Factors Related to Fatigue and Physical Function in COPD: A Secondary Analysis Using National Survey Data.

Fatigue in chronic obstructive pulmonary disease (COPD) is debilitating and associated with considerable morbidity. The aim of this study is to present a model based on the Theory of Unpleasant Symptoms of physiologic, psychologic, and situational factors with COPD-related fatigue and the relationship with physical functioning. This study used data collected from Wave 2 (2010-2011) of the National Social, Health, and Aging Project (NSHAP). A total of 518 adults with self-reported COPD were included in this study. Path analysis was used for hypothesis testing. Depression was the only psychologic factor found to have a direct relation to both fatigue (ß = 0.158, p < .001) and physical function (ß = -0.131, p = .001). Factors related to physical function included fatigue, depression, sleep, loneliness, and pain. Additionally, fatigue was indirectly associated with physical function via depression (ß = -0.064, p = .012). These findings suggest avenues for future research on predictors of COPD-related fatigue in relation to physical functioning.

Protein Changes After 6 weeks of Walking and the Relationship to Pain in Adults with Knee Osteoarthritis.

Background: Knee osteoarthritis (KOA) affects 22.9% of individuals over the age of 40 and causes significant pain and disability. Pain is the most prevalent and troublesome symptom of KOA leading patients to seek medical interventions for relief. Knee osteoarthritis pain has both peripheral and central mechanisms that vary by individual. Non-pharmacological pain management strategies such as walking is the first step in reducing KOA pain. However, initiation of a walking regime can induce knee pain for some and the mechanism by which habitual walking reduces KOA pain is unclear. Purpose: The purpose of this study was to use a discovery proteomics approach and quantitative sensory testing (QST) to determine the molecular changes that occur after habitual walking and their relationship to pain sensitivity. Research Design and Study Sample: We conducted a pre-test/post-test study using QST to measure neurophysiological parameters at the knee and contralateral forearm and examined platelet protein signatures before and after 6 weeks of walking 3 days per week for 30 minutes among six adults with KOA and six healthy controls. Results: Knee pain sensitivity did not change significantly after 6 weeks of walking among either KOA or healthy participants. However, forearm pressure pain sensitivity decreased for both groups after walking, indicating reduction in central pain pathways. Protein signatures showed downregulation of immune and inflammatory, pathways among KOA participants after walking which were upregulated in healthy controls. Conclusion: These differences may contribute differences in centralized pain thresholds seen between KOA and healthy participants.

Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood. OBJECTIVES: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships. METHODS: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression. RESULTS: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue. DISCUSSION: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue.

Inflammatory and Immune Protein Pathways Possible Mechanisms for Pain Following Walking in Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis affects nearly 30% of adults aged 60 years or older and causes significant pain and disability. Walking is considered a "gold standard" treatment option for reducing knee osteoarthritis pain and maintaining joint mobility but does not reduce pain for all adults with knee osteoarthritis pain and may induce pain-particularly when starting a walking routine. The mechanism by which walking is helpful for knee osteoarthritis pain is unclear. Quantitative sensory testing has revealed that knee osteoarthritis pain has both peripheral and central components, which vary by individual. OBJECTIVE: The purpose of this study was to better understand the mechanisms underlying the value of walking for knee pain. METHODS: We conducted a pretest/posttest study using quantitative sensory testing to measure neurophysiological parameters and examined systemic protein signatures. Adults with knee osteoarthritis and healthy controls underwent quantitative sensory testing and blood draw for platelet proteomics before and after a 30-minute walk at 100 steps per minute. RESULTS: A single 30-minute walk moderately increased pressure pain sensitivity at the affected knee among persons with knee osteoarthritis. Healthy adults showed no difference in pain sensitivity. Protein signatures among participants with knee osteoarthritis indicated changes in inflammatory and immune pathways, including the complement system and SAA1 protein that coincided with changes in pain with walking and differed from healthy participants. DISCUSSION: One goal of developing individualized interventions for knee osteoarthritis pain is to elucidate the mechanisms by which self-management interventions affect pain. The addition of therapies that target the complement system or SAA1 expression may improve the pain sensitivity after a moderate walk for adults with knee osteoarthritis.

Quantitative Sensory Testing Across Chronic Pain Conditions and Use in Special Populations.

