Biomedical subjects

M A Proschan

Publications and source records attributed to M A Proschan.

15 recordsLinked to original sources

PubMed1998

Statistical design of REACT (Rapid Early Action for Coronary Treatment), a multisite community trial with continual data collection.

Unusual problems in statistical design were faced by Rapid Early Action for Coronary Treatment (REACT), a multisite trial testing a community intervention to reduce the delay between onset of symptoms of acute myocardial infarction (MI) and patients' arrival at a hospital emergency department. In 20 pair-matched U.S. communities, hospital staff members recorded delay time throughout a 4-month baseline period and the subsequent 18-month intervention period, during which one randomly selected community of each pair received a campaign of public and professional education. To exploit the continual nature of its data-collection protocol, REACT estimated the trend of delay time separately in each community by linear regression, adjusting for age, sex, and history of MI, and compared the ten adjusted slopes from intervention communities with those from control communities by a paired t-test. Power calculations based on the analytical model showed that with K=600-800 cases per community, REACT would have 80% power to demonstrate a differential reduction of 30 min in mean delay time between intervention and control communities, as well as effects on a variety of secondary outcomes. Sensitivity analysis confirmed that the number of communities was optimal within constraints of funding and that the detectable effect depended weakly on the effectiveness of matching but strongly on K, helping the investigators set operational priorities. The methodologic strategy developed for REACT should prove useful in the design of similar trials in the future.

Emergencies↗

PubMed1998

Rapid early action for coronary treatment: rationale, design, and baseline characteristics. REACT Research Group.

OBJECTIVE: Early reperfusion for acute myocardial infarction (AMI) can reduce morbidity and mortality, yet there is often delay in accessing medical care after symptom onset. This report describes the design and baseline characteristics of the Rapid Early Action for Coronary Treatment (REACT) community trial, which is testing community intervention to reduce delay. METHODS: Twenty U.S. communities were pair-matched and randomly assigned within pairs to intervention or comparison. Four months of baseline data collection was followed by an 18-month intervention of community organization and public, patient, and health professional education. Primary cases were community residents seen in the ED with chest pain, admitted with suspected acute cardiac ischemia, and discharged with a diagnosis related to coronary heart disease. The primary outcome was delay time from symptom onset to ED arrival. Secondary outcomes included delay time in patients with MI/unstable angina, hospital case-fatality rate and length of stay, receipt of reperfusion, and ED/emergency medical services utilization. Impact on public and patient knowledge, attitudes, and intentions was measured by telephone interviews. Characteristics of communities and cases and comparability of paired communities at baseline were assessed. RESULTS: Baseline cases are 46% female, 14% minorities, and 73% aged > or =55 years, and paired communities have similar demographics characteristics. Median delay time (available for 72% of cases) is 2.3 hours and does not vary between treatment conditions (p > 0.86). CONCLUSIONS: REACT communities approximate the demographic distribution of the United States and there is baseline comparability between the intervention and comparison groups. The REACT trial will provide valuable information for community educational programs to reduce patient delay for AMI symptoms.

Adult↗

PubMed1996

On the distribution of the unpaired t-statistic with paired data.

I derive the exact distribution of the unpaired t-statistic computed when the data actually come from a paired design. I use this to prove a result Diehr et al. obtained by simulation, namely that the type I error rate of this procedure is no greater than alpha regardless of the sample size. I provide a formula to use in computation of power and type I error rate.

Analysis of Variance↗

PubMed1995

Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure.

Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current consumption. The first experimental diet, arguably termed "ideal," is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African-American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommendations to the general public.

Adult↗

PubMed1995

Designed extension of studies based on conditional power.

We propose a flexible method of extending a study based on conditional power. The possibility for extension when the p value at the planned end is small but not statistically significant is built in to the design of the study. The significance of the treatment difference at the planned end is used to determine the number of additional observations needed and the critical value necessary for use after accruing those additional observations. It may therefore be thought of as a two-stage procedure. Even though the observed treatment difference at stage 1 is used to make decisions, the Type I error rate is protected.

Biometry↗

PubMed1994

Morphology of the "athlete's heart" assessed by echocardiography in 947 elite athletes representing 27 sports.

