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Background: Cancer pain prevalence remains high, and variance in self-efficacy for managing pain may explain why some patients experience greater pain severity. Aim: This study explored perceptions of self-efficacy in relation to cancer pain severity and treatment related characteristics. Method: A descriptive cross-sectional survey was administered to 50 cancer outpatients. Data analysis involved descriptive and correlational statistical analyses. Results: Self-efficacy to manage pain was significantly associated with time since diagnosis and ability to deal with frustration, and inversely associated with pain severity level. A large proportion of patients reported low satisfaction self-managing their pain. Most patients reported independently self-managing their cancer pain; however, satisfaction with pain management was low for a large proportion of patients. Time since cancer diagnosis and ability to deal with frustration due to cancer pain were positively associated with cancer pain self-efficacy, whereas pain self-efficacy had a significant inverse correlation with cancer pain severity. Conclusions: Enhancing self-efficacy to self-manage under-treated cancer pain is important with implications for improving pain outcomes and quality of life. Further investigation on unmet needs and preferences for cancer pain self-management support is warranted.

Objective To synthesize the impact of health literacy on pain self-management contexts, processes, and outcomes. Methods This systematic review employed a narrative synthesis. We used databases, including PubMed and PsycINFO, and handsearching of the reference lists to identify articles published before December 2020. Pain self-management variables were chosen based on the Individual and Family Self-Management Theory. Quality was assessed using the National Institute of Health quality assessment tool for observational and cross-sectional studies. Results Twenty studies that included 6173 participants were used. Most studies measured functional domains of the health literacy concept. Twelve studies reported small to large associations between health literacy and pain knowledge, medication regimen adherence, or pain. Thirteen studies considered health literacy clinical risks in tailoring education, while seven viewed it as personal assets developed via education. Conclusions Limited information on the contribution of health literacy to pain self-management context factors and processes exists. Current evidence was limited by a lack of temporality, theoretical basis, and a priori sample estimation. Practice Implications Using brief functional literacy scales in the clinical environment can be more practical. Identifying patients’ literacy levels helps clinicians personalize education, which then promotes patients’ knowledge of pain, medication regimen adherence, and pain control.

BACKGROUND African American (AA) older adults with knee osteoarthritis experience more severe chronic pain and advanced physical disability. One of the most prominent stimuli that provokes knee pain is movement. Research suggests that, compared to Whites, AAs report significantly higher movement-evoked pain (MEP) in the knee. However, little is known about the biopsychosocial-behavioral mechanisms underlying MEP. OBJECTIVES The aim of the study was to present a study protocol to (a) characterize the biopsychosocial-behavioral mechanisms that predict MEP in AAs with knee osteoarthritis and (b) develop a targeted, mechanism-based self-management intervention to reduce MEP and maximize movement. METHODS An observational, mixed-methods cohort study will enroll 90 AA/Black adults (ages 55-90 years) to understand intraindividual and interindividual effects on MEP. Participants will complete assessments of MEP, function and gait, biopsychosocial-behavioral questionnaires, quantitative sensory testing, and 7-day ecological momentary assessments of pain and related symptoms. For the qualitative phase, focus groups will be conducted to co-construct a mechanism-based pain self-management intervention. RESULTS We will develop phenotypes of MEP based on biopsychosocial-behavioral predictors and correlate measures of MEP with function. Our central hypothesis is that higher levels of MEP will predict lower self-reported function and poorer performance on functional tasks and that multiple biopsychosocial and behavioral factors will be associated with MEP and function. Predictors may serve as risk or protective factors for MEP and physical function. In targeting the biopsychosocial-behavioral mechanisms of MEP, we anticipate that older AAs may request that intervention components include culturally tailored self-management education, movement/physical activity training, treatment decision-making skills, coaching, spirituality, and social/kinship support. CONCLUSION Osteoarthritis is now the single most common cause of disability, mobility limitations, and persistent pain in older adults-especially AA older adults. To our knowledge, this will be the first study to systematically phenotype MEP in an older racial minority population with knee osteoarthritis and will be relevant for reducing knee pain and improving function.

