PubMed Health⌕ Search

Biomedical subjects

M Proschan

Publications and source records attributed to M Proschan.

14 recordsLinked to original sources
PubMed2005

Comparing office-based and ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring (ABPM) is commonly used in clinical trials. Yet, its ability to detect blood pressure (BP) change in comparison to multiple office-based measurements has received limited attention. We recorded ambulatory and five daily pairs of random zero (RZ) BPs pre- and post-intervention on 321 adult participants in the multicentre Dietary Approaches to Stop Hypertension trial. Treatment effect estimates measured by ambulatory monitoring were similar to those measured by RZ and did not differ significantly for waking vs 24-h ambulatory measurements. For systolic BP, the standard deviations of change in mean 24-h ambulatory BP (8.0 mmHg among hypertensives and 6.0 mmHg among nonhypertensives) were comparable to or lower than the corresponding standard deviations of change in RZ-BP based on five daily readings (8.9 and 5.9 mmHg). The standard deviations of change for mean waking ambulatory BP (8.7 and 6.7 mmHg) were comparable to those obtained using three to four daily RZ readings. Results for diastolic BP were qualitatively similar. Ambulatory monitoring was more efficient (ie, a smaller sample size could detect a given BP change) than three to four sets of daily RZ readings and required fewer clinic visits. The average of 33 ambulatory BP readings during the waking hours had an efficiency comparable to that from the mean of four daily pairs of RZ-BPs. Participants readily accepted the ABPM devices, and their use requires less staff training. ABPM provides a useful alternative to RZ-BP measurements in clinical trials.

Adult↗
PubMed2004

Public-access defibrillation and survival after out-of-hospital cardiac arrest.

BACKGROUND: The rate of survival after out-of-hospital cardiac arrest is low. It is not known whether this rate will increase if laypersons are trained to attempt defibrillation with the use of automated external defibrillators (AEDs). METHODS: We conducted a prospective, community-based, multicenter clinical trial in which we randomly assigned community units (e.g., shopping malls and apartment complexes) to a structured and monitored emergency-response system involving lay volunteers trained in cardiopulmonary resuscitation (CPR) alone or in CPR and the use of AEDs. The primary outcome was survival to hospital discharge. RESULTS: More than 19,000 volunteer responders from 993 community units in 24 North American regions participated. The two study groups had similar unit and volunteer characteristics. Patients with treated out-of-hospital cardiac arrest in the two groups were similar in age (mean, 69.8 years), proportion of men (67 percent), rate of cardiac arrest in a public location (70 percent), and rate of witnessed cardiac arrest (72 percent). No inappropriate shocks were delivered. There were more survivors to hospital discharge in the units assigned to have volunteers trained in CPR plus the use of AEDs (30 survivors among 128 arrests) than there were in the units assigned to have volunteers trained only in CPR (15 among 107; P=0.03; relative risk, 2.0; 95 percent confidence interval, 1.07 to 3.77); there were only 2 survivors in residential complexes. Functional status at hospital discharge did not differ between the two groups. CONCLUSIONS: Training and equipping volunteers to attempt early defibrillation within a structured response system can increase the number of survivors to hospital discharge after out-of-hospital cardiac arrest in public locations. Trained laypersons can use AEDs safely and effectively.

Adolescent↗
PubMed1999

Internal pilot studies I: type I error rate of the naive t-test.

When sample size is recalculated using unblinded interim data, use of the usual t-test at the end of a study may lead to an elevated type I error rate. This paper describes a numerical quadrature investigation to calculate the true probability of rejection as a function of the time of the recalculation, the magnitude of the detectable treatment effect, and the ratio of the guessed to the true variance. We consider both 'restricted' designs, those that require final sample size at least as large as the originally calculated size, and 'unrestricted' designs, those that permit smaller final sample sizes than originally calculated. Our results indicate that the bias in the type I error rate is often negligible, especially in restricted designs. Some sets of parameters, however, induce non-trivial bias in the unrestricted design.