In the present study, we used echocardiography to investigate the morphologic adaptations of the heart to athletic training in 947 elite athletes representing 27 sports who achieved national or international levels of competition. Cardiac morphology was compared for these sports, using multivariate statistical models. Left ventricular (LV) diastolic cavity dimension above normal (> 54 mm, ranging up to 66 mm) was identified in 362 (38%) of the 947 athletes. LV wall thickness above normal (> 12 mm, ranging up to 16 mm) was identified in only 16 (1.7%) of the athletes. Athletes training in the sports examined showed considerable differences with regard to cardiac dimensions. Endurance cyclists, rowers, and swimmers had the largest LV diastolic cavity dimensions and wall thickness. Athletes training in sports such as track sprinting, field weight events, and diving were at the lower end of the spectrum of cardiac adaptations to athletic training. Athletes training in sports associated with larger LV diastolic cavity dimensions also had higher values for wall thickness. Athletes training in isometric sports, such as weightlifting and wrestling, had high values for wall thickness relative to cavity dimension, but their absolute wall thickness remained within normal limits. Analysis of gender-related differences in cardiac dimensions showed that female athletes had smaller LV diastolic cavity dimension (average 2 mm) and smaller wall thickness (average 0.9 mm) than males of the same age and body size who were training in the same sport.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Circadian variability in the occurrence of sudden cardiac death in patients with hypertrophic cardiomyopathy.

OBJECTIVES: The present study examined whether sudden death in patients with hypertrophic cardiomyopathy occurred with a particular pattern of frequency throughout the day. BACKGROUND: Previous investigators have shown a circadian distribution in the occurrence of sudden death and other cardiovascular events in patients with atherosclerotic coronary artery disease. Sudden death is also an important feature of the natural history of patients with hypertrophic cardiomyopathy. METHODS: The study group comprised 94 patients with a time of death (or cardiac arrest) that could be ascertained accurately to the nearest hour. This hourly distribution was analyzed by harmonic regression. RESULTS: Sudden death did not occur uniformly or randomly throughout the day. Rather, it was distributed in a bimodal pattern that conformed to a two-harmonic regression model. A disproportionate number of sudden deaths (43 [46%] of 94) occurred in the first peak in midmorning between 7 AM and 1 PM. The second peak of sudden death was less distinct but was in the early evening, between 8 PM and 10 PM. This periodicity in occurrence of sudden cardiac death was not evident for the days of the week or months of the year and, furthermore, did not appear to be influenced by other clinical variables, such as age, gender, severity of symptoms, subaortic gradient or left ventricular wall thickness. Sudden death occurred most commonly during periods of severe exertion (37 [39%] of 94). CONCLUSIONS: Sudden death in hypertrophic cardiomyopathy demonstrates a bimodal pattern of circadian variability over the 24-h day, with a prominent midmorning peak similar to that described in patients with coronary artery disease, and a less striking early-evening peak of occurrence. These findings suggest that temporally related physiologic changes, possibly in the electrical vulnerability of the myocardial substrate, may play a role in the sudden death of patients with hypertrophic cardiomyopathy.

Adolescent↗

PubMed1994

Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation.

PURPOSE: To assess the reliability of electron beam computed tomography (CT) in the detection of calcific deposits in coronary arteries. MATERIALS AND METHODS: The authors quantitatively evaluated a total of 4,298 segments of coronary arteries with electron beam CT and histomorphometry. RESULTS: Regression analysis of the electron beam CT calcium score versus histomorphometric calcium area produced an r2 value of .92 (r = .96; P < .0001). Ninety-three percent (78 of 84) of all coronary arteries with stenosis of 76%-100% contained calcific deposits, and 20% (17 of 83) of all coronary arteries with stenosis of 0%-50% contained calcific deposits. CONCLUSION: The amount of calcific deposits detected with electron beam CT correlates highly with histomorphometric measurements. Also, the amount of calcific deposits correlates well with the degree of coronary artery stenosis. Electron beam CT, therefore, is a promising noninvasive technique that can help depict the presence and extent of atherosclerotic plaques.

Adult↗

PubMed1994

Coronary artery disease: prediction with in vitro electron beam CT.

