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Precision medicine risk prediction

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https://www.readbyqxmd.com/read/28283684/pharmacogenetics-in-type-2-diabetes-precision-medicine-or-discovery-tool
#1
REVIEW
Jose C Florez
In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment...
March 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28281838/diagnostic-function-of-the-neuroinflammatory-biomarker-ykl-40-in-alzheimer-s-disease-and-other-neurodegenerative-diseases
#2
Filippo Baldacci, Simone Lista, Enrica Cavedo, Ubaldo Bonuccelli, Harald Hampel
Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 - an indicator of microglial activation - has recently been identified by proteomic studies as a candidate biomarker for Alzheimer's disease (AD). Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia...
March 20, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28273476/predicting-polygenic-obesity-using-genetic-information
#3
REVIEW
Ruth J F Loos, A Cecile J W Janssens
Except in rare cases, obesity tends to be a consequence of both an unhealthy lifestyle and a genetic susceptibility to gain weight. With more than 200 common genetic variants identified, there is a growing interest in developing personalized preventive and treatment strategies to predict an individual's obesity risk. We review the literature on the prediction of obesity and show that models based on the established genetic variants have poorer predictive ability than traditional predictors, such as family history of obesity and childhood obesity...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28261156/a-decision-tree-analysis-of-diabetic-foot-amputation-risk-in-indian-patients
#4
Prasad Umesh Kasbekar, Pranay Goel, Shailaja Prakash Jadhav
AIM: The aim of this study is to create an evidence-based tool that guides the risk of amputation in diabetic foot patients. MATERIALS AND METHODS: Hospital records of 301 diabetic foot patients were examined retrospectively for explanatory variables of foot amputation decisions. The study included all patients with a lower limb ulcer with a known history of diabetes mellitus or those diagnosed post-admission. The dataset was analyzed, and a risk scoring system was constructed using the decision tree algorithm, C5...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28245528/corrected-roc-analysis-for-misclassified-binary-outcomes
#5
Matthew Zawistowski, Jeremy B Sussman, Timothy P Hofer, Douglas Bentley, Rodney A Hayward, Wyndy L Wiitala
Creating accurate risk prediction models from Big Data resources such as Electronic Health Records (EHRs) is a critical step toward achieving precision medicine. A major challenge in developing these tools is accounting for imperfect aspects of EHR data, particularly the potential for misclassified outcomes. Misclassification, the swapping of case and control outcome labels, is well known to bias effect size estimates for regression prediction models. In this paper, we study the effect of misclassification on accuracy assessment for risk prediction models and find that it leads to bias in the area under the curve (AUC) metric from standard ROC analysis...
February 28, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28155639/inferring-new-indications-for-approved-drugs-via-random-walk-on-drug-disease-heterogenous-networks
#6
Hui Liu, Yinglong Song, Jihong Guan, Libo Luo, Ziheng Zhuang
BACKGROUND: Since traditional drug research and development is often time-consuming and high-risk, there is an increasing interest in establishing new medical indications for approved drugs, referred to as drug repositioning, which provides a relatively low-cost and high-efficiency approach for drug discovery. With the explosive growth of large-scale biochemical and phenotypic data, drug repositioning holds great potential for precision medicine in the post-genomic era. It is urgent to develop rational and systematic approaches to predict new indications for approved drugs on a large scale...
December 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28152863/breast-oncology-precision-medicine-genomic-testing-and-treatment-at-the-population-level
#7
Yun Li, Allison W Kurian, Steven J Katz
288 Background: The 21-gene assay used to estimate breast cancer recurrence and tailor chemotherapy (chemo) receipt has demonstrated predictive validity and clinical utility. Yet it is unclear how involved patients are in the decision to perform the test, or how oncologists use results to recommend systemic chemo. We examined the patient experience with assay testing, physician recommendations, and chemo receipt based on test results. METHODS: The iCanCare study surveyed a weighted random sample of newly diagnosed patients with early-stage breast cancer who were treated in 2013-14, identified through the population-based SEER registries of Los Angeles and Georgia about 3 months after surgical treatment, and merged with SEER data (N=2632, RR=70%)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28146085/gene-environment-interactions-in-preventive-medicine-current-status-and-expectations-for-the-future
#8
REVIEW
Hiroto Narimatsu
The progression of many common disorders involves a complex interplay of multiple factors, including numerous different genes and environmental factors. Gene-environmental cohort studies focus on the identification of risk factors that cannot be discovered by conventional epidemiological methodologies. Such epidemiological methodologies preclude precise predictions, because the exact risk factors can be revealed only after detailed analyses of the interactions among multiple factors, that is, between genes and environmental factors...
