Maragatha Kuchibhatla

Safety and Efficacy of Sertraline for Depression in Patients With Heart Failure: Results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) Trial

OBJECTIVES The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo. BACKGROUND Depression is common among HF patients. It is associated with increased hospitalization and mortality. METHODS The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks. RESULTS A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78). CONCLUSIONS Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Identifying frailty in hospitalized older adults with significant coronary artery disease

OBJECTIVES: To characterize physiological variation in hospitalized older adults with severe coronary artery disease (CAD) and evaluate the prevalence of frailty in this sample, to determine whether single‐item performance measures are good indicators of multidimensional frailty, and to estimate the association between frailty and 6‐month mortality.

Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women

OBJECTIVE To determine whether circulating metabolic intermediates are related to insulin resistance and β-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry–based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates. RESULTS The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (SI) (R2 = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R2 = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R2 = 0.39). Sex differences were found for metabolic predictors of SI and DI. CONCLUSIONS In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.

Prognostic Value of Anxiety and Depression in Patients With Chronic Heart Failure

Background—Anxiety is often present with depression and may be one of its manifestations. Although the adverse effects of depression in patients with chronic heart failure (CHF) have been well studied, the relation between anxiety and CHF prognosis has not been addressed. In a secondary analysis of data collected for a published study of depression and prognosis in patients with CHF, we examined the relations among anxiety, depression, and prognosis. Methods and Results—We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of cardiac events. We followed up these patients for all-cause mortality over 1 year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A) were identical at 33.5; the mean BDI score was 8.7±7.6. State-A and Trait-A scores correlated highly with each other (r=0.85; P<0.01) and with BDI score (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with and without confounding variables showed no relation between State-A or Trait-A and 1-year mortality. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase; P<0.01). Conclusions—Although anxiety and depression are highly correlated in CHF patients, depression alone predicts a significantly worse prognosis for these patients.

Pituitary volumes in pediatric maltreatment-related posttraumatic stress disorder.

BACKGROUND The results of previous studies suggest structural brain differences in pediatric maltreatment-related posttraumatic stress disorder (PTSD) However, posterior fossa volumes were not examined, despite the consensus that the cerebellum is important in emotional and cognitive development. We investigated the relationship between structural volumes of the cerebellum hemispheres, vermis, brainstem, and clinical variables in pediatric maltreatment-related PTSD. METHODS Fifty-eight psychotropic-naïve maltreated children and adolescents with DSM-IV PTSD were compared with two groups of pediatric subjects who had no DSM-IV criteria A trauma histories: 1) 13 with pediatric generalized anxiety disorder, and 2) 98 healthy non-abused children and adolescents. Subjects underwent a comprehensive psychiatric assessment and an anatomical magnetic resonance image brain scan. RESULTS Unadjusted means of the left, right, and total cerebellum were smaller in the PTSD group. The group differences remained significant in the left cerebellum, right cerebellum, and total cerebellum in the analyses adjusted for cerebral volume, sociodemographic, and IQ variables. Cerebellar volumes positively correlated with age of onset of the trauma that lead to PTSD and negatively correlated with the duration of the trauma that lead to PTSD. Cerebellar volumes were larger in boys versus girls, but there was no group x gender interaction. There were significant positive correlations between IQ measures and volumetric variables. CONCLUSIONS The results support cerebellar volume differences in maltreated children and adolescents with PTSD. Further studies are warranted.

What explains racial differences in the use of advance directives and attitudes toward hospice care

Cultural beliefs and values are thought to account for differences between African Americans and whites in the use of advance directives and beliefs about hospice care, but few data clarify which beliefs and values explain these differences. Two hundred five adults aged 65 and older who received primary care in the Duke University Health System were surveyed. The survey included five scales: Hospice Beliefs and Attitudes, Preferences for Care, Spirituality, Healthcare System Distrust, and Beliefs About Dying and Advance Care Planning. African Americans were less likely than white subjects to have completed an advance directive (35.5% vs 67.4%, P<.001) and had less favorable beliefs about hospice care (Hospice Beliefs and Attitudes Scale score, P<.001). African Americans were more likely to express discomfort discussing death, want aggressive care at the end of life, have spiritual beliefs that conflict with the goals of palliative care, and distrust the healthcare system. In multivariate analyses, none of these factors alone completely explained racial differences in possession of an advance directive or beliefs about hospice care, but when all of these factors were combined, race was no longer a significant predictor of either of the two outcomes. These findings suggest that ethnicity is a marker of common cultural beliefs and values that, in combination, influence decision‐making at the end of life. This study has implications for the design of healthcare delivery models and programs that provide culturally sensitive end‐of‐life care to a growing population of ethnically diverse older adults.

The reliability, validity, and stability of a measure of physical activity in the elderly.

