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An evaluation of a behavioral program for chronic pain.

The current study evaluated a behavioral program for the management of chronic pain. One hundred twenty-one patients were treated. Primary pain complaints were predominantly in the low back or head/neck/face regions. Patients participated in a 4-week inpatient treatment package consisting of controlled medication reduction, physical therapy, behavioral group therapy, self-monitoring, contracting, and biofeedback/relaxation training. Several measures of verbal/nonverbal pain behavior and physical functioning were obtained over the baseline, treatment, and follow-up periods. Results showed significant reductions in analgesic medication use and verbal/nonverbal pain behavior and improvements in physical functioning, employment status, and pro-health behaviors which were maintained at 12-month follow-up.

Adult↗

Functional and physical interactions between autonomously replicating sequence-binding factor 1 and the nuclear transport machinery.

Autonomously replicating sequence-binding factor 1 (Abf1p) is a site-specific DNA binding protein in Saccharomyces cerevisiae that functions to regulate multiple nuclear events including DNA replication, transcriptional activation, and gene silencing. Previous work indicates that the multiple functions of Abf1p are conferred by the carboxy-terminus of the protein, which can be further dissected into two important clusters of amino acid residues (CS1 and CS2). Here we present genetic and cell biological evidence for a critical role of CS1 in proper nuclear localization of Abf1p. Mutations in CS1 cause severe defects in cell growth, nuclear translocation, and Abf1p-mediated gene regulation, which can be rescued by a heterologous nuclear localization sequence (NLS). In addition, the CS1-domain can mediate the import of a CS1-GFP fusion protein. Importantly, the CS1-mediated nuclear import depends on the Ran guanine nucleotide exchange factor Prp20p. Interestingly, a single amino acid change in CS1 (K625I) also causes the protein to be exported out of the nucleus via the Crm1p-dependent pathway. The temperature-sensitive growth phenotype of this particular mutant can be overcome by overexpression of Kap121p/Pse1p, a well-established nuclear transport receptor. Biochemical studies indicate that Pse1p binds to a region of Abf1p upstream of CS1 in a RanGTP-sensitive manner, suggesting that Abf1p has a second distinct NLS and can be imported into the nucleus by several overlapping pathways. We propose that the link between Abf1p and the nuclear transport machinery may also be important for partitioning multiple Abf1p-mediated nuclear processes.

Active Transport, Cell Nucleus↗

Physical and functional association between thymic shared antigen-1/stem cell antigen-2 and the T cell receptor complex.

Thymic shared antigen-1 (TSA-1)/stem cell Ag-2 (Sca-2) is a glycosylphosphatidylinositol (GPI)-anchored antigen expressed on lymphocytes. We have previously demonstrated that a signal via TSA-1/Sca-2 inhibits T cell receptor (TCR)-mediated T cell activation and apoptosis. To elucidate a molecular mechanism for TSA-1-mediated modulation of the TCR-signaling pathway, we examined whether TSA-1 is physically coupled to the TCR in the present study. TSA-1 was clearly associated with CD3zeta chains in T cell hybridomas, activated T cells, and COS-7 cells transfected with TSA-1 and CD3zeta cDNA. The physical association was confirmed on the surface of T cells in immunoprecipitation and confocal microscopy. The analysis using stable and transient transfectants expressing a transmembrane form of TSA-1 revealed that the association of CD3zeta did not require the GPI anchor of TSA-1. Finally, tyrosine phosphorylation of CD3zeta chains was induced after stimulation with anti-TSA-1, suggesting that a functional association between these two molecules also exists. These results imply that the physical association to CD3zeta underlies a regulatory role of TSA-1/Sca-2 in the TCR-signaling pathway.

Animals↗

[The effects of trimetazidine on left ventricular function and physical exercise tolerance in patients with ischemic cardiomyopathy].

Trimetazidine is a new metabolic antiischemic agent, which increases the tolerance of cardiomyocytes to ischemia. The aim of the study was to evaluate the effect of additional trimatazidine therapy in patients with ischemic cardiomyopathy (ICMP) in comparison with standard therapy of cardiac insufficiency. According to the results of the study, trimetazidine improves the clinical status, functional class of cardiac insufficiency, left ventricular ejection fraction, in ICMP patients. Trimetazidine increases physical exercise tolerance according to the results of six-minute walking test. Thus, the optimization of myocardial energetic metabolism may be a promising perspective in the treatment of coronary heart disease with systolic dysfunction.