January 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28137987/diagnostic-performance-of-placental-growth-factor-in-women-with-suspected-preeclampsia-attending-antenatal-facilities-in-maputo-mozambique
#9
U Vivian Ukah, Francisco Mbofana, Beatriz Manriquez Rocha, Osvaldo Loquiha, Chishamiso Mudenyanga, Momade Usta, Marilena Urso, Sharla Drebit, Laura A Magee, Peter von Dadelszen
In well-resourced settings, reduced circulating maternal-free placental growth factor (PlGF) aids in either predicting or confirming the diagnosis of preeclampsia, fetal growth restriction, stillbirth, preterm birth, and delivery within 14 days of testing when preeclampsia is suspected. This blinded, prospective cohort study of maternal plasma PlGF in women with suspected preeclampsia was conducted in antenatal clinics in Maputo, Mozambique. The primary outcome was the clinic-to-delivery interval. Other outcomes included: confirmed diagnosis of preeclampsia, transfer to higher care, mode of delivery, intrauterine fetal death, preterm birth, and low birth weight...
March 2017: Hypertension
https://www.readbyqxmd.com/read/28130475/breast-cancer-screening-in-the-precision-medicine-era-risk-based-screening-in-a-population-based-trial
#10
REVIEW
Yiwey Shieh, Martin Eklund, Lisa Madlensky, Sarah D Sawyer, Carlie K Thompson, Allison Stover Fiscalini, Elad Ziv, Laura J Van't Veer, Laura J Esserman, Jeffrey A Tice
Ongoing controversy over the optimal approach to breast cancer screening has led to discordant professional society recommendations, particularly in women age 40 to 49 years. One potential solution is risk-based screening, where decisions around the starting age, stopping age, frequency, and modality of screening are based on individual risk to maximize the early detection of aggressive cancers and minimize the harms of screening through optimal resource utilization. We present a novel approach to risk-based screening that integrates clinical risk factors, breast density, a polygenic risk score representing the cumulative effects of genetic variants, and sequencing for moderate- and high-penetrance germline mutations...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28124081/lifestyle-and-precision-diabetes-medicine-will-genomics-help-optimise-the-prediction-prevention-and-treatment-of-type-2-diabetes-through-lifestyle-therapy
#11
REVIEW
Paul W Franks, Alaitz Poveda
Precision diabetes medicine, the optimisation of therapy using patient-level biomarker data, has stimulated enormous interest throughout society as it provides hope of more effective, less costly and safer ways of preventing, treating, and perhaps even curing the disease. While precision diabetes medicine is often framed in the context of pharmacotherapy, using biomarkers to personalise lifestyle recommendations, intended to lower type 2 diabetes risk or to slow progression, is also conceivable. There are at least four ways in which this might work: (1) by helping to predict a person's susceptibility to adverse lifestyle exposures; (2) by facilitating the stratification of type 2 diabetes into subclasses, some of which may be prevented or treated optimally with specific lifestyle interventions; (3) by aiding the discovery of prognostic biomarkers that help guide timing and intensity of lifestyle interventions; (4) by predicting treatment response...
January 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28116861/unprotected-left-main-disease-and-percutaneous-intervention-a-prototype-for-precision-medicine
#12
EDITORIAL
Arka Chatterjee, William B Hillegass
The SYNTAX Score based on angiographic findings is an actionable risk prediction model helping guide treatment for significant unprotected left main disease. Adding the clinical factor based EuroSCORE to SYNTAX improves outcome prediction for percutaneous coronary intervention of unprotected left main disease. Prediction models are an increasingly useful tool permitting cardiologists to optimize patient outcomes through "personalized" or precision medicine.
