Kenneth E. Freedland

A Multidisciplinary Intervention to Prevent the Readmission of Elderly Patients with Congestive Heart Failure

BACKGROUND Congestive heart failure is the most common indication for admission to the hospital among older adults. Behavioral factors, such as poor compliance with treatment, frequently contribute to exacerbations of heart failure, a fact suggesting that many admissions could be prevented. METHODS We conducted a prospective, randomized trial of the effect of a nurse-directed, multidisciplinary intervention on rates of readmission within 90 days of hospital discharge, quality of life, and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet, social-service consultation and planning for an early discharge, a review of medications, and intensive follow-up. RESULTS Survival for 90 days without readmission, the primary outcome measure, was achieved in 91 of the 142 patients in the treatment group, as compared with 75 of the 140 patients in the control group, who received conventional care (P = 0.09). There were 94 readmissions in the control group and 53 in the treatment group (risk ratio, 0.56; P = 0.02). The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group (54 vs. 24, P = 0.04), whereas the number of readmissions for other causes was reduced by 28.5 percent (40 vs. 29, P not significant). In the control group, 23 patients (16.4 percent) had more than one readmission, as compared with 9 patients (6.3 percent) in the treatment group (risk ratio, 0.39; P = 0.01). In a subgroup of 126 patients, quality-of-life scores at 90 days improved more from base line for patients in the treatment group (P = 0.001). Because of the reduction in hospital admissions, the overall cost of care was

ASSOCIATION OF DEPRESSION AND DIABETES COMPLICATIONS: A META-ANALYSIS

460 less per patient in the treatment group. CONCLUSIONS A nurse-directed, multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure.

Major depressive disorder predicts cardiac events in patients with coronary artery disease.

Objective The objective of this study was to examine the strength and consistency of the relationship between depression and diabetes complications in studies of type 1 and type 2 adult patients with diabetes. Method MEDLINE and PsycINFO databases were searched for articles examining depression and diabetes complications in type 1 and type 2 diabetes samples published between 1975 and 1999. Meta-analytic procedures were used. Studies were reviewed for diabetes type, sample size, statistical tests, and measures of diabetes complications and depression. Significance values, weighted effect sizes r, 95% confidence intervals (CI), and tests of homogeneity of variance were calculated for the overall sample (k = 27) and for subsets of interest. Results A total of 27 studies (total combined N = 5374) met the inclusion criteria. A significant association was found between depression and complications of diabetes (p < .00001, z = 5.94). A moderate and significant weighted effect size (r = 0.25; 95% CI: 0.22–0.28) was calculated for all studies reporting sufficient data (k = 22). Depression was significantly associated with a variety of diabetes complications (diabetic retinopathy, nephropathy, neuropathy, macrovascular complications, and sexual dysfunction). Effect sizes were in the small to moderate range (r = 0.17 to 0.32). Conclusions These findings demonstrate a significant and consistent association of diabetes complications and depressive symptoms. Prospective, longitudinal studies are needed to identify the pathways that mediate this association.

Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms.

&NA; Fifty‐two patients undergoing cardiac catheterization and subsequently found to have significant coronary artery disease (CAD) were given structured psychiatric interviews before catheterization. Nine of these patients met criteria for major depressive disorder. All 52 patients were contacted 12 months after catheterization, and the occurrence of myocardial infarction, angioplasty, coronary bypass surgery and death was determined. Results of the study show that major depressive disorder was the best predictor of these major cardiac events during the 12 months following catheterization. The predictive effect was independent of the severity of CAD, left ventricular ejection fraction, and the presence of smoking. Furthermore, with the exception of smoking, there were no statistically significant differences between those patients with major depressive disorder and the remaining patients on any variable studied. The possible mechanisms relating major depressive disorder to subsequent cardiac events are discussed. It is concluded that major depressive disorder is an important independent risk factor for the occurrence of major cardiac events in patients with CAD.

Cognitive Behavior Therapy for Depression in Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

Depression increases the risk of cardiac mortality and morbidity in patients with coronary heart disease (CHD), but the mechanisms that underlie this association remain unclear. This review considers the evidence for several behavioral and physiological mechanisms that might explain how depression increases the risk for incident coronary disease and for subsequent cardiac morbidity and mortality. The candidate mechanisms include: (1). antidepressant cardiotoxicity; (2). association of depression with cardiac risk factors such as cigarette smoking, hypertension, diabetes, and reduced functional capacity; (3). association of depression with greater coronary disease severity; (4). nonadherence to cardiac prevention and treatment regimens; (5). lower heart rate variability (HRV) reflecting altered cardiac autonomic tone; (6). increased platelet aggregation; and (7). inflammatory processes. Despite recent advances in our understanding of these potential mechanisms, further research is needed to determine how depression increases risk for cardiac morbidity and mortality.

