Background. Patients with acute myocardial infarction who were treated with accelerated tissue pl... more Background. Patients with acute myocardial infarction who were treated with accelerated tissue plas- minogen activator (t-PA) (given over a period of 11⁄2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day ...
Background: The period following hospital discharge is a vulnerable time for patients when errors... more Background: The period following hospital discharge is a vulnerable time for patients when errors and poorly coordinated care are common. Suboptimal care transitions for patients admitted with cardiovascular conditions can contribute to readmission and other adverse health outcomes. Little research has examined the role of health literacy and other social determinants of health in predicting post-discharge outcomes. Methods: The Vanderbilt Inpatient Cohort Study (VICS), funded by the National Institutes of Health, is a prospective longitudinal study of 3,000 patients hospitalized with acute coronary syndromes or acute decompensated heart failure. Enrollment began in October 2011 and is planned through October 2015. During hospitalization, a set of validated demographic, cognitive, psychological, social, behavioral, and functional measures are administered, and health status and comorbidities are assessed. Patients are interviewed by phone during the first week after discharge to assess the quality of hospital discharge, communication, and initial medication management. At approximately 30 and 90 days post-discharge, interviewers collect additional data on medication adherence, social support, functional status, quality of life, and health care utilization. Mortality will be determined with up to 3.5 years follow-up. Statistical models will examine hypothesized relationships of health literacy and other social determinants on medication management, functional status, quality of life, utilization, and mortality. In this paper, we describe recruitment, eligibility, follow-up, data collection, and analysis plans for VICS, as well as characteristics of the accruing patient cohort. Discussion: This research will enhance understanding of how health literacy and other patient factors affect the quality of care transitions and outcomes after hospitalization. Findings will help inform the design of interventions to improve care transitions and post-discharge outcomes.
Background: Critical to the development of molecular signatures from microarray and other high-th... more Background: Critical to the development of molecular signatures from microarray and other high-throughput data is testing the statistical significance of the produced signature in order to ensure its statistical reproducibility. While current best practices emphasize sufficiently powered univariate tests of differential expression, little is known about the factors that affect the statistical power of complex multivariate analysis protocols for high-dimensional molecular signature development.
Page 1. MEDICAL CARE May 1985, Vol. 23, No. 5 Clinical Data Bases Accomplishments and Unrealized ... more Page 1. MEDICAL CARE May 1985, Vol. 23, No. 5 Clinical Data Bases Accomplishments and Unrealized Potential DAVID B. PRYOR, MD,* ROBERT M. CALIFF, MD,* FRANK E. HARRELL, JR., PHD,t MARK A. HLATKY, MD ...
Page 1. Regression Modeling Strategies Frank E Harrell Jr Department of Biostatistics Vanderbilt ... more Page 1. Regression Modeling Strategies Frank E Harrell Jr Department of Biostatistics Vanderbilt University School of Medicine Nashville TN 37232 [email protected] biostat.mc.vanderbilt.edu/rms CDC Atlanta GA 6 Oct 2009 ...
Journal of The American College of Cardiology, 2001
This work was undertaken to define the intrinsic cardiac risk of the patient population referred ... more This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ( 99m Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND In animal models, dobutamine attenuates the myocardial uptake of 99m Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress 99m Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses.
A QRS scoring system for estimating the size of a myocardial infarct was evaluated in 55 patients... more A QRS scoring system for estimating the size of a myocardial infarct was evaluated in 55 patients who did not have left ventricular hypertrophy or conduction abnormalities. Serial 12-lead surface electrocardiograms were scored according to a 29-point system based on the duration of Q and R waves and on the ratios of R-to-Q amplitude and R-to-S amplitude. The scores were proportional to the severity of wall-motion abnormalities, which was determined by radionuclide blood-pool scanning and which correlated inversely with the radionuclide-determined left ventricular ejection fraction (LVEF). A score less than 3 was 93 per cent sensitive and 88 per cent specific for both severe regional dyssynergy and major depression of the global LVEF. The following equation was used to estimate the LVEF from the QRS score: LVEF (%) = 60 - (3 x QRS score). After acute myocardial infarction, an electrocardiogram can provide important indirect quantitative information about left ventricular function.
Abstract. Although ordinal data are not rare in ecology, ecological studies have, until now, seri... more Abstract. Although ordinal data are not rare in ecology, ecological studies have, until now, seriously neglected the use of specific ordinal regression models. Here, we present three models – the Proportional Odds, the Continuation Ratio and the Stereotype models – that can be successfully applied to ordinal data. Their differences and respective fields of application are discussed. Finally, as an example of application, PO models are used to predict spatial abundance of plant species in a Geographical Information System. It shows that ordinal models give as good a result as binary logistic models for predicting presence-absence, but are additionally able to predict abundance satisfactorily.
Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in t... more Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in the population tested, its sensitivity and specificity have been assumed to be constants. This assumption was examined in patients who had both exercise electrocardiography and cardiac catheterization. The effects on sensitivity of factors from clinical history, catheterization, and exercise performance were defined by multivariable logistic regression analysis in 1,401 patients with coronary disease; effects on specificity were defined by a similar analysis in 868 patients without coronary disease. Five factors had significant, independent effects on exercise electrocardiographic sensitivity: maximal exercise heart rate, number of diseased coronary arteries, type of angina, and the patient's age and sex. Only maximal exercise heart rate had a significant, independent effect on exercise electrocardiographic specificity. Thus, the sensitivity and specificity of exercise electrocardiography vary with clinical history, extent of disease, and treadmill performance; the sensitivity and specificity of other diagnostic tests may also vary.
Journal of The American College of Cardiology, 1988
To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutiv... more 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)
This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure... more This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensinconverting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death. (Am Heart J 1997;134:44-54) Congestive heart failure is an increasing cause of morbidity and mortality as the world's population continues to age. The advent of cardiac transplantation and of medical regimens--including angiotensin-converting enzyme inhibitors, 1 nitrates, and hydralazine2--and digitalis 3 have allowed practitioners to substantially affect the mortality rates and quality of life of patients with symptomatic heart failure. Nevertheless, heart failure inevitably progresses to an increasingly symptomatic stage, often in circumstances that preclude transplantation because of age, comorbidity, or lack of organ availability. Even with maximal conventional medical therapy, the 1-year mortality rate of patients with class IV heart failure is >25%. 4
The purpose of this investigation was to determine which variables obtained when performing radio... more The purpose of this investigation was to determine which variables obtained when performing radionuclide angiography predict subsequent survival or total events (cardiovascular death or nonfatal myocardial infarction) in stable patients with symptomatic coronary artery disease (CAD). Univariable and multivariable analyses of 6 variables, including ejection fraction (EF) at rest and exercise, change in EF with exercise, development of ischemic chest pain or electrocardiographic changes, left ventricular (LV) wall motion abnormalities and exercise time were examined in 366 patients followed up to 4.5 years. Univariate analyses revealed that the exercise EF was the variable most closely as-sociated with future events (p <O.Ol), followed by EF at rest, wall motion abnormalities and exercise time. Multivariable analyses revealed that once the exercise EF was known, no other radionuclide variables contributed independent information about the likelihood of future events. Multivariable analyses also revealed that the exercise EF describes much of the prognostic information of coronary anatomy. Our ftndings suggest that the radionuclide angiogram is useful in predicting future events in patients with stable CAD, although examination in conjunction with other clinical descriptors will be necessary to further quantify this contribution.
We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/i... more We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/inferior vena caval thrombus was treated with radical nephrectomy and thrombectomy. A total of 220 patients underwent radical nephrectomy for RCC at our institution from 1998 to 2002. Of them 49 patients with renal vein/inferior vena caval involvement (T3b/c) were selected for review. We evaluated demographics, presenting symptoms, imaging modalities, clinical staging, pathological features, adjuvant treatment and clinical outcomes. We also evaluated surgical incisions, liver mobilization procedures, blood loss, transfusion requirements and perioperative mortality/morbidity. Gross hematuria was the most common presenting symptom, seen in 22 patients (45%), followed by constitutional symptoms in 8 (16%). Stage T3b/c was clinically diagnosed in 44 patients, while 2 had T2 and 2 had T4 disease. A subcostal incision was made in 30 patients, a chevron incision was made in 18, and a sternotomy and flank incision were made in 1. Liver mobilization was necessary in 13 patients and 2 required a Pringle maneuver. Cardiopulmonary bypass was performed in a single patient. Lymph node involvement was seen in 4 patients (8%) and distant metastases were present in 10 (20%). Median tumor size was 10 cm. Clear cell carcinoma was most common, as seen in 42 patients. Early (30-day) mortality in this series was 8%. At a median followup of 15 months 21 patients (43%) were without evidence of disease, 14 (29%) had disease, 8 (16%) had died of disease and 2 (4%) had died of other causes. None of the patients with lymph node involvement survived beyond 8 months after surgery. Tumor grade and T stage were found to be significant negative predictors of survival on univariate analysis. Most patients with RCC and tumor thrombus are symptomatic at presentation and metastatic disease at presentation is not uncommon. These results support the role of aggressive surgical treatment as the best initial management of these tumors. The majority of tumors can be approached and safely controlled without the need for a thoracoabdominal incision. While surgery provides modest disease-free survival, most patients should be offered immunotherapy, particularly those with advanced stage, grade, nodal involvement or metastases.
Background. Patients with acute myocardial infarction who were treated with accelerated tissue pl... more Background. Patients with acute myocardial infarction who were treated with accelerated tissue plas- minogen activator (t-PA) (given over a period of 11⁄2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day ...
