Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

Relationship of fatigue with cognitive performance in women with early-stage breast cancer over 2 years.

OBJECTIVE: Fatigue and cognitive dysfunction are major concerns for women with early-stage breast cancer during treatment and into survivorship. However, interrelationships of these phenomena and their temporal patterns over time are not well documented, thus limiting the strategies for symptom management interventions. In this study, changes in fatigue across treatment phases and the relationship among fatigue severity and its functional impact with objective cognitive performance were examined. METHODS: Participants (N = 75) were assessed at five time points beginning prior to chemotherapy to 24 months after initial chemotherapy. Fatigue severity and impact were measured on the Brief Fatigue Inventory. Central nervous system (CNS) Vital Signs was used to measure performance based cognitive testing. Temporal changes in fatigue were examined, as well as the relationship between fatigue and cognitive performance, at each time point using linear mixed effect models. RESULTS: Severity of fatigue varied as a function of phase of treatment. Fatigue severity and its functional impact were moderate at baseline, increased significantly during chemotherapy, and returned to near baseline levels by 2 years. At each time point, fatigue severity and impact were significantly associated with diminished processing speed and complex attention performance. CONCLUSIONS: A strong association between fatigue and objective cognitive performance suggests that they are likely functionally related. That cognitive deficits were evident at baseline, whereas fatigue was more chemotherapy dependent, implicates that two symptoms share some common bases but may differ in underlying mechanisms and severity over time. This knowledge provides a basis for introducing strategies for tailored symptom management that vary over time.

Psychometric Evaluation of the Patient-Reported Outcomes Measurement Information System Fatigue-Short Form Across Diverse Populations.

BACKGROUND: The need for reliable, valid tools to measure patient-reported outcomes (PROs) is critical both for research and for evaluating treatment effects in practice. The Patient-Reported Outcomes Measurement Information System Fatigue-Short Form v1.0-Fatigue 7a (PROMIS F-SF) has had limited psychometric evaluation in various populations. OBJECTIVES: The aim of the study is to examine psychometric properties of PROMIS F-SF item responses across various populations. METHODS: Data from five studies with common data elements were used in this secondary analysis. Samples from patients with fibromyalgia, sickle cell disease, cardiometabolic risk, pregnancy, and healthy controls were used. Reliability was estimated using Cronbach's alpha. Dimensionality was evaluated with confirmatory factor analysis. Concurrent validity was evaluated by examining Pearson's correlations between scores from the PROMIS F-SF, the Multidimensional Fatigue Symptom Inventory-Short Form, and the Brief Fatigue Inventory. Discriminant validity was evaluated by examining Pearson's correlations between scores on the PROMIS F-SF and measures of stress and depressive symptoms. Known groups validity was assessed by comparing PROMIS F-SF scores in the clinical samples to healthy controls. RESULTS: Reliability of PROMIS F-SF scores was adequate across samples, ranging from .72 in the pregnancy sample to .88 in healthy controls. Unidimensionality was supported in each sample. Concurrent validity was strong; across the groups, correlations with scores on the Multidimensional Fatigue Symptom Inventory-Short Form and Brief Fatigue Inventory ranged from .60 to .85. Correlations of the PROMIS F-SF with measures of stress and depressive mood were moderate to strong, ranging from .37 to .64. PROMIS F-SF scores were significantly higher in clinical samples compared to healthy controls. DISCUSSION: Reliability and validity of the PROMIS F-SF were acceptable. The PROMIS F-SF is a suitable measure of fatigue across the four diverse clinical populations included in the analysis.

Integrative Review of Co-Occurring Symptoms Across Etiologies of Chronic Liver Disease and Implications for Symptom Management Research and Practice.

