Eric J. Topol

Bio: Eric J. Topol is an academic researcher from Scripps Health. The author has contributed to research in topics: Myocardial infarction & Angioplasty. The author has an hindex of 193, co-authored 1373 publications receiving 151025 citations. Previous affiliations of Eric J. Topol include Loyola University Chicago & Cleveland Clinic.

Direct-to-consumer pharmacogenomic testing is associated with increased physician utilisation

Abstract: Background Direct-to-consumer (DTC) genomic testing has generated controversy, however the actual impact of testing on consumer behaviour has been understudied, particularly for pharmacogenomic (PGx) testing. Methods We recruited a sample of adults who purchased a DTC genomic test and had previously received their genomic test results for complex disease risk. All participants additionally underwent PGx testing. At follow-up, to assess the impact of PGx testing on consumer behaviour, healthcare utilisation and psychological status were compared between approximately a third of participants who had received their PGx results and the remaining two-thirds of participants who were still awaiting results. The PGx test included genetic testing for drug effectiveness or risk of side effects for 12 medications. Results At follow-up, there were 481 PGx test recipients and 844 non-recipients still awaiting results. PGx test recipients had more physician visits (p=0.04) and were more likely to share their results with their physician (p=0.001). Both groups showed a decrease in anxiety symptoms from baseline to follow-up, with a trend for PGx recipients to show less of a decrease compared with non-recipients (p=0.10). PGx recipients were more likely to report that their physician ordered additional tests (p=0.01) based on their genomic test. There were no group differences in follow-up test-related distress (p=0.67). Conclusions DTC PGx risk profiling among a selected sample of individuals was associated with increased physician utilisation and did not result in any adverse changes in psychological health or follow-up test-related distress.

Clinical Trials to Prevent Restenosis after Percutaneous Coronary Revascularization

Abstract: Percutaneous transluminal coronary revascularization (PTCR) is effective in relieving symptoms in patients with angina pectoris. In selected patients, PTCR provides similar protection from cardiac death or myocardial infarction as surgical revascularization.’V2 However, restenosis following PTCR remains the procedure’s major limitation. Besides compromising clinical benefit in terms of recurrence of angina and need for repeat procedures, restenosis markedly increases health care cost by at least $2 billion per year in the United States.3 Despite extensive research on restenosis, the pathophysiologic mechanisms remain unclear. The process appears to be the result of a complex reparative process from vascular injury (FIG. l).4 The denudation to the endothelium exposes collagen, tissue, and other factors that in turn activate platelets and initiate the coagulation cascade, resulting in thrombus formation and reparatory response. Growth factors, such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), released from platelets and smooth muscle cells, induce the proliferation process via proto-oncogenes, such as c-fos and c-myc. In addition, the thrombus may act as a “bioabsorbable matrix”5 for cell migration and proliferation at the sites of treatment, with thrombin amplifying the response.6 Smooth muscle cells and fibroblasts also secrete large amounts of extracellular matrix, forming another important component in restenotic lesions. Contracting mechanical forces occurring in minutes to hours (vessel recoil) and days (remodeling) following vascular injury may lead to vessel contracture or “shrinkage” contributing to restenosis.’ In one recent stuTdy: immunochemical labeling for proliferating cell nuclear antigen (PCNA) was absent in 74% of restenotic coronary atherosclerotic specimens, suggesting the increasing importance of the remodeling process in restenosisY Based on this paradigm of thrombus formation, cellular proliferation, and vessel contracture, several pharmacological and mechanical approaches have been evaluated in clinical trials in limiting restenosis.