Association of depression witk reduced heart rate variability in coronary artery disease

Data from controlled studies [1-8] suggest that depression is more prevalent in diabetic patients than in the general U.S. population and that it is associated with poor glycemic control and decreased compliance with therapy [3, 5, 9-16]. Depression has also been associated with an increased risk for complications of diabetes, particularly cardiovascular disease and retinopathy [17-20]. The mechanisms of these associations are not fully understood, but it is plausible that alleviation of depression improves glycemic control and thereby decreases the risk for complications. Pharmacotherapy for depression may be poorly tolerated or may be insufficient to produce full remission in as many as 50% of diabetic patients with major depression [21-23]. The usefulness of nonpharmacologic approaches to the management of depression, such as psychotherapy, has not been systematically studied. Approximately two thirds of patients who have both diabetes and major depression do not receive specific antidepressant treatment, in part because their physicians tend to attribute their depression to poorly controlled or advancing diabetes [24, 25]. Therapy for these patients still largely centers on medical management, which may include emotional support and diabetes education; this approach is probably suboptimal. Our study was designed to determine the antidepressant efficacy of cognitive behavior therapy (CBT) added to supportive diabetes education. A secondary aim was to determine whether remission of depression is associated with improved glycemic control. Methods Patients Our study was advertised to primary care physicians working within the Washington University School of Medicine and BJC Healthcare System, St. Louis, Missouri, and it was publicized in various mass media advertisements. The study protocol was reviewed and approved by the Human Studies Committee of Washington University School of Medicine. Patients with type 2 diabetes mellitus who were 21 to 70 years of age were eligible for participation if they were able to answer questions, fill out study forms, and give informed consent. The diagnosis of type 2 diabetes was made according to the criteria developed by the American Diabetes Association [26] and was confirmed by a statement from the patients primary physician. Patients also had to meet the diagnostic criteria for major depression and had to have a score of at least 14 on the Beck Depression Inventory (BDI). Patients were excluded from participation if they had active suicidal ideation or a history of attempted suicide; had a history of panic disorder, bipolar depression, or any psychotic disorder; had a current substance abuse disorder; or were currently taking psychoactive medications. Assessment of Depression The presence of the major Axis I clinical syndromes was assessed by using the National Institute of Mental Health Diagnostic Interview Schedule (DIS) [27], and these syndromes were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders [28]. The reliability and validity of the DIS in psychiatric and epidemiologic studies have been extensively reported [29]. Evidence also indicates that the DIS is sensitive and useful for patients with diabetes, in whom the somatic manifestations of the medical disease (such as fatigue, weakness, sleep disturbances, and sexual dysfunction) mimic the symptoms of a psychiatric disorder [30, 31]. Although the DIS is suitable for use by trained lay personnel, diagnostic evaluations in our study were done by a clinical social worker and a psychologist, both of whom had been trained in the use of the DIS by the instruments developers and the staff of the St. Louis site of the National Institute of Mental Health Epidemiologic Catchment Area Study [27, 32]. The severity of current symptoms of depression was measured by using the BDI [33]. This measure asks patients to provide a self-rating from 0 to 3 on each of 21 items; these ratings are added together to produce a total score. The BDI has been studied extensively and has been shown to be a reliable and valid measure of the severity of depression [34]. Depression manifests similarly on this instrument in diabetic and psychiatric patients, particularly with regard to the cognitive symptoms of depression [31]. Assessment of Diabetes Glycosylated hemoglobin (GHb) levels were measured to assess average glycemic control in the 120-day period before testing [35-37]. Total GHb levels were measured with the Pierce Glyco-Test (Pierce Chemical, Rockford, Illinois), an affinity assay that removes confounding by hemoglobin variants, such as hemoglobin F. The range of GHb levels for normal, nondiabetic persons in the Barnes-Jewish Hospital outpatient laboratory is 4.4% to 6.3%. In this laboratory, the between-run coefficients of variation for values greater than 6.6% are all 5% or less, the recommended standard [38]. The presence of complications of diabetes (neuropathy, retinopathy, and nephropathy) was determined by a physician-investigator on the basis of review of each patients medical history, current symptoms, physical examination results, and objective test results (which were obtained through review of clinical records). Assessment of Compliance Compliance with self-monitoring of blood glucose levels was determined by using electronic memory glucometers (LifeScan, Inc., Milpitas, California), which recorded the date, time, and result of blood glucose testing. Patients were instructed to test their blood glucose levels four times per day on two nonconsecutive days each week. Values for weekly compliance with blood glucose monitoring were computed by dividing the number of samples measured on the two test days by 8 (the number of tests requested) and multiplying the result by 100%. Study Design Patients were informed that depression in diabetes can be a cause or a consequence of poor glycemic control and that the study would determine whether focusing on the mental or the physical side of the problem was the most effective way to relieve depression. These concepts were familiar to most patients and were generally well accepted. No patients declined further evaluation because they were unwilling to accept random assignment. Patients who met the inclusion criteria and gave informed consent underwent a 1-week period of glucometer training and baseline assessment, after which they were randomly assigned to study groups. The randomization pattern was determined by a computer algorithm, and assignments were concealed in sealed envelopes. A secretary who was not otherwise involved with the study opened each patients envelope after the patient had completed the baseline assessment. During the 10-week treatment period, all patients participated in a diabetes education program by meeting in 1-hour, biweekly, individual sessions with a certified diabetes educator. A variety of diabetes self-care topics were covered in these sessions, and diet and exercise regimens were systematically reviewed and modified as needed. Patients continued to see their diabetologists during the trial, and these physicians were given GHb and glucometer data from our study to facilitate management. The diabetes education program was designed to control for the nonspecific effects of supportive attention as well as the potential influence of enhanced self-care and glycemic control on mood and ideation. Patients were randomly assigned to receive CBT or to receive no specific antidepressant treatment other than the diabetes education program. Patients in the CBT group received 1 hour of treatment weekly for 10 weeks from a licensed psychologist who had been the principal cognitive therapist in an early empirical trial of CBT [39]. Cognitive behavior therapy treats depression by using 1) behavioral strategies to re-involve patients in pleasurable social and physical activities; 2) problem-solving procedures to resolve stressful circumstances; and 3) cognitive techniques to identify distorted or maladaptive thought patterns and replace them with more accurate, adaptive, and useful views. Study outcomes were measured immediately after the end of the 10-week treatment period and at a follow-up evaluation 6 months later. At each evaluation, assessments of diabetic control and depression were made and scored independently of one another. The study personnel who monitored patient progress were not involved in treatment, and assessors were blinded to treatment assignments. No additional study protocol treatment was provided after the end of the 10-week treatment period. Patients who remained depressed at that point (BDI score 10) were referred to their primary physician for antidepressant medication or to a psychotherapist. Glycemic control and severity of depression were measured again at the 6-month follow-up visit, and patients were restudied at that time with an abbreviated psychiatric interview. Self-monitoring of blood glucose levels was not measured after the end of the 10-week treatment period. Statistical Analysis Differences in the demographic and clinical characteristics of patients receiving CBT and controls were determined in the intention-to-treat and completer samples by using the Fisher exact test for categorical data and the Student t-test for continuous data. The results of an intention-to-treat analysis of the depression outcomes are provided for the purpose of comparison [40, 41]. The analyses of study outcomes focused on the completer sample. Analyses of covariance (ANCOVAs) were used to determine the effects of treatment on symptoms of depression and glycemic control after treatment and at 6-month follow-up with beginning levels of the dependent measures (BDI score and GHb level) as the covariates. The post-treatment and follow-up BDI data were not normally distributed. Consequently, the scores were categorized and Fisher exact tests were used to analyze the data. We used ANCOVA for a secondary analysis afte