PURPOSE: To investigate the potential to predict coronary artery disease with electron beam computed tomography (CT). MATERIALS AND METHODS: Fifty heart specimens were examined with electron beam CT and histomorphometric techniques to measure calcific deposits as a percentage of blockage. RESULTS: In group A specimens (from cadavers of patients with symptomatic coronary artery disease), calcific deposits were identified at electron beam CT in 41% (584 of 1,426) of all segments of coronary arteries; in group B specimens (with asymptomatic coronary artery disease), in 24% (369 of 1,535) of all segments; and in the normal control specimens, in 4% (47 of 1,337) of all segments; segments (group A vs control specimens, P < .0001; group B vs control specimens, P = .02). On the basis of logistic regression analysis, coronary artery disease would be predicted if the average electron beam CT calcium score exceeds 0.32. The sensitivity and specificity of electron beam CT in the detection of calcific deposits per coronary artery was 94% and 76%, respectively. CONCLUSION: The electron beam CT calcium score appears to be an effective predictor of coronary artery disease.

Adult↗

PubMed1994

Monitoring pairwise comparisons in multi-armed clinical trials.

This paper proposes a method for monitoring multi-armed clinical trials on the basis of pairwise comparisons between arms. The set of pairwise test statistics is examined during the course of the trial in order to make decisions about hypotheses, continuation of treatment arms, and continuation of the trial. Strong control of the Type I error rate is achieved by modifying two-armed group sequential procedures of Pocock (1977, Biometrika 64, 191-199), O'Brien and Fleming (1979, Biometrics 35, 549-556), and Lan and DeMets (1983, Biometrika 70, 659-663) to multi-armed trials. In the fixed-sample situation, these methods reduce to either Dunnett's or Tukey's procedure for multiple comparisons. A simpler, more flexible approximation based on the Bonferroni inequality is suggested, as well as an analogue to a sequentially rejective procedure.

Clinical Trials as Topic↗

PubMed1993

Comparison of mitral valve dimensions in adults with valvular aortic stenosis, pure aortic regurgitation and hypertrophic cardiomyopathy.

To assess the effect of left ventricular dilatation on mitral valve size, this study compared the dimensions of the mitral valve in patients with aortic valve disease and hypertrophic cardiomyopathy (HC). A total of 216 valves, removed at operation or necropsy, was analyzed by quantitative morphometric methods from: (1) 2 patient groups with dilated left ventricular cavities (i.e., 17 patients with dilated valvular aortic stenosis [AS] and 31 with pure aortic regurgitation), (2) 2 patient groups without dilated left ventricular cavities (i.e., 29 patients with nondilated AS and 94 with HC), and (3) 45 control subjects without heart disease. Mean mitral leaflet areas in patients with AS with dilated left ventricular cavities (13.1 +/- 3.0 cm2) and aortic regurgitation (12.0 +/- 3.6 cm2) were significantly greater than in control subjects (8.7 +/- 2.0 cm2; p < 0.001). Mean mitral leaflet areas in patients with AS without dilated left ventricular cavities (9.8 +/- 2.0 cm2) were similar to those of normal valves (p = NS). However, mean mitral leaflet area in patients with HC, in whom left ventricular cavities were also nondilated, was significantly greater (12.8 +/- 3.7 cm2) than in those with nondilated AS and in normal subjects (p < 0.001). Therefore, increased mitral leaflet area: (1) is often present in patients with aortic valve disease with dilated left ventricles in whom it appears to be secondary to left ventricular chamber dilatation; and (2) cannot be attributed to left ventricular cavity dilatation in patients with HC, since their cavities were of normal or small size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Echocardiographic assessment of mitral valve size in obstructive hypertrophic cardiomyopathy. Anatomic validation from mitral valve specimen.

BACKGROUND: In patients with hypertrophic cardiomyopathy, obstruction to left ventricular outflow is produced by systolic anterior motion of the mitral valve. In many of these patients, the mitral leaflets are elongated and increased in overall size. Mitral valve size may be responsible, in part, for the presence and magnitude of the outflow gradient and the pattern of systolic anterior motion of the leaflets. It may also influence the effectiveness of ventricular septal myotomy-myectomy in relieving subaortic obstruction. Therefore, the present study was undertaken to determine whether mitral valve dimensions could be assessed in quantitative terms from the echocardiogram in patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: A group of 37 patients with hypertrophic cardiomyopathy was selected for this study by virtue of having a high-quality transthoracic or intraoperative echocardiogram suitable for certain quantitative measurements from stop-frame images as well as a morphologically intact mitral valve specimen (removed during surgery). Seven measurements of mitral valve dimensions were obtained from the two-dimensional and M-mode echocardiograms. A univariate regression analysis identified the mitral valve opening area as the best single predictor of actual mitral leaflet area measured from the specimen (r2 = .75; r = .87). The linear relation between mitral valve opening area as assessed by two-dimensional echocardiography and actual mitral leaflet area measured from the mitral valve specimen accounted for approximately 75% of the variability in mitral leaflet area. With such statistical models, it was possible to reliably identify from the echocardiogram enlarged mitral valves (> or = 12.0 cm2) in 16 of 19 patients (84%) and normal-sized valves in 15 of 18 patients (83%). CONCLUSIONS: In a selected group of patients with obstructive hypertrophic cardiomyopathy, a model derived from a regression analysis of quantitative echocardiographic measurements permitted (with good precision) estimation of actual mitral leaflet area and consequently overall mitral valve size and the discrimination of enlarged from normal-sized mitral valves.