BACKGROUND The gut microbiome is an important determinant of health and disease in preterm infants. OBJECTIVES The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. METHODS This prospective, longitudinal study planned to recruit 160 preterm infants born

BACKGROUND Chronic low back pain (CLBP) is a significant cause of disability, lost wages, and healthcare costs. Inflammatory mediators, such as interleukin-6 (IL-6), have been associated with LBP severity. Patients with CLBP commonly experience sleep disturbance, and poor sleep has been shown to increase pain severity and inflammation. In contrast, social support may benefit patients with CLBP by reducing pain intensity and inflammation. OBJECTIVES The purpose of this study was to examine the influence of social support on the relationships among sleep disturbance, inflammation, and pain severity in patients with CLBP. METHODS In a cross-sectional study, men and women with CLBP were enrolled from an outpatient pain clinic. Participants completed psychometric instruments for social support, sleep quality, and pain severity. Blood samples were obtained for measurement of the pro-inflammatory cytokine IL-6 by enzyme-linked immunoassay. RESULTS Linear regression revealed greater sleep disturbance predicted greater pain severity. In contrast, participants who reported higher social support had lower sleep disturbance and lower pain severity. Mediation analysis revealed sleep disturbance to mediate the relationship between social support and pain, such that sleep disturbance reduced the benefit of social support on pain severity. Furthermore, greater sleep disturbance and lower social support predicted increased IL-6. However, IL-6 did not mediate the relationship between social support and pain. DISCUSSION The findings suggest that increased social support is associated with lower sleep disturbance, lower inflammation, and lower pain severity in patients with CLBP. Assessing the extent of social support and fostering social support as part of a comprehensive pain management program may benefit patients with CLBP. Interventions to strengthen social support systems and cultivate support from family and/or informal social networks may reduce symptom burden and improve quality of life.

Background Chronic low back pain is a prevalent condition, often involving an inflammatory process. Behavioral symptoms, including depressed mood, fatigue, and sleep disturbance, intensifies pain and reduces quality of life. Aims The objectives of this pilot study were to identify behavioral symptom clusters (depressive mood, fatigue, poor sleep) in individuals with chronic low back pain, and to determine whether there are differences in pain, quality of life and inflammation (plasma IL-6) based on cluster membership. Design and Settings A cross-sectional study was conducted in a pain clinic. Participants/ Subjects Participants between ages 21 to 70 years (N=69) were enrolled if they had chronic low back pain for at least six months. Methods Participants completed instruments measuring, pain, depressive mood, fatigue, sleep, and demographic form. Blood (10ml) was obtained. Latent class analysis was used to identify clusters. Results and Conclusions Findings revealed a two-class model, with Class 1 characterized by more depressive mood, fatigue, and sleep disturbance compared to Class 2. Class 1 participants reported worse quality of life than those in Class 2. Pain severity and pain interference were not significantly different between the classes. Levels of IL-6 were significantly greater in Class 1 participants compared to Class 2 with higher levels of IL-6 correlating with greater pain severity and sleep disturbances. Logistic regression revealed higher levels of IL-6 predicted Class 1 membership. Behavioral symptoms cluster exist in chronic low back pain patients and impact quality of life. Inflammation may contribute to relationship between behavioral symptoms and pain severity.

This study explored the association of back pain and heart failure (HF) with health outcomes among community-dwelling older adults. Older adults who completed a follow-up in the 11th year (2007–2008) of the Health, Aging, and Body Composition (Health ABC) study were included. The mean age was 83.4 ± 2.78 years. Back pain and heart failure were reported by 55.40% (n = 657) and 8.09 % (n = 96) of the total subjects (N = 1186), respectively. Regression analysis indicated that older adults with back pain reported worse depressive symptoms, fatigue, and physical performance and function compared with those without back pain (p < 0.05), and HF presence increased fatigue levels and decreased physical function (p < 0.05) among older adults with back pain. The high incidence and negative impact of back pain highlight the need to develop strategies for pain management among older adults with and without HF.

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.