PURPOSE: Chronic liver disease affects over 30 million people worldwide, and despite advances in medical management that have increased survival, a majority of these individuals report multiple symptoms that severely impair function and quality of life. The purpose of this integrative review was to examine and summarize the current literature focused on self-reported symptoms in individuals with chronic liver disease in order to inform the development and delivery of symptom management strategies in clinical practice. DESIGN AND METHODS: Combinations of search terms related to the symptom experience were used to search three electronic databases. Inclusion criteria were empirical studies that measured self-reported symptoms in populations with chronic liver disease published in English between 2003 and 2014. The literature search initially yielded 112 results; 26 quantitative studies met the inclusion criteria. FINDINGS AND CONCLUSIONS: The symptom of fatigue was commonly reported across chronic liver disease populations and was often found to co-occur with other distressing symptoms, including depression, sleep disturbance, pain, cognitive impairment, and dizziness associated with autonomic dysfunction. Due to the high prevalence and persistence of these "core" symptoms, the use of core symptom measures integrated longitudinally across populations would inform the development and delivery of symptom management interventions as well as enhance the ability of nurses to incorporate population-level symptom management programs. CLINICAL RELEVANCE: Nurses play an important role in symptom assessment and may use the findings from the integrative review to incorporate core symptom measures across chronic liver disease populations and advance the development and delivery of symptom management interventions.

Effects of guided imagery on biobehavioral factors in women with fibromyalgia.

Women diagnosed with fibromyalgia (N = 72) participated in a 10-week randomized trial to examine the effectiveness of guided imagery on self-efficacy, perceived stress, and selected biobehavioral factors (FMS symptoms; immune biomarkers). Participants in both guided imagery and usual care control conditions completed measures and donated 3 cc of blood at baseline, 6- and 10-weeks. A mixed effects linear model to test for differences between groups for all behavioral and biologic variables demonstrated that after 10 weeks of daily intervention use, guided imagery participants reported statistically significant increases in self-efficacy and statistically significant decreases in stress, fatigue, pain, and depression. There were no statistically significant changes in biomarker levels, although total group C-reactive protein was elevated at baseline (4.7 mg/L), indicating an inflammatory process. Subsequent studies should be undertaken to more fully elucidate the biobehavioral aspects of nonpharmacological intervention effectiveness.

Telomere length: a review of methods for measurement.

BACKGROUND: The exciting discovery that telomere shortening is associated with many health conditions and that telomere lengths can be altered in response to social and environmental exposures has underscored the need for methods to accurately and consistently quantify telomere length. OBJECTIVES: The purpose of this article is to provide a comprehensive summary that compares and contrasts the current technologies used to assess telomere length. DISCUSSION: Multiple methods have been developed for the study of telomeres. These techniques include quantification of telomere length by terminal restriction fragmentation-which was one of the earliest tools used for length assessment-making it the gold standard in telomere biology. Quantitative polymerase chain reaction provides the advantage of being able to use smaller amounts of DNA, thereby making it amenable to epidemiology studies involving large numbers of people. An alternative method uses fluorescent probes to quantify not only mean telomere lengths but also chromosome-specific telomere lengths; however, the downside of this approach is that it can only be used on mitotically active cells. Additional methods that permit assessment of the length of a subset of chromosome-specific telomeres or the subset of telomeres that demonstrate shortening are also reviewed. CONCLUSION: Given the increased utility for telomere assessments as a biomarker in physiological, psychological, and biobehavioral research, it is important that investigators become familiar with the methodological nuances of the various procedures used for measuring telomere length. This will ensure that they are empowered to select an optimal assessment approach to meet the needs of their study designs. Gaining a better understanding of the benefits and drawbacks of various measurement techniques is important not only in individual studies, but also to further establish the science of telomere associations with biobehavioral phenomena.

Biobehavioral examination of fatigue across populations: report from a P30 Center of Excellence.

