Biomedical subjects

Robert M Califf

Publications and source records attributed to Robert M Califf.

248 records · Page 14Linked to original sources

PubMed2002

TARGET versus GUSTO-IV: appropriate use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes and percutaneous coronary intervention.

Until recently, the selection of which glycoprotein IIb/IIIa inhibitor to use for patients with acute coronary syndromes or those undergoing percutaneous coronary intervention largely reflected physician preference, costs, and any evidence supporting the clinical indication. Clinicians often assumed a class effect for these agents: a benefit observed for one agent in one clinical setting (such as percutaneous coronary intervention) would confer benefit in another (such as non-ST-elevation acute coronary syndromes). The need for evidence to guide treatment selection motivated the design of the Do Tirofiban and ReoPro Give Similar Efficacy Trial (TARGET) and the Global Use of Strategies to Open occluded arteries (GUSTO-IV) trials with abciximab. This review examines the results from these and other recent trials of glycoprotein IIb/IIIa inhibition in acute coronary syndromes and percutaneous coronary intervention, presents a rationale for the lack of a consistent benefit with abciximab, and describes future directions for clinical investigation.

Abciximab↗

PubMed2002

Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion.

Adolescent↗

PubMed2002

Characteristics, treatment and outcome of patients with non-ST-elevation acute coronary syndromes and multivessel coronary artery disease: observations from PURSUIT (platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrelin therapy).

BACKGROUND: The 6-month clinical outcome of patients with multivessel disease enrolled in PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) is described. Patients with complete angiography data were included; multivessel disease was stratified according to the treatment strategy applied early during hospitalization, i.e. medical treatment, percutaneous coronary intervention (PCI) (balloon), PCI (stent), or coronary artery bypass grafting (CABG). METHODS: Patients were divided into three groups according to the treatment strategy applied during the first 30 days of enrolment. Patients who did not undergo a percutaneous or surgical coronary intervention were classified as medically treated. Patients who underwent a PCI (prior to a possible CABG) were separated from those who underwent a CABG (prior to a possible PCI). The PCI group was further subdivided: patients receiving >/=1 coronary stents were separated from those in whom no stents were used. RESULTS: The mortality rate at 30 days was 6.7, 3.9, 2.4 and 4.8% for the medical treatment, PCI (balloon), PCI (stent) and CABG groups, respectively (p value = 0.002). Differences as observed at 30 days were still present at 6-month follow-up with 11.1, 5.8, 5.5 and 6.5% mortality event rates for the aforementioned groups (p value = 0.002). The 30-day myocardial infarction (MI) rate according to the opinion of the Clinical Events Committee was lower among medically than non-medically treated patients, with the highest event rate observed in the CABG group (27.7%). Approximately half of the MIs in the PCI and CABG subgroups occurred within 48 h after the procedure. CONCLUSIONS: The observed differences in clinical outcomes are explained by an imbalance in baseline characteristics and comorbid conditions between the analyzed groups of patients.

Acute Disease↗

PubMed2002

Practitioner acceptance of the dofetilide risk-management program.

STUDY OBJECTIVE: To assess the opinions and knowledge retention of practitioners after participation in the dofetilide risk-management program. DESIGN: A 21-item questionnaire. SETTING: A large academic medical center. PARTICIPANTS: One hundred forty-six practitioners were given the questionnaire; 91 (62%) completed it. MEASUREMENTS AND RESULTS: The questionnaire assessed practitioners' opinions of the program and guidelines, preparation time for implementing dofetilide treatment, and retention of facts from the program. Responses were graded on a 5-point Likert scale. Practitioners took a mean of 0.86 +/- 0.44 hours to complete the program; physicians took the least time, pharmacists the most. Practitioners agreed the program was necessary but were undecided about whether the guidelines were easily understood or implemented. Nurses answered one of the two knowledge-retention questions incorrectly significantly more often than physicians or pharmacists. Identification of seven drugs that should not be taken with dofetilide differed significantly (p < 0.0001) across groups (mean accuracy score was 41% for nurses, 80% for pharmacists, and 86% for physicians). CONCLUSION: This risk-management program has been well received by practitioners at our institution. We are gathering data to determine whether the program is effective in reducing inappropriate administration of dofetilide.