Background: The period following hospital discharge is a vulnerable time for patients when errors... more Background: The period following hospital discharge is a vulnerable time for patients when errors and poorly coordinated care are common. Suboptimal care transitions for patients admitted with cardiovascular conditions can contribute to readmission and other adverse health outcomes. Little research has examined the role of health literacy and other social determinants of health in predicting post-discharge outcomes. Methods: The Vanderbilt Inpatient Cohort Study (VICS), funded by the National Institutes of Health, is a prospective longitudinal study of 3,000 patients hospitalized with acute coronary syndromes or acute decompensated heart failure. Enrollment began in October 2011 and is planned through October 2015. During hospitalization, a set of validated demographic, cognitive, psychological, social, behavioral, and functional measures are administered, and health status and comorbidities are assessed. Patients are interviewed by phone during the first week after discharge to assess the quality of hospital discharge, communication, and initial medication management. At approximately 30 and 90 days post-discharge, interviewers collect additional data on medication adherence, social support, functional status, quality of life, and health care utilization. Mortality will be determined with up to 3.5 years follow-up. Statistical models will examine hypothesized relationships of health literacy and other social determinants on medication management, functional status, quality of life, utilization, and mortality. In this paper, we describe recruitment, eligibility, follow-up, data collection, and analysis plans for VICS, as well as characteristics of the accruing patient cohort. Discussion: This research will enhance understanding of how health literacy and other patient factors affect the quality of care transitions and outcomes after hospitalization. Findings will help inform the design of interventions to improve care transitions and post-discharge outcomes.
Background: Critical to the development of molecular signatures from microarray and other high-th... more Background: Critical to the development of molecular signatures from microarray and other high-throughput data is testing the statistical significance of the produced signature in order to ensure its statistical reproducibility. While current best practices emphasize sufficiently powered univariate tests of differential expression, little is known about the factors that affect the statistical power of complex multivariate analysis protocols for high-dimensional molecular signature development.
Page 1. MEDICAL CARE May 1985, Vol. 23, No. 5 Clinical Data Bases Accomplishments and Unrealized ... more Page 1. MEDICAL CARE May 1985, Vol. 23, No. 5 Clinical Data Bases Accomplishments and Unrealized Potential DAVID B. PRYOR, MD,* ROBERT M. CALIFF, MD,* FRANK E. HARRELL, JR., PHD,t MARK A. HLATKY, MD ...
Page 1. Regression Modeling Strategies Frank E Harrell Jr Department of Biostatistics Vanderbilt ... more Page 1. Regression Modeling Strategies Frank E Harrell Jr Department of Biostatistics Vanderbilt University School of Medicine Nashville TN 37232 [email protected] biostat.mc.vanderbilt.edu/rms CDC Atlanta GA 6 Oct 2009 ...
Journal of The American College of Cardiology, 2001
This work was undertaken to define the intrinsic cardiac risk of the patient population referred ... more This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ( 99m Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND In animal models, dobutamine attenuates the myocardial uptake of 99m Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress 99m Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses.
A QRS scoring system for estimating the size of a myocardial infarct was evaluated in 55 patients... more A QRS scoring system for estimating the size of a myocardial infarct was evaluated in 55 patients who did not have left ventricular hypertrophy or conduction abnormalities. Serial 12-lead surface electrocardiograms were scored according to a 29-point system based on the duration of Q and R waves and on the ratios of R-to-Q amplitude and R-to-S amplitude. The scores were proportional to the severity of wall-motion abnormalities, which was determined by radionuclide blood-pool scanning and which correlated inversely with the radionuclide-determined left ventricular ejection fraction (LVEF). A score less than 3 was 93 per cent sensitive and 88 per cent specific for both severe regional dyssynergy and major depression of the global LVEF. The following equation was used to estimate the LVEF from the QRS score: LVEF (%) = 60 - (3 x QRS score). After acute myocardial infarction, an electrocardiogram can provide important indirect quantitative information about left ventricular function.
Abstract. Although ordinal data are not rare in ecology, ecological studies have, until now, seri... more Abstract. Although ordinal data are not rare in ecology, ecological studies have, until now, seriously neglected the use of specific ordinal regression models. Here, we present three models – the Proportional Odds, the Continuation Ratio and the Stereotype models – that can be successfully applied to ordinal data. Their differences and respective fields of application are discussed. Finally, as an example of application, PO models are used to predict spatial abundance of plant species in a Geographical Information System. It shows that ordinal models give as good a result as binary logistic models for predicting presence-absence, but are additionally able to predict abundance satisfactorily.
Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in t... more Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in the population tested, its sensitivity and specificity have been assumed to be constants. This assumption was examined in patients who had both exercise electrocardiography and cardiac catheterization. The effects on sensitivity of factors from clinical history, catheterization, and exercise performance were defined by multivariable logistic regression analysis in 1,401 patients with coronary disease; effects on specificity were defined by a similar analysis in 868 patients without coronary disease. Five factors had significant, independent effects on exercise electrocardiographic sensitivity: maximal exercise heart rate, number of diseased coronary arteries, type of angina, and the patient&amp;amp;#39;s age and sex. Only maximal exercise heart rate had a significant, independent effect on exercise electrocardiographic specificity. Thus, the sensitivity and specificity of exercise electrocardiography vary with clinical history, extent of disease, and treadmill performance; the sensitivity and specificity of other diagnostic tests may also vary.
Journal of The American College of Cardiology, 1988
To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutiv... more 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&amp;amp;amp;amp;amp;amp;#39;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 &amp;amp;amp;amp;amp;amp;quot;ischemic&amp;amp;amp;amp;amp;amp;quot; 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&amp;amp;amp;amp;amp;amp;#39;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)
This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure... more This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensinconverting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death. (Am Heart J 1997;134:44-54) Congestive heart failure is an increasing cause of morbidity and mortality as the world's population continues to age. The advent of cardiac transplantation and of medical regimens--including angiotensin-converting enzyme inhibitors, 1 nitrates, and hydralazine2--and digitalis 3 have allowed practitioners to substantially affect the mortality rates and quality of life of patients with symptomatic heart failure. Nevertheless, heart failure inevitably progresses to an increasingly symptomatic stage, often in circumstances that preclude transplantation because of age, comorbidity, or lack of organ availability. Even with maximal conventional medical therapy, the 1-year mortality rate of patients with class IV heart failure is >25%. 4
The purpose of this investigation was to determine which variables obtained when performing radio... more The purpose of this investigation was to determine which variables obtained when performing radionuclide angiography predict subsequent survival or total events (cardiovascular death or nonfatal myocardial infarction) in stable patients with symptomatic coronary artery disease (CAD). Univariable and multivariable analyses of 6 variables, including ejection fraction (EF) at rest and exercise, change in EF with exercise, development of ischemic chest pain or electrocardiographic changes, left ventricular (LV) wall motion abnormalities and exercise time were examined in 366 patients followed up to 4.5 years. Univariate analyses revealed that the exercise EF was the variable most closely as-sociated with future events (p <O.Ol), followed by EF at rest, wall motion abnormalities and exercise time. Multivariable analyses revealed that once the exercise EF was known, no other radionuclide variables contributed independent information about the likelihood of future events. Multivariable analyses also revealed that the exercise EF describes much of the prognostic information of coronary anatomy. Our ftndings suggest that the radionuclide angiogram is useful in predicting future events in patients with stable CAD, although examination in conjunction with other clinical descriptors will be necessary to further quantify this contribution.
We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/i... more We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/inferior vena caval thrombus was treated with radical nephrectomy and thrombectomy. A total of 220 patients underwent radical nephrectomy for RCC at our institution from 1998 to 2002. Of them 49 patients with renal vein/inferior vena caval involvement (T3b/c) were selected for review. We evaluated demographics, presenting symptoms, imaging modalities, clinical staging, pathological features, adjuvant treatment and clinical outcomes. We also evaluated surgical incisions, liver mobilization procedures, blood loss, transfusion requirements and perioperative mortality/morbidity. Gross hematuria was the most common presenting symptom, seen in 22 patients (45%), followed by constitutional symptoms in 8 (16%). Stage T3b/c was clinically diagnosed in 44 patients, while 2 had T2 and 2 had T4 disease. A subcostal incision was made in 30 patients, a chevron incision was made in 18, and a sternotomy and flank incision were made in 1. Liver mobilization was necessary in 13 patients and 2 required a Pringle maneuver. Cardiopulmonary bypass was performed in a single patient. Lymph node involvement was seen in 4 patients (8%) and distant metastases were present in 10 (20%). Median tumor size was 10 cm. Clear cell carcinoma was most common, as seen in 42 patients. Early (30-day) mortality in this series was 8%. At a median followup of 15 months 21 patients (43%) were without evidence of disease, 14 (29%) had disease, 8 (16%) had died of disease and 2 (4%) had died of other causes. None of the patients with lymph node involvement survived beyond 8 months after surgery. Tumor grade and T stage were found to be significant negative predictors of survival on univariate analysis. Most patients with RCC and tumor thrombus are symptomatic at presentation and metastatic disease at presentation is not uncommon. These results support the role of aggressive surgical treatment as the best initial management of these tumors. The majority of tumors can be approached and safely controlled without the need for a thoracoabdominal incision. While surgery provides modest disease-free survival, most patients should be offered immunotherapy, particularly those with advanced stage, grade, nodal involvement or metastases.
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Papers by Frank Harrell