Chronic pain imposes a significant burden to the healthcare system and adversely affects patients' quality of life. Traditional subjective assessments, however, do not adequately capture the complex phenomenon of pain, which is influenced by a multitude of factors including environmental, developmental, genetic, and psychological. Quantitative sensory testing (QST), established as a protocol to examine thermal and mechanical sensory function, offers insight on potential mechanisms contributing to an individual's experience of pain, by assessing their perceived response to standardized delivery of stimuli. Although the use of QST as a research methodology has been described in the literature in reference to specific pain populations, this manuscript details application of QST across a variety of chronic pain conditions. Specific conditions include lower extremity chronic pain, knee osteoarthritis, chronic low back pain, temporomandibular joint disorder, and irritable bowel syndrome. Furthermore, we describe the use of QST in placebo/nocebo research, and discuss the use of QST in vulnerable populations such as those with dementia. We illustrate how the evaluation of peripheral sensory nerve function holds clinical promise in targeting interventions, and how using QST can enhance patient education regarding prognostic outcomes with particular treatments. Incorporation of QST methodology in research investigations may facilitate the identification of common mechanisms underlying chronic pain conditions, guide the development of non-pharmacological behavioral interventions to reduce pain and pain-related morbidity, and enhance our efforts toward reducing the burden of chronic pain.

Genetic Testing for Inherited Cardiovascular Diseases: A Scientific Statement From the American Heart Association.

Advances in human genetics are improving the understanding of a variety of inherited cardiovascular diseases, including cardiomyopathies, arrhythmic disorders, vascular disorders, and lipid disorders such as familial hypercholesterolemia. However, not all cardiovascular practitioners are fully aware of the utility and potential pitfalls of incorporating genetic test results into the care of patients and their families. This statement summarizes current best practices with respect to genetic testing and its implications for the management of inherited cardiovascular diseases.

Measuring Fatigue in Older Adults With Joint Pain: Reliability and Validity Testing of the PROMIS Fatigue Short Forms.

BACKGROUND AND PURPOSE: Limited literature exists regarding the psychometric properties of the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 8a. This study compared the psychometric properties of the 8a to the established PROMIS Fatigue Short Form 7a. METHODS: This was a cross-sectional study of 31 older adults with joint pain. Equivalent forms reliability and a Rasch analysis explored reliability (equivalent forms, internal consistency), validity (unidimensionality, item INFIT/OUTFIT), and additional psychometrics (item mapping). RESULTS: The measures were equivalent in measuring fatigue (r = 0.75, p < .001) with good internal consistency (α = .87-.92). Both were unidimensional. Even though the 8a had better fitting items, neither measure could differentiate low levels of fatigue. CONCLUSION: The 8a has comparable psychometric properties to the 7a in this population. Future work is needed in larger, more diverse samples.

Genotype, resilience and function and physical activity post hip fracture.

BACKGROUND: Individuals who are resilient are more likely to engage in functional tasks and exercise post hip fracture. There may be a genetic predisposition to being resilient. OBJECTIVES: This study tested the direct and indirect association of 10 candidate genes, age, cognition, gender, comorbidities, pain and social activity on resilience, function and exercise post hip fracture. METHOD: This was a descriptive study including 172 community dwelling older adults. Measures included: age, gender, cognition (Modified Mini Mental Status Exam), comorbidities, social activities (self-report), DNA (GRM1, NTRK1, NTRK2, GNB3, NPY, SLC6A15. SLC6A4, BDNF, CR1TR1, FKBP5), pain (areas of pain and Numeric Rating Scale), function (Physical and Instrumental Activities of Daily Living; Lower Extremity Gains Score; Short Physical Performance Battery; Grip Strength) and exercise (Yale Physical Activity Scale). RESULTS: The majority of participants were Caucasian (93%), 50% were women and the average age was 81.09 (SD = 7.42). There were significant associations between resilience and single nucleotide polymorphisms from GRM1, NTRK1, NTRK2, GNB3, NPY and SLC6A15. Resilience, age, cognition, social activity, pain and genetic variability were directly and/or indirectly associated with exercise and/or function. DISCUSSION: This study highlights the importance of resilience for engagement in exercise and function after hip fracture and provides preliminary evidence for a genetic role for resilience.

Association of Systemic Inflammation and Fatigue in Osteoarthritis: 2007-2010 National Health and Nutrition Examination Survey.

