Biomedical subjects

F E Harrell

Publications and source records attributed to F E Harrell.

At least 73 records · Page 4Linked to original sources

PubMed1990

Cardiac rupture, mortality and the timing of thrombolytic therapy: a meta-analysis.

This study examined the relation between the risk of cardiac rupture and the timing of thrombolytic therapy for acute myocardial infarction. To test the hypothesis that cardiac rupture is prevented by early thrombolytic therapy but is promoted by late treatment, randomized controlled trials of thrombolytic agents for myocardial infarction were pooled. A logistic regression model including 58 cases of cardiac rupture among 1,638 patients from four trials showed that the odds ratio (treated/control) of cardiac rupture was directly correlated with time to treatment (p = 0.01); at 7 h, the odds ratio was 0.4 (95% confidence limits 0.17 to 0.93); at 11 h, it was 0.93 (0.53 to 1.60) and at 17 h, it was 3.21 (1.10 to 10.1). Analysis of data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial independently confirmed the relation between time to thrombolytic therapy and risk of cardiac rupture (p = 0.03). Analysis of 4,692 deaths in 44,346 patients demonstrated that the odds ratio of death was also directly correlated with time to treatment (p = 0.006); at 3 h, the odds ratio for death was 0.72 (0.67 to 0.77); at 14 h, it was 0.88 (0.77 to 1.00) and at 21 h, it was 1 (0.82 to 1.37). Thrombolytic therapy early after acute myocardial infarction improves survival and decreases the risk of cardiac rupture. Late administration of thrombolytic therapy also appears to improve survival but may increase the risk of cardiac rupture.

Drug Administration Schedule↗

PubMed1990

Statistical methods in SUPPORT.

The analysis and interpretation of the data collected in SUPPORT provide great potential for understanding the relationships among treatment choices, patient and physician values and preferences, perceptions about the risks and benefits of treatments, institutional characteristics, and outcomes (as measured by quality of life, survival, and satisfaction). The complicated analyses required to elucidate these relationships will pose many technical challenges in dealing with longitudinal observational data collected from seriously ill patients at multiple sites. Major challenges include the handling of incomplete data, proper parameterization of treatment effects, strategies to avoid various potential biases, validating predictive models, and constructing endpoints that combine survival with quality of life. Within the structure of the SUPPORT study, mechanisms have been established to guide the analyses and to ensure their quality and validity.

Confounding Factors, Epidemiologic↗

PubMed1990

Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables.

To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.

Cardiac Catheterization↗

PubMed1990

Studies of gastric ulcer disease by community-based gastroenterologists.

A community-based group of gastroenterologists examined 623 patients (541 prospectively and 82 retrospectively) with endoscopically diagnosed gastric ulcer disease during a 12-month period. Patients averaged 60 years of age; the majority were women (62%). Women were less likely to smoke, abuse alcohol, and were more likely to present with abdominal pain (p less than 0.05). Whereas patients presenting with bleeding or requiring transfusion were less likely to complain of pain (p less than 0.05), they were more likely to be taking aspirin or nonsteroidal anti-inflammatory drugs and have prior history of bleeding (p less than 0.05). Patients with a prior history of ulcer disease were more likely to smoke, present with pain and use acetaminophen (p less than 0.05). Patients with large ulcers were more likely to bleed, present with pain, and obstruct (p less than 0.05). Multiple gastric ulcers were seen in patients taking aspirin or nonsteroidal anti-inflammatory drugs (p less than 0.05).

Abdominal Pain↗

PubMed1989

Clinical correlates and prognostic significance of type A behavior and silent myocardial ischemia on the treadmill.

Type A patients with coronary artery disease (CAD) tend to ignore or underreport symptoms, especially during challenging tasks such as the treadmill exercise test. To determine whether type A CAD patients might be more likely than type B patients to have silent ischemia during exercise and consequently a worse prognosis, 403 patients with stable CAD who had significant coronary disease on angiography, a positive Bruce protocol treadmill test and a structured interview to assess type A behavior were studied. Median follow-up time was 6 years. Type A patients were more likely to experience silent ischemia during exercise than were type B patients (35 vs 25%, p = 0.05). Patients with silent ischemia during exercise had a history of fewer anginal episodes/week, and type A patients with silent ischemia were less likely to have had a history of typical angina. However, using the Cox model, there were no significant differences in survival between type A patients and B patients with silent ischemia (4-year survival 86 vs 79%, p = 0.44) and no significant differences in survival between type A patients with silent ischemia and type A patients with symptomatic ischemia (6-year survival 86 vs 80%, p = 0.59). Similar results were obtained for infarction-free survival. Type A patients are more likely than type B patients to have silent ischemia during exercise, but long-term survival is not affected.

