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Biomedical subjects

Kenneth E Freedland

Publications and source records attributed to Kenneth E Freedland.

At least 19 recordsLinked to original sources
PubMed2026

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P = .03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P = .005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P = .15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P = .54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans↗
PubMed2006

Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

CONTEXT: In patients with diabetes mellitus, depression is a prevalent and recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes. DESIGN: A randomized, double-blind, placebo-controlled, maintenance treatment trial. Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52 weeks or until depression recurred. SETTING: Outpatient clinics at Washington University, St Louis, MO, the University of Washington, Seattle, and the University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who recovered from major depression (43.3% of those initially assigned) during 16 weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d). INTERVENTION: Sertraline continued at recovery dose or identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured as the number of days after randomization) to recurrence of major depression as defined in DSM-IV. The secondary outcome was glycemic control, which was assessed via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02). Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline. Glycosylated hemoglobin levels decreased during the open treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/- 1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance (P = .002) and did not differ between treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.

Age of Onset↗
PubMed2006

Preexisting cognitive impairment in women before cardiac surgery and its relationship with C-reactive protein concentrations.

Preoperative cognitive state is seldom considered when investigating the effects of cardiac surgery on cognition. In this study we sought to determine the prevalence of cognitive impairment in women scheduled for cardiac surgery using nonhospitalized volunteers as a reference group and to examine the relationship between C-reactive protein levels and cognitive impairment. Psychometric testing was performed in 108 postmenopausal women scheduled for cardiac surgery and in 58 nonhospitalized control women. High sensitivity C-reactive protein levels were measured in the surgical patients. Preoperative cognitive impairment was defined as >2 sd lower scores on > or =2 tests compared with the controls. Cognitive impairment was present in 49 of 108 (45%) patients. C-reactive protein levels were higher for patients with compared with those without cognitive impairment (median, 8.1 mg/L versus 4.7 mg/L; P = 0.04). Based on multivariate logistic regression analysis, patient age, lower attained level of education, type 2 diabetes mellitus, and prior myocardial infarction identified risk for cognitive impairment (P < 0.05) but C-reactive protein levels did not (P = 0.09). In conclusion, cognitive impairment is prevalent in women before cardiac surgery. C-reactive protein levels are increased in women with this condition but the relationship between this inflammatory marker and preexisting cognitive impairment is likely secondary to the acute phase reactant serving as a marker for other predisposing conditions.

Aged↗
PubMed2005

Low heart rate variability and the effect of depression on post-myocardial infarction mortality.

BACKGROUND: Depression is associated with an increased risk for mortality after acute myocardial infarction (MI). The purpose of this study was to determine whether low heart rate variability (HRV) mediates the effect of depression on mortality. METHODS: Twenty-four-hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria. Standard HRV indexes were extracted from the recordings. RESULTS: The log of very low-frequency (LnVLF) power, an index of HRV derived from power spectral analysis of the electrocardiogram signal (0.0033-0.04 Hz [in milliseconds squared]), was lower in the depressed than in the nondepressed patients (P<.001). There were 47 deaths (6.1%) during a 30-month follow-up. After adjusting for potential confounders, the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.4; P<.003). When LnVLF power was entered into the model, the hazard ratio for depression dropped to 2.1 (95% CI, 1.1-4.2; P = .03). The proportion of the risk for depression attributable to LnVLF power was 0.27 (95% CI, 0.23-0.31; P<.001). CONCLUSIONS: Low HRV partially mediates the effect of depression on survival after acute MI. This finding helps to clarify the physiological mechanisms underlying depression's role as a risk factor for mortality in patients with coronary heart disease. It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients.

Circadian Rhythm↗
PubMed2005

Relation of depressive symptoms to C-reactive protein and pathogen burden (cytomegalovirus, herpes simplex virus, Epstein-Barr virus) in patients with earlier acute coronary syndromes.

Despite mounting evidence that depressive symptoms increase the risk of morbidity and mortality in patients who have coronary artery disease, little is known about the biologic mechanisms that underlie this association. This study examined whether depressive symptoms are associated with markers of infection and inflammation that have been implicated in the pathogenesis of coronary artery disease. Sixty-five patients who were recovering from an acute coronary syndrome were enrolled (63% men; mean age 61 years, 90% white). Depressive symptoms were assessed through self-report and observer ratings; the inflammatory molecules C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were measured in serum, as were antibody titers to 3 latent viruses associated with atherosclerosis. Patients who had more severe depressive symptoms exhibited higher levels of C-reactive protein (r = 0.27, p = 0.03) and higher rates of seropositivity to the latent viruses (r = 0.41, p = 0.001). These effects were large in magnitude: patients in the highest tertile of the depression distribution had C-reactive protein levels >50% higher than did patients in the middle and lowest tertiles; they also were 2 times as likely to show evidence of infection with all 3 latent viruses. Disparities in the extent, severity, or management of cardiac disease were not responsible for these associations. These findings provide evidence that depressive symptoms are associated with increases in C-reactive protein and pathogen burden in patients who have coronary artery disease. In doing so, they highlight a mechanism through which depressive symptoms might foster morbidity and mortality among patients who have cardiac disease.