OBJECTIVE To assess the reliability, validity, and stability of an accelerometer-based monitor of physical activity in an elderly population. DESIGN Six studies were conducted to assess the Tritrac, a newly available accelerometer capable of storing three-dimensional activity data collected in minute epochs. After initial bench testing, the waist-worn devices were assessed for test-retest reliability during sitting and treadmill walking at 1mph and 2mph. Validity testing examined the Tritracs ability to discriminate between different levels of physical activity and also compared the Tritrac with an established wrist-worn acclerometer, the Actigraph. Stability of the measure was examined over a period of 3 to 7 days, and in a subset of subjects this measurement was performed for a second week. SETTING AND SUBJECTS Residents of a VA Nursing Home (n = 40; mean age = 76), participants in an in-home nonaerobic exercise program (n = 36; mean age = 77), and community participants in an aerobic exercise program (n = 10; mean age = 71). RESULTS Intraclass correlation coefficients (ICC) for both the bench testing and test-retest reliability were .97. The device discriminated among subjects independently categorized as sedentary, moderately active, or active (F = 49.4, p = .0001) and between specific activities of varying intensity (F = 114.5, p = .0001). Tritrac and Actigraph measurement comparison showed a correlation of r = .77, p = .0001. Stability of the measure was demonstrated by ICCs = .81 and .78 for mean activity values and proportion of time spent in sedentary activity, respectively. No significant differences were observed when comparing activity measured for two separate weeks. CONCLUSION The Tritrac is a reliable and valid instrument producing activity measurement that was stable over time in the elderly population we studied. During our longitudinal testing, 20% of the subjects did not comply with wearing the device; this noncompliance issue must be considered in any use of the Tritrac.

Cortical White Matter Microstructural Abnormalities in Bipolar Disorder

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm2/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

Antidepressant Use, Depression, and Survival in Patients With Heart Failure

BACKGROUND Recent studies suggest that the use of antidepressants may be associated with increased mortality in patients with cardiac disease. Because depression has also been shown to be associated with increased mortality in these patients, it remains unclear if this association is attributable to the use of antidepressants or to depression. METHODS To evaluate the association of long-term mortality with antidepressant use and depression, we studied 1006 patients aged 18 years or older with clinical heart failure and an ejection fraction of 35% or less (62% with ischemic disease) between March 1997 and June 2003. The patients were followed up for vital status annually thereafter. Depression status, which was assessed by the Beck Depression Inventory (BDI) scale and use of antidepressants, was prospectively collected. The main outcome of interest was long-term mortality. RESULTS Of the study patients, 30.0% were depressed (defined by a BDI score > or =10) and 24.2% were taking antidepressants (79.6% of these patients were taking selective serotonin reuptake inhibitors [SSRIs] only). The vital status was obtained from all participants at an average follow-up of 972 (731) (mean [SD]) days. During this period, 42.7% of the participants died. Overall, the use of antidepressants (unadjusted hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.03-1.69) or SSRIs only (unadjusted HR, 1.32; 95% CI, 0.99-1.74) was associated with increased mortality. However, the association between antidepressant use (HR, 1.24; 95% CI, 0.94-1.64) and increased mortality no longer existed after depression and other confounders were controlled for. Nonetheless, depression remained associated with increased mortality (HR, 1.33; 95% CI, 1.07-1.66). Similarly, depression (HR, 1.34; 95% CI, 1.08-1.68) rather than SSRI use (HR, 1.10; 95% CI, 0.81-1.50) was independently associated with increased mortality after adjustment. CONCLUSION Our findings suggest that depression (defined by a BDI score > or =10), but not antidepressant use, is associated with increased mortality in patients with heart failure.

The Preventive Surgical Site Infection Bundle in Colorectal Surgery An Effective Approach to Surgical Site Infection Reduction and Health Care Cost Savings

IMPORTANCE Surgical site infections (SSIs) in colorectal surgery are associated with increased morbidity and health care costs. OBJECTIVE To determine the effect of a preventive SSI bundle (hereafter bundle) on SSI rates and costs in colorectal surgery. DESIGN Retrospective study of institutional clinical and cost data. The study period was January 1, 2008, to December 31, 2012, and outcomes were assessed and compared before and after implementation of the bundle on July 1, 2011. SETTING AND PARTICIPANTS Academic tertiary referral center among 559 patients who underwent major elective colorectal surgery. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of superficial SSIs before and after implementation of the bundle. Secondary outcomes included deep SSIs, organ-space SSIs, wound disruption, postoperative sepsis, length of stay, 30-day readmission, and variable direct costs of the index admission. RESULTS Of 559 patients in the study, 346 (61.9%) and 213 (38.1%) underwent their operation before and after implementation of the bundle, respectively. Groups were matched on their propensity to be treated with the bundle to account for significant differences in the preimplementation and postimplementation characteristics. Comparison of the matched groups revealed that implementation of the bundle was associated with reduced superficial SSIs (19.3% vs 5.7%, P < .001) and postoperative sepsis (8.5% vs 2.4%, P = .009). No significant difference was observed in deep SSIs, organ-space SSIs, wound disruption, length of stay, 30-day readmission, or variable direct costs between the matched groups. However, in a subgroup analysis of the postbundle period, superficial SSI occurrence was associated with a 35.5% increase in variable direct costs (