Postoperative cognitive dysfunction and mortality following lung transplantation.

Preliminary evidence suggests that postoperative cognitive dysfunction (POCD) is common after lung transplantation. The impact of POCD on clinical outcomes has yet to be studied. The association between POCD and longer-term survival was therefore examined in a pilot study of posttransplantation survivors. Forty-nine participants from a prior randomized clinical trial underwent a neurocognitive assessment battery pretransplantation and 6 months posttransplantation, including assessments of the domains of Executive Function (Trail Making Test, Stroop, Digit Span), Processing Speed (Ruff 2 and 7 Test, Digit Symbol Substitution Test), and Verbal Memory (Verbal Paired Associates, Logical Memory, Animal Naming, and Controlled Oral Word Association Test). During a 13-year follow-up, 33 (67%) participants died. Greater neurocognition was associated with longer survival (hazard ratio [HR] = 0.49 [0.25-0.96], P = .039), and this association was strongest on tests assessing Processing Speed (HR = 0.58 [0.36-0.95], P = .03) and Executive Function (HR = 0.52 [0.28-0.97], P = .040). In addition, unadjusted analyses suggested an association between greater Memory performance and lower risk of CLAD (HR = 0.54 [0.29-1.00], P = .050). Declines in Executive Function tended to be predictive of worse survival. These preliminary findings suggest that postoperative neurocognition is predictive of subsequent mortality among lung transplant recipients. Further research is needed to confirm these findings in a larger sample and to examine mechanisms responsible for this relationship.

Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation.

OBJECTIVE: To investigate the effects of pain coping skills training (PCST) and a lifestyle behavioral weight management (BWM) program on inflammatory markers and biomarker associations with pain and function in the OA LIFE study. METHOD: Serum samples were available from a subset (N = 169) of the overweight or obese knee OA participants in the OA LIFE study that evaluated: PCST, BWM, combined PCST + BWM, or standard care (SC). Inflammatory markers (hsCRP, IL-1ra, IL-1ß, IL-6, IL-8, TNF-α, TNFRI, TNFRII, and hyaluronic acid (HA)), and adipokines (leptin and adiponectin) were measured before and after the 24-week treatment period. Biomarkers were assessed for effects of treatment and for associations with change in weight, pain and disability (unadjusted and adjusted for age, race, sex, baseline body mass index (BMI), and baseline biomarker concentration). RESULTS: PCST + BWM was associated with significant reductions in hsCRP (P = 0.0014), IL-6 (P = 0.0075), and leptin (P = 0.0001). After adjustment, there was a significant effect of PCST + BWM on changes in leptin (b = -0.19, P = 0.01) and IL-6 (b = -0.25, P = 0.02) relative to SC. Reductions in leptin and IL-6 were significantly correlated with reductions in weight, BMI and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain; reductions in IL-6 were correlated with improvements in WOMAC and Arthritis Impact Measurement Scales (AIMS) physical function. By mediation analyses, weight loss was responsible for 54% of the change in IL-6 and all of the change in leptin. CONCLUSIONS: OA-related inflammatory markers were reduced by a 24-week combined PCST + BWM intervention. This suggests that the inflammatory state can be successfully modified in the context of a readily instituted clinical intervention with a positive clinical outcome.

Dietary Factors and Cognitive Decline.

Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing 'whole' diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed.

Psychosocial Predictors of Mortality Following Lung Transplantation.

Lung transplantation has become an increasingly common treatment for patients with end-stage lung disease. Few studies have examined psychosocial risk factors for mortality in transplant recipients, despite evidence suggesting that elevated levels of negative affect are associated with greater mortality following major cardiac surgery. We therefore examined the relationship between negative affect early after lung transplantation and long-term survival in a sample of 132 lung transplant recipients (28 cystic fibrosis, 64 chronic obstructive pulmonary disease, 26 idiopathic pulmonary fibrosis, 14 other) followed for up to 13.5 years (median 7.4 years) following transplantation. Patients underwent both medical and psychosocial assessments 6 months following transplantation, which included the Beck Depression Inventory-II (BDI-II), Spielberger Anxiety Inventory, and General Health Questionnaire (GHQ). Over the course of follow-up, 80 (61%) participants died. Controlling for demographic factors, native lung disease, disease severity, family income, education level, social support, and frequency of posttransplant rejection, elevated symptoms of depression (BDI-II: HR = 1.31, p = 0.011) and distress (GHQ: HR = 1.28, p = 0.003) were associated with increased mortality. Higher levels of depression and general distress, but not anxiety, measured 6 months following lung transplantation are associated with increased mortality, independent of background characteristics and medical predictors.

