk among men with markers of better health, suggesting the greater vulnerability of all older workers to unemployment-associated exposures.
Blank, Patricia R; Filipits, Martin; Dubsky, Peter; Gutzwiller, Florian; Lux, Michael P; Brase, Jan C; Weber, Karsten E; Rudas, Margaretha; Greil, Richard; Loibl, Sibylle; Szucs, Thomas D; Kronenwett, Ralf; Schwenkglenks, Matthias; Gnant, Michael
2015-02-01
The individual risk of recurrence in hormone receptor-positive primary breast cancer patients determines whether adjuvant endocrine therapy should be combined with chemotherapy. Clinicopathological parameters and molecular tests such as EndoPredict(®) (EPclin) can support decision making in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative cancer. Using a life-long Markov state transition model, we determined the health economic impact and incremental cost effectiveness of EPclin-based risk stratification in combination with clinical guidelines [German-S3, National Comprehensive Cancer Center Network (NCCN), and St. Gallen] to decide on chemotherapy use. Information on overall and metastasis-free survival came from Austrian Breast & Colorectal Cancer Study Group clinical trials 6/8 (n = 1,619) and published literature. Effectiveness was assessed as quality-adjusted life-years (QALYs). Costs (2010) were assessed from a German third-party payer perspective. Lifetime costs per patient ranged from
ERIC Educational Resources Information Center
Bodovski, Katerina; Kotok, Stephen; Henck, Adrienne
2014-01-01
Although communist ideology claimed to destroy former class stratification based on labour market capitalist relationships, "de facto" during socialism one social class hierarchy was substituted for another that was equally unequal. The economic transition during the 1990s increased stratification by wealth, which affected educational…
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…
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.
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.
Effect of sample stratification on dairy GWAS results
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
The correspondence of surface climate parameters with satellite and terrain data
NASA Technical Reports Server (NTRS)
Dozier, Jeff; Davis, Frank
1987-01-01
One of the goals of the research was to develop a ground sampling stragegy for calibrating remotely sensed measurements of surface climate parameters. The initial sampling strategy involved the stratification of the terrain based on important ancillary surface variables such as slope, exposure, insolation, geology, drainage, fire history, etc. For a spatially heterogeneous population, sampling error is reduced and efficiency increased by stratification of the landscape into more homogeneous sub-areas and by employing periodic random spacing of samples. These concepts were applied in the initial stratification of the study site for the purpose of locating and allocating instrumentation.
VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M
2017-12-01
Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver Diseases.
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
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.
ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias
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.
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.
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.
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.
Akiyoshi, Takashi; Maeda, Hiromichi; Kashiwabara, Kosuke; Kanda, Mitsuro; Mayanagi, Shuhei; Aoyama, Toru; Hamada, Chikuma; Sadahiro, Sotaro; Fukunaga, Yosuke; Ueno, Masashi; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki
2017-01-01
Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset. PMID:29228760
Chanouzas, Dimitrios; Small, Alexander; Borrows, Richard; Ball, Simon
2018-01-01
The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis. A pilot study of renal transplant recipient (RTR's) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR's were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR's were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay. At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x105 PBMC's; pp65 ≤ 3 spots / 2.5x105 PBMC's). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x105 PBMC's) and pp65 (>50 spots / 2.5x105 PBMC's), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02). In CMV seronegative RTR's, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR's, associated with protection from CMV infection. In seropositive RTR's, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group.
Kastritis, Efstathios; Terpos, Evangelos; Roussou, Maria; Gavriatopoulou, Maria; Migkou, Magdalini; Eleutherakis-Papaiakovou, Evangelos; Fotiou, Despoina; Ziogas, Dimitrios; Panagiotidis, Ioannis; Kafantari, Eftychia; Giannouli, Stavroula; Zomas, Athanasios; Konstantopoulos, Konstantinos; Dimopoulos, Meletios A.
