Satisfaction with life among veterans with spinal cord injuries completing multidisciplinary rehabilitation.

STUDY DESIGN: This is a single-group, retrospective study. OBJECTIVES: The objective of this study was to understand the factors contributing to satisfaction with life (SWL) among veterans with a spinal cord injury (SCI) completing rehabilitation. SETTING: This study was conducted at Veterans Administration Medical Center, San Diego.MethodsBetween 1998 and 2010, N=118 Veterans participated in a Commission on Accreditation of Rehabilitation Facilities (CARF)-accredited rehabilitation program after a new SCI. Pre-rehabilitation measures of impairment at the organ/body level, activity limitation at the person level and participation restriction at the societal level were used to predict Satisfaction with Life Scale (SWLS) scores upon discharge. RESULTS: Although overall mean SWLS admission and discharge scores were not significantly different (P>0.10), individual change in SWLS scores during rehabilitation was notable, ranging from a 17-point improvement to a 22-point decline across veterans (mean Δ=+1.18, s.d.=6.04). Veterans who exhibited less activity limitation (higher cognitive functioning, r=0.31, P<0.01) and less participation restriction (greater social integration, r=0.21, P<0.05; a trend toward greater economic sufficiency, r=0.16, P<0.10) at baseline had higher SWLS scores after rehabilitation. When these factors were entered together into a single regression model, only cognitive functioning remained statistically significant (P<0.05). CONCLUSION: Findings highlight potential targets for interventions, aiming to improve SWL post SCI among US veterans. In addition to directly targeting SWL with psychosocial interventions, results suggest that rehabilitation settings should continue and/or expand upon programs targeting cognitive functioning (activity limitation) and social integration (participation restriction). Nevertheless, additional research is warranted to identify the biopsychosocial factors most reliably associated with SWL and/or other aspects of quality of life.

Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer.

BACKGROUND: Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer. METHODS: Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS). RESULTS: Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome. CONCLUSION: PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.

Epidermal growth factor receptor as a biomarker for cervical cancer.

This review focuses on the different modes of expression of the epidermal growth factor receptor (EGFR). All methods used to assess EGFR expression are critically analyzed and insights into the use of inhibitors of EGFR for treatment of cervical cancer are discussed. Currently, expression of EGFR as a biomarker for prognosis or for treatment of cervical cancer is not defined for clinical use.

Acceptance and commitment therapy as an adjunct to the MOVE! programme: a randomized controlled trial.

OBJECTIVE: The current study tested the efficacy of an acceptance and commitment therapy (ACT) group intervention for disinhibited eating behaviour as an adjunct to the Veterans Affairs MOVE!© weight management programme. METHODS: Veterans (N = 88) with overweight or obesity who completed the MOVE! weight management programme and self-identified as having problems with 'stress-related eating' were randomized to four 2-h weekly ACT sessions or a continued behavioural weight-loss (BWL) intervention. Assessments were completed at baseline, post-treatment and 3- and 6-month follow-up on outcomes of interest including measures of disinhibited eating patterns, obesity-related quality of life, weight-related experiential avoidance and weight. RESULTS: The BWL group exhibited significantly greater reductions in binge eating behaviour at post-treatment compared with the ACT group. Significant improvements in other outcomes were found with minimal differences between groups. In both groups, decreases in weight-related experiential avoidance were related to improvements in binge eating behaviour. CONCLUSIONS: Taken together, the continued BWL intervention resulted in larger improvements in binge eating behaviour than the ACT intervention. The two groups showed similar improvements in other disinhibited eating outcomes. Future studies are encouraged to determine if more integrated or longer duration of ACT treatment may maximize eating outcomes in MOVE.Trial Registration Number: This trial was registered with ClinicalTrials.gov database (NCT01757847).

Incidence, location, pathology, and significance of pulmonary homograft stenosis after the Ross operation.

