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Precision medicine risk prediction

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https://www.readbyqxmd.com/read/29790107/the-role-of-pharmacogenomics-in-bipolar-disorder-moving-towards-precision-medicine
#1
REVIEW
Claudia Pisanu, Urs Heilbronner, Alessio Squassina
Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions...
May 22, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29784506/predicting-prognosis-in-resected-esophageal-squamous-cell-carcinoma-using-a-clinical-nomogram-and-recursive-partitioning-analysis
#2
Yuzhen Zheng, Shenshen Fu, Tiancheng He, Qihang Yan, Wenyu Di, Junye Wang
BACKGROUND: Development demand of precise medicine in resectable esophageal squamous cell carcinoma (ESCC) require to recognize patients at high risk treated by surgery alone. Thus, our aim was to construct a clinical nomogram and recursive partitioning analysis (RPA) to predict long-term survival in ESCC treated by surgery alone. METHODS: Based on the patients with ESCC who treated by three-incisional esophagectomy and two-field lymphadenectomy alone, we identified and integrated significant prognostic factors for survival to build a nomogram...
April 24, 2018: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29783934/the-impact-of-pharmacokinetic-gene-profiles-across-human-cancers
#3
Michael T Zimmermann, Terry M Therneau, Jean-Pierre A Kocher
BACKGROUND: The right drug to the right patient at the right time is one of the ideals of Individualized Medicine (IM) and remains one of the most compelling promises of the post-genomic age. The addition of genomic information is expected to increase the precision of an individual patient's treatment, resulting in improved outcomes. While pilot studies have been encouraging, key aspects of interpreting tumor genomics information, such as somatic activation of drug transport or metabolism, have not been systematically evaluated...
May 21, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29778312/biomarker-signatures-of-sickle-cell-disease-severity
#4
Mengtian Du, Sarah Van Ness, Victor Gordeuk, Sayed M Nouraie, Sergei Nekhai, Mark Gladwin, Martin H Steinberg, Paola Sebastiani
Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data...
May 16, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29756121/critically-dysregulated-signaling-pathways-and-clinical-utility-of-the-pathway-biomarkers-in-lymphoid-malignancies
#5
REVIEW
Rui-Fang Sun, Qian-Qian Yu, Ken H Young
Accumulating evidence confirmed that many dysregulated signaling pathways and aberrant genetic alterations contribute to the oncogenesis and heterogeneity of lymphoid malignancies. Therapeutically targeting dysregulating signaling pathways and their hidden oncogenic biomarkers are becoming available, but did not show desired therapeutic effect in current clinical practice. It is meaningful to further understand the underlying mechanisms of the dysregulated signaling pathways and to address the potential utility of pathway-related biomarkers...
March 2018: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29740579/the-role-of-genetics-in-advancing-precision-medicine-for-alzheimer-s-disease-a-narrative-review
#6
REVIEW
Yun Freudenberg-Hua, Wentian Li, Peter Davies
Alzheimer's disease (AD) is the most common type of dementia, which has a substantial genetic component. AD affects predominantly older people. Accordingly, the prevalence of dementia has been rising as the population ages. To date, there are no effective interventions that can cure or halt the progression of AD. The only available treatments are the management of certain symptoms and consequences of dementia. The current state-of-the-art medical care for AD comprises three simple principles: prevent the preventable, achieve early diagnosis, and manage the manageable symptoms...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29738334/precision-medicine-and-lymphoma
#7
James A Heward, Emil A Kumar, Koorosh Korfi, Jessica Okosun, Jude Fitzgibbon
PURPOSE OF REVIEW: The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment. RECENT FINDINGS: DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity...
May 5, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29733732/lack-of-diversity-in-genomic-databases-is-a-barrier-to-translating-precision-medicine-research-into-practice
#8
Latrice G Landry, Nadya Ali, David R Williams, Heidi L Rehm, Vence L Bonham
Precision medicine is predicted to revolutionize the clinical practice of medicine, in part by using molecular biomarkers to assess patients' risk, prognosis, and therapeutic response more precisely. However, reliance on biomarkers could present challenges for diverse populations that are not equitably represented in precision medicine research. We examined the populations included in genomic studies whose data were available in the following two public databases: the Genome-Wide Association Study Catalog and the database of Genotypes and Phenotypes...