Angina Pectoris↗

PubMed1989

Differential diagnosis of acute meningitis. An analysis of the predictive value of initial observations.

We analyzed data from the records of 422 patients with acute bacterial or viral meningitis. A cerebrospinal fluid (CSF) glucose level less than 1.9 mmol/L, a CSF-blood glucose ratio less than 0.23, a CSF protein level greater than 2.2 g/L, more than 2000 x 10(6)/L CSF leukocytes, or more than 1180 x 10(6)/L CSF polymorphonuclear leukocytes were individual predictors of bacterial infection with 99% certainty or better. Although any one of these tests could rule in bacterial meningitis with high probability, none could rule it out. To better predict whether a patient has bacterial vs viral infection, we developed a logistic multiple regression model using CSF-blood glucose ratio, total polymorphonuclear leukocyte count in CSF, age, and month of onset. This proved highly reliable when validated in an independent test sample, with an area under receiver operating characteristic curve of 0.97. The model should allow physicians to differentiate between acute viral and acute bacterial meningitis with greater accuracy.

Acute Disease↗

PubMed1989

Type A behavior and survival: a follow-up study of 1,467 patients with coronary artery disease.

Patients with documented coronary artery disease, admitted to Duke Medical Center between 1974 and 1980, were assessed for type A behavior pattern and were followed until 1984. The relation of type A behavior to survival was tested using data from coronary angiography to control for disease severity. Cox model regression analyses demonstrated an interaction (p less than 0.01) between type A behavior and an index of disease severity in the prediction of cardiovascular death. Among those with relatively poor left ventricular function, type A patients had better survival than type B. This difference was not present among patients with better prognoses. Type A behavior did not predict the subsequent incidence of nonfatal myocardial infarctions. Differential risk modification and differential selection into postinfarction status are possible explanations for the findings. These results need not conflict with the proposition that type A behavior plays a role in the pathogenesis of coronary artery disease.

Adult↗

PubMed1989

The evolution of medical and surgical therapy for coronary artery disease. A 15-year perspective.

To elucidate the factors associated with improved survival following coronary artery bypass surgery, we studied 5809 patients receiving medical or surgical therapy for coronary artery disease. Three factors were associated with a significant surgical survival benefit: more severe coronary disease, a worse prognosis with medical therapy, and a more recent operative date. Patients with more extensive coronary obstruction had the greatest improvement in survival. Patients with a poor prognosis because of factors such as older age, severe angina, or left ventricular dysfunction had a reduction in risk that was proportionate to their overall risk on medical therapy. Survival with surgery progressively improved over the study period and by 1984 surgery was significantly better than medical therapy for most patient subgroups. Thus, contemporary coronary revascularization is associated with improved longevity in many patients with ischemic heart disease, especially in those with adverse prognostic indicators.

Age Factors↗

PubMed1989

Randomized, double-blind comparison of famotidine with ranitidine in treatment of acute, benign gastric ulcer disease. Community-based study coupled with a patient registry.

A multicenter, double-blind, randomized controlled trial comparing the efficacy and safety of famotidine with ranitidine in the treatment of acute, benign gastric ulcer disease was coupled with a community-based gastric ulcer disease registry. One hundred ninety-five patients with endoscopically documented gastric ulcer disease were enrolled in the trial and randomly allocated to treatment with either famotidine 40 mg at bedtime or ranitidine 150 mg twice a day. Healing rates were similar in both groups: at four weeks 49% vs 48%, at six weeks 71% vs 69%, and at eight weeks 83% vs 81% for famotidine and for ranitidine, respectively. Pain relief, antacid tablet use, and adverse experiences were also similar in the two groups. Only 25% of patients entered in the gastric ulcer registry were enrolled in the trial. Given that patients with more severe or complicated gastric ulcer disease should be excluded from controlled trials of new drugs, the screening criteria used in the present study be excluded from findings being representative of a quarter of the patients seen in these practices. Therefore, coupling a patient registry with a clinical trial helps determine the applicability of its results. Famotidine 40 mg at bedtime is an effective and well-tolerated treatment of acute, benign gastric ulcer disease and is comparable in efficacy and safety to ranitidine 150 mg twice a day.