Adolescent↗

PubMed1991

The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes.

BACKGROUND: In some highly trained athletes, the thickness of the left ventricular wall may increase as a consequence of exercise training and resemble that found in cardiac diseases associated with left ventricular hypertrophy, such as hypertrophic cardiomyopathy. In these athletes, the differential diagnosis between physiologic and pathologic hypertrophy may be difficult. METHODS: To address this issue, we measured left ventricular dimensions with echocardiography in 947 elite, highly trained athletes who participated in a wide variety of sports. RESULTS: The thickest left ventricular wall among the athletes measured 16 mm. Wall thicknesses within a range compatible with the diagnosis of hypertrophic cardiomyopathy (greater than or equal to 13 mm) were identified in only 16 of the 947 athletes (1.7 percent); 15 were rowers or canoeists, and 1 was a cyclist. Therefore, the wall was greater than or equal to 13 mm thick in 7 percent of 219 rowers, canoeists, and cyclists but in none of 728 participants in 22 other sports. All athletes with walls greater than or equal to 13 mm thick also had enlarged left ventricular end-diastolic cavities (dimensions, 55 to 63 mm). CONCLUSIONS: On the basis of these data, a left-ventricular-wall thickness of greater than or equal to 13 mm is very uncommon in highly trained athletes, virtually confined to athletes training in rowing sports, and associated with an enlarged left ventricular cavity. In addition, the upper limit to which the thickness of the left ventricular wall may be increased by athletic training appears to be 16 mm. Therefore, athletes with a wall thickness of more than 16 mm and a nondilated left ventricular cavity are likely to have primary forms of pathologic hypertrophy, such as hypertrophic cardiomyopathy.

Adult↗

PubMedDate not supplied

Monitoring multi-armed trials.

We propose and discuss several methods of monitoring multi-armed trials comparing means or survival. These methods combine multiple comparison procedures such as Fisher's LSD, Newman-Keuls and Tukey's with monitoring boundaries such as those of O'Brien and Fleming and Lan and DeMets. Tables of boundaries are provided for the equal variance or equal censoring distribution case.

Bias↗

PubMedDate not supplied

Reproducibility of mental stress-induced myocardial ischemia in the Psychophysiological Investigations of Myocardial Ischemia (PIMI).

OBJECTIVE: Many patients with coronary artery disease (CAD) develop myocardial ischemia in response to mental stress. This has been documented both in the natural environment and in the laboratory. However, the reproducibility of laboratory mental stress-induced ischemia has not been investigated. METHOD: Sixty patients with documented CAD and a positive exercise stress test discontinued cardiac medications and underwent two standardized mental stress tests (a timed Stroop Color-Word test and a public speaking task) in a nuclear cardiology laboratory (Visit 1), and repeated this procedure between 2 and 8 weeks later (Visit 2). Measurements of cardiovascular function and neurohormonal responses were obtained throughout testing, and mood state was assessed before and after testing. RESULTS: Sixty-eight percent of the 56 patients with detailed radionuclide data from both visits had consistent responses (ie, ischemia either present during both sessions or absent during both) to the Stroop task (kappa = .29, p = .03), 61% had consistent responses to the speech task (kappa = .20, p = .12), and 60% had consistent responses when ischemia was considered present if it occurred during either the Stroop test, the speech task, or both, and absent if it did not occur during either task (kappa = .22, p = .07). Hemodynamic and neuroendocrine responses to the tests were moderately reproducible. CONCLUSIONS: We conclude that two popular laboratory tests for mental stress-induced myocardial ischemia are modestly reproducible. The relatively low reproducibility is probably influenced by uncertainties in detecting relatively small changes in wall motion, habituation of the patient to repeated exposure to psychological stressors, and physiological differences in threshold for ischemia on different days of testing.

Adult↗