Background:Nonpharmacologic stress reduction interventions provide an opportunity to modify chronic pain trajectories; however, the biological mechanisms underlying these interventions are poorly understood.Objectives:To examine clinical literature published in 2012–2018 with the goals of (1) identifying which biological mechanisms or biomarkers are currently being measured in nonpharmacologic stress reduction intervention studies for individuals with chronic pain and (2) evaluating the evidence to determine whether these stress reduction interventions lead to changes in (a) pain outcomes and/or (b) measured biomarkers.Data sources:Scientific articles in the electronic databases PubMed/Medline, Cumulative Index of Nursing and Allied Health Literature, PsychINFO, and SCOPUS following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Study selection:Randomized controlled trials and quasi-experimental studies that recruited subjects with a chronic pain condition, examined a relationship between a nonpharmacologic stress reduction intervention and pain-related outcome(s), and included measurement of a biomarker.Results:The 13 articles that met inclusion criteria spanned four nonpharmacologic stress reduction categories: mindfulness-based stress reduction, physical exercise, manual therapies, and biofeedback. Methods for studying biomarkers included measuring biological samples, neurological function, and autonomic control. Although all studies investigated both biological measures and pain outcomes, only three demonstrated an association between the biomarker(s) and pain-related outcomes.Conclusions:The results of this review highlight the complex nature of stress–pain relationships and the lack of rigorous clinical research identifying specific stress-related biological factors that modulate pain outcomes. Stress reduction interventions remain a favorable method for symptom management in patients living with chronic pain, but consistency in study measures and design is needed for robust evaluation.

Objectives A number of factors, including heritability and the environment, contribute to risk of transition from acute low back pain to chronic low back pain (CLBP). The aim of this study was to (1) compare somatosensory function and pain ratings at low back pain (LBP) onset between the acute low back pain and CLBP conditions and (2) evaluate associations between BDNF and COMT polymorphisms and expression levels at LBP onset to acute and chronic pain burden and risk for transition to the chronic pain state. Methods In this longitudinal study, 220 participants were enrolled following recent onset of LBP and data were collected until the LBP resolved or until the end of the study at 6 months. Forty-two participants' pain resolved before 6 weeks from onset and 42 participants continued to have pain at 6 months. Patient-reported pain burden, somatosensory function (quantitative sensory testing), and blood samples were collected at each study visit. Results CLBP is associated with greater pain burden and somatosensory hypersensitivity at the time of LBP onset. COMT rs4680 genotype (GG) was associated with acute cold pain sensitivity and with the risk for transition to CLBP while COMT expression was independently associated with risk for transition. Discussion CLBP was characterized by higher reported pain burden and augmented hypersensitivity at LBP onset. COMT expression and genotype were associated with acute pain burden and likelihood of transition to CLBP.

The biological basis underlying cognitive dysfunction in women with early-stage breast cancer (BC) remains unclear, but could reflect gene expression changes that arise from the acquisition and long-term retention of soma-wide alterations in DNA methylation in response to chemotherapy. In this longitudinal study, we identified differences in peripheral methylation patterns present in women prior to treatment (T1) and 1 year after receiving chemotherapy (T4) and evaluated relationships among the differential methylation (DM) ratios with changes in cognitive function. A total of 58 paired (T1 and T4) blood specimens were evaluated. Methylation values were determined for DNA isolated from whole blood using a genome-wide array . Cognitive function was measured using the validated, computerized CNS Vital Signs platform. Relationships between methylation patterns and cognitive domain scores were compared using a stepwise linear regression analysis, with demographic variables as covariates. The symptom comparison analysis was restricted to 2,199 CpG positions showing significant methylation ratio changes between T1 and T4. The positions with DM were enriched for genes involved in the modulation of cytokine concentrations. Significant DM ratios were associated with memory domain (56 CpGs). Eight of the ten largest DM ratio changes associated with lack of memory improvement were localized to genes involved in either neural function (ECE2, PPFIBP2) or signalling processes (USP6NL, RIPOR2, KLF5, UBE2V1, DGKA, RPS6KA1). These results suggest that epigenetic changes acquired and retained for at least one year in non-tumour cells following chemotherapy may be associated with a lack of memory improvement following treatment in BC survivors.

Concussion or mild traumatic brain injury (mTBI) is a common phenomenon in the United States, with up to 3.6 million sport-related mTBIs diagnosed annually. Return to learn protocols have been developed to facilitate the reintegration of students into school after mTBI, however, the implementation of return to learn protocols varies significantly across geographic regions and school districts. An integrative review of the literature was performed using Whittemore and Knalf's methodology. A search of published literature was conducted using the PRISMA checklist. Database searches were conducted from March 2,019 to October 2,021 using the terms “mild traumatic brain injury” and “return to learn.” Twenty-eight publications were included. Three themes were derived from this review: lack of policy, poor staff education on concussion symptoms and stakeholder communication breakdown. The development of communication patterns and use of a return to learn protocol could facilitate a gradual return to full academic workload after concussion.