Biomarkers↗
PubMed2005

Depression and heart failure in patients with a new myocardial infarction.

BACKGROUND: Heart failure (HF) is a disabling chronic illness that is increasing in prevalence. Despite advances in its medical treatment, little is known about its psychosocial correlates. This investigation compared the prevalence of depression in patients with and without HF who were hospitalized with myocardial infarction (MI) and also at high psychosocial risk. METHODS: Baseline data from the 2444 participants in the ENRICHD clinical trial were used. Within 28 days of the MI, all patients were assessed for depression using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, for HF based upon left ventricular dysfunction or history of HF and for demographic and medical confounders. RESULTS: Eight hundred forty-seven patients (34.7%) met the criteria for HF. Major depression was observed in 43% in the HF group compared with 36% in the non-HF group (P < .001). Multivariate modeling showed a 38% increase in odds of HF for patients with major depression, after adjustment for sociodemographic factors and medical comorbidities (adjusted OR 1.38, 95% CI 1.09-1.76). CONCLUSIONS: These findings suggest that in patients with new MI who are at psychosocial risk, major depression is more prevalent in those who also have HF. Because major depression undermines adherence and lowers quality of life, special efforts to diagnose and treat it in post-MI patients with HF appear warranted.

Aged↗
PubMed2005

Depressive symptoms and the regulation of proinflammatory cytokine expression in patients with coronary heart disease.

OBJECTIVE: Depressive symptoms increase the risk of morbidity and mortality in patients with coronary heart disease (CHD). Mounting evidence indicates that inflammatory processes may underlie this association. This study examined whether depressive symptoms are associated with the dysregulation of inflammatory cytokine production in response to an in vitro infectious challenge. METHODS: Forty-one patients with CHD were enrolled 3 months or more after an acute myocardial infarction or revascularization procedure. Depressive symptoms were assessed through self-report and interviewer ratings. Cytokine production was measured after white blood cells were cultured in vitro with endotoxin in the presence of varying concentrations of dexamethasone. RESULTS: Depressive symptoms were not associated with the quantity of in vitro inflammatory cytokine production. However, to the extent that they reported symptoms of depression, patients showed greater sensitivity to the anti-inflammatory properties of glucocorticoids. This was manifested by increased suppression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production by dexamethasone. CONCLUSIONS: Increased sensitivity to glucocorticoid inhibition could render depressed patients vulnerable to latent infections and inflammatory processes that accelerate the progression of cardiac disease.

Adult↗
PubMed2005

Effects of anxiety and depression on heart disease attributions.

Cardiac patients' beliefs about the causes of their illness may influence their receptivity to psychosocial interventions. The purpose of this study was to determine whether depression or anxiety influence patients' attributions about the causes of their heart disease. The primary hypothesis was that depressed or anxious patients are more likely to endorse negative emotions as among the causes of their heart disease than are patients who are not depressed or anxious. Sixty-nine patients with documented ischemic heart disease recruited from an exercise stress testing laboratory completed the Beck Depression and Anxiety Inventories and a heart disease attribution checklist. Univariate analyses confirmed that patients who are depressed or anxious are more likely than other patients to endorse negative emotions as causes of their heart disease. Anxiety but not depression was retained as an independent predictor of negative emotion attributions in a logistic regression analysis. We conclude that mood state influences cardiac patients' beliefs about the causes of their heart disease.

Aged↗
PubMed2004

Religious beliefs shorten hospital stays? Psychology works in mysterious ways: comment on Contrada et al. (2004).

A study by R. J. Contrada et al. (2004; see record 2004-13299-001) suggested that religious involvement affects recovery from coronary artery bypass graft surgery. This finding makes a significant contribution to the growing literature on the role of religion in health and illness, yet it is unlikely to have a comparable impact on coronary artery bypass graft surgery research. Why? What determines the importance of psychosocial predictors of medical outcomes? How can health psychologists increase the impact of biopsychosocial research?

Cardiac Surgical Procedures↗
PubMed2003

Depression as a risk factor for mortality after acute myocardial infarction.

The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.

Aged↗
PubMed2003

Depression, mortality, and medical morbidity in patients with coronary heart disease.

There is substantial evidence that depression is a risk factor for cardiac morbidity and mortality, both for patients without clinical evidence of coronary heart disease at index examination and for patients with established coronary disease. The relationship is most apparent for patients with a recent acute myocardial infarction. Many questions about the impact of depression on heart disease remain unresolved.

Comorbidity↗
PubMed2003

Cognitive and somatic symptoms of depression are associated with medical comorbidity in patients after acute myocardial infarction.