BACKGROUND: The Ross operation has several theoretical advantages. However, concern exists regarding evolving pathology in the pulmonary homograft. METHODS AND RESULTS: Consecutive patients (n=144; mean age 31 years, range 2 months to 64 years) undergoing the Ross operation were studied between 1993 and 2000. Echocardiographic examination of the pulmonary homograft was performed immediately after surgery, then at yearly intervals for a mean interval of 48 months. Fifteen patients (mean age 37 years) in whom echocardiography revealed peak pulmonary gradients >/=30 mm Hg (mean 46+/-18 mm Hg) underwent MRI with velocity mapping in a Picker 1.5-T magnet. No patient had more than mild pulmonary regurgitation. Four patients required reoperation for rapidly progressive pulmonary homograft stenosis; in all 4, there was macroscopic and microscopic evidence of a pronounced chronic adventitial reaction, with perivascular infiltration producing extrinsic compression. Freedom from any pulmonary homograft stenosis at 7-year follow-up was 79.7%, with instantaneous hazard falling to zero after 4 years. Freedom from reoperation at 7 years was 96.7%. In those studied with MRI, there was evidence of narrowing of the whole homograft or distal suture line in 14 of 15 patients, with obvious excess surrounding tissue in 11. Mean minimum diameter and peak velocity by MRI were 11+/-2 mm and 3.2+/-0.7 m/s, respectively. Multivariate analysis of patient-, surgery-, and homograft-related variables did not reveal any significant risk factors for development of neopulmonary stenosis. CONCLUSIONS: Pulmonary homograft stenosis after the Ross operation is clinically important and appears to represent an early postoperative inflammatory reaction to the pulmonary homograft that leads to extrinsic compression and/or shrinkage.

History of anxiety disorders is associated with a decreased likelihood of angiographic coronary artery disease in women with chest pain: the WISE study.

OBJECTIVES: We sought to evaluate the ability of psychiatric anxiety-disorder history to discriminate between women with and without angiographic coronary artery disease (CAD) in a population with chest pain. BACKGROUND: A total of 435 women with chest pain underwent a diagnostic battery including coronary angiography in order to improve testing guidelines for women with suspected CAD. METHODS: Women referred for coronary angiography completed questionnaires assessing prior treatment history for anxiety disorder and current anxiety-related symptoms. Analyses controlled for standard CAD risk factors. RESULTS: Forty-four women (10%) reported receiving prior treatment for an anxiety disorder. This group acknowledged significantly higher levels of autonomic symptoms (e.g., headaches, muscle tension [F = 25.0, p < 0.0011 and higher behavioral avoidance scores (e.g., avoidance of open places or traveling alone by bus [F = 4.2, p < 0.05]) at baseline testing compared with women without prior anxiety problems. Women with an anxiety-disorder history did not differ from those without such a history with respect to the presence of inducible ischemia or use of nitroglycerin, although they were younger and more likely to describe both "tight" and "sharp" chest pain symptoms and to experience back pain and episodes of nocturnal chest pain. Logistic regression results indicated that the positive-anxiety-history group was more likely to be free of underlying significant angiographic CAD (odds ratio = 2.74, 95% confidence interval 1.15 to 6.5, p = 0.03). CONCLUSIONS: Among women with chest pain symptoms, a history of anxiety disorders is associated with a lower probability of significant angiographic CAD. Knowledge of anxiety disorder history may assist in the clinical evaluation of women with chest pain.

Defensiveness status predicts 3-year incidence of hypertension.

OBJECTIVE: A growing body of research indicates that defensive personality styles (in particular, self-deception) may be related to higher resting blood pressure and stress reactivity levels. This study is the first, however, to examine the value of defensiveness as a prognostic indicator for the development of clinical hypertension. METHODS: Participants were 127 initially normotensive male and female adults who completed a comprehensive protocol including psychological testing, assessment of smoking, physical activity and body fat levels, and 8-12 h ambulatory blood pressure monitoring. Participants returned 3-years later for an identical follow-up protocol. Defensiveness was assessed using the Balanced Inventory of Desirable Responding. RESULTS: At 3-year testing, 15 of 127 participants (12%) met criteria for hypertension (i.e. ambulatory mean blood pressure > 140/90). Comparisons between defensiveness groups showed that 12 of 60 (20%) high defensiveness participants met hypertension criteria, whereas only three of 67 (4.5%) low defensiveness participants were hypertensive. Logistic regression equations adjusted for age, alcohol usage, bodyfat, self-reported exercise levels, smoking, and year-1 ambulatory blood pressure, revealed that membership in the high defensiveness group was associated with more than a sevenfold risk of 3-year hypertension (adjusted risk ratio, 7.5; 95% confidence interval, 1.5-39.2). CONCLUSIONS: These findings link defensive characteristics to an increased prospective risk of hypertension using state of the art ambulatory monitoring techniques, and were robust after controlling for established risk factors. We conclude that the current results add to the hypertension literature by demonstrating associations between personality and clinically relevant blood pressure criteria.