2017-01-01
The Revised International Staging System (R-ISS) was recently introduced in order to improve risk stratification over that provided by the widely used standard International Staging System. In addition to the parameters of the standard system, the R-ISS incorporates the presence of chromosomal abnormalities detected by interphase fluorescence in situ hybridization [t(4;14), t(14;16) and del17p] and elevated serum lactate dehydrogenase. The R-ISS was formulated on the basis of a large dataset of selected patients who had participated in clinical trials and has not been validated in an independent cohort of unselected patients. Thus, we evaluated the R-ISS in 475 consecutive, unselected patients, treated in a single center. Our patients were older and more often had severe renal dysfunction than those in the original publication on the R-ISS. As regards distribution by group, 18% had R-ISS-1, 64.5% R-ISS-2 and 18% R-ISS-3. According to R-ISS group, the 5-year survival rate was 77%, 53% and 19% for R-ISS-1, -2 and -3, respectively (P<0.001). The R-ISS could identify three groups with distinct outcomes among patients treated with or without autologous stem cell transplantation, among those treated with either bortezomib-based or immunomodulatory drug-based primary therapy and in patients ≤65, 66–75 or >75 years. However, in patients with severe renal dysfunction the distinction between groups was less clear. In conclusion, our data in consecutive, unselected patients, with differences in the characteristics and treatment approaches compared to the original International Myeloma Working Group cohort, verified that R-ISS is a robust tool for risk stratification of newly diagnosed patients with symptomatic myeloma. PMID:27789676
Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan
2018-04-23
Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.
Exploring a new bilateral focal density asymmetry based image marker to predict breast cancer risk
NASA Astrophysics Data System (ADS)
Aghaei, Faranak; Mirniaharikandehei, Seyedehnafiseh; Hollingsworth, Alan B.; Wang, Yunzhi; Qiu, Yuchen; Liu, Hong; Zheng, Bin
2017-03-01
Although breast density has been widely considered an important breast cancer risk factor, it is not very effective to predict risk of developing breast cancer in a short-term or harboring cancer in mammograms. Based on our recent studies to build short-term breast cancer risk stratification models based on bilateral mammographic density asymmetry, we in this study explored a new quantitative image marker based on bilateral focal density asymmetry to predict the risk of harboring cancers in mammograms. For this purpose, we assembled a testing dataset involving 100 positive and 100 negative cases. In each of positive case, no any solid masses are visible on mammograms. We developed a computer-aided detection (CAD) scheme to automatically detect focal dense regions depicting on two bilateral mammograms of left and right breasts. CAD selects one focal dense region with the maximum size on each image and computes its asymmetrical ratio. We used this focal density asymmetry as a new imaging marker to divide testing cases into two groups of higher and lower focal density asymmetry. The first group included 70 cases in which 62.9% are positive, while the second group included 130 cases in which 43.1% are positive. The odds ratio is 2.24. As a result, this preliminary study supported the feasibility of applying a new focal density asymmetry based imaging marker to predict the risk of having mammography-occult cancers. The goal is to assist radiologists more effectively and accurately detect early subtle cancers using mammography and/or other adjunctive imaging modalities in the future.
Genetic Modifiers of Ovarian Cancer
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
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.
Golliot, F; Astagneau, P; Cassou, B; Okra, N; Rothan-Tondeur, M; Brücker, G
2001-12-01
To compute a risk index for nosocomial infection (NI) surveillance in geriatric long-term-care facilities (LTCFs) and rehabilitation facilities. Analysis of data collected during the French national prevalence survey on NIs conducted in 1996. Risk indices were constructed based on the patient case-mix defined according to risk factors for NIs identified in the elderly. 248 geriatric units in 77 hospitals located in northern France. All hospital inpatients on the day of the survey were included. Data from 11,254 patients were recorded. The overall rate of infected patients was 9.9%. Urinary tract, respiratory tract, and skin were the most common infection sites in both rehabilitation facilities and LTCFs. Eleven risk indices, categorizing patients in 3 to 7 levels of increasing NI risk, ranging from 2.7% to 36.2%, were obtained. Indices offered risk adjustment according to NI rate stratification and clinical relevance of risk factors such as indwelling devices, open bedsores, swallowing disorders, sphincter incontinence, lack of mobility, immunodeficiency, or rehabilitation activity. The optimal index should be tailored to the strategy selected for NI surveillance in geriatric facilities in view of available financial and human resources.
