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Precision medicine risk prediction

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https://www.readbyqxmd.com/read/28636403/applying-precision-medicine-to-trial-design-using-physiology-extracorporeal-co2-removal-for-ards
#1
Ewan C Goligher, Marcelo B P Amato, Arthur S Slutsky
In clinical trials of therapies for ARDS, the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultra-protective ventilation in ARDS...
June 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28624849/the-accuracy-of-68-ga-psma-pet-ct-in-primary-lymph-node-staging-in-high-risk-prostate-cancer
#2
Can Öbek, Tünkut Doğanca, Emre Demirci, Meltem Ocak, Ali Rıza Kural, Asıf Yıldırım, Uğur Yücetaş, Çetin Demirdağ, Sarper M Erdoğan, Levent Kabasakal
PURPOSE: To assess the diagnostic accuracy of (68)Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging. METHODS: This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included...
June 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28598966/joint-modeling-of-genetically-correlated-diseases-and-functional-annotations-increases-accuracy-of-polygenic-risk-prediction
#3
Yiming Hu, Qiongshi Lu, Wei Liu, Yuhua Zhang, Mo Li, Hongyu Zhao
Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS) in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes...
June 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28594818/leveraging-functional-annotations-in-genetic-risk-prediction-for-human-complex-diseases
#4
Yiming Hu, Qiongshi Lu, Ryan Powles, Xinwei Yao, Can Yang, Fang Fang, Xinran Xu, Hongyu Zhao
Genetic risk prediction is an important goal in human genetics research and precision medicine. Accurate prediction models will have great impacts on both disease prevention and early treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome wide association studies (GWAS), genetic risk prediction accuracy remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes in the presence of linkage disequilibrium...
June 8, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28573413/-molecular-biomarkers-and-prognostic-factors-for-prostate-cancer
#5
A Kretschmer, Y Tolkach, J Ellinger, G Kristiansen
In the era of personalized medicine and precision oncology, innovative genetic biomarkers are of emerging interest to close the diagnostic and prognostic gap that is left by current clinicopathologic risk classifiers. The current review article summarizes evidence regarding prognostic and predictive genetic biomarkers that are currently in widespread clinical use at initial diagnosis as well as following definitive treatment of prostate cancer. We give a brief summary about basic principles of biomarker research studies and present current data for the Progensa PC3 test, TMPRSS2:ERG gene fusion, ConfirmMDx, Prolaris gene panel, OncotypeDX Genomic Prostate score, and Decipher classifier...
June 1, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28570546/electrophysiological-analysis-of-human-pluripotent-stem-cell-derived-cardiomyocytes-hpsc-cms-using-multi-electrode-arrays-meas
#6
Luca Sala, Dorien Ward-van Oostwaard, Leon G J Tertoolen, Christine L Mummery, Milena Bellin
Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine...
May 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28562095/the-advancement-of-multidimensional-qsar-for-novel-drug-discovery-where-are-we-headed
#7
Tao Wang, Xin-Song Yuan, Mian-Bin Wu, Jian-Ping Lin, Li-Rong Yang
The Multidimensional quantitative structure-activity relationship (multidimensional-QSAR) method is one of the most popular computational methods employed to predict interesting biochemical properties of existing or hypothetical molecules. With continuous progress, the QSAR method has made remarkable success in various fields, such as medicinal chemistry, material science and predictive toxicology. Areas covered: In this review, the authors cover the basic elements of multidimensional -QSAR including model construction, validation and application...
June 8, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28561668/established-and-novel-prognostic-biomarkers-in-multiple-myeloma
#8
Mark Bustoros, Tarek H Mouhieddine, Alexandre Detappe, Irene M Ghobrial
Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by notable interpatient heterogeneity. There have been important advances in therapy and overall survival, but some patients with high-risk features still have poor survival rates. Therefore, accurate identification of this subset of patients has been integral to improvement of patient outcome. During the last few years, cytogenetics, gene expression profiling, MRI and PET/CT, as well as serum free light chain assays have been used as accurate biomarkers to better characterize the diverse course and outcome of the disease...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28560038/mutational-status-predicts-the-risk-of-thromboembolic-events-in-lung-adenocarcinoma
#9
Elsa Davidsson, Nicola Murgia, Cristian Ortiz-Villalón, Emil Wiklundh, Magnus Sköld, Karl Gustav Kölbeck, Giovanni Ferrara
BACKGROUND: Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR and rearrangement in the ALK genes identify specific subgroups of patients. Aim of this study was to investigate the role of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status on the risk of venous thromboembolism (VTE) in lung adenocarcinoma...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28559747/structure-leveraged-methods-in-breast-cancer-risk-prediction
#10
Jun Fan, Yirong Wu, Ming Yuan, David Page, Jie Liu, Irene M Ong, Peggy Peissig, Elizabeth Burnside
Predicting breast cancer risk has long been a goal of medical research in the pursuit of precision medicine. The goal of this study is to develop novel penalized methods to improve breast cancer risk prediction by leveraging structure information in electronic health records. We conducted a retrospective case-control study, garnering 49 mammography descriptors and 77 high-frequency/low-penetrance single-nucleotide polymorphisms (SNPs) from an existing personalized medicine data repository. Structured mammography reports and breast imaging features have long been part of a standard electronic health record (EHR), and genetic markers likely will be in the near future...
