Michael Kutner

Emory University | EU · Department of Biostatistics and Bioinformatics

Unlabelled: The Centers for Disease Control has well-established surveillance programs to monitor preventable conditions in patients supported by mechanical ventilation (MV). The aim of the study was to develop a data-driven methodology to examine variations in the first tier of the ventilator-associated event surveillance definition, described as...

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T‐wave alternans (TWA), a measure of repolarization...

Importance Mental stress–induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated. Objective To compare the association of mental stress–induced or conventional stress–induced ischemia with adverse cardiovascular ev...

The combined treatments with multiple drugs are very common in the contemporary medicine, especially for medical oncology. Therefore, we developed a Bayesian adaptive Phase I clinical trial design entitled escalation with overdoing control using normalized equivalent toxicity score for estimating maximum tolerated dose (MTD) contour of two drug com...

Background: Noninvasive ventilation (NIV), a form of positive airway pressure (PAP) therapy, is the standard of care for various forms of acute respiratory failure (ARF). Communication impairment is a side effect of NIV, impedes patient care, contributes to distress and intolerance, and potentially increases intubation rates. This study aimed to e...

High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwen...

Background Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promi...

Importance Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown. Objective To investigate the association between the change in CPC counts during stress testing...

Importance Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown. Objective To determine the association between mental stress–induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes...

Leukocyte telomere length (LTL) may be sensitive to psychosocial stressors such as discrimination. An inclusive examination of experiences of discrimination on LTL across racial/ethnic and sex groups is currently lacking. Baseline data were obtained from 369 White and African American patients with coronary artery disease (CAD) in the Mental Stress...

Background: The autonomic response to acute emotional stress can be highly variable, and pathological responses are associated with increased risk of adverse cardiovascular events. We evaluated the autonomic response to stress reactivity of young healthy subjects and aging subjects with coronary artery disease to understand how the autonomic stress...

Effects of a behavioral intervention using biofeedback on myocardial blood flow changes during mental stress in patients with coronary artery disease. Protocol document provides detailed description of each intervention applied to patients with CAD. (PDF)

R-squared values and 95% CI for stress reactivity and Gensini scores. R-squared values and 95% CI (lower bound, upper bound) values from the linear models derived from the change in each physiological measure and the corresponding Gensini score. The changes were assessed as the difference between stress and rest values for each physiological measur...

Consolidated Standards of Reporting Trials (CONSORT) checklist of the manuscript. (DOC)

Lists the physiological outcomes for each young, heathy and aging subject with CAD, each are in separate sheets. (XLSX)

Statistical analyses on the CAD group’s baseline, first minute of stress, and overall stress on HR, SBP, DBP, PP. Baseline, first minute of stress, overall stress values represent mean (SD). P-values were calculated from ANOVA (for normal data) or Kruskal-Wallis (for non-normal data) on the three intervals (baseline, first minute of stress, overall...

Background: Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it. Objective: To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia. Design: Observational study. Set...

Among various Phase I clinical trial designs, rule-based standard 3 + 3 designs are the most widely utilized for their simplicity and robustness. It is necessary to define crucial operating characteristics of a Phase I clinical trial before it starts. Based on the assumed probability of dose limiting toxicity (DLT) at each tested dose level, Lin an...

Living in neighborhoods characterized by poverty may act as a chronic stressor that results in physiological dysregulation of the sympathetic nervous system. No previous study has assessed neighborhood poverty with hemodynamic, neuroendocrine, and immune reactivity to stress. We used data from 632 patients with coronary artery disease. Patients’ re...

The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional chang...

1 Background Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based o...

Table S1. Hemodynamic and Intracoronary Doppler Measurements During the Individual Steps of the Study Protocol Figure S1. Intracoronary Doppler tracing and respective hemodynamic measurements of a subject during the study protocol. Baseline (A) was the reference for acetylcholine (B) and adenosine (C). Pre‐MS (D) was the reference for MS (E), and...

Background Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvasc...

Objective: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed to the role of behavioral factors like emotional stress on CAD risk. Brain areas involved in...

Background: Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown....

Ischemia results from an imbalance between myocardial oxygen supply and demand. Ischemia associated with mental stress (MS) has been associated with adverse outcomes in patients with coronary artery diseases (CAD). Higher heart rate (HR) and blood pressure responses to MS are associated with a greater likelihood of MS-induced ischemia. Although mul...

Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and ResultsA total of 356 patients with sta...