BACKGROUND: Depression is common in patients with acute myocardial infarction (AMI) and is associated with adverse health outcomes. However, the extent to which clinical depression is related to comorbid medical conditions is unknown. This study examined the degree of association between clinical depression and medical comorbidity in patients hospitalized with AMI. METHODS: Two thousand four hundred and eighty-one depressed or socially isolated patients with AMI were enrolled, as part of the National Heart, Lung, and Blood Institute-sponsored Enhancing Recovery in Coronary Heart Disease clinical trial. A structured interview was used to diagnose major and minor depression and dysthymia; severity of depression was measured by the Hamilton Rating Scale for Depression and the Beck Depression Inventory. Level of social support was measured by the ENRICHD Social Support Instrument. A modified version of the Charlson Comorbidity Index was used to measure the cumulative burden of medical comorbidity. RESULTS: The adjusted odds ratios (ORs) for having major depression increased linearly with medical comorbidity (ORs 1.6, 2.2, 2.7 for each increasing medical comorbidity category). This relationship remained after adjusting for coronary heart disease severity (ORs 1.4, 1.7, 1.9, P <.001). The relationship between severity of depression and medical comorbidity was also maintained after excluding somatic symptoms of depression (F = 21.5, P <.0001). CONCLUSIONS: Patients with AMI and clinical depression have significantly greater levels of medical comorbidity than nondepressed, socially isolated patients. Further research is needed to determine whether comorbid medical illness contributes to the more frequent rehospitalizations and increased risk of mortality associated with depression.

Adult↗
PubMed2003

Predictors of mortality in younger and older patients with heart failure and preserved or reduced left ventricular ejection fraction.

BACKGROUND: Although half of elderly patients with heart failure have preserved left ventricular ejection fraction (LVEF), little is known about predictors of mortality in this group. METHODS: We reviewed the charts of 400 patients hospitalized at an academic medical center in 1999 with a principal discharge diagnosis of heart failure. Patients were divided into 4 groups on the basis of age > or =75 or <75 years and the presence of preserved or reduced LVEF. Vital status was ascertained as of October 2001. RESULTS: A total of 373 patients (mean age 69.1 years, 56.0% female, 47.5% nonwhite) underwent echocardiography to assess LVEF. Of these, 216 patients were <75 years of age (81 with preserved LVEF [group 1, 21.7%] and 135 with reduced LVEF [group 2, 36.2%]), and 157 were > or =75 years of age (81 with preserved LVEF [group 3, 21.7%] and 76 with reduced LVEF [group 4, 19.6%]). After a mean follow-up of 25 months, independent predictors of mortality among the 4 groups differed substantially: group 1, male sex, prescription of a calcium-channel blocker, and diuretic dose at discharge; group 2, blood urea nitrogen (BUN), lower hemoglobin level, and not being prescribed a beta-blocker at discharge; group 3, BUN; and group 4, older age, history of myocardial infarction, severity of reduced LVEF, and diuretic dose. CONCLUSION: In patients with heart failure, predictors of mortality vary by age and by the presence of preserved or reduced LVEF. Traditional predictors of mortality in patients with reduced LVEF may not apply to elderly patients with preserved LVEF.

Age Factors↗
PubMed2003

Gender influence on cognitive function after cardiac operation.

BACKGROUND: Women are at higher risk than men for stroke after cardiac operation. The purpose of this study was to evaluate for gender influences on the more common postoperative neurologic complication, cognitive dysfunction. METHODS: A standard battery of neuropsychological tests was administered to 117 patients (79 men and 38 women) the day before and again 4 to 6 weeks after cardiac operation. The battery assessed a broad array of cognitive domains, including attention, memory, executive function, and psychomotor processing speed. Analysis was performed only on patients with data from both testing sessions. Data were analyzed to assess for a dichotomous definition of postoperative cognitive impairment and to evaluate for factors influencing test results for specific cognitive domains. RESULTS: The frequency of one standard deviation decline on two or more cognitive tests compared with preoperative results (women, 10.7 % versus men, 9.9 %; p = 0.527), no decline, or one standard deviation improvement on each test postoperatively was no different between genders. After adjusting for age, gender, preexisting medical conditions, level of attained education, preoperative cognitive tests results, type of operation, and duration of cardiopulmonary bypass, female gender was independently associated with poorer performance postoperatively on visuospatial tasks. Other variables significantly related to postoperative cognitive function varied among the specific cognitive domains. CONCLUSIONS: These data suggest that, although the frequency of cognitive dysfunction after cardiac operation is similar for women and men, women appear more likely to suffer injury to brain areas subserving visuospatial processing. Risk factors for postoperative cognitive impairment vary depending on cognitive domain, suggesting multiple etiologies for this form of perioperative neurologic injury.

Cardiac Surgical Procedures↗