Bias↗
PubMed1998

Clinical and detailed angiographic findings in patients with ambulatory electrocardiographic ischemia without critical coronary narrowing: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study.

BACKGROUND: Patients with ambulatory electrocardiographic (AECG) ST-segment depression and critical coronary narrowing are known to be at increased risk for adverse outcome, but little is known about patients with AECG ST-segment depression without critical coronary narrowing. HYPOTHESIS: The objectives of this study were to characterize the coronary angiographic pathology in patients with AECG ST-segment depression but without critical (< 50% diameter stenosis) coronary narrowing and to compare demographic and clinical findings in these patients with those enrolled in the Asymptomatic Cardiac Ischemia Pilot Study with AECG ST-segment depression and critical (> or = 50% diameter stenosis) coronary narrowing. METHODS: Coronary angiograms from patients with AECG ST-segment depression were reviewed in a central laboratory and quantitative measurement of percent stenosis was performed. Clinical and angiographic comparisons were made between patients with and without critical coronary narrowing. RESULTS: Patients without critical coronary narrowing (n = 64) were younger (p = 0.02), less likely to be male (p < 0.001) or to have risk factors for coronary atherosclerosis or a history of myocardial infarction (p < 0.001), and had fewer ischemic episodes per 24 h on the screening AECG (p = 0.02) than patients with critical coronary narrowing (n = 441). Of patients without critical narrowing, one half had angiographic evidence for coronary artery disease (> or = 20% stenosis) and 60% had an ejection fraction > 70%. CONCLUSIONS: Patients with AECG ST-segment depression without critical coronary narrowing are heterogeneous, with half having measurable coronary artery disease. Demographically and clinically, they appear to be different than patients with AECG ST-segment depression with critical coronary narrowing.

Coronary Angiography↗
PubMed1996

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.

BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Coronary Disease↗
PubMed1996

Patterns and behavior of transient myocardial ischemia in stable coronary disease are the same in both men and women: a comparative study.

OBJECTIVES: This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease. BACKGROUND: There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects. METHODS: Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring. RESULTS: There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.0001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 PM, corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemic threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase > 5 beats/min in the 5 min before ischemia, but there were no gender differences. CONCLUSIONS: Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation in underlying coronary vascular tone.

Acute Disease↗
PubMed1996

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents↗
PubMed1996

Meta-analysis of clinical trials: a consumer's guide.

Meta-analysis is a popular statistical tool allowing the synthesis of related research studies in a quantitative manner. Components of a good meta-analysis are first discussed, with a view toward critical reading of reports of meta-analyses. Examples include lipid-lowering drugs and coronary artery bypass graft surgery. A role for meta-analysis in the design and monitoring of clinical trials was examined at a workshop held at the National Institutes of Health and aspects of these uses of meta-analyses are considered. Basic analytical and graphical methods of meta-analysis are briefly reviewed. The goal is to encourage more thoughtful evaluation of the many meta-analyses that are published or are presented.

Clinical Trials as Topic↗
PubMed1994

Sample size calculation for clinical trials in which entry criteria and outcomes are counts of events. ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot.

In many chronic diseases, therapy aims to prevent or reduce the frequency of episodes of a disease manifestation, for example cardiac ischaemic episodes or epileptic seizures. Entry criteria for clinical trials typically include a minimum number of episodes within a baseline period, and regression to the mean should be anticipated. The distribution of the number of episodes at follow-up, the statistical power for treatment comparisons, and the difficulty of recruitment will depend on the entry criterion chosen. A gamma-Poisson mixture model is employed to describe the regression to the mean when the entry criterion and outcome measure are counts of discrete events. Sample size formulae which take account of the entry criterion are derived for comparison of mean number of events at follow-up and the proportion of patients with zero events at follow-up. Application of these formulae to screening data from the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study is presented as an example.

Clinical Trials as Topic↗
PubMed1993

Data monitoring in the cardiac arrhythmia suppression trial.