Objectives: The transition from acute low back pain (aLBP) to chronic LBP (cLBP) results from a variety of factors, including epigenetic modifications of DNA. The aim of this study was to (1) compare global DNA (gDNA) methylation and histone acetylation at LBP onset between the aLBP and cLBP participants, (2) compare mRNA expression of genes with known roles in the transduction, maintenance, and/or modulation of pain between the aLBP and cLBP participants, (3) compare somatosensory function and pain ratings in our participants, and (4) determine if the aforementioned measurements were associated.Methods: A total of 220 participants were recruited for this prospective observational study following recent onset of an episode of LBP. We retained 45 individuals whose gDNA was of sufficient quality for analysis. The final sample included 14 participants whose pain resolved within 6 weeks of onset (aLBP),15 participants that reported pain for 6 months (cLBP), and 16 healthy controls. Participants were subjected to quantitative sensory testing (QST), blood was drawn via venipuncture, gDNA isolated, and global DNA methylation and histone acetylation, as well as mRNA expression of 84 candidate genes, were measured.Results: Individuals that develop cLBP display multimodal somatosensory hypersensitivity relative to aLBP participants. cLBP participants also had significantly lower global DNA methylation, which was negatively correlated with interleukin-2 (IL2) mRNA expression.Discussion: cLBP is characterized by somatosensory hypersensitivity, lower global DNA methylation, and higher IL2 expression level compared to those whose pain will resolve quickly (aLBP). These results suggest potential diagnostic and therapeutic relevance for global DNA methylation and IL2 expression in the pathology underlying the transition from acute to chronic LBP.

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

Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut–brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.

Background With a nearly 89% 5-year survival rate for women with early-stage breast cancer, symptoms are a priority. Healthy lifestyle behaviors may be temporally associated with symptoms; however, evidence is lacking. Objective This research examined temporal relationships among healthy lifestyle behaviors and symptoms in women diagnosed with breast cancer receiving chemotherapy. Methods This research was part of a study (R01NR012667) approved by the institutional review board. Women (n = 76) providing written informed consent participated in this longitudinal study examining health-promoting lifestyle behaviors and symptoms (fatigue, anxiety, depression, and pain). Participants completed well-validated self-report questionnaires primarily at a clinic visit. Statistical methods included descriptive statistics, linear mixed-effects models, and pairwise comparisons using SAS 9.4; α was set at .05. Results Lowest healthy lifestyle behavior scores for physical activity and highest scores for spiritual growth were reported. Significant changes in physical activity and stress management were noted. Fatigued patients had lower physical activity and nutrition scores than did patients without fatigue. Patients with anxiety had lower spiritual growth and interpersonal relation scores than did patients without anxiety. Relationships demonstrated temporal differences. Conclusions Breast cancer survivors did not routinely engage in healthy lifestyle behaviors. Significant temporal changes in healthy lifestyle behaviors and symptoms and significant associations among healthy lifestyle behaviors, symptoms, and demographic and clinical factors were noted in this study. Implications for practice Knowing the temporal relationships among these variables provides insight that could be useful for nurses so they can encourage healthy lifestyle behaviors to mitigate symptoms throughout the cancer trajectory.

AIMS To assess associations among cannabis use, health-related quality of life, exercise, depression and sleep among a nationally representative sample of US adults living with cancer. DESIGN A cross-sectional correlational study. METHODS We used survey data from the 2016-2018 Behavioral Risk Factor Surveillance System. Analyses were considered for sample weights and the complex designs. Logistic regression was performed to assess associations among cannabis use (0, 1-19, vs. 20-30 [frequent] days), health-related quality of life (0-13 vs. ≥14 mentally or physically unhealthy days in the past 30 days; 0-13 vs. ≥14 functionally limited days), exercise, depression, and sleep after accounting for covariates. Reason for cannabis use (medical vs. non-medical) was also assessed. RESULTS Frequent users had significantly more physically unhealthy days (adjusted odds ratio [OR]: 1.79, 95% CI: 1.28-2.51, p

