Marc A. Pfeffer

Bio: Marc A. Pfeffer is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Heart failure & Myocardial infarction. The author has an hindex of 166, co-authored 765 publications receiving 133043 citations. Previous affiliations of Marc A. Pfeffer include Partners HealthCare & University of Miami.

Left ventricular size, mass, and shape: is the sum greater than the parts?

Abstract: Alterations in cardiac structure and function have long been recognized as markers of heightened risk for cardiovascular events. Indeed, even before the advent of noninvasive imaging, electrocardiographic left ventricular hypertrophy (LVH) was identified as one of the earliest “factors of risk”

Anemia treatment in chronic kidney disease: shifting uncertainty.

Abstract: Epidemiologic observations showing associations between higher levels of some biologic markers such as blood pressure and serum cholesterol with heightened risk of death and non-fatal cardiovascular events have provided important data to develop hypotheses regarding pharmacologic therapies to modify these markers to improve prognosis. Randomized controlled trials have shown that strategies to reduce blood pressure with a variety of antihypertensive agents and LDL cholesterol with statins do, indeed, result in important improvements in clinical outcomes. However, there are several instances where a hypothesis based on strong observational data has been rejected based on surprising counterintuitive evidence generated from randomized controlled clinical trials. Use of inotropic therapies for patients with reduced left ventricular ejection fraction heart failure, administration of class I antiarrhythmic agents to suppress ventricular arrhythmias in high-risk patients, and use of hormone replacement therapy for postmenopausal women have each shown that therapies presumed to be of benefit may actually be producing unfavorable clinical results. Use of erythropoietic stimulating agents (ESA) in chronic kidney disease patients with anemia is similarly based on strong observational data indicating that the degree of anemia is independently associated with higher risk for cardiovascular morbidity and mortality. In non-dialysis patients with mild to moderate anemia, current clinical outcome studies have only addressed arbitrary hemoglobin targets for ESA therapy and have shown that targeting the higher hemoglobin levels was not associated with the benefit and may even result in harm. This review will outline the importance of having a placebo-controlled trial in this patient population to better assess the risk benefit profile of this therapy.

Moving beyond the conventional stratified analysis to estimate an overall treatment efficacy with the data from a comparative randomized clinical study.

Abstract: For a two-group comparative study, a stratified inference procedure is routinely used to estimate an overall group contrast to increase the precision of the simple two-sample estimator. Unfortunately, most commonly used methods including the Cochran-Mantel-Haenszel statistic for a binary outcome and the stratified Cox procedure for the event time endpoint do not serve this purpose well. In fact, these procedures may be worse than their two-sample counterparts even when the observed treatment allocations are imbalanced across strata. Various procedures beyond the conventional stratified methods have been proposed to increase the precision of estimation when the naive estimator is consistent. In this paper, we are interested in the case when the treatment allocation proportions vary markedly across strata. We study the stochastic properties of the two-sample naive estimator conditional on the ancillary statistics, the observed treatment allocation proportions and/or the stratum sizes, and present a biased-adjusted estimator. This adjusted estimator is asymptotically equivalent to the augmentation estimators proposed under the unconditional setting. Moreover, this consistent estimation procedure is also equivalent to a rather simple procedure, which estimates the mean response of each treatment group first via a stratum-size weighted average and then constructs the group contrast estimate. This simple procedure is flexible and readily applicable to any target patient population by choosing appropriate stratum weights. All the proposals are illustrated with the data from a cardiovascular clinical trial, whose treatment allocations are imbalanced.

New treasures from old? EPHESUS. Eplerenome Post-AHI Heart Failure Efficacy and Survival Study.

Abstract: Impressive clinical benefits have been derived by inhibiting the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors. There is growing evidence that aldosterone plays a contributing role in the pathogenesis of heart failure beyond its sodium retention properties. EPHESUS, a trial of a novel aldosterone antagonist, eplerenone, in patients with myocardial infarction, left ventricular dysfunction and pulmonary congestion will determine whether this approach produces additive clinical benefits in modernly managed patients.

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.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

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。

A New Equation to Estimate Glomerular Filtration Rate

Abstract: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates glomerular filtration rate (GFR) in patients with mild kidney disease. Levey and associates therefore developed and va...

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.