Psychological response styles and cardiovascular health: confound or independent risk factor?

Using results from 2 large cardiovascular studies, the authors examined the utility of treating psychological response styles as confounds (e.g., factors undermining relationships with other self-report variables) versus distinct personality traits in the prediction of cardiovascular health. Study 1 consisted of a 3-year prospective study of ambulatory blood pressure levels in healthy adults (N = 125). Study 2 comprised a 12-week drug treatment program for ischemic heart disease patients (N = 95). Participants completed measures of psychological factors and self-deception and impression management in each study. Results consistently favored using response styles as direct predictors. Self-deception scores predicted elevated 3-year diastolic and systolic blood pressure changes in Study 1 and poorer treatment outcomes in Study 2. Statistically controlling for response style effects within the psychological factors generally did not improve predictions. These findings argue against the conceptualization of response styles as stylistic confounds.

Behavioural weight management for the primary careprovider.

Primary care providers (PCPs) provide the majority of weight management care in clinical settings; however, they often lack the time or resources to apply strategies recommended in treatment guidelines. This review surveyed randomized clinical trials and prospective weight management studies from 1990 to present to identify evidence-based behavioural strategies for weight management applicable to the PCP treatment environment. Data supported, time-limited weight management strategies included self-monitoring, portion control, sleep hygiene, restaurant eating and television viewing. The current review suggests that a number of behavioural strategies are available to enhance the effectiveness of PCPs weight management interventions. Increasing PCP awareness of these evidence-based strategies may increase their attention to overweight and obesity concerns in clinical encounters and encourage more collaborative efforts with patients towards weight management goals.

Psychotropic medication use and risk of adverse cardiovascular events in women with suspected coronary artery disease: outcomes from the Women's Ischemia Syndrome Evaluation (WISE) study.

OBJECTIVE: This study investigated the relation between psychotropic medication use and adverse cardiovascular (CV) events in women with symptoms of myocardial ischaemia undergoing coronary angiography. METHOD: Women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) were classified into one of four groups according to their reported antidepressant and anxiolytic medication usage at study intake: (1) no medication (n = 352); (2) anxiolytics only (n = 67); (3) antidepressants only (n = 58); and (4) combined antidepressant and anxiolytics (n = 39). Participants were followed prospectively for the development of adverse CV events (for example, hospitalisations for non-fatal myocardial infarction, stroke, congestive heart failure and unstable angina) or all-cause mortality over a median of 5.9 years. RESULTS: Use of antidepressant medication was associated with subsequent CV events (HR 2.16, 95% CI 1.21 to 3.93) and death (HR 2.15, 95% CI 1.16 to 3.98) but baseline anxiolytic use alone did not predict subsequent CV events and death. In a final regression model that included demographics, depression and anxiety symptoms, and risk factors for cardiovascular disease, women in the combined medication group (that is, antidepressants and anxiolytics) had higher risk for CV events (HR 3.98, CI 1.74 to 9.10, p = 0.001 and all-cause mortality (HR 4.70, CI 1.7 to 2.97, p = 0.003) compared to those using neither medication. Kaplan-Meier survival curves indicated that there was a significant difference in mortality among the four medication groups (p = 0.001). CONCLUSIONS: These data suggest that factors related to psychotropic medication such as depression refractory to treatment, or medication use itself, are associated with adverse CV events in women with suspected myocardial ischaemia.

To eat or not to eat: affective and physiological mechanisms in the stress-eating relationship.

The current study aggregated methods from the cardiovascular reactivity and dietary restraint paradigms in an attempt to advance our understanding of stress-induced eating behavior. Seventy-seven female subjects completed a protocol consisting of distinct baseline, stress-induction, and recovery phases during which we monitored blood pressure, heart rate, and self-reported affect. Food was inconspicuously made available to participants during the recovery phase. Our results replicated the restraint x affect level interaction observed in the restraint literature, while showing that physiological measures could further explain distressed eating behavior. Physiological arousal was found reliably to predict reduced food consumption, but only among unrestrained eaters. Analysis of the recovery data showed that food consumption was associated with impaired physiological recovery rates for restrained but not for unrestrained participants. We believe that our results help to reconcile findings in the stress, eating, and dietary restraint fields and offer support for recently developed theories of stress-induced overeating.

Cardiovascular recovery from acute laboratory stress: reliability and concurrent validity.