December 2016: Journal of Machine Learning Research: JMLR
https://www.readbyqxmd.com/read/28524737/utilizing-next-generation-sequencing-in-the-management-of-multiple-myeloma
#11
Marta Lionetti, Antonino Neri
Multiple myeloma (MM) is a bone marrow plasma cell malignancy characterized by wide clinical presentation and heterogeneous genetic background. Despite the recent advances in patient outcome, new markers are needed for improving risk prediction and choice of a more appropriate therapy. In this perspective, the genetic makeup of MM cells is being better characterized by means of next-generation sequencing (NGS) technologies. Areas covered: The authors discuss how the application of NGS has improved our knowledge of MM biology by discovering its mutational landscape, identifying the operating mutational processes, and revealing the clonal composition of tumors and the dynamics of its evolution; and how this can have important clinical implications in terms of prognostication, therapeutic choices, and response assessment...
July 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28523274/identification-of-braf-positive-cases-based-on-whole-slide-image-analysis
#12
Vlad Popovici, Aleš Křenek, Eva Budinská
A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28499030/moderator-s-view-predictive-models-a-prelude-to-precision-nephrology
#13
Carmine Zoccali
Appropriate diagnosis is fundamental in medicine because it sets the basis for the prediction of disease outcome at the single patient level (prognosis) and decisions regarding the most appropriate therapy. However, given the large series of social, clinical and biological factors that determine the likelihood of an individual's future outcome, prognosis only partly depends on diagnosis and aetiology and treatment is not decided solely on the basis of the underlying diagnosis. This issue is crucial in multifactorial diseases like atherosclerosis, where the use of statins has now shifted from 'treating hypercholesterolaemia' to 'treating the risk of adverse cardiovascular events'...
May 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28497916/emerging-endotypes-of-chronic-rhinosinusitis-and-its-application-to-precision-medicine
#14
REVIEW
Dae Woo Kim, Seong H Cho
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS...
July 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28497027/data-based-radiation-oncology-design-of-clinical-trials-in-the-toxicity-biomarkers-era
#15
REVIEW
David Azria, Ariane Lapierre, Sophie Gourgou, Dirk De Ruysscher, Jacques Colinge, Philippe Lambin, Muriel Brengues, Tim Ward, Søren M Bentzen, Hubert Thierens, Tiziana Rancati, Christopher J Talbot, Ana Vega, Sarah L Kerns, Christian Nicolaj Andreassen, Jenny Chang-Claude, Catharine M L West, Corey M Gill, Barry S Rosenstein
The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28493232/anthracycline-induced-cardiotoxicity-biomarkers-and-omics-technology-in-the-era-of-patient-specific-care
#16
REVIEW
Shayan Moazeni, Martin Cadeiras, Eric H Yang, Mario C Deng, Kim-Lien Nguyen
Anthracyclines are highly effective against a variety of malignancies. However, their dose-dependent cardiotoxic effects can potentially limit their use. In the past decade, serum biomarkers have been used to diagnose, monitor, predict, and prognosticate disease. Biomarkers such as cardiac troponin and natriuretic peptides have some predictive value, but still lack reliability in this patient population. Novel biomarkers such as galectin-3, soluble ST-2 proteins, myeloperoxidase, and fibrocytes are being explored as potential biomarkers to reliably predict the onset of cardiotoxicity...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28490744/precision-radiology-predicting-longevity-using-feature-engineering-and-deep-learning-methods-in-a-radiomics-framework
#17
Luke Oakden-Rayner, Gustavo Carneiro, Taryn Bessen, Jacinto C Nascimento, Andrew P Bradley, Lyle J Palmer
Precision medicine approaches rely on obtaining precise knowledge of the true state of health of an individual patient, which results from a combination of their genetic risks and environmental exposures. This approach is currently limited by the lack of effective and efficient non-invasive medical tests to define the full range of phenotypic variation associated with individual health. Such knowledge is critical for improved early intervention, for better treatment decisions, and for ameliorating the steadily worsening epidemic of chronic disease...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28456503/novel-oxytocin-receptor-variants-in-laboring-women-requiring-high-doses-of-oxytocin
#18
Erin L Reinl, Zane A Goodwin, Nandini Raghuraman, Grace Y Lee, Erin Y Jo, Beakal M Gezahegn, Meghan K Pillai, Alison G Cahill, Cristina De Guzman Strong, Sarah K England
BACKGROUND: Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. OBJECTIVES: To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. STUDY DESIGN: Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose requiring, n = 83) or ≥20 mU/min (high-dose requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA...
April 26, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28439188/next-generation-sequencing-reveals-high-prevalence-of-brca1-and-brca2-variants-of-unknown-significance-in-early-onset-breast-cancer-in-african-american-women
#19
Luisel Ricks-Santi, J Tyson McDonald, Bert Gold, Michael Dean, Nicole Thompson, Muneer Abbas, Bradford Wilson, Yasmine Kanaan, Tammey J Naab, Georgia Dunston
BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer...
2017: Ethnicity & Disease
https://www.readbyqxmd.com/read/28432351/early-measurement-of-il-10-predicts-the-outcomes-of-patients-with-acute-respiratory-distress-syndrome-receiving-extracorporeal-membrane-oxygenation
#20
Chia-Hsiung Liu, Shuenn-Wen Kuo, Wen-Je Ko, Pi-Ru Tsai, Shu-Wei Wu, Chien-Heng Lai, Chih-Hsien Wang, Yih-Sharng Chen, Pei-Lung Chen, Tze-Tze Liu, Shu-Chien Huang, Tzuu-Shuh Jou
Patients diagnosed with acute respiratory distress syndrome are generally severely distressed and associated with high morbidity and mortality despite aggressive treatments such as extracorporeal membrane oxygenation (ECMO) support. To identify potential biomarker of predicting value for appropriate use of this intensive care resource, plasma interleukin-10 along with relevant inflammatory cytokines and immune cell populations were examined during the early and subsequent disease courses of 51 critically ill patients who received ECMO support...
April 21, 2017: Scientific Reports
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