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Biomedical subjects

L M Friedman

Publications and source records attributed to L M Friedman.

36 records · Page 2Linked to original sources
PubMed1987

Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction.

Twenty-four hour ambulatory electrocardiography was performed on 3,290 survivors of acute myocardial infarction participating in the Beta-Blocker Heart Attack Trial (BHAT). History of myocardial infarction before the qualifying event, congestive heart failure and age were independently associated with the frequency and complexity of ventricular premature beats. Of the 1,640 patients randomized to placebo therapy, 163 died (76 suffered sudden death) during a 25 month average follow-up period. Ventricular ectopic activity was an independent predictor of total mortality after taking into consideration 16 other prognostic factors describing past history, risk factors, physical examination and laboratory investigations. Seven categoric definitions of ventricular ectopic activity predicted mortality, with similar odds ratios ranging from 2.27 to 2.69. A reciprocal relation of the sensitivity and specificity of each definition in predicting mortality was observed. Three clinical criteria (ST depression, cardiomegaly and prior infarction) allowed stratification of patients into four subsets with respective mortality rates of 35.5% (three criteria present), 19.0% (two criteria), 11.5% (one criterion) and 4.7% (none). Presence of ventricular ectopic activity (greater than or equal to 10 ventricular premature beats/h or pairs, ventricular tachycardia or multiform complexes) was associated with higher mortality rates in all four risk strata. The relative risk was higher (3.86) in the lowest risk stratum (mortality 2.4% without and 9.1% with ventricular ectopic activity). Thus, in survivors of acute myocardial infarction, ventricular ectopic activity was more pronounced in patients with prior myocardial infarction and congestive heart failure. It predicted mortality independently of other factors. Although mortality ratios were similar for all seven arrhythmia definitions, a reciprocal relation between sensitivity and specificity of the definitions in predicting mortality existed; ventricular ectopic activity was associated with increased mortality in all risk strata, but with a higher risk ratio in the numerically larger, low risk subset.

Arrhythmias, Cardiac↗
PubMed1986

Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia.

The Beta-Blocker Heart Attack Trial was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to patients who had had at least one myocardial infarction. Among 3,837 patients followed up for an average of 25 months, 3,290 (85.7%) had 24 hour ambulatory electrocardiograms performed at the baseline examination. Four classifications of arrhythmia were examined. One of these, the presence of complex ventricular arrhythmias (at least 10 ventricular premature beats/h, or at least one pair or run of ventricular premature beats or multiform ventricular premature beats) was the subgroup of major interest. Regardless of the classification, the presence of arrhythmia identifies a group of patients with a higher risk of total mortality, coronary heart disease mortality, sudden cardiac death and instantaneous cardiac death. The a priori subgroup hypothesis that sudden death would be preferentially reduced by propranolol in patients with complex ventricular arrhythmias was not supported. The relative benefit of propranolol in reducing sudden death for this subgroup was 28 versus 16% for the subgroup without ventricular arrhythmia (relative risk of 0.72 versus 0.84, a nonsignificant relative difference of 14%). There were similar findings for two of the three other classifications of arrhythmia and for the other response variables. Although propranolol does not appear to be of special relative benefit in patients with ventricular arrhythmia, the presence of the arrhythmia does identify a high-risk group. The mechanism by which propranolol reduces mortality is still unclear, but is probably not solely an antiarrhythmic one.

Adult↗
PubMed1985

Enhancement of visit adherence in the national beta-blocker heart attack trial.

Efforts were made in the Beta Blocker Heart Trial (BHAT), a double-blind study of 3837 post-MI patients, to enhance visit adherence, a measure of compliance that is not subjective and can be easily monitored. Of the required visits, 93.9% were completed in the window, 3.9% of the patients were classified as dropouts and 12 persons were lost to follow-up. Methods used to enhance compliance varied with circumstances but included appointment reminders, assistance with transportation, minimal waiting times, newsletters, continuity of care, involvement of family members, and close contact with private physicians. Comparisons of the BHAT visit adherence rates to those from other clinical trials are difficult to make because there are few reports in the literature regarding follow-up in large multicenter clinical trials. However, data obtained through personal communications, as well as published reports, indicate that adherence in primary prevention trials was generally less than that of secondary prevention trials. Adherence rates in the BHAT tended to be slightly higher than those of comparable trials.

Adult↗
PubMed1985

Termination of clinical trials: the beta-blocker heart attack trial and the hypertension detection and follow-up program experience.