Raffel, Katie E; Beach, Leila Y; Lin, John; Berchuck, Jacob E; Abram, Shelly; Markle, Elizabeth; Patel, Shalini
2018-03-30
Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. The number of patients identified at high risk and rates of naloxone training/distribution. There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care.
Raffel, Katie E; Beach, Leila Y; Lin, John; Berchuck, Jacob E; Abram, Shelly; Markle, Elizabeth; Patel, Shalini
2018-01-01
Context Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. Objective To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. Design The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. Main Outcome Measures The number of patients identified at high risk and rates of naloxone training/distribution. Results There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). Conclusion This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care. PMID:29616917
Intermediate outcomes in randomized clinical trials: an introduction
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
Bhatia, Triptish; Gettig, Elizabeth A; Gottesman, Irving I; Berliner, Jonathan; Mishra, N N; Nimgaonkar, Vishwajit L; Deshpande, Smita N
2016-12-01
Schizophrenia (SZ) has an estimated heritability of 64-88%, with the higher values based on twin studies. Conventionally, family history of psychosis is the best individual-level predictor of risk, but reliable risk estimates are unavailable for Indian populations. Genetic, environmental, and epigenetic factors are equally important and should be considered when predicting risk in 'at risk' individuals. To estimate risk based on an Indian schizophrenia participant's family history combined with selected demographic factors. To incorporate variables in addition to family history, and to stratify risk, we constructed a regression equation that included demographic variables in addition to family history. The equation was tested in two independent Indian samples: (i) an initial sample of SZ participants (N=128) with one sibling or offspring; (ii) a second, independent sample consisting of multiply affected families (N=138 families, with two or more sibs/offspring affected with SZ). The overall estimated risk was 4.31±0.27 (mean±standard deviation). There were 19 (14.8%) individuals in the high risk group, 75 (58.6%) in the moderate risk and 34 (26.6%) in the above average risk (in Sample A). In the validation sample, risks were distributed as: high (45%), moderate (38%) and above average (17%). Consistent risk estimates were obtained from both samples using the regression equation. Familial risk can be combined with demographic factors to estimate risk for SZ in India. If replicated, the proposed stratification of risk may be easier and more realistic for family members. Copyright © 2016. Published by Elsevier B.V.
The Role of Intelligence and Education in the Division of Labor. Report No. 355.
ERIC Educational Resources Information Center
Gottfredson, Linda S.
This paper suggests that the occupational hierarchy is based on functionally important differences among workers and their jobs and proposes a modified functional theory of occupational stratification. Section I examines the role of education in social stratification. Sections II, III, and IV review (1) functions of schooling, (2) evidence about…
Using classified Landsat Thematic Mapper data for stratification in a statewide forest inventory
Mark H. Hansen; Daniel G. Wendt
2000-01-01
The 1998 Indiana/Illinois forest inventory (USDA Forest Service, Forest Inventory and Analysis (FIA)) used Landsat Thematic Mapper (TM) data for stratification. Classified images made by the National Gap Analysis Program (GAP) stratified FIA plots into four classes (nonforest, nonforest/ forest, forest/nonforest, and forest) based on a two pixel forest edge buffer zone...
Using Classified Landsat Thematic Mapper Data for Stratification in a Statewide Forest Inventory
Mark H. Hansen; Daniel G. Wendt
2000-01-01
The 1998 Indiana/Illinois forest inventory (USDA Forest Service, Forest Inventory and Analysis (FIA)) used Landsat Thematic Mapper (TM} data for stratification. Classified images made by the National Gap Analysis Program (GAP) stratified FIA plots into four classes (nonforest, nonforest/forest, forest/nonforest, and forest) based on a two pixel forest edge buffer zone...
