Robert Talbert - Academia.edu (original) (raw)

Papers by Robert Talbert

Annals of Pharmacotherapy, 2006

Pharmacotherapy: A PathophysiologicApproach, 6th Edition Edited by Joseph T DiPiro PharmD FCCP,Ro... more Pharmacotherapy: A PathophysiologicApproach, 6th Edition Edited by Joseph T DiPiro PharmD FCCP,Robert L Talbert PharmD FCCPBCPS,GaryC Yee PharmDFCCP, Gary R Matzke PharmD FCP FCCP,BarbaraG WellsPharmD FASHPFCCP BCPP,and L Michael Posey BS Pharm. Published by McGraw-HillCompanies, Inc., New York,NY,2005. ISBN0-07-141613-7. Clothbound,xxxiii+ 2802 pp. (28 x 22 ern),$159.95. www.pharmacotherapyonline.com

PubMed, Aug 6, 1998

Numerous factors must be considered when determining the formulary status of thrombolytic agents ... more Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.

American Journal of Health-System Pharmacy, 1988

The Lancet Neurology, 2016

Background The discovery of disease-associated loci through genome-wide association studies (GWAS... more Background The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identifi cation of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. Methods To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the fi rst stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certifi ed investigators who used the web-based protocol, Causative Classifi cation of Stroke (CCS). We constructed casecontrol strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fi xed-eff ects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identifi ed from the fi rst stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classifi cation system, in accordance with local standards. Results from the two stages were then jointly analysed in a fi nal meta-analysis. Findings We identifi ed a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (fi rst stage odds ratio [OR] 1•21, 95% CI 1•13-1•30, p=4•50 × 10-⁸; joint OR 1•19, 1•12-1•26, p=1•30 × 10-⁹). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (fi rst stage OR 1•39, 1•29-1•49, p=3•26 × 10-¹⁹; joint OR 1•37, 1•30-1•45, p=2•79 × 10-³²) and ZFHX3 (fi rst stage OR 1•19, 1•11-1•27, p=2•93 × 10-⁷; joint OR 1•17, 1•11-1•23, p=2•29 × 10-¹⁰) for cardioembolic stroke, and HDAC9 (fi rst stage OR 1•29, 1•18-1•42, p=3•50 × 10-⁸; joint OR 1•24, 1•15-1•33, p=4•52 × 10-⁹) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specifi c subtype, exceeded genome-wide signifi cance in the meta-analysis of small artery stroke (fi rst stage OR 1•20, 1•12-1•28, p=6•82 × 10-⁸; joint OR 1•17, 1•11-1•23, p=2•92 × 10-⁹). Other loci associated with stroke in previous studies, including NINJ2, were not confi rmed. Interpretation Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specifi c. We identifi ed a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specifi city of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.

Journal of the American Heart Association, Jun 15, 2015

Background-The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with... more Background-The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. Methods and Results-CYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. Conclusions-There were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication.

American Journal of Health-system Pharmacy, Feb 15, 1998

The Neurologist, Nov 1, 1996

Circulation, 2015

Introduction: Resistant hypertension (RHTN), a blood pressure (BP) ≥140/90 mm Hg despite ≥ 3 anti... more Introduction: Resistant hypertension (RHTN), a blood pressure (BP) ≥140/90 mm Hg despite ≥ 3 antihypertensive drugs or BP < 140/90 mm Hg using ≥ 4 drugs, is associated with increased incidence of adverse cardiovascular outcomes, especially stroke. Hypothesis and objective: We hypothesize common variants exist in the genes regulating BP response and may lead to RHTN in some patients. Methods: A discovery cohort of hypertensive participants were included as cases (as defined above) or controls (N=719; 263 whites, 322 Hispanics, and 134 African Americans) from SPS3-GENES. They were genotyped on the Illumina Omni 5 Exome chip. Multiple logistic regression analysis was conducted separately in each race using an additive genetic model, adjusting for predictors for RHTN, principle components for ancestry and BP target treatment arms. Results from the 3 racial groups were combined using meta-analysis with inverse-variance weighting, with the hypothesis that functional variants are consis...