Drug Information Services↗

PubMed2002

Disease management in healthcare organizations: results of in-depth interviews with disease management decision makers.

BACKGROUND: Despite the widening use of disease management (DM) programs throughout the country, little is understood about the "state of DM" in healthcare systems and managed care organizations. OBJECTIVE: To better characterize the range of users of DM in healthcare and to identify critical issues, both present and future, for DM. STUDY DESIGN: Qualitative survey. PARTICIPANTS AND METHODS: Forty-seven healthcare systems (n = 22) and managed care organizations (n = 25) were randomly selected. Decision makers were identified and interviewed between January 1, 2000, and March 31, 2000. We limited quantitative analysis to tabulations of suitable responses, without statistical testing. Responses were organized around 3 themes: models for DM, implementation strategies, and measurements of success. RESULTS: Of 47 decision makers surveyed, 42 (89%) reported that their organizations currently have (75%) or are working to develop (14%) DM programs. Although the goals of DM programs were similar, organizations took a variety of approaches to achieving these ends. There were typically 3 steps in implementing a DM program: analysis of patient data, external analysis, and organizational analysis. Decision makers believed that DM programs had only achieved partial success in reaching the 2 main goals of improved quality of care and cost savings. CONCLUSIONS: Given the variety of DM programs, there is a need to develop a classification scheme to allow for better comparison between programs. Further quantitative studies of decision makers' opinions would be helpful in developing programs and in designing necessary studies of patient management strategies.

Decision Making, Organizational↗

PubMed2001

Systematic adjudication of myocardial infarction end-points in an international clinical trial.

BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.

Journal Article↗

PubMed2001

Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study.

BACKGROUND: Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and electrocardiographic data. RESULTS: The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. CONCLUSION: CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials.

Journal Article↗

PubMedDate not supplied

What clinicians should know about the QT interval.

CONTEXT: Of the several factors implicated in causing QT interval prolongation and torsades de pointes, errors in the use of medications that may prolong this interval deserve special attention. OBJECTIVE: To systematically summarize the available clinical data on the QT interval and to offer improved recommendations for the use of QT-prolonging medications. DATA SOURCES: We searched MEDLINE from 1966 through 2002 for all English-language articles related to the QT interval. Additional data sources included bibliographies of articles identified on MEDLINE, a survey of experts, and data presented at a meeting of experts on long QT syndrome. STUDY SELECTION: We selected for review registries and case series examining clinical outcomes of patients with prolonged QT interval and the effect of different methods of measurement of the QT interval on patient outcomes. Ten studies were identified, of which 6 were included in the analysis. DATA EXTRACTION: Data quality was determined by publication in the peer-reviewed literature. DATA SYNTHESIS: Optimal measurement of the QT interval is problematic because of lack of standardization and lack of data regarding the best way to adjust for heart rate. Reliable information on the proper use of QT-prolonging medications is scarce. Although a QT interval of at least 500 milliseconds generally has been shown to correlate with a higher risk of torsades de pointes, there is no established threshold below which prolongation of the QT interval is considered free of proarrhythmic risk. The risk of torsades de pointes should be assessed in patients who are about to begin taking a QT-prolonging medication. Although inadequate clinical studies preclude prediction of absolute risk for individual patients, particularly high-risk situations can be defined based on clinical variables. We propose recommendations on proper monitoring of the QT interval in patients receiving QT-prolonging medications. CONCLUSION: Although the use of QT-prolonging medications can predispose to torsades de pointes, there is a relative paucity of information that can help clinicians and patients make optimal informed decisions about how best to minimize the risk of this serious complication.

Drug Interactions↗

PubMedDate not supplied

Improving communication of drug risks to prevent patient injury: proceedings of a workshop.