Picturing Sex Education: Notes on the Politics of Visual Stratification
ERIC Educational Resources Information Center
Janssen, Diederik F.
2006-01-01
This paper addresses the scarcity of research on depictions and layout in sex education materials. It is argued that pictures and layout can inform an analysis of social stratification based on visual access. This process of social organization is located using four theoretical models. However these models do not lend themselves to a close reading…
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
Oerlemans, Anoek M; Burmanje, Marlot J; Franke, Barbara; Buitelaar, Jan K; Hartman, Catharina A; Rommelse, Nanda N J
2016-07-01
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Besides shared genetic factors, pre- and perinatal risk factors (PPFs) may determine if ASD, ADHD, or the combination of both disorders becomes manifest. This study aimed to test shared and unique involvement of PPFs for ASD and ADHD, using an approach that stratifies the sample into affected/unaffected offspring and single-incidence (SPX) versus multi-incidence (MPX) families. Pre- perinatal data based on retrospective parent-report were collected in 288 children (71 % males) from 31 SPX and 59 MPX ASD families, 476 children (65 % males) from 31 SPX and 171 MPX ADHD families, and 408 control children (42 % males). Except for large family size and more firstborns amongst affected offspring, no shared PFFs were identified for ASD and ADHD. PPFs predominantly related to ASD (maternal infections and suboptimal condition at birth) were more often reported in affected than unaffected siblings. PPFs associated with ADHD (low parental age, maternal diseases, smoking and stress) were shared between affected and unaffected siblings. Firstborn-ship was more frequent in SPX than MPX ASD probands. Our results suggest that the co-morbidity of ASD and ADHD is not likely explained by shared PPFs. Instead, PPFs might play a crucial role in the developmental pathways leading up to either disorder. PPFs in ADHD appear to index an increased shared risk, whereas in ASD PPFs possibly have a more determining role in the disorder. SPX-MPX stratification detected possible etiological differences in ASD families, but provided no deeper insight in the role of PPFs in ADHD.
Zhang, Yunlin; Wu, Zhixu; Liu, Mingliang; He, Jianbo; Shi, Kun; Zhou, Yongqiang; Wang, Mingzhu; Liu, Xiaohan
2015-05-15
From January 2010 to March 2014, detailed depth profiles of water temperature, dissolved oxygen (DO), and chromophoric dissolved organic matter (CDOM) were collected at three sites in Lake Qiandaohu, a large, deep subtropical reservoir in China. Additionally, we assessed the changes in DO stratification over the past 61 years (1953-2013) based on our empirical models and long-term air temperature and transparency data. The DO concentration never fell below 2 mg/L, the critical value for anoxia, and the DO depth profiles were closely linked to the water temperature depth profiles. In the stable stratification period in summer and autumn, the significant increase in CDOM in the metalimnion explained the decrease in DO due to the oxygen consumed by CDOM. Well-developed oxygen stratification was detected at the three sites in spring, summer and autumn and was associated with thermal stratification. Oxycline depth was significantly negatively correlated with daily air temperature and thermocline thickness but significantly positively correlated with thermocline depth during the stratification weakness period (July-February). However, there were no significant correlations among these parameters during the stratification formation period (March-June). The increase of 1.67 °C in yearly average daily air temperature between 1980 and 2013 and the decrease of 0.78 m in Secchi disk depth caused a decrease of 1.65 m and 2.78 m in oxycline depth, respectively, facilitating oxygen stratification and decreasing water quality. Therefore, climate warming has had a substantial effect on water quality through changing the DO regime in Lake Qiandaohu. Copyright © 2015 Elsevier Ltd. All rights reserved.
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.
Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru
2014-05-01
Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors. © 2013 Published by Elsevier Inc.
Effect of Neurocognition and Concussion on Musculoskeletal Injury Risk
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
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.
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.