OBJECTIVE: This report discusses practical aspects of data monitoring in a clinical trial which stopped ahead of schedule due to adverse findings. DESIGN: A review of the considerations and decisions made by the data-monitoring committee of the Cardiac Arrhythmia Suppression Trial (CAST), a randomized, double-blind clinical trial. PATIENTS: CAST consisted of men and women with a recent myocardial infarction, asymptomatic or minimally symptomatic ventricular arrhythmias, and reduced left ventricular ejection fraction. INTERVENTIONS: In CAST, 3 antiarrhythmic agents, encainide, flecainide, and moricizine, were compared against placebo. MAIN OUTCOME MEASURES: The main outcome measures in CAST were arrhythmic death and total mortality. RESULTS: CAST found the 3 agents to be harmful. Encainide and flecainide were stopped first. Subsequently, moricizine was discontinued ahead of schedule. CONCLUSIONS: The complexity of the study design and a midcourse protocol modification raise several data-monitoring issues not previously discussed. These include how to handle apparently dramatic yet unexpected results, the need for flexibility in modifying study design and goals, and the conflict between existing study data and both conventional wisdom and medical practice.

Anti-Arrhythmia Agents↗
PubMed1993

Identification of a secondary peak in myocardial infarction onset 11 to 12 hours after awakening: the Cardiac Arrhythmia Suppression Trial (CAST) experience.

OBJECTIVES: The purpose of this study was to assess the relation between the time of awakening and the time of onset of acute myocardial infarction. BACKGROUND: Previous investigation has shown the onset of symptoms of acute myocardial infarction to have a primary peak 1 to 2 h after awakening. In studies not corrected for time of awakening, there appears to be a late afternoon/early evening peak, but data correlating the onset of symptoms with awakening have been limited by small numbers of patients, perhaps precluding identification of a secondary peak. METHODS: In the Cardiac Arrhythmia Suppression Trial (CAST), 3,549 patients had a documented myocardial infarction and entered antiarrhythmic drug titration. Of these, 3,309 had data on the onset of symptoms relative to the time of awakening and form the basis of this report. RESULTS: A total of 870 patients (26.3%) were awakened by symptoms. Of the remaining 2,439 patients who were not awakened by symptoms, 798 (32.7%) experienced the onset of symptoms in the 1st 4 h after awakening (with the highest number in the 1st h), after which the incidence of symptom onset decreased in a linear fashion, with a secondary peak 11 to 12 h after awakening. Both peaks are statistically significant. A similar pattern was seen in most of the subgroups examined (based on age, gender and various other demographic characteristics). CONCLUSIONS: Analysis of the very large CAST data base confirms the relation between awakening and onset of symptoms of myocardial infarction, suggesting involvement of the morning catecholamine surge. A secondary peak in symptom onset, occurring 11 to 12 h after awakening, is a new observation and may relate to ingestion of the evening meal or other trigger factors concentrated in those hours.

Aged↗
PubMed1991

Errors in pressure gradient measurement by continuous wave Doppler ultrasound: type, size and age effects in bioprosthetic aortic valves.

The accuracy of continuous wave Doppler ultrasound in deriving pressure gradients across bioprosthetic heart valves was evaluated in an in vitro pulse duplicator. Simultaneous pressure transducer and Doppler measurements were made in new and explanted aortic bioprosthetic valves of several sizes and four types: Carpentier-Edwards, Ionescu-Shiley, Hancock standard and Hancock modified. The mean and peak gradients calculated by the modified Bernoulli equation from Doppler velocity measurements were always greater than those measured manometrically, despite corrections for location dependence of the manometric gradient (or pressure recovery). The relation between manometric and ultrasonically determined gradient was found to be statistically dependent on the valve type (mean gradient p less than 0.0001; peak gradient p = 0.0003) and size (mean gradient p = 0.0089; peak gradient p = 0.0107). Effects of implantation were observed, but were not shown to be significant. It is concluded that the continuous wave Doppler velocity data overestimated prosthetic valve pressure gradient in all cases, even when pressure recovery was taken into account. Clinicians should be wary of Doppler data when making major diagnostic or therapeutic decisions.

Aortic Valve↗