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

The Strategic Plan of the American College of Clinical Pharmacy The strategic planning process of... more The Strategic Plan of the American College of Clinical Pharmacy The strategic planning process of the American College of Clinical Pharmacy typically occurs on a three-to five-year cycle. Every fourth or fifth year, ACCP organizes a major planning initiative that includes a broad representation of its membership. This initiative updates and creates a new strategic plan, identifies goals and objectives, and begins the process of developing action-oriented strategies to achieve the stated objectives. In the interim, the ACCP Board of Regents, Research Institute Board of Trustees, and Pharmacotherapy Board of Directors assume primary responsibility for establishing priorities, working on selected goals and objectives, monitoring progress, and refining the plan as needed to reflect changes in environmental conditions. Over 1000 ACCP members have provided input to the College's strategic plan by participating in surveys, focus groups, and strategic planning retreats. The goal of ACCP's strategic planning effort is to develop, implement, and monitor an integrated strategic plan for all facets of the organization. This requires a shared vision of where we are trying to move the entire organization while recognizing that the individual missions of ACCP, the Research Institute, and Pharmacotherapy all contribute to achieving this vision in their unique ways. The process and timeline used to develop this planning document are depicted in Figure 1.

Pharmacotherapy

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The present invention includes compositions and methods for making and using a rapid dissolving, ... more The present invention includes compositions and methods for making and using a rapid dissolving, high potency, substantially amorphous nanostructured aggregate for pulmonary delivery of tacrolimus and a stabilizer matrix comprising, optionally, a polymeric or non-polymeric surfactant, a polymeric or non-polymeric saccharide or both, wherein the aggregate comprises a surface area greater than 5 m2/g as measured by BET analysis and exhibiting supersaturation for at least 0.5 hours when 11-15-times the aqueous crystalline solubility of tacrolimus is added to simulated lung fluid.

American Journal of Health-System Pharmacy, 2002

The advantages of dual antiplatelet therapy over monotherapy in preventing recurrent ischemic eve... more The advantages of dual antiplatelet therapy over monotherapy in preventing recurrent ischemic events are examined. Atherosclerosis is an insidious systemic process involving multiple vascular beds, including the cerebral, coronary, and peripheral arteries. Atherosclerotic plaque rupture is one of the inciting events in the progression of platelet activation, aggregation, and thrombus formation. Patients with any clinical manifestation of atherosclerosis are vulnerable to others in different vascular beds since the disease develops throughout the vasculature, and different vascular events have common predisposing risk factors. Ischemic coronary heart disease and cerebrovascular disease are two of the three most frequent causes of death in the United States. The efficacy of aspirin in the secondary prevention of myocardial infarction (MI) and stroke has been demonstrated in numerous trials. While dipyridamole has not been linked with a greater odds reduction than aspirin in the development of MI, stroke, and vascular death, ticlopidine and clopidogrel have been associated with a greater reduction in the development of acute MI, stroke, and vascular death than aspirin. Clinical trials evaluating the efficacy and safety of combination antiplatelet therapy in the prevention of recurrent ischemic events are ongoing. The rationale for using a combination of two mechanistically different antiplatelet agents is supported by ex vivo and clinical studies. Inhibition of platelet aggregation and thrombus formation is enhanced with dual antiplatelet therapy. Combination antiplatelet regimens with different mechanisms of action to inhibit multiple sites in the thrombotic pathway may further improve long-term clinical outcomes. Dual antiplatelet therapy may have advantages over monotherapy in the prevention of recurrent ischemic events.

Value in Health, 1999

Regardless of LVERSUSF, prescribed drug therapies at discharge were similar among patients hospit... more Regardless of LVERSUSF, prescribed drug therapies at discharge were similar among patients hospitalized for CHF in the hospital. Findings indicate a need to better understand the role and actual implementation of guidelines that recommend customized CHF drug therapy tailored to LVERSUSF.