Skinner, James E; Meyer, Michael; Dalsey, William C; Nester, Brian A; Ramalanjaona, George; O’Neil, Brian J; Mangione, Antoinette; Terregino, Carol; Moreyra, Abel; Weiss, Daniel N; Anchin, Jerry M; Geary, Una; Taggart, Pamela
2008-01-01
Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, ∼15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment. PMID:19209249
Mandalapu, Rao S; Remzi, Mesut; de Reijke, Theo M; Margulis, Vitaly; Palou, J; Kapoor, A; Yossepowitch, Ofer; Coleman, Jonathan; Traxer, Olivier; Anderson, J Kyle; Catto, James; de la Rosette, Jean; O'Brien, Timothy; Zlotta, Anthony; Matin, Surena F
2017-03-01
The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space. We update these publications and provide a summary of that original report. There are no prospective randomized controlled studies to support surgical management guidelines. A risk-stratified approach based on clinical, endoscopic, and biopsy assessment allows selection of patients who could benefit from kidney-preserving procedures with oncological outcomes potentially similar to radical nephroureterectomy with bladder cuff excision, with the added benefit of renal function preservation. These treatments are aided by the development of high-definition flexible digital URS, multi-biopsies with the aid of access sheaths and other tools, and promising developments in the use of adjuvant topical therapy. Recent developments in imaging, minimally invasive techniques, multimodality approaches, and adjuvant topical regimens and bladder cancer prevention raise the hope for improved risk stratification and may greatly improve the endoscopic treatment for low-risk UTUC.
Munretnam, Khamsigan; Alex, Livy; Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Kavitha, I S; Hashim, Nikman Adli Nor; Lye, Say Hean; Velapasamy, Sharmila; Ler, Lian Wee
2014-01-01
There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.
Saba, Luca; Banchhor, Sumit K; Suri, Harman S; Londhe, Narendra D; Araki, Tadashi; Ikeda, Nobutaka; Viskovic, Klaudija; Shafique, Shoaib; Laird, John R; Gupta, Ajay; Nicolaides, Andrew; Suri, Jasjit S
2016-08-01
This study presents AtheroCloud™ - a novel cloud-based smart carotid intima-media thickness (cIMT) measurement tool using B-mode ultrasound for stroke/cardiovascular risk assessment and its stratification. This is an anytime-anywhere clinical tool for routine screening and multi-center clinical trials. In this pilot study, the physician can upload ultrasound scans in one of the following formats (DICOM, JPEG, BMP, PNG, GIF or TIFF) directly into the proprietary cloud of AtheroPoint from the local server of the physician's office. They can then run the intelligent and automated AtheroCloud™ cIMT measurements in point-of-care settings in less than five seconds per image, while saving the vascular reports in the cloud. We statistically benchmark AtheroCloud™ cIMT readings against sonographer (a registered vascular technologist) readings and manual measurements derived from the tracings of the radiologist. One hundred patients (75 M/25 F, mean age: 68±11 years), IRB approved, Toho University, Japan, consisted of Left/Right common carotid artery (CCA) artery (200 ultrasound scans), (Toshiba, Tokyo, Japan) were collected using a 7.5MHz transducer. The measured cIMTs for L/R carotid were as follows (in mm): (i) AtheroCloud™ (0.87±0.20, 0.77±0.20); (ii) sonographer (0.97±0.26, 0.89±0.29) and (iii) manual (0.90±0.20, 0.79±0.20), respectively. The coefficient of correlation (CC) between sonographer and manual for L/R cIMT was 0.74 (P<0.0001) and 0.65 (P<0.0001), while, between AtheroCloud™ and manual was 0.96 (P<0.0001) and 0.97 (P<0.0001), respectively. We observed that 91.15% of the population in AtheroCloud™ had a mean cIMT error less than 0.11mm compared to sonographer's 68.31%. The area under curve for receiving operating characteristics was 0.99 for AtheroCloud™ against 0.81 for sonographer. Our Framingham Risk Score stratified the population into three bins as follows: 39% in low-risk, 70.66% in medium-risk and 10.66% in high-risk bins. Statistical tests were performed to demonstrate consistency, reliability and accuracy of the results. The proposed AtheroCloud™ system is completely reliable, automated, fast (3-5 seconds depending upon the image size having an internet speed of 180Mbps), accurate, and an intelligent, web-based clinical tool for multi-center clinical trials and routine telemedicine clinical care. Copyright © 2016 Elsevier Ltd. All rights reserved.