OBJECTIVES: This article reports the cross-studies analysis of projects from the P30 Center of Excellence for Biobehavioral Approaches to Symptom Management. Although the projects investigated diverse populations, a consistent theoretical and empirical approach guided each project. METHODS: Common data elements included the following measures of psychobehavioral variables: the PROMIS Short-Form Fatigue Scale, the Center of Epidemiologic Studies Depression Scale, and the Perceived Stress Scale. Plasma cytokines were measured as the shared biological data element. RESULTS: Data were analyzed from 295 participants with fibromyalgia (n = 72), second trimester pregnancy (n = 73), sickle cell anemia (n = 60), and cardiometabolic risk (n = 91). The mean age of participants was 35.4 years, and the most participants were female. Levels of symptoms were generally elevated across samples; the level of fatigue ranged from 18.9 to 24.7, depressive symptoms from 12.5 to 23.4, and perceived stress from 16.5 to 21.8. Intercorrelations among symptom measures and perceived stress were strong across the samples. However, correlations among psychobehavioral variables and cytokines were variable, indicating a separate relationship for the measures with cytokines. CONCLUSIONS: Future work in symptom science could benefit from common data elements, including biomarkers, across populations to better develop the taxonomy of symptom profiles across conditions.

Mindfulness as a Symptom Management Strategy for Fibromyalgia: An Integrative Review.

Introduction: Mindfulness Meditation is a complementary and alternative medicine (CAM) modality growing in popularity. Currently, mindfulness is under-studied regarding efficacy; however, it offers a potentially accessible way to contribute to symptom management in chronic pain conditions. The purpose of this integrative review was to examine the literature for the use of mindfulness as symptom management strategy for persons diagnosed with the chronic pain condition, fibromyalgia. Methods: Six scientific databases were searched, using various keywords. Inclusion criteria were: (a) fibromyalgia, (b) English language, (c) experimental research designs; (d) adults age ≥ 18 years, and (e) mindfulness. Results: Seven studies were reviewed. Most interventions were completed over several months in the form of multiple group sessions lasting several hours each. Evaluations of effectiveness varied by study, but variables most commonly demonstrating improvement from mindfulness were anxiety, depression, sleep-related symptoms, coping and perceived stress. Mechanisms by which these outcomes may have been mediated included increases in self-compassion and psychological flexibility. Discussion: There is insufficient evidence to recommend mindfulness as an effective way to manage all fibromyalgia symptoms; however, promise lies in its usefulness addressing mood- and sleep-related symptoms. We suggest that further, more rigorous, research is warranted.

Racial Disparities in Pain Among Women with Fibromyalgia: Secondary Data Analysis of Severity, Interference with Function, and Response to Guided Imagery.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread persistent musculoskeletal pain. Mostly prevalent among White women, little is known about FMS in other population cohorts. This study examined secondary data of a racially diverse sample of women with FMS that were collected as part of a randomized controlled clinical trial that examined the effect of a complementary therapy intervention over the course of a 10-week guided imagery intervention to identify demographic, social, or economic differences in self-reported pain. Materials and Methods: The Brief Pain Inventory (BPI), which measures pain severity and interference, was administered to 72 women (21 Black and 51 Whites) at baseline, 6 and 10 weeks. Student's t tests and time series regression models examined racial difference in pain dimensions and treatment response. Regression models accounted for age, race, income, duration of symptoms, treatment group, pain at baseline, smoking, alcohol use, comorbid conditions, and time. Results: Black women experienced significantly higher pain severity (ß = 5.52, standard deviation [SD] = 2.13) and interference (ß = 5.54, SD = 2.74) than Whites (severity ß = 4.56, SD = 2.08; interference ß = 4.72, SD = 2.76) (interference: t = 1.92, p = 0.05; severity: t = 2.95, p = 0.00). Disparities persisted over time. Controlling for differences in age, income, and previous pain levels, Black women had 0.26 (standard error [SE] = 0.065) higher pain severity and 0.36 (SE = 0.078) higher interference than Whites. Low-income earners also experienced 2.02 (SE = 0.38) and 2.19 (SE = 0.46) higher pain severity and interference, respectively, than other earners. Results were robust to inclusion of comorbidities. Conclusions: Black women and low-income earners experienced significantly higher levels of pain severity and interference and a lower dose response to the intervention. Differentials were robust to inclusion of demographic, health, and behavioral characteristics. Findings suggest that external factors may contribute to pain perception among women with FMS.