Aged↗

Social support and stressful life events: age differences in their effects on health-related quality of life among the chronically ill.

There is substantial evidence of individual variation in health-related quality of life measures that is not accounted for by age or disease condition. An understanding of factors that determine good health is necessary for maintained function and improved quality of life. This study examines the extent to which social support and stressful life events were more or less beneficial for the long-term physical functioning and emotional well-being of 1,402 chronically ill patients. Analyses, conducted separately in three age groups, showed that social support was beneficial for health over time regardless of age. In addition, low levels of support were particularly damaging for the physical functioning of older patients. Stressful life events impacted differentially on health-related quality of life; relationship events had an immediate effect on well-being which diminished with time; financial events had an immediate negative effect on functioning and well-being which persisted over time for middle-aged patients; bereavement had a delayed impact on quality of life, with the youngest patients especially vulnerable to its negative effects; work-related events had both negative and positive effects, depending on age group. Results reinforce the importance of identifying and dealing with psychosocial problems among patients with chronic disease.

Activities of Daily Living↗

Models of health-related quality of life in a population of community-dwelling Dutch elderly.

OBJECTIVE: Though health-related quality of life (HRQoL) is now commonly measured as an outcome in clinical trials, the relationships between its components remain unclear. The relation of physical symptoms, physical function, and psychological symptoms to each other and to overall quality of life is of special interest. METHOD: Cross-sectional data from 5,279 community-dwelling elders who participated in the Groningen Longitudinal Aging Study were analyzed using structural equation modeling techniques. Three models were examined. One "Linear" model included: number of chronic medical conditions, physical symptoms, physical functioning, activity interference, social function, perceived health and overall quality of life in a simple linear progression. Another 'non-linear' model included these variables, but allowed effects between non-adjacent variables. A third 'non-linear' model included these variables plus anxiety and depressive symptoms. RESULTS: The Linear Model did not satisfactorily account for the observed data [X2(15df) = 2946.96], so the saturated Non-Linear Model, incorporating paths between non-adjacent components, is described. When anxiety and depressive symptoms were added to this Non-Linear Model, they fit best in a position mediating the relation between perceived health and overall quality of life [X2(5df) = 136.78]. CONCLUSIONS: Overall quality of life appears to be related to symptom status as directly as it is related to functional status. Anxiety and depressive symptoms appear to mediate the relation between general health perceptions and overall quality of life. Quality of life measures should therefore include assessments of physical and psychological symptom severity as well as functional status if they are to truly reflect what matters to patients. The disability-adjusted life year (DALY) measure used by the WHO may inadequately reflect the effect of symptoms on patient's quality of life.

Aged↗

Clinical risk factors for methicillin-resistant Staphylococcus aureus bacteriuria in a skilled-care nursing home.

OBJECTIVE: To establish the risk factors for methicillin-resistant Staphylococcus aureus (MRSA) bacteriuria in a nursing home population. DESIGN, SETTING, AND SUBJECTS: A case-control study was conducted in a 360-bed skilled-care nursing facility in the northeastern United States that was experiencing an outbreak of MRSA. Fifteen residents were identified as having had MRSA isolated from their urine over an 18-month period and were compared with 40 controls who were randomly selected from all nursing facility residents. RESULTS: In bivariate analysis, MRSA bacteriuria was associated with the presence of an indwelling urinary catheter (odds ratio [OR], 36; 95% confidence interval [CI], 7.0 to 184.2), antibiotic use in the prior 6 months (OR, 2.9; 95% CI, 1.5 to 5.5), and impaired physical function (OR, 5.8; 95% CI, 1.3 to 26.6). Urinary catheter use and antibiotic use remained significantly associated with MRSA bacteriuria even when controlling for impaired physical function. CONCLUSIONS: Methicillin-resistant S aureus is being isolated with increasing frequency in nursing homes, and MRSA bacteriuria may prove to be an important reservoir for the spread of organisms in long-term-care settings. Conservative use of indwelling urinary catheters and of broad-spectrum antibiotics should be investigated as potential control measures to reduce the spread of MRSA in nursing homes.

Bacteriuria↗

Clinical factors associated with suicidality in cancer patients.