January 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28109319/for-robust-big-data-analyses-a-collection-of-150-important-pro-metastatic-genes
#13
REVIEW
Yan Mei, Jun-Ping Yang, Chao-Nan Qian
Metastasis is the greatest contributor to cancer-related death. In the era of precision medicine, it is essential to predict and to prevent the spread of cancer cells to significantly improve patient survival. Thanks to the application of a variety of high-throughput technologies, accumulating big data enables researchers and clinicians to identify aggressive tumors as well as patients with a high risk of cancer metastasis. However, there have been few large-scale gene collection studies to enable metastasis-related analyses...
January 21, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28078311/common-variant-rs356182-near-snca-defines-a-parkinson-s-disease-endophenotype
#14
Christine A Cooper, Nimansha Jain, Michael D Gallagher, Daniel Weintraub, Sharon X Xie, Yosef Berlyand, Alberto J Espay, Joseph Quinn, Karen L Edwards, Thomas Montine, Vivianna M Van Deerlin, John Trojanowski, Cyrus P Zabetian, Alice S Chen-Plotkin
OBJECTIVE: Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. METHODS: We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#15
REVIEW
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
https://www.readbyqxmd.com/read/28067676/severe-community-acquired-pneumonia-optimal-management
#16
Davide Leoni, Jordi Rello
PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is the leading cause of mortality among infectious diseases. Several efforts have been implemented to achieve better outcomes, but an important proportion of patients continue dying. This review focuses on the newest research on prognostic factors and diagnostics, opening new perspectives in the management of CAP. RECENT FINDINGS: CAP survival improved in recent years despite an increasing incidence of severe presentations...
April 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28059156/genetic-screening-in-arterial-hypertension
#17
REVIEW
Gian Paolo Rossi, Giulio Ceolotto, Brasilina Caroccia, Livia Lenzini
Studies involving adoptive families and twins have demonstrated the genetic basis of hypertension and shown that genetic factors account for about 40% of the variance in blood pressure among individuals. Arterial hypertension is genetically complex: multiple genes influence the blood pressure phenotype through allelic effects from single genes and gene-gene interactions. Moreover, environmental factors also modify the blood pressure phenotype. This complexity explains why the identification of the underlying genes has not been as successful in hypertension as in other diseases (such as type 1 and type 2 diabetes mellitus)...
January 6, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28035251/role-of-circulating-free-dna-in-colorectal-cancer
#18
REVIEW
Alexios Matikas, Alexandra Voutsina, Maria Trypaki, Vassilis Georgoulias
The gradual elucidation of the underlying biology of colorectal cancer has provided new insights and therapeutic options for patients with metastatic disease which are selected according to predictive biomarkers. This precision medicine paradigm, however, is incomplete since not all eligible patients respond to these agents and prognostic stratification is largely based on clinicopathologic variants. Importantly, no robust data exist to help properly select patients with localized disease at high risk for recurrence and most likely to benefit from adjuvant chemotherapy...
December 15, 2016: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28018236/host-microbiome-interaction-and-cancer-potential-application-in-precision-medicine
#19
REVIEW
Alejandra V Contreras, Benjamin Cocom-Chan, Georgina Hernandez-Montes, Tobias Portillo-Bobadilla, Osbaldo Resendis-Antonio
It has been experimentally shown that host-microbial interaction plays a major role in shaping the wellness or disease of the human body. Microorganisms coexisting in human tissues provide a variety of benefits that contribute to proper functional activity in the host through the modulation of fundamental processes such as signal transduction, immunity and metabolism. The unbalance of this microbial profile, or dysbiosis, has been correlated with the genesis and evolution of complex diseases such as cancer...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27975229/introduction-to-clinical-proteomics
#20
John E Wiktorowicz, Allan R Brasier
Within the context of this section, biomarkers are defined as a panel of proteins and peptides that are predictive of the risk for developing a pathological condition. It is important to note here that the use of the descriptor 'panel' is purposeful in that single "biomarkers" are rarely sufficient to permit accurate prediction of a pathological condition. More specifically, the primary application of a biomarker panel is that it serves as a molecular indicator of the severity of a disease or its early response to treatment...
2016: Advances in Experimental Medicine and Biology
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