Application of a prediction model for work-related sensitisation in bakery workers.
Meijer, E; Suarthana, E; Rooijackers, J; Grobbee, D E; Jacobs, J H; Meijster, T; de Monchy, J G R; van Otterloo, E; van Rooy, F G B G J; Spithoven, J J G; Zaat, V A C; Heederik, D J J
2010-10-01
Identification of work-related allergy, particularly work-related asthma, in a (nationwide) medical surveillance programme among bakery workers requires an effective and efficient strategy. Bakers at high risk of having work-related allergy were indentified by use of a questionnaire-based prediction model for work-related sensitisation. The questionnaire was applied among 5,325 participating bakers. Sequential diagnostic investigations were performed only in those with an elevated risk. Performance of the model was evaluated in 674 randomly selected bakers who participated in the medical surveillance programme and the validation study. Clinical investigations were evaluated in the first 73 bakers referred at high risk. Overall 90% of bakers at risk of having asthma could be identified. Individuals at low risk showed 0.3-3.8% work-related respiratory symptoms, medication use or absenteeism. Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals. This prediction based stratification procedure appeared effective in detecting work-related allergy among bakers and can accurately be used for periodic examination, especially in small enterprises where delivery of adequate care is difficult. This approach may contribute to cost reduction.
2010-01-01
Background The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care. Methods The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose. Results The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions. Conclusions The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes. PMID:20465815
The physical phenotype of frailty for risk stratification of older medical inpatients.
Forti, P; Maioli, F; Zagni, E; Lucassenn, T; Montanari, L; Maltoni, B; Luca Pirazzoli, G; Bianchi, G; Zoli, M
2014-12-01
To determine the usefulness of physical phenotype of frailty, cognitive impairment, and serum albumin for risk stratification of elderly medical impatients. Prospective, observational cohort study. A general internal medicine unit of a university hospital in Italy. Inpatients with an average age of 80.8 ± 7.5 yr (N = 470). Frailty was defined using the Study of Osteoporotic Fractures Index, a parsimonious version of the physical phenotype (two of the following markers: weight loss, inability to rise five times from a chair, and exhaustion). Two frailty markers from non-physical dimensions were also evaluated: cognitive impairment (Mini-Cog score < 3) and low serum albumin on ward admission (< 3,5 gr/dl). Logistic regression adjusted for preadmission and admission-related confounders was used to investigate whether the physical phenotype of frailty and the two non-physical markers were associated with ward length of stay and unfavorable discharge (death plus any other ward discharge disposition different from direct return home). Areas Under the receiver operating characteristic Curve (AUCs) and Likelihood Ratios (LRs) were used for evaluation of discriminatory ability and clinical usefulness of significant predictors. The physical phenotype of frailty was associated with both study outcomes (p < 0.010) but the association was mainly mediated by chair standing ability. Non-physical markers were associated only with unfavourable discharge (p < 0.001). All of these predictors, either alone or in combination, had poor discriminatory ability (AUCs < 0.70) and poor clinical usefulness (+LRs near 1) for the study outcomes. The physical phenotype of frailty appears of limited clinical use for risk stratification of older medical inpatients. Combination with markers from non-physical dimensions does not improve its prognostic abilities.
Mental health in primary care: an evaluation using the Item Response Theory.
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.
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.
Predicting relapse risk in childhood acute lymphoblastic leukaemia.
