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P Peduzzi

Publications and source records attributed to P Peduzzi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Analysis as-randomized and the problem of non-adherence: an example from the Veterans Affairs Randomized Trial of Coronary Artery Bypass Surgery.

In most randomized clinical trials not all patients adhere to the therapy to which they were randomly assigned. Instead, they may receive the therapy assigned to another treatment group, or a therapy different from any prescribed in the protocol. When non-adherence occurs, problems occur with the analysis comparing the treatments under study. Rigorous statistical principles require attributing outcome events to the original random treatment assignment ('intent-to-treat' analysis). Using data from the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery, we report the intent-to-treat analysis and apply four other methods of analysis for analysing non-adherers: 1. exclude non-adherers from analysis; 2. transfer them to the alternative treatment group at the time of randomization; 3. censor them at the time of treatment change, and 4. transfer them to the alternative treatment group at the time of treatment change. Inherent problems and biases of these four other methods are discussed.

Angina Pectoris↗
PubMed1993

Distribution of Viruses and Dissolved DNA along a Coastal Trophic Gradient in the Northern Adriatic Sea.

The distribution of viral and other microbial abundances as well as the concentrations of dissolved DNA (D-DNA) along a trophic gradient in the northern Adriatic Sea were determined. Virus abundances, covering a range of 1.2 x 10 to 8.7 x 10 liter were on average 2.5-fold higher in eutrophic than in mesotrophic stations. A 2.5-fold enrichment was also measured for chlorophyll a concentrations, whereas the densities of bacteria and heterotrophic nanoflagellates were only approximately 1.5-fold higher. The frequency of bacteria containing mature phage increased linearly with bacterial abundance. Assuming that mature phage is only visible during the last 14 to 27% of the latent period (L. M. Proctor, A. Okubo, and J. A. Fuhrman, Microb. Ecol. 25:161-182, 1993), we estimated that between 3.5 and 7.3% of the bacterial population was infected at mesotrophic stations versus between 7.0 and 19.5% at eutrophic stations, indicating that the bacterial mortality due to viral lysis might increase with the degree of eutrophication. The frequency of bacteria with mature phage and the burst size varied significantly with the bacterial morphotype; rod-shape cells, the most abundant morphotype, showed low infection rates but a high burst size. Concentrations of D-DNA varied significantly with season but not with trophic conditions. The estimated percentage of viral DNA on total D-DNA concentrations averaged 17.1% (range, 0.7 to 88.3%). Some kind of interaction between heterotrophic nanoflagellates and viruses is proposed. We conclude (i) that the significance of viruses varies with changing trophic conditions and (ii) that viral activity may play a significant role in food web structure under changing trophic conditions.

Journal Article↗
PubMed1992

Predictors of bacteremia and gram-negative bacteremia in patients with sepsis. The Veterans Affairs Systemic Sepsis Cooperative Study Group.

BACKGROUND: We analyzed data from the Department of Veterans Affairs trial of steroid therapy for systemic sepsis to identify predictors of bacteremia and gram-negative bacteremia. METHODS: Of the 2568 patients screened for entry in the trial, 465 met the following criteria: presence of four of seven clinical signs of sepsis; blood cultures at the time of screening; and complete data on nine clinical parameters. The multivariate logistic regression model was used to identify predictors of bacteremia and gram-negative bacteremia. Predicted probabilities of having these types of infections were calculated using the identified predictors. Patients were then classified into groups with and without bacteremia (and gram-negative bacteremia) based on the predicted probability. Misclassification error rates were calculated for each method of categorization by comparing the true with the predicted grouping of patients. RESULTS: Three factors were independently predictive of bacteremia and gram-negative bacteremia: elevated temperature, low systolic blood pressure, and low platelet count. Using these three factors, classification methods were identified that predicted blood infection better than chance, but misclassification was also high. For predicting bacteremia, the maximum predicted positive rate was 83%, with a specificity of nearly 100% and a sensitivity of only 5%. For predicting gram-negative bacteremia, the maximum predicted positive accuracy was 100%, with a specificity also of 100% and a sensitivity of almost 0%. CONCLUSIONS: Using simple clinical parameters, we could not predict either bacteremia or gram-negative bacteremia with sufficient accuracy to be clinically meaningful; however, our approach represents a step in the direction of forecasting the bacterial organism responsible for sepsis in advance of culture results.

Adrenal Cortex Hormones↗
PubMed1991

Termination of the Department of Veterans Affairs Cooperative Study of steroid therapy for systemic sepsis.