BACKGROUND/PURPOSE: Mechanistic insight into osteoarthritis fatigue is needed as clinical management of this condition is nonspecific. Systemic inflammation is associated with fatigue in other chronic diseases. The purpose of this study was to explore the relationship between systemic inflammation and fatigue in osteoarthritis, while controlling for covariates. METHOD: This secondary analysis with a cross-sectional, multiyear retrospective design used data from the 2007-2010 National Health and Nutrition Examination Survey. Adults with self-reported osteoarthritis who participated in an examination at a mobile center and had no comorbidities associated with fatigue or systemic inflammation were included (n = 296). Complex sample analysis, independent samples t tests, and χ2 tests of independence were used to explore differences between nonfatigued and fatigued adults with osteoarthritis. Adjusted hierarchical logistic regression models were used to calculate odds of fatigue as a function of two systemic inflammatory markers, C-reactive protein (CRP), and white blood cell (WBC) count. RESULTS: Fatigued adults with osteoarthritis had significantly higher CRP levels and WBC counts compared to nonfatigued adults with osteoarthritis. In adjusted logistic regression models, increased CRP was associated with higher odds of fatigue when controlling for age, days affected by pain, depressive symptoms, sleep quantity, and body mass index (Odds ratio [OR] = 3.38, 95% CI [1.18, 9.69]). WBC count was not associated with higher odds of fatigue when controlling for these variables (OR = 1.10, 95% CI [0.92, 1.32]). CONCLUSION: Systemic inflammation may have a relationship with fatigue in osteoarthritis. Future work is necessary to replicate these findings in more robust studies.

A review and synthesis of correlates of fatigue in osteoarthritis.

Fatigue affects nearly half of all adults with osteoarthritis. Affected individuals report difficulty with daily functioning, requiring more time and rest during activities, feeling easily exhausted, and having to give up on social and volunteer activities known to improve quality of life. Because its etiology is poorly understood, clinical practice guidelines are unable to address management of fatigue in osteoarthritis. Elucidating a mechanism of osteoarthritis fatigue is a high priority, but few studies have identified key factors associated with fatigue in osteoarthritis. Thus, the purpose of this narrative literature review is to present the current evidence of known and potential correlates of fatigue in osteoarthritis, and synthesize our findings into a conceptual framework. The overarching goal of this work is to provide insight into areas of needed research and guide future work toward mechanistic insight of osteoarthritis fatigue. This knowledge could lead to novel nursing interventions for prevention, management, and treatment of fatigue among adults with osteoarthritis.

The Feasibility and Impact of the EMOVE Intervention on Self-efficacy and Outcome Expectations for Exercise in Epilepsy.

The purpose of this pilot study was to evaluate the feasibility of the self-efficacy based Epilepsy-Motivate and Outcome Expectations for Vigorous Exercise (EMOVE) intervention and report on the preliminary efficacy of this intervention aimed at improving exercise behaviors in adults with epilepsy. Methods: A single-group, repeated-measures design was used in 30 outpatients. Data were collected at baseline and 12 weeks after the intervention. Participant outcomes included Self-Efficacy and Outcome Expectations for Exercise in Epilepsy, Beck Depression Inventory-II, Quality of Life in Epilepsy Inventory-31, seizure frequency, average daily steps, and body mass index. Daily number of steps was measured using a wrist-worn activity monitor. Feasibility data were assessed using evidence of treatment fidelity including intervention delivery, receipt, and enactment. Results: Participants were single (63%), white (53%), female (63%), had a mean (SD) age of 46.7 (13) years (range, 26-68 years), had low levels of self-efficacy (mean, 5.10; range, 0-10) and high outcome expectations (mean, 3.90; range, 0-5), took under the recommended 10 000 steps per day (mean, 5107), and had an average of 6 seizures per month. Postintervention testing showed statistical improvement in depressive symptoms (mean [SD], 9.95 [9.47]; P < .05). There were no significant differences found for the other study outcomes. Our study showed the EMOVE intervention was feasible. Study participants had improved depressive symptoms. Future research should focus on increasing the sample size, improving exercise performance through group or individualized exercise sessions, and adding a control group to better evaluate the relationship between the intervention and improved depressive symptoms.

Post-stroke fatigue as an indicator of underlying bioenergetics alterations.

Approximately half of stroke survivors suffer from clinically significant fatigue, contributing to poor quality of life, depression, dependency, and increased mortality. The etiology of post-stroke fatigue is not well understood and treatment is limited. This study tested the hypothesis that systemic aerobic energy metabolism, as reflected by platelet oxygen consumption, is negatively associated with fatigue and systemic inflammation is positively associated with fatigue in chronic ischemic stroke survivors. Data on self-reported level of fatigue, platelet oxygen consumption rates (OCR) and plasma inflammatory markers were analyzed from 20 ischemic stroke survivors. DNA copy number for two mitochondrial genes was measured as a marker of platelet mitochondrial content. Basal and protonophore-stimulated maximal platelet OCR showed a biphasic relationship to fatigue. Platelet OCR was negatively associated with low to moderate fatigue but was positively associated with moderate to high fatigue. DNA copy number was not associated with either fatigue or platelet OCR. Fatigue was negatively associated with C-reactive protein but not with other inflammatory markers. Post-stroke fatigue may be indicative of a systemic cellular energy dysfunction that is reflected in platelet energy metabolism. The biphasic relationship of fatigue to platelet OCR may indicate an ineffective bioenergetic compensatory response that has been observed in other pathological states.