Cognitive Impairment, Physical Impairment, and Psychological Symptoms in Intensive Care Unit Survivors.

BACKGROUND: Post-intensive care syndrome (PICS) affects 25% to 50% of adults who survive an intensive care unit (ICU) stay. Although the compounding of PICS impairments (cognitive, physical, and psychological) could intensify the syndrome, research on relationships among impairments is limited, particularly in patients with delirium. OBJECTIVES: To examine associations among PICS impairments and examine delirium status and its relationship to PICS impairments at ICU discharge and 1 month later. METHODS: A descriptive, correlational study of adults who survived an ICU stay. Participants completed measures for depression, anxiety, posttraumatic stress, physical function, functional status, and cognition at ICU discharge and 1 month later. Relationships among PICS impairments were examined with Spearman correlations; differences in impairments by delirium status were assessed with t tests. RESULTS: Of 50 enrolled participants, 46 were screened for PICS impairment at ICU discharge and 35 were screened 1 month later. Cognitive impairment was the most common impairment at both time points. A positive correlation was found between cognition and functional status at ICU discharge (ρ = 0.50, P = .001) and 1 month later (ρ = 0.54, P = .001). Cognition and physical functioning were positively correlated 1 month after discharge (ρ = 0.46, P = .006). The group with delirium had significantly lower functional status scores than the group without delirium at ICU discharge (P = .04). CONCLUSIONS: The findings suggest a moderate correlation between cognitive and physical impairments. This relationship should be explored further; ICU survivors with undiagnosed cognitive impairment may have delayed physical recovery and greater risk for injury.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

A systematic review of the association between fatigue and cognition in chronic noncommunicable diseases.

OBJECTIVES: Fatigue is one of the most common symptoms associated with chronic noncommunicable diseases, and it may also increase cognitive impairment. However, associations between fatigue and cognitive impairment in chronic illnesses remain unclear. Therefore, the purpose of this systematic review was to examine research that investigated associations between level of fatigue and cognitive status. METHODS: PubMed/Medline, PsycINFO, CINAHL, and Cochrane Database were searched for articles published between 2012 and 2018 using search terms fatigue, cognition, and various iterations of these terms. Study quality was assessed by the Joanna Briggs Institute Critical Appraisal Checklist tool. RESULTS: Of 1799 citations, 10 studies in samples of individuals with cancer, multiple sclerosis, neurosarcoidosis, and chronic fatigue syndrome met the inclusion criteria. Fatigue was found to be significantly correlated with cognitive impairment in one cancer-related study (r = -.480, p < .001), one multiple sclerosis study (ß= -0.52, p < .0001), and two chronic fatigue syndrome studies (r = 0.397, p < .001; r = 0.388, p < .001). DISCUSSION: There is insufficient evidence examining the relationship between fatigue and cognitive impairment in patients with chronic illnesses. As a result, more studies are needed that examine potential relationships between these two symptoms in order to develop effective treatments for individuals living with a chronic noncommunicable disease.

Exploring Associations Between Metabolites and Symptoms of Fatigue, Depression and Pain in Women With Fibromyalgia.