Major Depression and Medication Adherence in Elderly Patients With Coronary Artery Disease

Abstract Decreased heart rate (HR) variability is an independent risk factor for mortality in cardiac populations. Clinical depression has also been associated with adverse outcomes in patients with coronary artery disease (CAD). This study tests the hypothesis that depressed patients with CAD have decreased HR variability compared with nondepressed CAD patients. Nineteen patients with angiographically documented CAD and either major or minor depression were compared with a sample of nondepressed CAD patients according to age, sex, and smoking status. All patients underwent 24-hour Holter monitoring, and the standard deviation of all normal-to-normal intervals was used as the primary index of HR variability. HR variability was significantly lower in depressed than nondepressed patients (90 ± 35 vs 117 ± 26 ms; p

Depression, the autonomic nervous system, and coronary heart disease.

Little is known about the effects of depression on adherence to medical treatment regimens in older patients with chronic medical illnesses. Poor adherence may explain the increased risk of medical morbidity and mortality found in depressed medical patients. Ten of 55 patients over the age of 64 with coronary artery disease met the criteria for major depression from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987). All patients were prescribed a twice-per-day regimen of low dose aspirin to reduce their risk for myocardial infarction. Medication adherence was assessed for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p < .02). Thus, major depression is associated with poor adherence to a regimen of prophylactic aspirin after the diagnosis of coronary artery disease.

Depression as a Risk Factor for Poor Prognosis Among Patients With Acute Coronary Syndrome: Systematic Review and Recommendations A Scientific Statement From the American Heart Association

Depression is a risk factor for medical morbidity and mortality in patients with coronary heart disease (CHD). Dysregulation of the autonomic nervous system (ANS) may explain why depressed patients are at increased risk. Studies of medically well, depressed psychiatric patients have found elevated levels of plasma catecholamines and other markers of altered ANS function compared with controls. Studies of depressed patients with CHD have also uncovered evidence of ANS dysfunction, including elevated heart rate, low heart rate variability, exaggerated heart rate responses to physical stressors, high variability in ventricular repolarization, and low baroreceptor sensitivity. All of these indicators of ANS dysfunction have been associated with increased risks of mortality and cardiac morbidity in patients with CHD. Further research is needed to determine whether ANS dysfunction mediates the effects of depression on the course and outcome of CHD, and to develop clinical interventions that improve cardiovascular autonomic regulation while relieving depression in patients with CHD. ANS = autonomic nervous system; CHD = coronary heart disease; HRV = heart rate variability; MI = myocardial infarction; NE = norepinephrine; SNS = sympathetic nervous system.

Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.

Background— Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Methods and Results— Writing group members were approved by the American Heart Association’s Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Conclusions— Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.