Clinical Trials as Topic↗

PubMed1989

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.

Adult↗

PubMed1989

Clinical experience and predicting survival in coronary disease.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions obtained from a large, diverse sample of practicing cardiologists were compared with predictions from a multivariable statistical model. Test samples of 10 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed clinical summaries, 49 cardiologists each predicted the probability of 3-year survival and infarction-free survival for 10 patients. Cox regression models, developed using patients who were not in the test samples, were also used to predict corresponding outcome probabilities for each test patient. Overall, the model estimates of prognosis were significantly better than the doctors' predictions. The rank correlation of model predictions with 3-year survival was 0.60, compared with 0.52 for the physicians. Model predictions added significant prognostic information to the doctors' predictions, whereas the converse was not true. Where predictions were made by multiple doctors, the inter-physician variability was substantial. Neither practice characteristics nor extent of clinical experience significantly affected the physicians' predictive accuracy. In coronary artery disease, statistical models developed from carefully collected data can provide prognostic predictions that are more accurate than predictions of experienced clinicians made from detailed case summaries.

Coronary Disease↗

PubMed1988

Regression models in clinical studies: determining relationships between predictors and response.

Multiple regression models are increasingly being applied to clinical studies. Such models are powerful analytic tools that yield valid statistical inferences and make reliable predictions if various assumptions are satisfied. Two types of assumptions made by regression models concern the distribution of the response variable and the nature or shape of the relationship between the predictors and the response. This paper addresses the latter assumption by applying a direct and flexible approach, cubic spline functions, to two widely used models: the logistic regression model for binary responses and the Cox proportional hazards regression model for survival time data.

Humans↗

PubMed1988

Comparison of predictions based on observational data with the results of randomized controlled clinical trials of coronary artery bypass surgery.

Clinical decisions are most secure when based on findings from several large randomized clinical trials, but relevant randomized trial data are often unavailable. Analyses using clinical data bases might provide useful information if statistical methods can adequately correct for the lack of randomization. To test this approach, the findings of the three major randomized trials of coronary bypass surgery were compared with predictions of multivariable statistical models derived from observations in the Duke Cardiovascular Disease Databank. Clinical characteristics of patients at Duke University Medical Center who met eligibility requirements for each major randomized trial were used in the models to predict 5 year survival rates expected for medical and surgical therapy in each randomized trial. Model predictions agreed well with randomized trial results and were within the 95% confidence limits of the observed survival rates in 24 (92%) of 26 clinical subgroups. The overall correlation between predicted and observed survival rates was good (Spearman coefficient 0.73, p less than 0.0001). These results suggest that carefully performed analyses of observational data can complement the results of randomized trials.

Angina Pectoris↗

PubMed1988

Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease.

To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (greater than or equal to 75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course X (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of "ischemic" ST-T changes. This angina score was then validated in an independent patient sample. The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score greater than or equal to 9. With an ejection fraction less than 50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1988

Prognostic value of the simplified Selvester QRS score in patients with coronary artery disease.

The relation of the simplified Selvester QRS scoring system for the estimation of myocardial infarct size to survival was studied in 1,915 nonsurgically treated patients with documented coronary artery disease. Electrocardiograms (ECGs) were scored according to a simplified 29 point QRS scoring system. Using Cox model analyses, QRS scores were found to provide strong prognostic information by themselves (p less than 0.0001). Higher QRS scores were associated with lower survival rates. Patients with a score of 0 had a 1 year survival rate of 95% and a 5 year survival rate of 88%; patients with a score of 10 or more had survival rates of 81 and 52%, respectively, at the same intervals. Directly compared with the presence or absence of Q waves on the ECG, QRS scores provided greater prognostic information (p less than 0.001). When compared with 13 individual factors previously shown to provide the greatest independent prognostic information, the QRS score was the third most powerful individual prognostic factor. It did not contribute independent prognostic information in combination with the whole group, but did provide independent information in combination with the six most predictive factors. Its prognostic information overlapped mostly with clinical factors related to heart failure, and combined best with clinical factors related to the severity of ongoing myocardial ischemia. Because it is inexpensive and simple and maximizes the prognostic information from the ECG, the simplified Selvester QRS scoring system can be a useful clinical descriptor for practitioners and clinical investigators.