The Department of Veterans Affairs Cooperative Study Program conducted a randomized, double-masked trial of steroid therapy versus placebo therapy for patients with systemic sepsis from 1983 to 1986. Treatment was initiated as soon as sepsis was recognized and before results of cultures confirmed infection. The original hypothesis was to test the effect of therapy on short-term (14-day) mortality in patients with gram-negative bacteremia. Because therapy had to begin before culture results were available, all septic patients had to be enrolled. Consequently, the study was modified to evaluate therapy in all patients with sepsis, and by post-stratification in those with gram-negative bacteremia. Patient enrollment was planned to continue for 3.5 years to achieve a sample size of 276 patients. After 223 patients were randomized, 14-day mortalities were 22% in the placebo-treated group versus 21% in the steroid-treated group (p = 0.97). In contrast, for the 51 patients with gram-negative bacteremia, mortalities were 27% placebo-treated versus 7% steroid-treated (p = 0.11). The Data Monitoring Board recommended continuation of the trial to evaluate what appeared to be an emerging gram-negative trend, but the Cooperative Studies Evaluation Committee decided to end the trial 12 months early because of the lack of efficacy in all septic patients. The reasons for the proposed extension and for the termination of the trial are presented. The more general problem of evaluating a biologically important subgroup imbedded in a large clinical trial is also discussed.

Bacterial Infections↗
PubMed1991

Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery.

BACKGROUND: The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery. METHODS AND RESULTS: Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings. Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period. The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group). The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20). According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001). The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001). The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative infarctions did not alter the findings. CONCLUSIONS: Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions).

Angina Pectoris↗
PubMed1991

Intent-to-treat analysis and the problem of crossovers. An example from the Veterans Administration coronary bypass surgery study.

In randomized clinical trials of treatment for ischemic heart disease that compare medical with surgical treatment, many persons initially assigned to medical therapy eventually receive surgical intervention. For example, in the three major trials of bypass grafting for stable angina, crossover rates from medical to surgical therapy were approximately 25% at 5 years. For this reason, the classic intent-to-treat analyses have been criticized for their inability to evaluate the "true" effect of treatment. In this article we emphasize the concept of "initial treatment" as it applies to intent-to-treat analyses and examine four proposed alternative methods of analysis based on adherence with survival data from the Veterans Administration Cooperative Study to illustrate the concepts. The alternative methods include (1) censoring crossovers when treatment changes, (2) transferring crossovers from the original to the new treatment group when treatment changes, (3) excluding all crossovers from analysis, and (4) counting crossovers from the date of randomization in the treatment ultimately received group. We point out the biases attendant on analyses based on adherence and reaffirm the validity of intent-to-treat analysis.

Actuarial Analysis↗
PubMed1989

A computer program for calculating ratio estimates.

A computer program is described to calculate ratio estimates for an endpoint measured on patient subunits, such as progression of disease in coronary arteries and extent of dental caries. The program calculates ratio estimates for levels of stratification factors measured in the patient as a unit, e.g. age and sex. Test statistics are computed to evaluate differences in ratio estimates for factors with two levels. A method for making pairwise comparisons for factors with more than two levels is also described, but is not computed by the program. Data from the Veterans Administration Study of Bypass Surgery (Am. J. Cardiol. 40 (1977) 212-225) are used to illustrate the features of the program.

Analysis of Variance↗
PubMed1988

General statistical design considerations of randomized clinical trials.

Randomized clinical trials are the most objective method for evaluating new therapies, but they are subject to the same biases as nonrandomized studies unless the principles of statistical design are observed at the planning stage. Estimation of sample size also requires early careful consideration, since studies of inadequate size will not have sufficient statistical power to detect meaningful treatment differences. For ethical reasons, interim data monitoring procedures should be used to detect early treatment responses that may lead to alteration or interruption of the planned study to give patients early benefit from a superior treatment or diminish their risk from ineffective or harmful treatment. Additional important aspects of clinical trial design that were not addressed in this report include: definition of study objectives and endpoints, description of data to be collected, details of the treatment regimens, informed consent and plans for data analysis. The science of clinical trial design is complex; only some of the key statistical issues have been addressed briefly in this report.

Clinical Trials as Topic↗
PubMed1987

Ten-year effect of medical and surgical therapy on quality of life: Veterans Administration Cooperative Study of Coronary Artery Surgery.

