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Biomedical subjects

F E Harrell

Publications and source records attributed to F E Harrell.

At least 127 records · Page 7Linked to original sources
PubMed1982

Assessment of the use of the age- and sex-specific United States population as a control group for analysis of survival in coronary artery disease.

The use of the age- and sex-specific U.S. population as a control group for analysis of survival in coronary artery disease was assessed. Population-based survival rates were calculated for nonsurgically treated patients evaluated for coronary artery disease at Duke University Medical Center. Survival of the overall group of medically treated patients with significant coronary artery disease was lower than the corresponding age- and sex-specific U.S. population rates. However, survival of patients with significant disease who had normal left ventricular contraction and stable chest pain was similar to the age- and sex-specific population survival rates. Both the observed survival and the population-based survival estimates for patients with normal left ventricular contraction and stable pain were lower than the survival of patients with normal coronary arteriograms. Even after deaths from ischemic heart disease are eliminated from the population rates, survival of patients with normal coronary arteries exceeded the age-and sex-specific population survival. Because of biases inherent in the selection of patients for cardiac catheterization and the presence of other serious diseases in persons in the general population is not an adequate control group for rigorous analysis of the effect of therapy in coronary artery disease.

Actuarial Analysis↗
PubMed1982

Pirmenol kinetics and effective oral dose.

The oral form of pirmenol has not been administered to man. Pirmenol was given by mouth to eight patients with chronic, stable premature ventricular beats (PVBs) to determine effective dose and kinetics. The patients were evaluated with a dose-ranging protocol following by a double-blind, crossover, placebo-controlled study of doses that were effective during dose ranging. Oral doses of 150 to 250 mg induced at least 90% suppression of PVBs 18 of the 19 times they were administered during both protocols. During the double blind experiment, a single oral dose of pirmenol suppressed 95 +/- 8% PVBs/hr (mean +/- SD) for 3 consecutive hr, while placebo suppressed 4 +/- 42% PVBs/hr (P less than 0.01). a 90% or greater reduction in PVBs persisted for a median of 6 hr (range 1 to 8 hr). The range of plasma pirmenol concentrations associated with an at last 90% reduction in PVBs was 0.7 to 2.0 micrograms/ml. Median half-life (t1/2) was 9.3 hr (range 6.0 to 12.4) with 86.6 +/- 2.4% protein binding and 82.6 +/- 23.6% bioavailability. At peak drug level there was lengthening of the QTc interval (0.036 sec, P less than 0.05), but no change in heart rate, blood pressure, PR interval or QRS duration, or symptoms. In this single-dose study, pirmenol effectively reduced PVBs, has a relatively long t1/2, and was minimally toxic.

Administration, Oral↗
PubMed1982

Effect of myocardium at risk on outcome after coronary artery occlusion and release.

The relationship between the probability of sustaining ventricular fibrillation during occlusion or release of a canine coronary artery and the amount of myocardium made ischemic has never been carefully assessed. We occluded the left anterior descending coronary artery above or below the septal artery for 20 min and then released the ligation. The amount of left ventricle perfused by the ligated vessel was determined by injection of different color monastral dyes above and below the ligation. Despite careful ligature placement immediately proximal or distal to the septal artery, there was wide variation in the amount of left ventricle perfused by the ligated vessel, or myocardium "at risk." Myocardium at risk ranged between 24 and 51 g for ligations placed above the septal artery and 14 and 27 g for ligations placed below the septal artery. Ventricular fibrillation during occlusion and after release correlated significantly with the amount of myocardium at risk. This relationship was well described using the logistic risk regression model. The model predicts uniformly low and uniformly high probability of ventricular fibrillation with small and large amounts of myocardium at risk, respectively, and a direct correlation for midrange values of myocardium at risk. This relationship can account for a substantial portion of non-drug related variability in outcome of antiarrhythmic trials using the canine coronary occlusion or release model.

Animals↗
PubMed1982

Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement.

We evaluated a simplified version of a previously developed QRS scoring system for estimating infarct size using observations of Q- and R-wave durations and R/Q and R/S amplitude ratios in the standard 12-lead ECG. Groups of subjects with a minimal likelihood of having myocardial infarcts and minimal likelihood of having common noninfarction sources of QRS modification were studied to establish the specificity of each of the 37 criteria. Only two criteria required modification to achieve 95% specificity. These 37 criteria form the basis of a 29-point QRS scoring system. A 98% specificity was achieved when a score of more than 2 points was required to identify a myocardial infarct. Fifty patients were studied to determine the intra- and interobserver agreement with this scoring system. Each criterion achieved at least 91% intra- and interobserver agreement. These impressive levels of specificity and observer agreement must be matched by high sensitivity of the scoring system and a good correlation between the point score and infarct size in patients with proven infarcts if the point score is to be useful for detecting and sizing infarcts. Sensitivity and correlation between point score and infarct size are evaluated in later studies in this series. The standard ECG is inexpensive and can be obtained repetitively and noninvasively; its QRS complex may be an important means of estimating the size, presence and location of myocardial infarcts.

Adolescent↗
PubMed1982

Problems and advantages of an observational data base approach to evaluating the effect of therapy on outcome.