The interplay between diet and gut microbiota has gained interest as a potential contributor in pathophysiology of irritable bowel syndrome (IBS). The purpose of this study was to compare food components and gut microbiota patterns between IBS patients and healthy controls (HC) as well as to explore the associations of food components and microbiota profiles. A cross-sectional study was conducted with 80 young adults with IBS and 21 HC recruited. The food frequency questionnaire was used to measure food components. Fecal samples were collected and profiled by 16S rRNA Illumina sequencing. Food components were similar in both IBS and HC groups, except in caffeine consumption. Higher alpha diversity indices and altered gut microbiota were observed in IBS compared to the HC. A negative correlation existed between total observed species and caffeine intake in the HC, and a positive correlation between alpha diversity indices and dietary fiber in the IBS group. Higher alpha diversity and gut microbiota alteration were found in IBS people who consumed caffeine more than 400 mg/d. Moreover, high microbial diversity and alteration of gut microbiota composition in IBS people with high caffeine consumption may be a clue toward the effects of caffeine on the gut microbiome pattern, which warrants further study.

Background Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction. Methods To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23–71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay]. Results Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014–0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores). Conclusions We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman’s treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment.

BACKGROUND: Children born prematurely (

AIM Our study aimed to examine factors that contribute to cognitive dysfunction in patients with heart failure (HF). BACKGROUND Although a majority of patients with HF have mild to moderate cognitive impairment, little is known about factors that influence progressive cognitive decline in this population. METHODS We examined the influence of physiological factors (NYHA functional class II - IV, ejection fraction, co-morbidity burden, polypharmacy), psychosocial factors (anxiety, depression, evaluation for advanced therapy), and associated toxicities (anticholinergic drug burden), on cognitive dysfunction. Data were analyzed using mean (SE) for continuous variables and frequency and percent for categorical variables. Differences between NYHA functional classification (Class II vs. Class III/IV) were examined using Chi Square. Linear regression models were used to assess associations among model variables. RESULTS Of the 113 participants with HF, Class III-IV HF were more cognitively impaired than those with NYHA Class II (p

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.

Background Traumatic injury is a major source of chronic pain, particularly for individuals with traumatic fracture of the fibula and/or tibia (lower extremity fracture [LEFx]). Although several factors (e.g., older age, being female, high pain intensity at time of initial injury) have been identified as risk factors for chronic pain associated with LEFx. Comprehensive biopsychosical models to predict the odds of transitioning from acute to chronic pain after LEFx are needed to better understand the underlying processes, predict risk for chronic pain, and develop personalized therapies for individuals at higher risk for developing chronic pain. Objective The aim of the study was to outline the study design that will be used to examine the physiological, psychological, and genetic/genomic variables-models that predict the transition from acute to chronic pain after LEFx. Method This prospective descriptive cohort study will enroll 240 participants with a fibula and/or tibia fracture and 40 controls with no LEFx. Data will be collected during an in-hospital baseline visit, five in-person clinic visits (6 weeks, 12 weeks, 24 weeks, 52 weeks, and 24 months), and seven online between-visit surveys (2 weeks, 4 weeks, 8 weeks, 10 weeks, 16 weeks, 20 weeks, and 18 months) from participants with LEFx and at concordant intervals from controls. Measures will consist of 19 questionnaires characterizing pain and psychological status, neurophysiological testing for peripheral sensory nerve function, and peripheral blood samples collections for RNA sequencing. Illumina standard protocols will be used to sequence RNA, and read counts will be used to measure gene expression. Analysis Direct-entry, multiple logistic regression will be used to produce odds ratios expressing the relative risk on each explanatory variable when controlling for other predictors/covariates in the model. Conclusion This study is one of the first to longitudinally characterize the biopsychosocial variables associated with a clinically relevant problem of the transition from acute to chronic posttraumatic fracture pain in individuals with LEFx. Results from this study will be used to construct predictive risk models of physiological, psychological, and genetic/genomic variables associated with increased risk for transitioning from acute to chronic pain status after LEFx. This work will lead to a better understanding of the trajectory of pain and relevant variables over time; initiate a better understanding of variables associated with risk for transitioning from acute to chronic pain; and, in the future, could provide a foundation for the identification of novel therapeutic targets to improve the outcomes of individuals with LEFx.