BACKGROUND: Previous epidemiological studies have indicated that the risk of suicide in cancer patients is higher than that of the general population. In addition, euthanasia and physician-assisted suicide (PAS) have recently become controversial medical, ethical and legal issues all over the world. Although suicide in cancer patients and appropriate management of cancer patients with suicidality are critical issues in clinical oncology practice, there have been very few studies to understand suicidality in cancer patients. The purpose of this study was to explore the clinical factors associated with suicidality in Japanese patients with cancer. METHODS: We investigated the clinical factors associated with suicidality in cancer patients by analyzing the consultation data of patients referred to the Psychiatry Division, National Cancer Centre Hospital and Hospital East, Japan. RESULTS: Of 1713 psychiatric referrals, 62 (3.6%) were related to suicidality, including 44 cases with suicidal ideation, 10 suicide attempts and eight cases who had requested euthanasia and/or continuous sedation. Most of the patients suffered from physical distress and/or psychiatric disorders. The results of a multivariate analysis comparing cancer patients with a psychiatric referral related to suicidality and those referred for other reasons indicated that impaired physical functioning and major depression were significant associated factors. CONCLUSIONS: Our findings suggest that early detection and appropriate management of major depression and comprehensive care improving physical functioning may help to prevent suicide and manage suicidality in Japanese cancer patients.

Adult↗

Survival of hospitalized elderly patients with delirium: a prospective study.

The authors tested the relationship between clinically diagnosed delirium during hospitalization and increased mortality after accounting for pre-hospital measures of global cognition, physical functioning, and medical comorbidity. Patients (N=102), 53 of which were hospitalized during the course of a year, received the Mini-Mental State Exam, Physical Self-Maintenance Scale, Cumulative Illness Rating Scale, and 15-item Geriatric Depression Scale. Mortality rates were determined at discharge and after 3 years. Patients who developed delirium did not differ on pre-hospitalization levels of depression, global cognitive performance, physical functioning, or medical comorbidity. Three-year mortality in the hospitalized subjects was 75% for delirium patients vs. 51% for control patients (risk ratio=2.24). Delirium occurring during hospitalization places elderly subjects at long-term risk of mortality. This effect is not accounted for by earlier measures of cognitive, functional, or health status.

Aged↗

[A symptom profile of hospitalization-requiring depression among the elderly related to clinical subgroups. A way to improve diagnostics].

UNLABELLED: The objectives were to study clinical symptoms of major depression in later life by using relevant assessment scales of psychopathology, behavioural disorders, and physical functioning. The evaluations on admission and at discharge were based on interdisciplinary observations and interview of patients. The study was carried out during twelve months in a psychogeriatric university department and encompassed 202 patients. All (N = 80) (40%) patients who had a principal diagnosis of major depression are accounted for. Mean age was 79.5 years. Results of the assessments all showed significant improvements (p = 0.0000-0.0024). The overall results of the assessments show that the key symptom of sadness is often missing, muted, or overshadowed by other symptoms, and that behavioural disturbancies and functional disability may be important symptoms in geriatric depression. IN CONCLUSION: adequate treatment of major depression in the elderly significantly improves psychopathology, behavioural disorders and physical functioning. When dealing with mental disorders in this age group, awareness of the five clinical presentations in major geriatric depression, i.e. dementoform, somatoform neurotiform, eretic and classic geriatric depression, may target the diagnostic procedure.

Aged↗

Correlates of sleep behavior among hemodialysis patients. The kidney outcomes prediction and evaluation (KOPE) study.

BACKGROUND: Given the importance of sleep to overall physical and mental well-being, we sought to identify the correlates of seven sleep disturbances in a cross-sectional study of a biracial population of male and female patients treated with hemodialysis. METHODS: Univariate and multivariate analyses of a cohort study of adult patients with end-stage renal disease. Demographic, psychosocial, clinical, and health and physical functioning variables were included. RESULTS: Waking up during the night (57%) and waking up too early (55%) were the most commonly reported sleep problems. Multivariate analyses consistently indicated that levels of pain, depressive symptoms, and physical functioning were consistently associated with the seven sleep disturbances. CONCLUSION: Sleep disturbances are common in patients with end-stage renal disease. Physical and mental well-being were consistently related to the seven sleep disturbances.

Activities of Daily Living↗

The effect of type 2 diabetes mellitus on health-related quality of life (HRQOL).