The long-term effect of medical vs surgical therapy on quality of life was evaluated by New York Heart Association functional classification, severity of angina and exercise performance in 427 surviving patients with stable angina at 10 years. Surgically assigned patients had significantly more improvement in functional classification, relief of angina and exercise performance at 1 and 5 years than medically assigned patients. Relative to entry, functional classification was improved in 65% of surgically treated patients at 1 year and in 51% at 5 years, compared with 45% and 40%, respectively, of medically treated patients. Marked improvement in angina was observed in 49% of surgical patients at 1 year and in 41% at 5 years, vs 12% and 17%, respectively, in medical patients. At 10 years, quality of life was not significantly different in the 2 treatment groups: 52% of surgical patients had an improved functional classification, compared with 46% of medical patients, while 33% of surgical and 37% of medical patients had a marked improvement in angina. Exclusion of medical and surgical nonadherers had little effect on the 1- and 5-year comparisons. The 10-year treatment differences, however, were accentuated when 123 medically assigned patients who later underwent operation and who benefited from it were excluded from the analysis. In surgical patients, a strong association was observed between graft patency and functional class at 1 year, but not at 5 and 10 years. In general, patients with some or all grafts open had more improvement in functional classification than patients with all grafts closed.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1987

Comparison of the logistic and Cox regression models when outcome is determined in all patients after a fixed period of time.

This paper presents an evaluation of the logistic and Cox regression models for a prospective study when the outcome is binary and is determined in all patients after a fixed period of time. The similarities and differences between the regression coefficients and test statistics are given for the two-sample case. Extension of results to the multivariate case and under product binomial sampling are discussed. The results are illustrated using data from a clinical trial designed to evaluate the effect of a lipid lowering drug on progression of coronary artery disease.

Coronary Disease↗
PubMed1987

Coordinating center follow-up in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.

In the VA Cooperative Study of Coronary Artery Bypass Surgery, follow-up by the participating investigators was completed in 1984 and annual centralized follow-up by the coordinating center for an additional 5 years was initiated in 1985. Follow-up was restricted to key outcomes that could be reliably obtained in most patients-survival, severity of angina, myocardial infarction and bypass surgery. Ninety-five percent of patients consented to annual follow-up by telephone or mail. At the first annual follow-up, 95% of all survivors were contacted; 95% were also contacted at the second follow-up. In the initial follow-up, survival status was known in all patients and severity of angina was recorded in 93% of survivors; all bypass operations and all but one infarct identified were documented by a discharge summary. Our results indicate that coordinating center follow-up was effective in a long-term study of a chronic disease and depended on the willingness of patients to participate, the experience of the interviewers, and the ability of the coordinating center to contact patients and retrieve outcome data. This report describes the methods used for the centralized follow-up of the surviving patients and summarizes the initial follow-up results. The limitations and advantages of this approach are also discussed.

Clinical Trials as Topic↗
PubMed1985

Angina scoring method in the Veterans Administration randomized study of bypass surgery.

An angina scoring method was designed in the Veterans Administration Coronary Artery Bypass Surgery Study in 1973 to evaluate the effect of medical versus surgical therapy on relief of angina. The score measures the frequency of angina, type of activity producing angina, and use of medications. The score is based on objective responses to specific questions, is easy to compute, and is designed to be administered by a physician familiar with symptoms of angina and coronary artery disease. In this report, the authors evaluate the reproducibility, validity, and utility of the angina score in Veterans Administration study patients. Extensions of the scoring method to include newer cardiac drugs and comparison with other methods of grading the severity of angina are also discussed.

Angina Pectoris↗
PubMed1985

The 5 year effect of bypass surgery on relief of angina and exercise performance.

The 5 year effect of medical vs surgical treatment on symptoms and exercise performance was evaluated in patients with stable angina who entered the Veterans Administration Cooperative Study from 1972 to 1974. Severity of angina was evaluated by a physician-administered angina questionnaire and physical working capacity was assessed by exercise testing. Angina was substantially relieved in surgical patients at 1 year, with 78% having mild or no angina compared with only 28% at entry. The corresponding rates in medical patients showed little change: 38% at 1 year and 32% at entry. At 5 years the percentage of surgical patients with mild or absent angina decreased from the 1 year rate of 78% to 64%, whereas the medical group exhibited a small increase from 38% to 49%. Similar results were obtained by evaluating changes in angina compared to entry. At 1 year 49% of surgical patients were markedly improved compared with only 12% of medical patients. At 5 years the percentage of surgical patients who remained markedly improved decreased to 41%, whereas the medical group with marked improvement increased slightly from 12% at 1 year to 17% at 5 years. Medication requirements were markedly reduced in surgical patients with only a slight increase in medical patients. Exclusion of nonadherers from the analysis did not change the results. Exercise testing revealed comparable changes in physical performance. At 1 year surgical patients had fewer tests stopped by angina compared with medical patients (28% vs 64%), a higher estimated oxygen consumption (26 vs 21 ml/kg/min) and treadmill exercise duration (7.3 vs 4.9 min). Other measures of exercise performance were comparably improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1985

Long-term mortality and morbidity results of the Veterans Administration randomized trial of coronary artery bypass surgery.