Work and home stress: associations with anxiety and depression symptoms.

BACKGROUND: In the evolving work environment of global competition, the associations between work and home stress and psychological well-being are not well understood. AIMS: To examine the impact of psychosocial stress at work and at home on anxiety and depression. METHODS: In medically healthy employed men and women (aged 30-60), serial regression analyses were used to determine the independent association of psychosocial stress at work and at home with depression symptoms, measured using the Beck Depression Inventory-II (BDI-II), and anxiety symptoms, measured using the Spielberger Trait Anxiety Inventory (STAI). Psychosocial stress at work was measured using the Job Content Questionnaire to assess job psychological demands, job control, job social support and job insecurity. Psychosocial stress at home was assessed by 12 questions including stress at home, personal problems, family demands and feelings about home life. RESULTS: Serial regression analyses in 129 subjects revealed that job insecurity and home stress were most strongly associated with depression and anxiety symptoms. Job insecurity accounted for 9% of the variation both in BDI-II scores and in STAI scores. Home stress accounted for 13 and 17% of the variation in BDI-II scores and STAI scores, respectively. In addition, job social support was significantly and independently associated with STAI scores but not BDI-II scores. CONCLUSIONS: Work and home stress were associated with anxiety and depression symptoms in both men and women. Both work and home stress should be considered in studies evaluating anxiety and depression in working populations.

Delirium affects length of hospital stay after lung transplantation.

BACKGROUND: Delirium is relatively common after lung transplantation, although its prevalence and prognostic significance have not been systematically studied. The purpose of the present study was to examine pretransplant predictors of delirium and the short-term impact of delirium on clinical outcomes among lung transplant recipients. METHODS: Participants underwent pretransplant cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test. After transplant, delirium was assessed using the Confusion Assessment Method until discharge. RESULTS: Sixty-three patients were transplanted between March and November 2013, of which 23 (37%) developed delirium. Among transplanted patients, 48 patients completed pretransplant cognitive testing. Better pretransplant cognitive function was associated with lower risk of delirium (odds ratio, 0.69 [95% confidence interval 0.48, 0.99], P = .043); and demographic and clinical features including native disease (P = .236), the Charlson comorbidity index (P = .581), and the lung allocation score (P = .871) were unrelated to risk of delirium, although there was a trend for women to experience delirium less frequently (P = .071). The presence (P = .006) and duration (P = .027) of delirium were both associated with longer hospital stays. CONCLUSION: Delirium occurs in more than one-third of patients after lung transplantation. Delirium was associated with poorer pretransplant cognitive functioning and longer hospital stays, after accounting for other medical and demographic factors.

Changes in neurocognitive functioning following lung transplantation.

Although neurocognitive impairment is relatively common among patients with advanced lung disease, little is known regarding changes in neurocognition following lung transplantation. We therefore administered 10 tests of neurocognitive functioning before and 6 months following lung transplantation and sought to identify predictors of change. Among the 49 study participants, native diseases included chronic obstructive pulmonary disease (n = 22), cystic fibrosis (n = 12), nonfibrotic diseases (n = 11) and other (n = 4). Although composite measures of executive function and verbal memory scores were generally within normal limits both before and after lung transplantation, verbal memory performance was slightly better posttransplant compared to baseline (p < 0.0001). Executive function scores improved in younger patients but worsened in older patients (p = 0.03). A minority subset of patients (29%) exhibited significant cognitive decline (i.e. >1 standard deviations on at least 20% of tests) from baseline to posttransplant. Patients who declined were older (p < 0.004) and tended to be less educated (p = 0.07). Lung transplantation, like cardiac revascularization procedures, appears to be associated with cognitive decline in a subset of older patients, which could impact daily functioning posttransplant.

Cardiovascular disease risk, vascular health and erectile dysfunction among middle-aged, clinically depressed men.