May 2018: Health Affairs
https://www.readbyqxmd.com/read/29730081/eosinophilic-oesophagitis-endotype-classification-by-molecular-clinical-and-histopathological-analyses-a-cross-sectional-study
#9
Tetsuo Shoda, Ting Wen, Seema S Aceves, J Pablo Abonia, Dan Atkins, Peter A Bonis, Julie M Caldwell, Kelley E Capocelli, Christina L Carpenter, Margaret H Collins, Evan S Dellon, Michael D Eby, Nirmala Gonsalves, Sandeep K Gupta, Gary W Falk, Ikuo Hirano, Paul Menard-Katcher, Jonathan T Kuhl, Jeffrey P Krischer, John Leung, Vincent A Mukkada, Jonathan M Spergel, Michael P Trimarchi, Guang-Yu Yang, Nives Zimmermann, Glenn T Furuta, Marc E Rothenberg
BACKGROUND: Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical-pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. METHODS: We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers...
May 2, 2018: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29728395/-scn5a-na-v-1-5-variant-functional-perturbation-and-clinical-presentation-variants-of-a-certain-significance
#10
Brett M Kroncke, Andrew M Glazer, Derek K Smith, Jeffrey D Blume, Dan M Roden
BACKGROUND: Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel SCN5A (protein NaV 1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare SCN5A variants also occur in ≈1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance...
May 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29714580/advancing-drug-safety-through-prospective-pharmacovigilance
#11
Peter J Pitts, Hervé Le Louet
Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time...
January 1, 2018: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/29700787/exploring-the-use-of-molecular-biomarkers-for-precision-medicine-in-age-related-macular-degeneration
#12
REVIEW
Laura Lorés-Motta, Eiko K de Jong, Anneke I den Hollander
Precision medicine aims to improve patient care by adjusting medication to each patient's individual needs. Age-related macular degeneration (AMD) is a heterogeneous eye disease in which several pathways are involved, and the risk factors driving the disease differ per patient. As a consequence, precision medicine holds promise for improved management of this disease, which is nowadays a main cause of vision loss in the elderly. In this review, we provide an overview of the studies that have evaluated the use of molecular biomarkers to predict response to treatment in AMD...
April 26, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29692203/a-new-generalized-cycle-ergometry-equation-for-predicting-maximal-oxygen-uptake-the-fitness-registry-and-the-importance-of-exercise-national-database-friend
#13
Peter Kokkinos, Leonard A Kaminsky, Ross Arena, Jiajia Zhang, Jonathan Myers
Background To develop a clinically applicable equation derived from direct assessment of maximal oxygen uptake (VO2max ) to predict VO2max assessed indirectly during cycle ergometry. Design VO2max was assessed by open-circuit spirometry during a graded maximal exercise test using cycle ergometry. Multivariable linear regression analysis was applied to identify the most relevant variables and construct the best prediction model for VO2max using a random sample of 70% from each of the following age categories: <40, 40-50, 50-70 and >70 years; the remaining 30% was used for validation...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29671356/extracellular-vesicles-pathogenetic-diagnostic-and-therapeutic-value-in-traumatic-brain-injury
#14
Stefania Mondello, Eric P Thelin, Gerry Shaw, Michelle Salzet, Carmela Visalli, Dasa Cizkova, Firas Kobeissy, Andras Buki
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Accurate classification according to injury-specific and patient-specific characteristics is critical to help informed clinical decision-making and to the pursuit of precision medicine in TBI. Reliable biomarker signatures for improved TBI diagnostics are required but still an unmet need. Areas covered: Extracellular vesicles (EVs) represent a new class of biomarker candidates in TBI. These nano-sized vesicles have key roles in cell signaling profoundly impacting pathogenic pathways, progression and long-term sequelae of TBI...
April 19, 2018: Expert Review of Proteomics
https://www.readbyqxmd.com/read/29664813/development-and-validation-of-nomograms-predicting-overall-and-cancer-specific-survival-of-spinal-chondrosarcoma-patients
#15
Kehan Song, Jian Song, Xio Shi, Hongli Wang, Xiaosheng Ma, Xinlei Xia, Xin Liang, Kaiyuan Lin, Jianyuan Jiang
STUDY DESIGN: Retrospective analysis. OBJECTIVE: To develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) of spinal chondrosarcoma patients. SUMMARY OF BACKGROUND DATA: In this era of personalized medicine, data those are available to predict the survival of spinal chondrosarcoma patients are still limited due to the rarity of the disease. Nomogram, which has been widely used in clinical oncology, could conveniently and precisely predict survival outcome for individual patient...