Objective: To investigate sex-specific vascular mechanisms for mental stress-induced myocardial ischemia (MSIMI). Approach and results: Baseline data from a prospective cohort study of 678 patients with coronary artery disease underwent myocardial perfusion imaging before and during a public speaking stressor. The rate-pressure product response...

Introduction: Mental Stress-Induced Myocardial Ischemia (MSIMI) can occur in patients with coronary artery disease (CAD) during acute mental stress challenge and is associated with an increased risk of adverse cardiovascular events. Adverse dynamic changes in repolarization with stress may also be particularly important when assessing risk of MSIMI...

Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothes...

Background: Acute stress may trigger atrial fibrillation (AF), but the underlying mechanisms are unclear. We examined if acute mental stress results in abnormal left atrial electrophysiology as detected by more negative deflection of P-wave terminal force in lead V1 (PTFV1 ), a well-known marker of AF risk. Methods and results: We examined this...

Aims Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and results We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial...

Background: Acute stress may trigger atrial fibrillation, but the mechanisms are not clear. We hypothesized that acute mental stress results in abnormal atrial remodeling via electrophysiologic effects. Methods: We examined our hypothesis in 168 patients (mean age=63±8.7 years; 74% men; 65% Caucasian) with stable coronary heart disease who underwen...

Rationale: Leukocyte telomere length (LTL) is an indicator of biological aging. Telomere shortening may be sensitive to social stressors such as discrimination, but this has not been previously examined in a biracial cohort of patients with coronary heart disease (CHD). Objective: To explore differences in LTL by race and gender and examine whether...

Objectives This study sought to investigate whether patients with mental stress–induced myocardial ischemia will have high resting and post–mental stress high-sensitivity cardiac troponin I (hs-cTnI). Background Hs-cTnI is a marker of myocardial necrosis, and its elevated levels are associated with adverse outcomes. Hs-cTnI levels may increase wit...

Background Many biomarkers have been shown to be associated with the efficacy of cancer therapy. Estimation of personalized maximum tolerated doses (pMTDs) is a critical step toward personalized medicine, which aims to maximize the therapeutic effect of a treatment for individual patients. In this study, we have established a Bayesian adaptive Phas...

The W.J. Dixon Award for Excellence in Statistical Consulting is given by the American Statistical Association to “a distinguished individual who has demonstrated excellence in statistical consulting or developed and contributed new methods, software, or ways of thinking that improve statistical practice in general.” In this article, five of the se...

Objective: Mental stress-induced myocardial ischemia (MSIMI) is a common phenomenon in patients with coronary artery disease (CAD), but contemporary studies of its prognostic significance and its underlying pathophysiology are limited. Methods: We prospectively enrolled patients with confirmed CAD in the Mental Stress Ischemia Prognosis Study (M...

Rationale: Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. Objective: To examine the relationsh...

Background Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI). Me...

Introduction: Endothelial dysfunction is associated with short term and long term cardiovascular events. African Americans (AA) have worse cardiovascular outcomes than Non-African Americans (NAA). AAs have higher chronic stress exposure due to socioeconomic deprivation which may affect vascular responses to stress and contribute to health dispariti...

Introduction: Synchronized contraction of left ventricle (LV) is necessary for normal cardiac pump function. Delayed activation of LV segments, known as “dyssynchrony,” can result in systolic and diastolic function deterioration and clinical heart failure. The autonomic nervous system regulates LV conduction and is influenced by psychological stres...

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. H...

Introduction: Mental stress ischemia (MSI) is an independent risk factor for cardiovascular outcomes and death in CAD patients, but little is known about the mechanisms behind this phenomenon. We hypothesized that alterations in autonomic function before, during, or after mental stress may play a role. We examined whether MSI positive patients with...

Background: Patients with CAD develop varying degrees of microvascular vasoconstriction in response to mental stress, leading to myocardial ischemia. Catecholamine increases during mental stress may explain this effect. We hypothesized, in a cohort of stable CAD patients, that increased epinephrine and norepinephrine levels from rest to peak mental...

Introduction: Depression and posttraumatic stress disorder (PTSD) are associated with impaired baroreflex sensitivity, a risk factor for sudden death. Unlike depression, PTSD is associated with hyperarousal. We hypothesized that, in patients with CAD, depressive and PTSD symptoms associate with different autonomic responses to standing (baroreflex...

Introduction: Previous studies have found that lower resting short-term heart rate variability (HRV), a measure of autonomic dysfunction, predicts adverse cardiac events. Abnormal autonomic function may precipitate myocardial ischemia. Physiologic challenges like Valsalva and deep breathing may also provide important data by modulating preload/afte...