Improving the quality of life of all South Africans has become a major concern to health care practitioners, organisations and politicians. However, the paucity of local information on health-related quality of life (HRQOL) does not allow us to address this public health challenge. In order to rectify this deficiency and complement international research, we undertook a study with 281 Type 2 Black diabetic patients and 437 controls, with no self-reported chronic conditions, to ascertain HRQOL. We used the SF-20 to measure functioning, general health, well-being and bodily pain (HRQOL). It was hypothesised that diabetes mellitus significantly affects functioning, general health and well-being. Multiple analyses of covariance controlled for age, schooling, marital status, employment status and commodity ownership (a socio-economic measure). Patients were significantly more likely to report poorer role functioning, poorer general health and more pain than controls, providing partial support for the hypothesis. Reliability (internal consistency) coefficients on the four multi-item SF-20 sub-scales ranged between 0.79 (well-being), 0.81 (general health), 0.83 (physical functioning) and 0.94 (role functioning) for patients: for controls these coefficients ranged between 0.70 (well-being), 0.78 (general health), 0.80 (physical functioning) and 0.90 (role functioning). Inter-correlations among the sub-scales were significant for patients and controls (p = 0.01). It was concluded that the SF-20 is a reliable instrument for measuring HRQOL in both patient and control samples, and diabetes mellitus has more impact on general health and level of pain than on well-being.

Adolescent↗

Cognitive functioning and disturbances of mood in UK veterans of the Persian Gulf War: a comparative study.

BACKGROUND: Complaints of poor memory and concentration are common in veterans of the 1991 Persian Gulf War as are other symptoms. Despite a large research effort, such symptoms remain largely unexplained. METHOD: A comprehensive battery of neuropsychological tests and rating scales was administered to 341 UK servicemen who were returnees from the Gulf War and peace keeping duties in Bosnia, plus non-deployed military controls. All were drawn from a large randomized survey. Most were selected on the basis of impaired physical functioning defined operationally. RESULTS: Group comparisons revealed an association between physical functioning and symptoms of depression, post-traumatic stress reactions, increased anger and subjective cognitive failures. Poorer performance on some general cognitive measures, sequencing and attention was also seen in association with being 'ill' but virtually all differences disappeared after adjusting for depressed mood or multiple comparisons. Deployment was also associated with symptoms of post-traumatic stress and subjective cognitive failures, independently of health status, as well as minor general cognitive and constructional impairment. The latter remained significantly poorer in the Gulf group even after adjusting for depressed mood. CONCLUSIONS: Disturbances of mood are more prominent than quantifiable cognitive deficits in Gulf War veterans and probably lead to subjective underestimation of ability. Task performance deficits can themselves be explained by depressed mood although the direction of causality cannot be inferred confidently. Reduced constructional ability cannot be explained in this way and could be an effect of Gulf-specific exposures.

Adult↗

Reliability of a brief outpatient functional outcome assessment measure.

The stability of the musculoskeletal form of the Medical Rehabilitation Follow Along (MRFA) instrument was examined in 47 patients receiving outpatient rehabilitation services. The MRFA instrument was designed to provide information on quality of daily living, including physical function, pain, satisfaction, and emotional/psychological well-being. The instrument consists of thirty questions and can be administered as an interview or a written questionnaire. The MRFA instrument was developed using Rasch analysis procedures and is an extension of previous research involving the Functional Assessment Screening Questionnaire. Forty-seven patients completed the musculoskeletal form of the MRFA on two occasions separated by an interval of 1 to 7 days. The stability of responses was examined using the intraclass correlation coefficient (ICC) and kappa. ICC values for the sections of the MRFA instrument examining quality of daily living and physical functioning ranged from 0.74 to 0.97. ICC values for items assessing pain and feelings of well-being were more variable, ranging from 0.36 to 0.93. The kappa values displayed a similar pattern. The overall stability of the MRFA instrument was found to be adequate for gathering screening information in outpatient settings. Additional research is necessary to confirm the findings of this investigation and extend the results to a larger outpatient population.

Activities of Daily Living↗

Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging.

Several regulatory concerns have hindered development of androgens as anabolic therapies, despite unequivocal evidence that testosterone supplementation increases muscle mass and strength in men; it induces hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of androgen receptors with beta-catenin and activating T-cell factor 4. Meta-analyses indicate that testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with weight loss, glucocorticoid-treated men, and older men with low or low-normal testosterone levels. The effects of testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent, testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for testosterone use as anabolic therapy. Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies. We need more studies to determine whether testosterone or selective androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with chronic illness or aging.

Aging↗

Antiischemic therapy in patients with coronary heart disease living in long-term care. Systematic Assessment of Geriatric Drug Use by Epidemiology (SAGE) Group.