Teachey, David T; Hunger, Stephen P
2013-09-01
Intensive multi-agent chemotherapy regimens and the introduction of risk-stratified therapy have substantially improved cure rates for children with acute lymphoblastic leukaemia (ALL). Current risk allocation schemas are imperfect, as some children are classified as lower-risk and treated with less intensive therapy relapse, while others deemed higher-risk are probably over-treated. Most cooperative groups previously used morphological clearance of blasts in blood and marrow during the initial phases of chemotherapy as a primary factor for risk group allocation; however, this has largely been replaced by the detection of minimal residual disease (MRD). Other than age and white blood cell count (WBC) at presentation, many clinical variables previously used for risk group allocation are no longer prognostic, as MRD and the presence of sentinel genetic lesions are more reliable at predicting outcome. Currently, a number of sentinel genetic lesions are used by most cooperative groups for risk stratification; however, in the near future patients will probably be risk-stratified using genomic signatures and clustering algorithms, rather than individual genetic alterations. This review will describe the clinical, biological, and response-based features known to predict relapse risk in childhood ALL, including those currently used and those likely to be used in the near future to risk-stratify therapy. © 2013 John Wiley & Sons Ltd.
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
Levitzky, Benjamin E; Brown, Colin C; Heeren, Timothy C; Schroy, Paul C
2011-06-01
Tailoring the use of screening colonoscopy based on the risk of advanced proximal neoplasia (APN) has been advocated as a strategy for reducing demand and optimizing effectiveness. A 7-point index based on age, sex, and distal findings at sigmoidoscopy has been proposed that stratifies individuals into low, intermediate, and high-risk categories. The aim of this cross-sectional analysis was to determine the validity of this index, which was originally derived and validated among mostly whites, for black and Hispanic patients. Data, including age, sex, colonoscopic findings, and pathology, were collected retrospectively from 1,481 white, 1,329 black, and 689 Hispanic asymptomatic, average-risk patients undergoing screening colonoscopy between 2000 and 2005. Cumulative scores ranging from 0 to 7 were derived for each subject and categorized as low, intermediate, or high risk. Rates of APN were assessed for each risk category after stratification by race/ethnicity. Index performance was assessed using the C-statistic and compared across the three racial groups. Rates of APN among patients categorized as low, intermediate, or high risk increased from 1.0 to 2.8 to 3.7% for whites, 1.0 to 2.2 to 4.2% for blacks, and 0.6 to 1.9 to 3.7% for Hispanics. The index performed similarly for all three groups, but showed limited ability to discriminate low from intermediate-risk patients, with C-statistic values of 0.62 for whites, 0.63 for blacks, and 0.68 for Hispanics. A risk index based on age, sex, and distal endoscopic findings has limited ability to discriminate low from intermediate-risk white, black, and Hispanic patients for APN.
Wolff-Parkinson-White syndrome: a single exercise stress test might be misleading.
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.
Inactive fibrotic lesions versus pulmonary tuberculosis with negative bacteriology.
Solsona Peiró, Jordi; de Souza Galvão, Maria Luiza; Altet Gómez, Maria Neus
2014-11-01
This article analyzes the concept of inactive fibrotic lesions of presumed tuberculous origin (old healed tuberculosis), defined by radiological characteristics and a positive tuberculin skin test (TST), and we examine the evidence-based foundation for the indication of treatment of latent tuberculosis infection in these cases. We explore the risk of reactivation in older and recent literature, and the problems raised by the differential diagnosis with active tuberculosis with negative bacteriology. We also analyze data on the prevalence of fibrotic lesions in the recent literature. We examine the possible role of Interferon Gamma Release Assays (IGRAs) versus TST and other molecular antigen detection techniques in sputum that can aid in establishing the diagnosis and we discuss the current indications for chemoprophylaxis and the different options available. We propose diagnostic guidelines and therapeutic algorithms based on risk stratification by age and other factors in the management of radiological lesions that raise a differential diagnosis between fibrotic lesions and active pulmonary tuberculosis with negative bacteriology. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.
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.
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.