Erectile dysfunction (ED) is especially common in men with major depressive disorder (MDD). This study examined the extent to which risk factors for cardiovascular disease (CVD) and vascular endothelial dysfunction were associated with ED severity in MDD patients. The sample included 46 middle-aged [M (s.d.)=53 (7) years], sedentary men diagnosed with MDD. ED severity was assessed by the Arizona Sexual Experiences Scale (ASEX), item 3. Depression severity was measured by the Beck Depression Inventory-II (BDI). The Framingham risk score was calculated as a composite measure of CVD risk factors. Vascular endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. Regression analysis showed that ASEX scores were predicted by the greater Framingham risk score (beta=0.41, P=0.008) and lower FMD (beta=-0.38, P=0.01), but not by BDI scores (beta=0.00, P=0.99). When FMD was included in the regression model, the relationship between Framingham risk and ASEX scores was partially attenuated (beta=0.27, P=0.08). ED was associated with greater CVD risk and impaired vascular endothelial function in depressed men. CVD risk factors may affect ED through impairment of vascular endothelial function.

Baseline 6-min walk distance predicts survival in lung transplant candidates.

In a large, prospectively followed, two-center cohort of patients listed for lung transplantation (n = 376), we used Cox proportional hazards models to determine the importance of baseline 6-min walk distance (6MWD) in predicting patient survival. 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time-varying covariate (HR for each 500 ft increase in 6MWD = 0.57, 95% CI: 0.43-0.77, p = 0.0002). 6MWD remained an important predictor of survival in models that considered only survival to transplant (HR for each 500 ft increase in 6MWD = 0.41, 95% CI: 0.27-0.62, p < 0.0001) or survival only after transplant (HR for each 500 ft increase in 6MWD = 0.40, 95% CI: 0.22-0.72, p = 0.002). Unadjusted Kaplan-Meier analysis demonstrates significantly different survival by 6MWD tertiles (<900, 900-1200, or >1200 ft, p-value = 0.0001). In the overall model, 6MWD prediction of survival was relatively homogeneous across disease category (6MWD by disease interaction term, p-value = 0.63). Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation. The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation.

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

BACKGROUND AND PURPOSE: The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. METHODS: After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. RESULTS: Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. CONCLUSIONS: Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Effects of exercise and weight loss on blood pressure during daily life.

PURPOSE: The objective of this study was to investigate the effects of exercise training and weight loss on blood pressure (BP) associated with physical activity and emotional stress during daily life. METHODS: One hundred twelve participants with unmedicated high normal or stage 1 to stage 2 hypertension were randomized to one of three conditions: a combined exercise and behavioral weight management group (WM), an exercise-only group (EX), or a wait list control group (CON). BP was assessed in the clinic and during 15 h of daytime ambulatory BP monitoring at baseline and after 6 months of treatment. RESULTS: Increased levels of physical activity and emotional distress measured during daily life were associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and rate pressure product (RPP). After treatment, the WM group had significantly lower DBP, HR, and RPP responses during both high and low levels of physical activity and emotional distress compared with the CON group. The EX group had similar BP levels as the WM group, although the EX group had significantly lower BP than the CON group during low but not high levels of physical activity and emotional distress. CONCLUSION: These findings indicate that exercise, especially when combined with weight loss, reduces BP levels at rest and in situations that typically elevate BP such as intense physical activity and emotional distress.

Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery.

BACKGROUND: Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery. METHODS: Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale. RESULTS: Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment. CONCLUSIONS: Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.

Depression, heart rate variability, and acute myocardial infarction.

BACKGROUND: Clinical depression is associated with an increased risk for mortality in patients with a recent myocardial infarction (MI). Reduced heart rate variability (HRV) has been suggested as a possible explanation for this association. The purpose of this study was to determine if depression is associated with reduced HRV in patients with a recent MI. METHODS AND RESULTS: Three hundred eighty acute MI patients with depression and 424 acute MI patients without depression were recruited. All underwent 24-hour ambulatory electrocardiographic monitoring after hospital discharge. In univariate analyses, 4 indices of HRV were significantly lower in patients with depression than in patients without depression. Variables associated with HRV were then compared between patients with and without depression, and potential confounds were identified. These variables (age, sex, diabetes, and present cigarette smoking) were entered into an analysis of covariance model, followed by depression status. In the final model, all but one HRV index (high-frequency power) remained significantly lower in patients with depression than in patients without depression. CONCLUSIONS: We conclude that greater autonomic dysfunction, as reflected by decreased HRV, is a plausible mechanism linking depression to increased cardiac mortality in post-MI patients.

Religious coping, ethnicity, and ambulatory blood pressure.