We evaluated antiischemic therapy in elderly nursing home residents with a diagnosis of coronary heart disease (CHD) using a population-based data base with over 300,000 residents (1992-1995) of all Medicare/Medicaid-certified nursing homes of five states. We identified 72,263 patients age 65 years or older with a diagnosis of CHD. We examined data collected with the federally mandated Minimum Data Set, drug information, and Medicare hospital claims. Antiischemics were defined as beta-adrenergic blockers, long-term nitrates, and calcium channel blockers. We determined factors associated with use of the drugs by logistic regression. Antiischemic therapy was inversely related to age and cognitive and physical functioning, but positively associated with recent hospitalization and concomitant cardiovascular diseases. beta-Adrenergic blockers were least likely to be administered regardless of age, gender, or cognitive or physical function. We conclude that antiischemic therapy in nursing home residents may not be optimal.

Adrenergic beta-Antagonists↗

Rehabilitation and the long-term outcomes of persons with trauma-related amputations.

OBJECTIVE: To examine the long-term outcomes of persons undergoing trauma-related amputations, and to explore factors affecting their physical, social, and mental health and the role of inpatient rehabilitation in improving such outcomes. DESIGN: Abstracted medical records and interview data sought for a retrospective cohort of persons who had undergone a lower-limb trauma-related amputation. PARTICIPANTS: Patients identified with a principal or secondary diagnosis of a trauma-related amputation to the lower extremity at the University of Maryland Shock Trauma Center between 1984 and 1994. Patients with spinal cord injury or traumatic brain injury were excluded. RESULTS: Of 146 patients who had trauma-related amputations to the lower limb at the University of Maryland Shock Trauma Center during the study period, nearly 9% died during the acute admission and 3.5% died after discharge. About 87% of all trauma-related amputations involved males, and roughly three quarters involved white persons. About 80% of all amputations occurred before age 40. The health profile of traumatic amputee subjects interviewed in the study (n = 78, 68% response rate) was systematically lower than that of the general US population for all SF-36 scores. The differences in profiles were largest among SF-36 scales sensitive to differences in physical health status, particularly physical functioning, role limitations due to physical health, and bodily pain. About one fourth of persons with a trauma-related amputation reported ongoing severe problems with the residual limb, including phantom pain, wounds, and sores. The number of inpatient rehabilitation nights significantly improved the ability of patients with amputation to function in their physical roles, increased vitality, and reduced bodily pain. Inpatient rehabilitation was also significantly correlated with improved vocational outcomes. CONCLUSIONS: These findings suggest a substantial effect of inpatient rehabilitation in improving long-term outcomes of persons with trauma-related amputations.

Adult↗

The influence of place of administration on health-related quality-of-life assessments: findings from the Veterans Health Study.

Patient-based assessments of functional status and well-being, such as the short form survey (SF-36) developed in the Medical Outcomes Study, are increasingly used to monitor patient health status and the effects of medical care. Although they have been used in many populations under a variety of circumstances, little is known about how environmental factors, such as place of administration, influence patients' responses. We administered the SF-36 as part of comprehensive quality-of-life assessments to 304 participants in the pilot phase of the Veterans Health Study, a large observational study of health outcomes in VA ambulatory care. SF-36 questionnaires were self-administered twice by patients, once at home and again as part of an interview in a clinic setting. For most participants, less than a week passed between the 2 administrations. Scores from these questionnaires were compared as a measure of reliability and of the possible influence of place of administration. Questionnaires self-administered at the time of the interview yielded mean scores that were significantly (P<.05) higher across all 8 SF-36 scales (physical function, role function with physical and emotional limitations, vitality, bodily pain, social function, mental health, general health perceptions) and both the physical and mental component summary scales. With scores scaled from 0 to 100, differences ranged from 2.1 (bodily pain) to 5.7 (role limitations due to emotional problems). Mean physical function was 56.8 at the time of the interview, and 52.4 at home. Higher scores from questionnaires administered at interview outnumbered lower scores by 3 to 2 for most scales. These differences remained even after restricting the sample to those with the highest cognitive function scores and the shortest interval between administrations. Because selection factors and order of administration could not be completely dismissed, a large number of other administrative, clinical, and sociodemographic factors were examined, which, however, failed to provide adequate explanation for these differences. Careful consideration should be given concerning the physical and social environment in the administration of health-related quality-of-life assessments. Findings from this study suggest that more favorable measures of self-reported functional status and well-being may be expected from clinic administrations of instruments.

Aged↗