In this report, we summarize the strengths and problems of an observational data base approach to evaluating therapy and studying patient outcomes in long-term chronic disease. Because this approach includes a greater spectrum of patients than randomized clinical trials, it offers a definite advantage with regard to the elucidation of prognostic factors and the application of results to specific patients. The major difficulty with the observational data base approach is that the important prognostic factors must be known for treatment comparisons to be valid. Both the observational data base and randomized trial approaches are susceptible to criticism because the multiple comparisons and multiple experiments usually involved make the results of any one study not definitive. Either approach is useful in generating or confirming a hypothesis about particular subgroups. Regardless of the method used, proof that a particular therapy increases survival in any group or subgroup of patients with coronary artery disease usually requires confirmation by multiple studies. Finally, observational data base approach, because it capitalizes on data generated and paid for in the patient care process, offers the most feasible approach for evaluating whether changes in prognosis are occurring over time and whether such changes are independent of the mix of the patient population.

Clinical Trials as Topic↗
PubMed1982

Survival of coronary artery disease patients with stable pain and normal left ventricular function treated medically or surgically at Duke University.

We evaluated the survival rates of medically and surgically treated patients with one-, two- or three-vessel coronary disease (CAD), stable pain, and normal left ventricular function observed at the Duke University Medical Center over an 11-year period. There was no statistical difference in survival when medical and surgical treatment were compared in patients with one-, two- or three-vessel disease (greater than or equal to 75% vessel occlusion). However, the survival curve of patients with three-vessel disease treated surgically consistently exceeded that of those treated medically over a 7-year follow-up period. This difference was not statistically significant, but suggests the need for further study in this group. When patients with 50% or greater lesions in three vessels, stable angina and normal left ventricular function were evaluated, surgical survival was greater than medical survival, although the difference is not statistically significant. The survival in the Duke medical group is substantially higher than that reported for medical patients in the European Cooperative Trial, which suggests that the significant differences surgical in survival in the European Cooperative Trial were largely due to a lower medical survival than that in the Duke medical group.

Coronary Artery Bypass↗
PubMed1980

Nonfatal myocardial infarction in medically treated patients with coronary artery disease.

The purpose of this study was to identify patient characteristics associated with nonfatal myocardial infarction as the first event after cardiac catheterization in medically treated patients with coronary artery disease. Multiple logistic risk analysis of 81 baseline characteristics in 354 patients who died or had nonfatal infarction identified 10 characteristics (5 clinical and 5 cardiac catheterization variables) as independently discriminating between the two events. Left ventricular function, specific coronary anatomy, previous myocardial infarction and age were the most important discriminators. Poor left ventricular function and left main coronary stenosis were associated with death. Subtotal left anterior descending and right coronary arterial stenosis, normal hemodynamics, absence of previous infarction and young age were associated with nonfatal infarction. Thus, in any subset of patients who have a uniform risk of ischemic events (nonfatal infarction or death), nonfatal infarction is most likely to occur in those who are young, have had no previous infarction, have subtotal left anterior descending and right coronary arterial stenosis and normal hemodynamics.

Adult↗
PubMed1980

Outcome in medically treated coronary artery disease. Ischemic events: nonfatal infarction and death.

In this study we extended the characterization of outcome in 1214 medically treated patients with coronary disease by considering nonfatal infarction and death together as ischemic events. At 7 years, the cumulative event rate was 47% (18% for nonfatal infarction as the initial event and 29% for death as the initial event). In multivariable analysis of 81 baseline descriptors, 11 (six clinical and five catheterization) were independent predictors of events. Progressive chest pain, number of diseased vessels, left main stenosis and left ventricular (LV) function were the most important predictors. Progrressive pain was a more important predictor of total events than of survival alone. In patients with one-, two- or three-vessel disease and normal LV function, nonfatal infarcation accounted for at least 50% of initial events. In patients with left main disease or severe LV dysfunction, death was the predominant event. These results have important implications for interpreting the natural history of coronary artery disease.

Adrenergic beta-Antagonists↗
PubMed1980

On the complexity of investigating chronic illness.

Chronic diseases are in many ways more complex than acute diseases. In chronic diseases, response times to environmental effects are long, and confounding variables are numerous and may fluctuate with time. Treatment schedules are complicated and may be unique to the individual patient. Controlled trials deal with rigid hypotheses and permit control of error rates; prospective registries permit access to homogeneous subgroups. There is now a need for a new methodology for the study of the treatment of chronic diseases, which combines the merits of both approaches.

Chronic Disease↗
PubMedDate not supplied

Regression modelling strategies for improved prognostic prediction.

Regression models such as the Cox proportional hazards model have had increasing use in modelling and estimating the prognosis of patients with a variety of diseases. Many applications involve a large number of variables to be modelled using a relatively small patient sample. Problems of overfitting and of identifying important covariates are exacerbated in analysing prognosis because the accuracy of a model is more a function of the number of events than of the sample size. We used a general index of predictive discrimination to measure the ability of a model developed on training samples of varying sizes to predict survival in an independent test sample of patients suspected of having coronary artery disease. We compared three methods of model fitting: (1) standard 'step-up' variable selection, (2) incomplete principal components regression, and (3) Cox model regression after developing clinical indices from variable clusters. We found regression using principal components to offer superior predictions in the test sample, whereas regression using indices offers easily interpretable models nearly as good as the principal components models. Standard variable selection has a number of deficiencies.

Coronary Disease↗