Journal of the American Pharmacists Association, 2006

Objective: To describe the most important potential adverse effects related to statin therapy, di... more Objective: To describe the most important potential adverse effects related to statin therapy, discuss mechanisms of toxicity and drug interactions, and suggest approaches for enhancing safety with statin therapy. Data Sources: Large-scale clinical trials, government databases and papers, and recent studies of statin safety. Study Selection: By the author. Data Extraction: By the author. Data Synthesis: The number of patients requiring intensive therapy with statins to achieve lipid goals is climbing, and as the number grows, so does the potential for adverse effects with these agents. The most detrimental adverse effects of statins are hepatotoxicity and myopathy. Liver dysfunction induced by statins is rare and usually mild, with asymptomatic transaminase elevation or acute cholecystitis. Progression to liver failure is exceedingly rare, and transaminase elevations is usually reversible with dose reduction. Statin-associated myopathy is generally a concern when patients have more than one risk factor for muscle syndromes, such as an elderly patient with poor renal function. Drug interactions represent an additional concern, especially for atorvastatin, lovastatin, and simvastatin, all of which are metabolized by the important 3A4 isoenzyme of the cytochrome P450 system of the liver. Conclusion: The benefits of all available statins for the treatment or prevention of cardiovascular disease outweigh any potential risks of therapy. For patient groups most susceptible to adverse effects, such as the elderly and those on multiple medications, clinicians should consider the use of statins that are least likely to interact with other medications.

Journal of General Internal Medicine, 1987

The American Journal of Medicine, 1987

Journal of the American Pharmaceutical Association (1996), 2002

Objectives. To present two case reports of patients who received suboptimal oral antiplatelet the... more Objectives. To present two case reports of patients who received suboptimal oral antiplatelet therapy and to review recent changes in national guidelines for management of acute coronary syndromes. Data Sources. Personal observation by the authors, and clinical practice guidelines and related clinical trials of the American Heart Association and the American College of Cardiology. Summary. The American College of Cardiology and the American Heart Association revised the guidelines for administration of antiplatelet and anticoagulant therapy in patients with unstable angina and non-ST-segment elevation myocardial infarction in March 2002. Two cases observed by the authors illustrate the consequences of suboptimal antiplatelet therapy when a combination of two antiplatelet drugs should have been administered. Conclusion. Evidence from recent randomized controlled trials led to changes in the national guidelines for administration of oral antiplatelet therapy in patients with acute coronary syndromes. Pharmacists should be aware of these changes and counsel patients about appropriate administration of antiplatelet drugs.

American Journal of Hypertension, 2003

High blood pressure, and other cardiovascular disese (CVD) risk factors are increasingly prevalen... more High blood pressure, and other cardiovascular disese (CVD) risk factors are increasingly prevalent in the urban Indian population. Data regarding this clustering of risk factors is scarce from developing countries. We carried out a comprehensive cross-sectional CVD risk factor prevalence study on 2200 male employees aged 21-59 years of an urban industrial population in India employing questionnaire, clinical examination and biochemical estimations. Most of the employees were below 45 years of age and the mean age was 42 years. The prevalence of hypertension (as per JNC VI criteria) and high-normal blood pressure was 30% and 17% respectively. Only 25% of the population had optimal blood pressure. Only a third of the hypertensives were aware of their status, while just 8% had their blood pressure controlled. Even in the age group 21-29 years, the prevalence of hypertension was 18%. The prevalence of other CVD risk factors in the hypertensive population was as follows: diabetes 20%, impaired fasting glucose 23%, total cholesterolϾ200mg/dl 35%, total cholesterol/HDL-C ratioՆ4.5 67% , hypertriglyceridemia 48%, and central obesity (waist hip ratioՆ 0.95) 80%. The mean BMI for this population was 24 kg/m 2 and the mean waist circumference was high at 97 cm.. 41% of the study population was actively smoking at the time of the study. While the overall population had high prevalence of these risk factors, adverse trends in risk factors were significantly higher in the hypertensives as compared to non-hypertensives. As per the NCEP guidelines, about 25% of the overall population had metabolic syndrome. The prevalence rose further if the proposed lower cutoffs for obesity in Asian population were employed. While only 15% of the study population was free of any of traditional four risk factors, 45% had at least two risk factors. The prevalence of coronary heart disease, using modified Rose angina questionnaire and/or Minnesota-coded ECG abnormalities, in this population was 7.3%. This study demonstrates the high prevalence of adverse blood pressure profile in this comparatively young population and a low awareness of the same. The significant clustering of risk factors in this population is likely to increase greatly the absolute cardiovascular risk and underscores the urgent preventive measures which need to be implemented in developing countries like India.

American Journal of Health-System Pharmacy, 1983

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking ag... more The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.