Ralph B. D'Agostino

Bio: Ralph B. D'Agostino is an academic researcher from Wake Forest University. The author has contributed to research in topics: Framingham Heart Study & Framingham Risk Score. The author has an hindex of 226, co-authored 1287 publications receiving 229636 citations. Previous affiliations of Ralph B. D'Agostino include VA Boston Healthcare System & University of Illinois at Urbana–Champaign.

Developing points-based risk-scoring systems in the presence of competing risks.

Abstract: Predicting the occurrence of an adverse event over time is an important issue in clinical medicine. Clinical prediction models and associated points-based risk-scoring systems are popular statistical methods for summarizing the relationship between a multivariable set of patient risk factors and the risk of the occurrence of an adverse event. Points-based risk-scoring systems are popular amongst physicians as they permit a rapid assessment of patient risk without the use of computers or other electronic devices. The use of such points-based risk-scoring systems facilitates evidence-based clinical decision making. There is a growing interest in cause-specific mortality and in non-fatal outcomes. However, when considering these types of outcomes, one must account for competing risks whose occurrence precludes the occurrence of the event of interest. We describe how points-based risk-scoring systems can be developed in the presence of competing events. We illustrate the application of these methods by developing risk-scoring systems for predicting cardiovascular mortality in patients hospitalized with acute myocardial infarction. Code in the R statistical programming language is provided for the implementation of the described methods. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Changing End Points in Breast-Cancer Drug Approval — The Avastin Story

Abstract: In December 2007, the Oncologic Drugs Advisory Committee (ODAC) of the Food and Drug Administration (FDA) met to discuss the risks and benefits of Genentech's Avastin (bevacizumab) for use in combination with paclitaxel for first-line treatment of locally recurrent or metastatic HER2-negative breast cancer. In an unusual move, Genentech and the FDA proposed that the committee (on which I serve as a voting consultant) consider progression-free survival rather than overall survival as the primary end point. In the key study submitted, bevacizumab plus paclitaxel was statistically superior to paclitaxel alone in terms of progression-free survival but not overall survival. Surprisingly, . . .

Risk factor profile and management of cerebrovascular patients in the REACH Registry.

Abstract: Background: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk

Genetics of the Framingham Heart Study Population

Abstract: This chapter provides an introduction to the Framingham Heart Study and the genetic research related to cardiovascular diseases conducted in this unique population It briefly describes the origins of the study, the risk factors that contribute to heart disease, and the approaches taken to discover the genetic basis of some of these risk factors The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, and phenotypic and genetic correlations Many quantitative trait loci underlying cardiovascular diseases have been discovered using different molecular markers Additionally, initial results from genome‐wide association studies using 116,000 markers and the prospects of using 550,000 markers for association studies are presented Finally, the use of this unique sample to study genotype and environment interactions is described

Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study.

Abstract: Previous studies have indicated that β-cell dysfunction predicts the development of diabetes, although it is unknown whether the use of combinations of insulin secretory measures further improves prediction. The Insulin Resistance Atherosclerosis Study is a prospective, multicenter, epidemiological study of the relationship between insulin sensitivity and the risk of diabetes and cardiovascular disease. At baseline, fasting concentrations of insulin, intact proinsulin (PI), and split PI were measured, and acute insulin response (AIR) was determined during a frequently sampled intravenous glucose tolerance test (FSIGTT). Subjects who were nondiabetic at baseline ( n = 903) were reexamined after 5 years of follow-up; 148 had developed diabetes. In separate logistic regression models adjusted for age, sex, clinic, and ethnicity, 1 SD differences in measures of β-cell dysfunction were associated with diabetes incidence (AIR: odds ratio [OR] 0.37, 95% CI 0.27–0.52; intact PI: OR 1.90, 95% CI 1.57–2.30; split PI: OR 1.94, 95% CI 1.63–2.31). After additional adjustment for BMI, impaired glucose tolerance, and insulin sensitivity, these measures continued to be significantly associated with risk of diabetes (all P < 0.0001). Furthermore, in models that included both PI and AIR, each was an independent predictor, and individuals who had combined low AIR and high PI experienced the highest diabetes risk. In conclusion, both low AIR and high PI independently predicted diabetes in a well-characterized multiethnic population. Although fasting PI is simpler to assess, determining AIR from an FSIGTT may further improve prediction. If pharmacological agents to prevent diabetes are proved to be efficacious in ongoing clinical trials, then it may be beneficial to perform FSIGTTs to identify better (for intensive intervention) prediabetic subjects who would ultimately require lifelong pharmacological therapy.

G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

Abstract: G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of thet, F, and χ2 test families. In addition, it includes power analyses forz tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.