Reliability and Validity of the Self-Efficacy for Exercise in Epilepsy and the Outcome Expectations for Exercise in Epilepsy Scales.

PURPOSE: The purpose of this study was to test the psychometric properties of the revised Self-Efficacy for Exercise With Epilepsy (SEE-E) and Outcome Expectations for Exercise with Epilepsy (OEE-E) when used with people with epilepsy. METHODS: The SEE-E and OEE-E were given in face-to-face interviews to 26 persons with epilepsy in an epilepsy clinic. RESULTS: There was some evidence of validity based on Rasch analysis INFIT and OUTFIT statistics. There was some evidence of reliability for the SEE-E and OEE-E based on person and item separation reliability indexes. CONCLUSIONS: These measures can be used to identify persons with epilepsy who have low self-efficacy and outcome expectations for exercise and guide design of interventions to strengthen these expectations and thereby improve exercise behavior.

Pain, Genes, and Function in the Post-Hip Fracture Period.

Post-hip fracture generalized pain can lead to a progressive decline in function and greater disability. The purpose of this study was to explore the factors that influence pain among older adults post-hip fracture, including genetic variability, and evaluate whether pain directly or indirectly influenced upper and lower extremity function. This was a secondary data analysis using data from the first 200 participants in a Baltimore Hip Study (BHS), BHS-7. Assessments were done at 2 months post-hip fracture and included age, sex, marital status, education, cognitive status, comorbidities, body mass index (BMI), upper and lower extremity function, single nucleotide polymorphisms (SNPs) from 10 candidate genes, and total areas of pain and pain intensity. Model testing was done using the AMOS statistical program. The full sample included 172 participants with an average age of 81. Fifty percent were female and the majority was Caucasian (93%). Model testing was done on 144 individuals who completed 2 month surveys. Across all models, age, cognition, and BMI were significantly associated with total areas of pain. Thirty SNPs from five genes (BDNF, FKBP5, NTRK2, NTRK3, and OXTR) were associated with areas of pain and/or pain intensity. Together, age, cognition, BMI, and the SNP from one of the five genes explained 25% of total areas of pain and 15% of pain intensity. Only age and cognition were significantly associated with lower extremity function, and only cognition was significantly associated with upper extremity function. The full model was partially supported in this study. Our genetic findings related to pain expand prior reports related to BDNF and NTRK2.

The Volunteering-in-Place (VIP) Program: Providing meaningful volunteer activity to residents in assisted living with mild cognitive impairment.

The Volunteering-in-Place (VIP) Program was developed to provide individualized meaningful volunteer activities matched to interests and capabilities for older adults with MCI in assisted living. The purposes of this single-site pre-test/post-test pilot study were to (1) establish feasibility of the VIP Program based on treatment fidelity (design, treatment, delivery, enactment); and (2) evaluate preliminary efficacy via improvement in psychological health (depressive symptoms, usefulness, purpose, resilience, and life satisfaction) and decreased sedentary activity (survey and Fitbit) at 3 and 6 months. Ten residents participated. The majority was white, female and educated, and on average 88 years old. The VIP Program was feasible and most participants continued to volunteer at 6 months. There were non-significant improvements in depressive symptoms, usefulness, purpose, resilience and recreational physical activity. The results of this study provide support for the feasibility of the VIP Program. Further study is necessary to examine efficacy.

Measurement of Function Post Hip Fracture: Testing a Comprehensive Measurement Model of Physical Function.

BACKGROUND: Measurement of physical function post hip fracture has been conceptualized using multiple different measures. PURPOSE: This study tested a comprehensive measurement model of physical function. DESIGN: This was a descriptive secondary data analysis including 168 men and 171 women post hip fracture. METHODS: Using structural equation modeling, a measurement model of physical function which included grip strength, activities of daily living, instrumental activities of daily living, and performance was tested for fit at 2 and 12 months post hip fracture, and among male and female participants. Validity of the measurement model of physical function was evaluated based on how well the model explained physical activity, exercise, and social activities post hip fracture. FINDINGS: The measurement model of physical function fit the data. The amount of variance the model or individual factors of the model explained varied depending on the activity. CONCLUSION: Decisions about the ideal way in which to measure physical function should be based on outcomes considered and participants. CLINICAL RELEVANCE: The measurement model of physical function is a reliable and valid method to comprehensively measure physical function across the hip fracture recovery trajectory.