Fibromyalgia (FM) is a chronic noncommunicable disorder characterized by a constellation of symptoms that include fatigue, depression and chronic pain. FM affects 2%-8% of the U.S. population, 2% of the global population, with 61%-90% of FM diagnoses attributed to women. Key causal factors leading to the development and severity of FM-related symptoms have not yet been identified. The purpose of this article is to report relationships among identified metabolites and levels of fatigue, depression, pain severity, and pain interference in a sample of 20 women with FM. In this secondary analysis, we conducted global metabolomic analysis and examined the data for relationships of metabolite levels with self-reported symptoms of fatigue, depression, pain severity, and pain interference. Results revealed six metabolites (6-deoxy-hexose; pantothenic acid; ergothioneine; l-carnitine; n-acetylserotonin; butyrobetaine) and their associated metabolic pathways such as carnitine synthesis, lipid oxidation, tryptophan metabolism, beta-alanine metabolism and pantothenic and Coenzyme-A biosynthesis that were either positively or inversely related to pain severity, pain interference, or both. The preliminary data presented suggest that metabolites representing energy, amino acid, or lipid classification may be associated with pain symptom severity and interference in women with FM. Future work will confirm these findings in a large, comparative cohort, targeting metabolites and metabolite pathways to better understand the relationships of metabolites and symptomology.

Metabolomic Differentials in Women With and Without Fibromyalgia.

A nontargeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with FM (n = 20) and comparative data collected from newly recruited age-matched women (n = 20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with fold change (>2 or <0.5) and variable importance of projection scores ≥1 revealed statistically significant metabolites comparing samples from women with and without FM. Metabolite profiles in patients with FM differed from the comparison group in energy, lipid and amino acid metabolites reflecting heightened oxidative stress, inflammation, and tryptophan degradation in patients with FM. Study results may contribute to further identification of unique metabolomic profiles enhancing understanding of the pathophysiology of FM and for the development of effective therapeutic options.

Relationship of symptoms associated with ICU-survivorship: An integrative literature review.

BACKGROUND: The number of adults who survive a critical illness involving admission to an intensive care unit is increasing. These survivors have an increased risk of developing impairments in cognition, physical function and psychological health. OBJECTIVE: This integrative literature review examined the literature for studies exploring the relationships among two or more of the variables of interest, i.e. cognitive, physical, and psychological symptoms (depressive, anxiety, or posttraumatic stress) in intensive care unit survivors post-hospital discharge. METHODS: A literature search was conducted using PubMed, CINHAL and PsycINFO databases. FINDINGS: While all 13 studies included in the review explored some aspect of a relationship among the variables of interest, none explored associations among all three variables. Five studies explored physical function and psychological symptoms, four studies explored cognitive impairment and psychological symptoms and five studies explored the association among different psychological symptoms. Inconsistencies were found in the study designs, follow-up time frames, patient populations and measures used. CONCLUSIONS: Further research using well-designed methodologies and standardized instruments is warranted. Gaining a better understanding of the relationships among these impairments has the potential to contribute to the development of screening guidelines, preventative strategies, and treatments.

Relaxation and guided imagery in Hispanic persons diagnosed with fibromyalgia: a pilot study.

Fibromyalgia (FM) is a chronic pain disorder affecting 2% of the population in the United States. Another 16 million Hispanics suffer from generically identified rheumatic diseases that likely include FM. Because there are few reported studies of Hispanics with FM, a pilot study using a repeated-measures pretest-posttest design investigated the effects of a 10-week mind-body intervention (visual imagery with relaxation) on symptom management. The change in means from baseline to week 10 demonstrated improvement in self-efficacy for managing pain and other symptoms and functional status. Visual imagery with relaxation is a mind-body intervention that may be used for symptom management in this population.

Absorption: an individual difference to consider in mind-body interventions.

Given that mind-body interventions constitute a major portion of complementary and alternative medicine used by the public, it seems important to explore those human characteristics that may contribute to the efficacy of mind-body interventions in those who are most likely to benefit. One such characteristic, absorption, reflects an individual's cognitive capacity for involvement in sensory and imaginative experiences in ways that alter an individual's perception, memory, and mood with behavioral and biological consequences. Thus, one's level of absorption may potentially create differential treatment effects in mind-body intervention outcomes. Conducting practical clinical trials helps address the challenge of determining whether a specific mind-body modality intervention may be effective. Such trials may be strengthened by including measures of personality dimensions such as absorption.