Introduction: Increased hemodynamic responses to psychological stress have been associated with adverse CAD events. African Americans (AA) have worse CAD outcomes than other groups. Heightened hemodynamic responses to stress may play a role. Our hypothesis was that AA would have higher hemodynamic reactivity to a standardized mental stress compared...

Supplemental melatonin may ameliorate metabolic syndrome (MetS) components, but data from placebo-controlled trials are lacking. We conducted a double-blind, placebo-controlled, crossover, Phase II randomized pilot clinical trial to estimate the effects of melatonin supplementation on MetS components and the overall prevalence of MetS. We randomize...

Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depression. Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone (...

Background Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impac...

Lonafarnib (LNF) is a protein farnesyl transferase (FTase) inhibitor that has shown synergistic activity with taxanes in preclinical models and early stage clinical trials. Preclinical findings suggested tubulin acetylation and FTase expression levels may be important determinants of drug sensitivity that would help identify patient populations mor...

The objective of the current study was to delineate the optimal cutpoints for depression rating scales during pregnancy and the postpartum period and to assess the perinatal factors influencing these scores. Women participating in prospective investigations of maternal mental illness were enrolled prior to 28 weeks gestation and followed through 6...

The transfusion-transmitted cytomegalovirus (TT-CMV) can cause serious morbidity and mortality in low-birth weight infants (LBWIs). Transfusion-transmitted cytomegalovirus can be minimized in LBWIs born to cytomegalovirus (CMV)-seronegative mothers with the use of CMV-seronegative blood components. Despite evidence that has independently shown that...

Sleep-disordered breathing (SDB) is associated with pathophysiology that may influence the development and progression of frailty. Using data collected in 1995-1996, the authors explored the relation between SDB and components of frailty among 1,042 participants of the Cardiovascular Health Study. Diagnosis of SDB was based on the results of overni...

To examine the association between sleep-disordered breathing (SDB) and 24-hour blood pressure (BP) pattern among community-dwelling older adults. A convenience sample of 70 community-dwelling older adults, recruited from senior housing, community centers, and learning centers, were admitted to General Clinical Research Center, Emory University Hos...

Women experience greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB). The objective of this study was to determine whether off-pump CABG (OPCAB) alters this gender-based disparity. Retrospective review of risk factors and clinical outcomes for 11 413 consecutive patients...

Variceal bleeding refractory to medical treatment with beta-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have signi...

Few data exist to evaluate whether Tai Chi (TC) training improves physical performance and hemodynamic outcomes more than a wellness education (WE) program does among older fallers transitioning to frailty. This 48-week randomized clinical trial was provided at 10 matched pairs of congregate living facilities in the Atlanta metropolitan area to 291...

Studies in animals showed that the hippocampus, a brain area involved in learning and memory, is sensitive to stress. Although several MRI studies showed smaller hippocampal volume in adults with chronic PTSD, others did not show significant differences from controls. These studies are typified by small sample sizes which may limit the ability to s...

To test the effects of a rehabilitative intervention directed at continence, mobility, endurance, and strength (Functional Incidental Training (FIT)) in older patients in Department of Veterans Affairs (VA) nursing homes. Randomized, controlled, crossover trial. Four VA nursing homes. All 528 patients in the nursing homes were screened; 178 were el...

To determine whether an intense tai chi exercise program could reduce fear of falling better than a wellness education (WE) program in older adults who had fallen previously and meet criteria for transitioning to frailty. Cluster-randomized, controlled trial of 48 weeks' duration. Ten matched pairs of congregate living facilities in the greater Atl...

The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study designed to elucidate aspects of hemodialysis practice that are associated with the best outcomes for hemodialysis patients. In DOPPS I, 308 hemodialysis units from 7 countries participated, including 145 facilities from the United States (1996-2001), 62...

Examining gait characteristics in older adults who are transitioning to frailty enhances our understanding of movement control in this fall-prone population and helps to better target preventive interventions. This work presents data on temporal and spatial gait parameters of a group of older adults who have been operationally defined as "transitio...

The objective of this study was to examine the association between psychoactive medications and sleep quality in a sample of nursing home patients. We studied a baseline data collection for a clinical trial of a nonpharmacologic sleep intervention program. This study was conducted at six community nursing homes. We studied 168 nursing home patients...

To investigate the relationship between sleep-disordered breathing (SDB) and nocturia episodes in community-dwelling older adults. A cross-sectional study. Community. Community-dwelling older adults (N=72) recruited from independent living facilities and adult learning centers in Atlanta, Georgia. Three-day voiding diary, ambulatory sleep recording...