The close-out of clinical trials that end ahead of schedule often involves problems that differ from those of trials that end as planned. The Beta-Blocker Heart Attack Trial (BHAT), a double-blind study of 3837 post-myocardial infarction patients, was a multicenter clinical trial that ended early because therapeutic benefit had been demonstrated. The Hypertension Detection and Follow-up Program (HDFP), a randomized unblinded study of 10,940 hypertensive individuals, was a multicenter trial that ended as planned. Using these trials as illustrations, the issues arising in multicenter trials that end ahead of schedule are contrasted to those that arise in trials that end as scheduled. Close-out activities that are discussed include documentation of close-out procedures, release of trial information, preparation of trial participants and staff, ascertaining vital status, continuing patient care, data collection and coding, and publication of trial results. Because of the possibility a study might end early, advance planning for close-out is essential.

Adult↗
PubMed1985

Assessment of angina pectoris after myocardial infarction: comparison of "Rose Questionnaire" with physician judgment in the Beta-Blocker Heart Attack Trial.

The London School of Hygiene Cardiovascular Questionnaire (Rose Questionnaire) was compared with physician opinion in assessment of angina pectoris in the Beta-Blocker Heart Attack Trial, a long-term (June 1978-October 1981), multicenter study of 3,837 post-myocardial infarction patients, half of whom were treated with propranolol and half with placebo. At baseline, about three times as many patients were thought to have angina by the physician as were diagnosed by the Questionnaire (36.1% vs. 11.5%). Over the average 25-month follow-up period, angina was identified by the physician 50% more often than by the Questionnaire (60.3% vs. 38.6%). The results for each treatment group (propranolol or placebo) were very similar to these overall results. Associations between diagnosis of angina and other patient characteristics were similar for the two measures at baseline. Although the physician diagnosis of angina identified more patients who suffered a subsequent fatal or nonfatal event than did the Questionnaire, it also diagnosed more angina patients who did not have an event. Thus, each of the measures of angina predicted total mortality and coronary heart disease mortality to similar extents (comparable relative risks), even after adjustment for covariates. Neither measure was significantly predictive of recurrent nonfatal myocardial infarction. One measure is not clearly superior to the other in this population. Other factors, such as cost and type of personnel available to conduct the study, may determine which measure is preferred.

Angina Pectoris↗
PubMed1984

Issues in medication adherence assessment in clinical trials of the National Heart, Lung, and Blood Institute.

The mission of the National Heart, Lung, and Blood Institute is to sponsor research in the prevention, diagnosis, and treatment of heart, lung, and blood diseases. As a part of its activities toward this end, the Institute plans and conducts clinical trials that test the safety and efficacy of a broad range of preventive and treatment regimens. Many of these trials involve thousands of patients and require the cooperation of many research clinics under a common protocol, often for many years. An essential component in these efforts is a standardized methodology to allow accurate tracking of adherence patterns so that problem adherence situations can be identified and rectified. This article reviews the methods that have been used to assess adherence patterns in selected clinical trials supported by the NHLBI. The most frequently used methods have been pill count and direct measurement of the drug, its metabolites, or physiological effects in some bodily fluid. Supplementary information is frequently obtained by self-report. Experience with markers has been very limited and no systematic data are available. The Aspirin Myocardial Infarction Study is used as a case study to illustrate specific strengths and weaknesses of three types of adherence assessment methods, namely, assay of salicylates in the urine, platelet aggregation, and pill count. Generalizations to other clinical trials are discussed. Based on experience to date with traditional methods of compliance assessment, several conclusions are drawn. Combinations of measures, in general, provide the most useful profiles of adherence patterns in clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗
PubMed1984

Statistical aspects of early termination in the beta-blocker heart attack trial.

The Beta-Blocker Heart Attack Trial was a randomized double blind controlled trial comparing propranolol with placebo in 3837 patients with a recent myocardial infarction. The trial was terminated on recommendation of the Policy and Data Monitoring Board 9 months before the scheduled closing date. The propranolol group, at the time of the decision, had a 26% lower mortality (z = 2.82). Many issues were considered in this decision. These included the magnitude of the overall results; consistency of results across subgroups, clinical centers, and cause of death; and completeness of follow-up. Two basic statistical methods were used in declaring the overall mortality results significant. The first method evaluated the current survival data taking into account the issue of repeated significance testing. The second method evaluated whether the observed trend was so impressive that the conclusion was unlikely to change even if the trial should continue to the scheduled end. These two methods, as well as other considerations led to the recommendation to discontinue the trial.

Adrenergic beta-Antagonists↗
PubMed1984

Can chronic antidysrhythmic treatment prevent sudden death?