PURPOSE: The Centers for Education & Research on Therapeutics (CERTs) is conducting a series of workshops on managing the risks of therapeutics, with the ultimate goal to develop an agenda for research and education about risk and its management. This paper presents the results of the first workshop in the series, a 2-day meeting focused on communication of drug risks to healthcare professionals and patients. METHODS: The 50 workshop participants represented the medical-products industry, academia, consumer groups, regulatory bodies and the media. Together, they sought to identify and understand barriers to successful risk communication, to identify tools or methods that could improve risk communication, and to develop research and education agendas that would lead to better risk communication in the future. RESULTS: Limitations of current methods of risk communication were identified, and research and education agendas were proposed to clarify and resolve these issues. CONCLUSION: Common themes for potential solutions include enhanced education of healthcare providers, increased motivation of patients and families, use of creative communication technologies, and better organization of and access to medical records and information.

Communication↗

PubMedDate not supplied

AHA scientific statement: practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association Scientific Statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized electrocardiology and the American Association of Critical-Care Nurses.

The goals of electrocardiographic (ECG) monitoring in hospital settings have expanded from simple heart rate and basic rhythm determination to the diagnosis of complex arrhythmias, myocardial ischemia, and prolonged QT interval. Whereas Computerized arrhythmia analysis is automatic in cardiac monitoring systems, computerized ST-segment ischemia analysis is available only in newer-generation monitors, and computerized QT-interval monitoring is currently unavailable. Even in hospitals with ST-monitoring capability, ischemia monitoring is vastly underutilized by healthcare professionals. Moreover, because no computerized analysis is available for QT monitoring, healthcare professionals must determine when it is appropriate to manually measure QT intervals (eg, when a patient is started on a potentially proarrhythmic drug). The purpose of the present review is to provide "best practices" for hospital ECG monitoring. Randomized clinical trials in this area are almost nonexistent; therefore, expert opinions are based upon clinical experience and related research in the field of electrocardiography. This consensus document encompasses all areas of hospital cardiac monitoring in both children and adults. The emphasis is on information clinicians need to know to monitor patients safely and effectively. Recommendations are made with regard to indications, time frames, and strategies to improve the diagnostic accuracy of cardiac arrhythmia, ischemia, and QT-interval monitoring. Currently available ECG lead systems are described, and recommendations related to staffing, training, and methods to improve quality are provided.

Arrhythmias, Cardiac↗

PubMedDate not supplied

Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report.

OBJECTIVE: The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD). METHOD: Consensus of experts. RESULTS: Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients. CONCLUSIONS: This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area.

Antidepressive Agents↗

PubMedDate not supplied

Defining the balance of risk and benefit in the era of genomics and proteomics.

The ability to measure the function of genes and proteins has spawned the construct of personalized medicine, in which patients' own risks and preferences are used to choose diagnostic and therapeutic strategies. The complexity of clinical data required to guide personalized medicine calls for improvements in our system of clinical research, including (1) overhauling it to produce networks that can do adequate-size pragmatic trials; (2) synchronization of regulatory and payment systems to encourage adequate studies; and (3) an investment in education of providers and patients to improve the understanding of the probabilistic predictions forming the basis of personalized medicine.

Clinical Trials as Topic↗

PubMedDate not supplied

How changes in drug-safety regulations affect the way drug and biotech companies invest in innovation.

Changes in the economics of product development resulting from heightened safety regulations could have a sizable negative impact on drug and biotechnology companies' decisions about investing in innovation. We developed a model to compare the potential economic effects of pre- and postmarketing strategies to identify safety problems with new drugs. Although expanding Phase III clinical testing and postmarketing safety surveillance are not perfect substitutes, our findings suggest that even a large increase in funding for the latter will have a relatively small adverse impact on investment decisions by drug companies and venture capital firms, compared with the former.

Biotechnology↗

PubMedDate not supplied

Curbing the cardiovascular disease epidemic: aligning industry, government, payers, and academics.

Despite decades of progress in the diagnosis, treatment, and prevention of cardiovascular disease, its prevalence continues to grow in both developed and developing countries. We have constructed a model, the "cycle of quality," which connects the innovation of initial scientific discovery with validated methods of translating research into effective delivery. This model can serve as a basis for evaluating proposed efforts to improve interactions among private and public aspects of health care to accelerate development and appropriate adoption of new treatments, and to achieve greater penetration of effective behavioral therapies and established technologies, resulting in major improvements in cardiovascular health.

Cardiovascular Diseases↗