Aim To investigate the degree to which psychological stress, self-reported pain scores, and pain sensitivity during an acute state of low back pain (LBP) predict the development of persistent LBP trajectories. Background Identifying which factors influence LBP trajectories is critical to understand why some individuals experience persistent LBP and to illuminate areas for nursing intervention. Methods A secondary data analysis of a prospective study examining trajectories of LBP was conducted. The sample was comprised of 217 adults with acute-onset LBP recruited from the community and followed over 24 weeks. Variables of interest included demographic data, perceived stress scores, self-reported pain scores, and somatosensory characteristics collected within the first 4 weeks of LBP onset. The data were analyzed using non-parametric bivariate comparisons and a semi-parametric Cox proportional hazards model with interval-censoring. Results Individuals with higher psychological stress scores were less likely to experience pain resolution (Hazard ratio [HR] = 0.555, 95% confidence interval [CI] = 0.36–0.85, p = 0.02). After adjustment for covariates in the final model, the analysis revealed household income (HR = 2.79, 95% CI [1.63–4.67], p Conclusion Heightened psychological stress and pain severity as well as decreased pressure pain thresholds were indicated as influential factors of LBP trajectories. Household income was identified as the dominant predictor, demonstrating that individuals with a higher household income were more likely to resolve their pain. Strategies which integrate assessment of stress, self-reported pain scores, pain sensitivity, and social determinants for patients experiencing pain are needed to advance nursing care.

This chapter provides an overview of various theoretical models and genomic research that has been performed to develop a deeper understanding of the symptom experience in individuals with breast cancer. Methods for applying genomics in cancer symptom research, and importantly, integrating omic findings across datasets are discussed.

Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. IBS patients report that pain is the most distressing symptom with the greatest impact on quality of life. Pain-sensitivity genes and the gut microbiome may influence severity of symptoms as well as response to self-management (SM) interventions. Based on current understanding of the science of SM, pain neurophysiology, and the gut-brain axis, our team developed a pain SM intervention to be added to evidence-based self-management instruction to increase the individual's SM knowledge and skills (self-efficacy, self-regulation, and goal-setting). The purpose of this randomized controlled longitudinal pilot study is to examine the feasibility, acceptability, and preliminary effectiveness of the IBS-pain SM intervention on IBS-pain SM behaviors and related health outcomes. A sample of 80 young adults (age 18–29 years old) will be recruited and randomly assigned to the experimental or control group. Both groups will receive 10 electronic video modules focused on IBS-pain SM knowledge and skills. The experimental group also will receive nurse-led one-on-one phone consultations to facilitate monitoring and problem-solving. All participants will be followed over 12 weeks. Primary outcomes will be measured at baseline, 6 weeks, and 12 weeks, including IBS-pain SM behaviors, quality of life, and well-being. The influence of pain-sensitivity genes and the gut microbiome on IBS-pain SM behaviors and health outcomes also will be assessed.

Multiple intrinsic and extrinsic mechanisms contribute to vulnerability of cognitive decline and nurses play a significant role in assisting individuals and families to use strategies for healthy cognitive aging. The objective of this narrative review is to provide a synthesis of the intrinsic and extrinsic mechanisms of cognitive decline and conditions that are associated with cognitive decline. Well-established intrinsic mechanisms of cognitive decline include aging, apolipoprotein E (APOE) ε4 carrier status, SORL1 mutations, neuroinflammation, mitochondrial dysfunction, amyloid deposition, and demyelination. Extrinsic risk factors include obesity, diabetes, hypertension, elevated lipid panel, metabolic syndrome, depression, traumatic brain injury, substance use, heart failure, and stroke. The various definitions of cognitive decline as well as the intrinsic and extrinsic factors that impact cognition as humans age should be incorporated in future clinical research studies. Nurses may use this information to help patients make lifestyle choices regarding cognitive health.