OBJECTIVE: To investigate the relationship between religious coping, ethnicity, and ambulatory blood pressure (ABP) measured during daily life. METHODS: A 24-hour ABP was obtained from 155 men and women (78 African American and 77 white) on a typical workday. ABP was averaged over awake and sleep periods, and clinic BP was also assessed. Psychosocial measures of coping style, negative affect, social support, stress, and health behaviors were completed before ABP measurement. RESULTS: Multiple regression analyses, controlling for demographic variables, revealed a significant religious coping by ethnicity interaction for ABP (p < .01) and clinic BP (p < .05). Religious coping was not related to BP among whites. Among African Americans, however, higher levels of religious coping were associated with lower awake (p < .05) and sleep (p < .01) ABP. Social support satisfaction also was related to lower awake ABP among African Americans, but it did not mediate the relationship between religious coping and ABP. CONCLUSIONS: The results of this study extend previous findings by showing that, among African Americans, religious coping and BP are related during daily activities as well as in the clinic. Lower 24-hour BP load may be a pathway through which religiosity and cardiovascular health are related.

Blunted nighttime blood pressure dipping in postmenopausal women.

Blunting of the normal drop in blood pressure (BP) from day to night is emerging as a strong prognostic indicator of cardiovascular morbidity and mortality. This study evaluated the effects of natural menopause on BP dipping in African American and white women. A total of 112 women (62 premenopausal and 50 postmenopausal) took part in the study. Pre- and postmenopausal groups were comparable in terms of clinic BP, body mass index, and ethnic composition. Ambulatory BP was recorded over 24 h during a typical workday, with measurements programmed to be taken every 15 min during waking hours and every 30-minutes during sleeping hours. Nocturnal BP dipping was defined as the difference between waking and sleep BP. Waking BP did not differ by menopausal status. However, nocturnal systolic BP (SBP) and diastolic BP (DBP) dipping were attenuated in postmenopausal women, with both SBP (P < .05) and DBP (P < .05) higher during nighttime sleep in postmenopausal than in premenopausal women. Ethnicity was also related to BP dipping, with African American women tending to show blunted SBP dipping (P = .055) compared with white women; BP dipping was most blunted in postmenopausal African American women. These observations suggest that blunted nighttime BP dipping may contribute to increased cardiovascular disease risk in postmenopausal women.

Binge eating disorder and night eating syndrome: psychological and behavioral characteristics.

OBJECTIVE: The present study was designed to examine the psychological and behavioral characteristics associated with both night eating syndrome (NES) and binge eating disorder (BED) in 42 males and 41 females who were enrolled in a university-based weight loss center. METHOD: Individuals were classified into one of four groups: NES only (N = 23), BED only (N = 13), both NES and BED (N = 13), or no diagnoses of an eating disorder (N = 34). Analyses of covariance (covarying for age and gender) were conducted to compare patients with BED and NES. RESULTS: NES patients scored lower on disinhibition than BED patients (p <.01). Also, individuals who met criteria for both disorders scored higher than NES only patients on state anxiety (p <.01), disinhibition (p =.08), and trait anxiety (p =.08). DISCUSSION: These results suggest that NES represents a subcategory among the obese, which also overlaps with binge eaters. In addition, anxiety distinguished individuals who met criteria for both disorders from patients who were diagnosed with either NES or BED.

Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.

BACKGROUND: Cognitive decline complicates early recovery after coronary-artery bypass grafting (CABG) and may be evident in as many as three quarters of patients at the time of discharge from the hospital and a third of patients after six months. We sought to determine the course of cognitive change during the five years after CABG and the effect of perioperative decline on long-term cognitive function. METHODS: In 261 patients who underwent CABG, neurocognitive tests were performed preoperatively (at base line), before discharge, and six weeks, six months, and five years after CABG surgery. Decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of four domains of cognitive function. (A reduction of 1 SD represents a decline in function of approximately 20 percent.) Overall neurocognitive status was assessed with a composite cognitive index score representing the sum of the scores for the individual domains. Factors predicting long-term cognitive decline were determined by multivariable logistic and linear regression. RESULTS: Among the patients studied, the incidence of cognitive decline was 53 percent at discharge, 36 percent at six weeks, 24 percent at six months, and 42 percent at five years. We investigated predictors of cognitive decline at five years and found that cognitive function at discharge was a significant predictor of long-term function (P<0.001). CONCLUSIONS: These results confirm the relatively high prevalence and persistence of cognitive decline after CABG and suggest a pattern of early improvement followed by a later decline that is predicted by the presence of early postoperative cognitive decline. Interventions to prevent or reduce short- and long-term cognitive decline after cardiac surgery are warranted.

Temperature during coronary artery bypass surgery affects quality of life.

BACKGROUND: The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. METHODS: A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. RESULTS: Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices. CONCLUSIONS: The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.