The long-term effect of coronary artery bypass grafting on mortality and the incidence of nonfatal myocardial infarction was evaluated in 686 patients in the randomized Veterans Administration study of medical vs surgical treatment for stable angina. Average follow-up was 11.2 years. The 11 year cumulative mortality rates for all patients and for the 595 patients without left main diseases were not significantly different in the two treatment groups. The 7 year mortality rates were 30% in medically assigned and 23% in surgically assigned patients (p = .043) and the 11 year rates were 43% and 42% (p = .45), respectively. The rates in patients without left main disease were 28% for medical and 23% for surgical treatment policy at 7 years (p = .267) and rose to 42% in both groups at 11 years (p = .813). A statistically significant reduction in mortality with surgical policy was found both at 7 and 11 years in high-risk patients without left main disease who had multiple clinical or angiographic risk factors or both. In the subgroup with angiographic high risk, the 7 year mortality rates were 48% in medically assigned and 24% in surgically assigned patients (p = .002); the 11 year rates were 62% and 50%, respectively (p = .026). Corresponding rates in the clinically defined high-risk group were 48% vs 28% (p = .003) at 7 years and 64% vs 51% (p = .015) at 11 years for medical vs surgical policy, respectively. For the subgroup of patients with combined angiographic and clinical high risk, the 7 year mortality rates were 64% for medical and 24% for surgical policy (p = .002); the 11 year rates were 76% and 46%, respectively (p = .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Relation of severity of symptoms to prognosis in stable angina pectoris.

To determine if severity of angina is related to the extent of coronary artery disease (CAD) or prognosis, 341 patients were evaluated by a systematic physician-administered angina questionnaire at entry into a large-scale randomized study of medical vs surgical treatment of stable angina pectoris. Severity of angina was numerically scored; scores were based on frequency of pain, rest pain, amount of daily medication, and level of daily activity. Severity scores were separated into mild, moderate and severe groups of approximately equal numbers and correlated with (1) number of coronary arteries narrowed, (2) presence of left main CAD, (3) ejection fraction less than 50%, (4) abnormalities of left ventricular function, (5) 3-vessel CAD with abnormal left ventricular function, (6) increased heart size by chest x-ray, (7) a noninvasive measure of prognosis, and (8) mortality. Severity of angina was not significantly related to any of the above variables except for the presence of left main CAD (p = 0.046) and increased heart size by chest x-ray (p = 0.001), both of which had low prevalence rates. Severity of angina at baseline was not related to 7-year survival in patients treated medically or surgically. Severity of angina at baseline, however, did predict 1- to 2-year survival in medically treated patients. Similarly, the severity of angina at 1 year and severity at 5 years predicted survival in the subsequent 4 years in the medical group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Five-year effect of medical and surgical therapy on resting left ventricular function in stable angina: Veterans Administration Cooperative Study.

The effect of coronary artery bypass grafting (CABG) and medical therapy on 5-year resting left ventricular (LV) function was studied in 194 randomized patients with stable angina in the Veterans Administration Study of Coronary Artery Bypass Surgery. LV ejection fraction (EF) was determined in a central laboratory. The 92 medical and 102 surgical patients were comparable at entry with respect to historic, angiographic and electrocardiographic prognostic indicators. Twenty-eight percent of the medical and 30% of the surgical patients had a baseline EF of less than 50%. There was no significant change in mean EF between baseline and 5-year values in either treatment group. The baseline and 5-year values were 56 and 58% in each treatment group. Intervening myocardial infarction (MI) had an adverse effect in medically treated patients (59 to 46%, p less than 0.01) and in surgically treated patients with late MI (58 to 47%, difference not significant). Perioperative MI was not associated with a decrease in EF (56 to 58%, difference not significant). These findings extend the similar results of previous short-term studies of the effect of coronary bypass surgery on resting LV function to 5 years, and provide data in a comparable medical control group.

Angina Pectoris↗