Cardiac Catheterization↗

PubMed1988

Current prognosis of ischemic mitral regurgitation. Implications for future management.

Ischemic mitral regurgitation is a serious and increasingly common clinical disorder, but at present, little is known of the associated prognostic implications, especially in specific therapeutic subgroups. Over a 6.5-year period beginning January 1, 1981, postinfarction mitral regurgitation was demonstrated ventriculographically in 2,343 (19%) of 11,748 patients having significant coronary artery disease defined at cardiac catheterization. Moderate or severe regurgitation was observed in 381 (3%), and among these patients, four treatment groups were defined: Group I (medical, n = 165), Group II (reperfusion, n = 63), Group III (coronary artery bypass only, n = 94), and Group IV (valve replacement or repair in addition to coronary bypass, n = 59). Multivariable regression analysis of survival data in the overall population and in specific treatment groups was performed with the Cox proportional hazards model. Defined and undefined selection biases precluded formal quantitative survival comparisons among some treatment groups; however, unadjusted and adjusted survival analysis for each group revealed several interesting concepts. First, increasing severity of mitral regurgitation had a progressively negative impact on survival prognosis regardless of treatment. Congestive heart failure, the number of associated disorders, acute presentation requiring cardiac care unit admission, diminished ejection fraction, increasing coronary obstruction, and advanced age all worsened prognosis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

Surgical survival benefits for coronary disease patients with left ventricular dysfunction.

Controversy still exists about the proper selection of patients with coronary artery disease and left ventricular dysfunction for coronary bypass surgery. To examine this issue, we studied 710 patients with significant coronary artery disease and left ventricular dysfunction (ejection fraction less than or equal to 40%). Of 301 patients treated surgically, 232 had bypass grafts; 17, left ventricular surgery; and 52, both procedures. At 3 years after treatment, unadjusted survival was 84% for surgical patients and 64% for medical patients. At baseline, medical patients had more left ventricular dysfunction than surgical patients, but surgical patients had more coronary artery disease and angina than medical patients. In Cox survival models, two invasive factors (ejection fraction and extent of coronary artery disease) and three noninvasive indexes (assessment of myocardial infarction, angina, and conduction disturbances) were the five best predictors of survival (p less than 0.001). After adjustment for these factors between the two treatment groups, overall surgical survival at 3 years after treatment was 86%, and medical survival was 68%. Long-term surgical survival benefits appeared greatest in patients with the most severe left ventricular dysfunction, most extensive coronary artery disease, and most severe anginal symptoms. We conclude that surgery provides significant survival benefits for coronary disease patients with left ventricular dysfunction; in general, the sicker the patient, the greater the benefit.

Angina Pectoris↗

PubMed1988

Changing efficacy of coronary revascularization. Implications for patient selection.

To evaluate the potential impact of patient selection for coronary artery bypass graft surgery on long-term survival, the outcomes of 5,809 consecutive patients with symptomatic coronary disease documented by angiography at Duke University Medical Center were examined. Over the entire study period (1969-1984), surgical therapy was associated with improved survival compared with medical therapy whether or not adjustment was made for imbalances in baseline prognostic factors. When patients were categorized according to coronary anatomy and left ventricular function, patients with multivessel disease and poor left ventricular function had a greater long-term survival benefit with surgery than did patients with less coronary artery disease and better left ventricular function. When 5-year survival rates were examined as a function of operative risk, a direct relation was found between estimated operative risk and the medical-surgical survival difference. For patients with an operative risk of 1%, the expected 5-year mortality with surgical therapy was 3% versus 8% with medical therapy (an absolute survival difference at 5 years of 5%). In comparison, for patients with an operative risk of 5%, the expected 5-year mortality with surgery was 10% versus 23% with medical therapy (an absolute survival difference at 5 years of 13%). Over 50% of patients with significant coronary artery disease undergoing cardiac catheterization have an estimated operative mortality risk under 2.5%. These patients would be expected to have a small survival advantage treated surgically. As operative mortality rates are subjected to increasing public scrutiny, selection of low-risk patients will reduce the overall benefit of the operation to the population.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