With the exception of beta-blockers, the potential benefits of chronic treatment with antidysrhythmic agents have been inadequately evaluated. Six randomized controlled clinical trials with at least 100 post-myocardial infarction in patients have been reported. The largest study had 568 patients. For total mortality, no significant difference between treatment and control was noted. Sudden cardiac death was reported in only three of the trials. The clinical trial data for patients without acute myocardial infarction are also scanty and inconclusive. Additional clinical trials of adequate sample size and appropriate design are needed in order to assess whether chronic antidysrhythmic therapy prevents sudden death.

Anti-Arrhythmia Agents↗
PubMed1981

The randomized clinical trial: bias in analysis.

The realization that bias in patient selection may influence the results of clinical studies has helped to establish the randomized controlled clinical trial in medical research. However, bias can be equally important at other stages of a trial, especially at the time of analysis. Withdrawing patients from consideration in the analysis because of ineligibility on account of study entry criteria, lack of compliance to the protocol, or data of poor quality may be a source of systematic error. Examples to illustrate the possible consequences are taken from trials in the cardiovascular field. We recommended that reported study results should include outcome data from all subjects randomized in the group to which they were originally assigned.

Acute Disease↗
PubMed1980

Summary of design features: clinical trials of platelet-active drugs in cerebrovascular disease.

Two randomized, double-blind clinical trials in cerebrovascular disease are described. The Controlled trial of Aspirin in Cerebral Ischemia compared aspirin (650 mg twice daily) with placebo in medically and surgically treated groups of patients who had experienced transient ischemic attacks. The Randomized Trial of Aspirin and Sulfinpyrazone in Threatened Stroke compared aspirin (325 mg four times daily), sulfinpyrazone (200 mg four times daily) and aspirin plus sulfinpyrazone with placebo in patients with transient cerebral ischemia.

Aspirin↗
PubMed1978

Comparison of women seeking early and late abortion.

The differential characteristics of 697 women desiring induced abortion were studied according to when in pregnancy they presented. Age, marriage, and level of formal education were inversely related, those with greatest delay tending to be young, unmarried, and minimally educated. Religion was relevant, but generally was not. Nulliparity was only a weak correlate of delay. Contributory factors of denial, ambivalence, fear, and preceding menstrual irregularity accounted for two thirds of cases; they were uniformly distributed over the range of gestational age, but constituted the greatest proportion of reasons among those delaying decision longest. Physician delay and laboratory error accounted for all but one tenth of the remainder; they were concentrated particularly among gravidas presenting for care in the early part of the midtrimester. Fear characterized the young, poorly informed noncontraceptors, and had the greatest relative impact in protracted delays; denial was more likely to be found among older and ostensibly better informed women.

Abortion Applicants↗
PubMed1977

Relative birthweights of twins.

In a series of 182 twin gestations second-born twins were more often heavier than first-born twins (55%), but overall they weighed less by an average of 21 g. This paradox was shown to be due to the skewed distribution of weight differences favoring the first-born twin, most apparent among pairs in which one or both weighed at least 3000 g. The larger the difference between birthweights, the greater the likelihood that the heavier twin would be delivered first.

Birth Order↗
PubMedDate not supplied

The prognostic value of the duration of the ambulatory electrocardiogram after myocardial infarction.

The purpose of this study was to examine the value of various durations of ambulatory ECG recording with regard to providing useful prognostic information. The authors explored a decision theoretic approach to determine the most useful period of monitoring for making a treatment decision based upon postulated benefit-to-risk ratios of antiarrhythmic therapies. They used data collected as part of the Beta-Blocker Heart Attack Trial (BHAT), a randomized clinical trial of propranolol versus placebo in 3,837 post-myocardial-infarction patients. In BHAT, 1,336 placebo-treated patients had a 24-hour ambulatory ECG that had at least 23 readable hours. Sensitivity and specificity were calculated for eight definitions of ventricular arrhythmia using either total mortality or sudden death (death within one hour of symptoms) as an endpoint. These indices were obtained using the first 1, 2, 4, 6, 12, and 24 hours plus a random hour, a random daytime hour, and a random nighttime hour of the 24-hour ECG of 1,336 placebo-treated patients. The study showed that in the case of high-risk, low-benefit therapies, no test is needed to make a treatment decision. No one should be treated. In the case of high-benefit, low-risk therapies, again, no test is required. Everyone should be treated. For therapies in the middle benefit-to-risk ratio range the most appropriate test for a treatment decision changes from the very specific to the most sensitive. Twenty-four hours of ambulatory monitoring is usually not necessary for a treatment decision, since four hours is likely to be sufficient.

Adult↗