OBJECTIVE: We assessed the value of laboratory measures of cardiovascular recovery across four criteria: reliability across multiple tasks, reliability across a 3-year time interval, ability to predict daily ambulatory blood pressure, and interrelationships with coronary risk factors and psychosocial variables. METHODS: Three hundred twenty-nine healthy adults (mean age = 27.1 years) completed a two-part protocol consisting of 1 day of laboratory testing and 1 day of ambulatory monitoring. The laboratory protocol included a 15-minute baseline assessment followed by three 5-minute laboratory challenges (mental arithmetic, speech, and handgrip). Five-minute recovery periods followed each exercise. One hundred twenty-five participants returned after 3 years to repeat the protocol. RESULTS: When aggregated across tasks, cardiovascular recovery showed acceptable levels of internal consistency (alpha values = 0.7) and proved relatively stable across time (r values = 0.22-0.35). Recovery values statistically improved the prediction of daily ambulatory readings above baseline and stress reactivity laboratory values (p values < .001) but were largely unrelated to coronary risk factors or psychosocial measures. CONCLUSION: These results suggest that cardiovascular recovery from acute laboratory stress can be treated as a stable individual difference variable that can -improve standard laboratory-based predictor models of ambulatory readings.

A case for the usefulness of laboratory social stressors.

Although laboratory stress research is a popular and vibrant area of research activity, there is surprisingly little evidence that laboratory stress models are clinically useful (i.e. that they can explain and predict the development of disease). This article summarizes evidence that the usefulness of lab stress research can be improved with the use of social stressors. Two lines of evidence are presented in support of this argument: (a) studies comparing physiological reactivity to different lab stressors with ambulatory activity, and (b) a meta-analysis of investigations of cortisol responses to laboratory stressors. Further issues of importance in understanding social stressors are gender differences and the vulnerability (i.e. weak reliability) of social stressor impact to relatively small changes in the experimental protocol itself.

Psychological risk factors may moderate pharmacological treatment effects among ischemic heart disease patients. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

BACKGROUND: Numerous research findings support the proposed connection between such psychological characteristics as stress and hostility and the manifestation of disease. However, less evidence is available concerning the role(s) psychological factors might play in the process of disease recovery. METHODS: Eighty patients with known coronary disease and exercise-induced ischemia underwent treadmill exercise testing and 48-hour ambulatory electrocardiographic monitoring and completed a battery of standardized psychological tests assessing hostility, depression, and daily stress on four occasions during a 12-week pharmacological treatment study. After withdrawal of antiischemic drugs at baseline, patients returned for subsequent tests at 3-week intervals. During the second and third intervals, patients were prescribed one of two antiischemic medications, atenolol or amlodipine, or given a placebo. All patients were then placed on a combination treatment protocol for the 3 weeks before the final testing date. RESULTS: The combination treatment produced highly significant benefits across all measured cardiac variables (20.3% improvement in exercise performance, 13% reduction in reported angina, 64.0% reduction in the frequency of ischemic episodes; for all, p < .01). However, results showed that high baseline levels of daily stress were associated with reliably smaller treatment effects on measures of ischemia frequency and treadmill exercise time and with a significantly greater likelihood of reporting angina after treatment (r = -0.24, -0.25, and -0.33, respectively; p <.05). In addition, high baseline hostility predicted significantly smaller diastolic blood pressure improvements (r = -0.29, p < .05). CONCLUSIONS: These results indicate that psychological risk factors may have globally negative effects on the course of treatment and suggest particular factors that may warrant attention in trials targeting cardiac symptom reduction.

Transmembrane helical interactions: zeta chain dimerization and functional association with the T cell antigen receptor.

Members of the zeta family of receptor subunits (zeta, eta and gamma) are structurally related proteins found as components of the T cell antigen receptor (TCR) and certain Fc receptors. These proteins share the ability to form disulfide-linked dimers with themselves and with other members of the family. Comparison of the amino acid sequences of zeta and gamma reveals a significant degree of homology, which is highest within their membrane-spanning domains. Analysis of their transmembrane sequences on a helical wheel projection suggests that all of the identical amino acids are clustered on one face of a potential alpha-helix. This face contains the only cysteine residue within zeta, suggesting that this conserved region may function to mediate dimerization. Indeed, replacing the transmembrane domain of the Tac antigen (alpha chain of the interleukin-2 receptor) by that of the zeta chain resulted in the formation of disulfide-linked dimers of Tac. The conserved aspartic acid residue found in the zeta and gamma transmembrane sequences was found to play a role in disulfide linkage. Replacing the aspartic acid with a lysine but not with an alanine or valine residue allowed formation of disulfide-linked dimers. The ability of the aspartic acid residue to support dimerization was dependent upon its position within the helix. Thus, these observations indicate that residues within the zeta transmembrane domain play a critical role in the formation of disulfide-linked dimers. Expression of zeta mutants in zeta-deficient T cells revealed that the zeta transmembrane domain is also responsible for reconstituting transport of functional TCR complexes to the cell surface and differentiated the requirements for disulfide-linked dimerization per se from assembly of the TCR complex.