How Consumers and Physicians View New Medical Technology: Comparative Survey

Abstract: Background: As a result of the digital revolution coming to medicine, a number of new tools are becoming available and are starting to be introduced in clinical practice. Objective: We aim to assess health care professional and consumer attitudes toward new medical technology including smartphones, genetic testing, privacy, and patient-accessible electronic health records. Methods: We performed a survey with 1406 health care providers and 1102 consumer responders. Results: Consumers who completed the survey were more likely to prefer new technologies for a medical diagnosis (437/1102, 39.66%) compared with providers (194/1406, 13.80%; P <.001), with more providers (393/1406, 27.95%) than consumers (175/1102, 15.88%) reporting feeling uneasy about using technology for a diagnosis. Both providers and consumers supported genetic testing for various purposes, with providers (1234/1406, 87.77%) being significantly more likely than consumers (806/1102, 73.14%) to support genetic testing when planning to have a baby ( P <.001). Similarly, 91.68% (1289/1406) of providers and 81.22% (895/1102) of consumers supported diagnosing problems in a fetus ( P <.001). Among providers, 90.33% (1270/1406) were concerned that patients would experience anxiety after accessing health records, and 81.95% (1149/1406) felt it would lead to requests for unnecessary medical evaluations, but only 34.30% (378/1102; P <.001) and 24.59% (271/1102; P <.001) of consumers expressed the same concerns, respectively. Physicians (137/827, 16.6%) reported less concern about the use of technology for diagnosis compared to medical students (21/235, 8.9%; P =.03) and also more frequently felt that patients owned their medical record (323/827, 39.1%; and 30/235, 12.8%, respectively; P <.001). Conclusions: Consumers and health professionals differ significantly and broadly in their views of emerging medical technology, with more enthusiasm and support expressed by consumers. [J Med Internet Res 2015;17(9):e215]

Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997.

Abstract: Randomized trials have demonstrated the superiority of coronary stents in combination with a platelet-focused pharmacologic approach in percutaneous coronary intervention (PCI). However, nationally representative data examining the impact of these technologies on patient outcomes and costs remain scarce. This study sought to determine the real-world impact of changes in the use of stents and anticoagulant agents in PCI on outcomes and costs. A nationally representative sample of 37,088 patients who underwent PCI from October 1995 to October 1997 was identified from in-patient hospital claims data acquired from HCIASachs. Utilization of coronary stents, antiplatelet and anticoagulant agents, and outcome measurements of in-hospital death, coronary artery bypass grafting (CABG), repeat PCI, bleeding, and costs were analyzed in 6-month intervals. Acute events (death, urgent CABG, or PCI) decreased (p <0.001), whereas use of stents, abciximab, or both, increased (p <0.001). Dosages of heparin and bleeding complications declined significantly (p <0.001) over the 2-year period. Heparin dosages were higher in patients who experienced bleeding or death than in those who did not (p <0.001). The average hospital length of stay decreased significantly (p <0.001), largely driven by a reduction in time between the procedure and hospital discharge. By the end of the study period, bleeding was the most frequent (5.5%) complication of PCI and was associated with considerable costs, adding $10,225 to baseline costs.

Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites

Abstract: SPECIFIC AIMSRecent genetic studies have associated members of the thrombospondin gene family with premature cardiovascular disease. The disease-associated polymorphisms lead to single amino acid changes in thrombospondin-4 (A387P) and thrombospondin-1 (N700S). Since Ca2+ binding is critical for the structure and function of thrombospondin family members, direct evidence for differences in Ca2+ binding by the polymorphic forms was sought. The goal of this study was to identify and characterize how the N700S substitution in TSP-1 and the A387P substitution in TSP-4 affect Ca2+ binding.PRINCIPAL FINDINGS1. Putative Ca2+ binding sites altered in TSP-1 and TSP-4 variantsAs an initial step in considering the molecular effects of the SNPs on TSP-1 and TSP-4, we analyzed the homologies of the domains containing the SNPs to known structural motifs. In TSP-4, the change of Ala to Pro at the position 387 occurs in an EGF-like domain, a structure present in multiple proteins including cell surface receptors, extrace...

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

Abstract: Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

An integrated encyclopedia of DNA elements in the human genome

Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.