April 16, 2018: Spine
https://www.readbyqxmd.com/read/29623670/epidemiology-in-wonderland-big-data-and-precision-medicine
#16
Rodolfo Saracci
Big Data and precision medicine, two major contemporary challenges for epidemiology, are critically examined from two different angles. In Part 1 Big Data collected for research purposes (Big research Data) and Big Data used for research although collected for other primary purposes (Big secondary Data) are discussed in the light of the fundamental common requirement of data validity, prevailing over "bigness". Precision medicine is treated developing the key point that high relative risks are as a rule required to make a variable or combination of variables suitable for prediction of disease occurrence, outcome or response to treatment; the commercial proliferation of allegedly predictive tests of unknown or poor validity is commented...
April 5, 2018: European Journal of Epidemiology
https://www.readbyqxmd.com/read/29623052/the-relationship-between-range-of-motion-and-injuries-in-adolescent-dancers-and-sportspersons-a-systematic-review
#17
Joyce M Storm, Roger Wolman, Eric W P Bakker, Matthew A Wyon
Background: The frequent and intensive training and performance of pre-professional ballet dancers and sportspersons is offered at a time when young ballet dancers and young athletes may be vulnerable to injury due to the progress through adolescence and growth spurts. Hypothesis: There are changes in range of motion during the progress through adolescence and growth periods in dancers and sportspersons. These changes in ROM can be linked to the increase of injury. Objectives: The primary aim of this systematic review is to determine whether there are changes in ROM during the progress through adolescence and growth spurts in dancers and sportspersons...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29605707/epigenome-wide-association-studies-for-systemic-autoimmune-diseases-the-road-behind-and-the-road-ahead
#18
Elena Carnero-Montoro, Marta E Alarcón-Riquelme
Epigenetics is known to be an important mechanism in the pathogenesis of autoimmune diseases. Epigenetic variations can act as integrators of environmental and genetic exposures and propagate activated states in immune cells. Studying epigenetic alterations by means of genome-wide approaches promises to unravel novel molecular mechanisms related to disease etiology, disease progression, clinical manifestations and treatment responses. This paper reviews what we have learned in the last five years from epigenome-wide studies for three systemic autoimmune diseases, namely systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis...
March 29, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29602394/the-warburg-effect-in-diabetic-kidney-disease
#19
REVIEW
Guanshi Zhang, Manjula Darshi, Kumar Sharma
Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in diabetic patients. Defining risk factors for DKD using a reductionist approach has proven challenging. Integrative omics-based systems biology tools have shed new insights in our understanding of DKD and have provided several key breakthroughs for identifying novel predictive and diagnostic biomarkers. In this review, we highlight the role of the Warburg effect in DKD and potential regulating factors such as sphingomyelin, fumarate, and pyruvate kinase muscle isozyme M2 in shifting glucose flux from complete oxidation in mitochondria to the glycolytic pathway and its principal branches...
March 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29572664/identification-of-cytochrome-p450-mediated-drug-drug-interactions-at-risk-in-cases-of-gene-polymorphisms-by-using-a-quantitative-prediction-model
#20
Nicolas Fermier, Laurent Bourguignon, Sylvain Goutelle, Nathalie Bleyzac, Michel Tod
BACKGROUND AND OBJECTIVE: The magnitude of drug-drug interactions mediated by cytochrome P450 (CYP) may depend on the genotype of polymorphic cytochromes. The objective of this study was to identify drug-drug interactions with greater magnitude in CYP variant groups than in extensive metabolizers. METHODS: The in-vivo mechanistic static model was used to predict the area under the curve ratio of drug-drug interactions. Five cytochromes (CYP3A4/5, 2D6, 2C9, 2C19, 1A2) and five groups of genotypes for each polymorphic cytochrome (CYP2D6, 2C9, 2C19) were considered...
March 23, 2018: Clinical Pharmacokinetics
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