Structure/function analysis of the invariant subunits of the T cell antigen receptor.

The T cell antigen receptor (TCR) is a multimeric surface receptor on T cells responsible for recognizing MHC-restricted antigens and initiating the cellular immune response. The clonotypic nature of the TCR resides in the antigen binding TCR-alpha beta or TCR-gamma delta heterodimer. The CD3 complex of gamma, delta and epsilon and the zeta-family disulfide dimer comprise the invariant TCR chains. Assembly of the mature TCR complex requires specific subunit interactions, the detailed nature of which is becoming more evident. Surface targetting of the TCR appears dependent on a region of the zeta chain near its transmembrane domain. A functional role attributable to zeta residing in the cytoplasmic tail is the capacity to couple antigen stimulation to IL-2 secretion, likely through activation of a tyrosine kinase. Assignment of functional roles for the remaining CD3 chains is not as clear; the removal of the cytoplasmic tail of CD3-delta does not affect TCR-mediated IL-2 signalling. Mounting evidence indicates that the structural complexity of the TCR is further enhanced by the various zeta family disulfide dimer pairs that can associate with the other TCR chains. This subunit diversification may offer the possibility of multiple coupling pathways available to the TCR as it responds to foreign antigens in various contexts.

Social determinants of experienced anger.

We investigated two social determinants (i.e., availability of social support and status differentials of the provocateur) for the degree of perceived anger in two populations. Because no suitable tool was available, the conceptual and psychometric development and validation of a new vignette-based measure for anger level (STandardized Experience of Anger Measure, STEAM) is described first. Two versions of STEAM were developed: one for students and one for community-living adults. Through a series of four studies, two sets of a 12-item vignette-based questionnaire were developed and validated. The resulting test had excellent test-retest stability and high internal consistency. Using the new STEAM measure, a variety of analyses were conducted to test the hypothesized influence of social determinants of anger. In the student sample, presence of social support was associated with lessened anger, and in both samples decreasing status of the provocateur also led to lessened anger arousal. In addition, findings in both samples revealed that social support reduced anger when the provocateur was of higher status relative to situations of equal and lesser status. In the community sample, the availability of support was associated with greater intensity of the anger experience in the lesser status condition than in the equal or greater status condition. No gender main effects or interactions were noted.

Psychosocial variables are associated with atherosclerosis risk factors among women with chest pain: the WISE study.

OBJECTIVE: We investigated associations between atherosclerosis risk factors (smoking behavior, serum cholesterol, hypertension, body mass index, and functional capacity) and psychological characteristics with suspected linkages to coronary disease (depression, hostility, and anger expression) in an exclusively female cohort. METHODS: Six hundred eighty-eight middle-aged women with chest pain warranting clinical investigation completed a comprehensive diagnostic protocol that included quantitative coronary angiography to assess coronary artery disease (CAD). Primary analyses controlled for menopausal status, age, and socioeconomic status variables (income and education). RESULTS: High depression scores were associated with a nearly three-fold risk of smoking (odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.4-5.7) after covariate adjustment, and women reporting higher depression symptoms were approximately four times more likely to describe themselves in the lowest category of functional capacity (OR = 3.7, 95% CI = 1.7-7.8). High anger-out scores were associated with a four-fold or greater risk of low high-density lipoprotein cholesterol concentration (<50 mg/dl; OR = 4.0, 95% CI = 1.4-11.1) and high low-density lipoprotein cholesterol concentration (>160 mg/dl; OR = 4.8, 95% CI = 1.5-15.7) and a larger body mass index (OR = 3.5, 95% CI = 1.1-10.8) after covariate adjustment. CONCLUSIONS: These results demonstrate consistent and clinically relevant relationships between psychosocial factors and atherosclerosis risk factors among women and may aid our understanding of the increased mortality risk among women reporting high levels of psychological distress.