The Useful Depression Screening Tool for Older Adults: Psychometric Properties and Clinical Applicability.

BACKGROUND AND PURPOSE: The purpose of this study is to test the reliability and validity of the 3-item Useful Depression Screening Tool (UDST) for use with older adults in congregate living settings. METHODS: There were 176 residents of senior housing or assisted living who completed the UDST. Rasch analysis and test criterion relationships with pain, physical activity, and depression diagnosis were used to determine validity. Test-retest reliability was conducted with 29 senior housing residents. RESULTS: Rasch analysis demonstrated good fit of all items to the concept of depression. Criterion validity was supported, F(5) = 14.17, p < .001. Test-retest showed no significant differences in UDST scores over time (p = .29). CONCLUSIONS: The findings provide support for the validity and reliability of the UDST for use with older adults in congregate living settings.

The Interplay of Genetics, Behavior, and Pain with Depressive Symptoms in the Elderly.

PURPOSE OF STUDY: About 25% of older adults suffer from depressive symptoms. Commonly studied candidate genes associated with depression include those that influence serotonin (SLC6A4), dopamine (COMT), or neuroplasticity (BDNF, NTRK3). However, the majority of candidate gene studies do not consider the interplay of genetics, demographic, clinical, and behavioral factors and how they jointly contribute to depressive symptoms among older adults. The purpose of this study was to gain a more comprehensive understanding of depressive symptoms among older adults. DESIGN AND METHODS: In this descriptive study, demographic, behavioral, and clinical characteristics (age, gender, comorbidities, volunteering, physical activity, pain, and fear of falling) were obtained via interview of 114 residents in a continuing care retirement community. Peripheral whole blood was collected for DNA extraction. We examined common single nucleotide polymorphisms (SNPs) in the aforementioned genes using path analyses. RESULTS: SNPs in the NTRK3 gene, pain, physical activity, and fear of falling were directly associated with depressive symptoms in older adults. Those who had polymorphisms in the NTRK3 gene, pain, fear of falling, and were less physically active were more likely to exhibit depressive symptoms. None of the SNPs in SLC6A4, COMT, or BDNF genes were significantly associated with depressive symptoms. IMPLICATIONS: Our use of a path analysis to examine a biopsychosocial model of depressive symptoms provided the opportunity to describe a comprehensive clinical picture of older adults at risk for depressive symptoms. Thus, interventions could be implemented to identify older adults at risk for depressive symptoms.

The Impact of Genetics on Physical Resilience and Successful Aging.

OBJECTIVE: To better understand the impact of genetics on resilience and successful aging, we tested a model of successful aging. METHOD: This was a descriptive study with a single interview and blood draw done with residents in a continuing care retirement community. Five genes associated with resilience were included in the model. The hypothesis was tested using structural equation modeling. RESULTS: A total of 116 participants completed the survey. Two SNPs from SLC6A4 (rs25533 and rs1042173) and age were the only variables associated with physical resilience and explained 9% of the variance. Cognitive status, age, and depression were directly associated with successful aging; variance in rs25532 or rs1042173, resilience, and pain were indirectly associated with successful aging through depression. DISCUSSION: Continued research to replicate these findings is needed so as to be able to recognize older adults at risk of low physical resilience and implement appropriate interventions.

A mitochondrial bioenergetic basis of depression.

Major depressive disorder (MDD) is an important public health problem affecting 350 million people worldwide. After decades of study, the pathophysiology of MDD remains elusive, resulting in treatments that are only 30-60% effective. This review summarizes the emerging evidence that implicates impaired mitochondrial bioenergetics as a basis for MDD. It is suggested that impaired mitochondrial bioenergetic function contributes to the pathophysiology of MDD via several potential pathways including: genetics/genomics, inflammation, oxidative stress, and alterations in neuroplasticity. A discussion of mitochondrial bioenergetic pathways that lead to MDD is provided. Evidence is reviewed regarding the mito-toxic or mito-protective impact of various antidepressant medications currently in use. Opportunities for further research on novel therapeutic approaches, including mitochondrial modulators, as stand-alone or adjunct therapy for reducing depression are suggested. In conclusion, while there is substantial evidence linking mitochondrial bioenergetics and MDD, there are currently no clear mitochondrial phenotypes or biomarkers to use as guides in targeting therapies beyond individuals with MDD and known mitochondrial disorders toward the general population of individuals with MDD. Further study is needed to develop these phenotypes and biomarkers, to identify therapeutic targets, and to test therapies aimed at improving mitochondrial function in individuals whose MDD is to some extent symptomatic of impaired mitochondrial bioenergetics.