Many women with breast cancer experience symptoms of pain, fatigue, and depression, collectively known as psychoneurologic (PN) symptoms, during and after chemotherapy treatment. Evidence that inflammatory dysfunction related to cancer and its treatments contributes to the development and persistence of PN symptoms through several interrelated pathways is accumulating. However, a major limiting factor in more precisely identifying the biological mechanisms underlying these symptoms is the lack of biological measures that represent a holistic spectrum of biological responses. Metabolomics allows for examination of multiple, co-occurring metabolic pathways and provides a systems-level perspective on biological mechanisms that may contribute to PN symptoms. Methods: In this pilot study, we performed serum metabolome analysis using liquid chromatography high-resolution mass spectrometry of global and targeted metabolomics from the tryptophan pathway from archived samples from 19 women with early-stage breast cancer. We used paired t tests to compare metabolite concentrations and Pearson’s correlation coefficients to examine concomitant changes in metabolite concentrations and PN symptoms before and after chemotherapy. Results: Levels of pain, fatigue, and depression increased after chemotherapy. Compared with pre-chemotherapy, global metabolites post-chemotherapy were characterized by higher concentrations of acetyl-l-alanine and indoxyl sulfate and lower levels of 5-oxo-l-proline. Targeted analysis indicated significantly higher kynurenine levels and kynurenine/tryptophan ratios post-chemotherapy. Symptoms of pain and fatigue had strong associations with multiple global and several targeted metabolites. Conclusion: Results demonstrated that metabolomics may be useful for elucidating biological mechanisms associated with the development and severity of PN symptoms, specifically pain and fatigue, in women with early-stage breast cancer.

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase ( COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants ( N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

Cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). While CRCI has been associated with linked to chemotherapy, there is increasing evidence that the condition may start prior to treatment and for some, remain unresolved after active treatment and into survivorship. Although the pathophysiology of the condition is complex, alterations in systemic cytokines, signaling molecules activated in response to infection or injury that trigger inflammation, are a possible mechanism linked to cognitive dysfunction in breast cancer and other conditions. Given the conflicting results in the literature, the lack of focus on domain specific cognitive testing, and the need for a longer time period given the multiple modalities of standard treatments for early-stage breast cancer, this longitudinal study was conducted to address these gaps. Methods We assessed 75 women with early-stage breast cancer at five points over two years, starting prior to the initial chemotherapy through 24 months after chemotherapy initiation. Measures included a validated computerized evaluation of domain-specific cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations to each cognitive domain. Results Levels and patterns of cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12, IL-17, G-CSF, MIPS-1β, and MCP-1) had the most variability. Some cytokine levels (e.g., IL-6) increased during chemotherapy but then decreased subsequently, while others (e.g., IL-17) consistently declined from baseline over time. There were multiple relationships among cytokines and cognition, which varied over time. At baseline, elevated concentrations of G-CSF and reduced concentrations of IL-17 were associated with faster psychomotor speed. At the second time-point (prior to the mid-chemotherapy), multiple cytokines had significant associations with psychomotor speed, complex attention, executive function, verbal memory, cognitive flexibility, composite memory and visual memory. Six months after chemotherapy initiation and at the one-year point, there were multiple, significant relationships among cytokines and multiple cognitive. At two years, fewer significant relationships were noted; however, lower concentrations of IL-7, a hematopoietic cytokine, were associated with better psychomotor speed, complex attention, and memory (composite, verbal and visual). MCP-1 was inversely associated with psychomotor speed and complex attention and higher levels of MIP-1β were related to better complex attention. Conclusion Levels and patterns of cytokines changed over time and demonstrated associations with domain-specific cognitive functioning that varied over time. The observed associations between cytokines and cognitive performance provides evidence that not only prototypical cytokines (i.e., IL-6, TNF-α, and IL1-β) but also cytokines from multiple classes may contribute to the inflammatory environment that is associated with cognitive dysfunction. Future studies to better delineate the cytokine changes, both individually and in networks, are needed to precisely assess a mechanistic link between cytokines and cognitive function in women receiving treatments for breast cancer.

Many people with HIV (PWH) experience chronic pain that limits daily function and quality of life. PWH with chronic pain have commonly been prescribed opioids, sometimes for many years, and it is unclear if and how the management of these legacy patients should change in light of the current US opioid epidemic. Guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain (CDCG), provide recommendations for the management of such patients but have yet to be translated into easily implementable interventions; there is also a lack of strong evidence that adhering to these recommendations improves patient outcomes such as amount of opioid use and pain levels. Herein we describe the development and preliminary testing of a theory-based intervention, called TOWER (TOWard SafER Opioid Prescribing), designed to support HIV primary care providers in CDCG-adherent opioid prescribing practices with PWH who are already prescribed opioids for chronic pain. TOWER incorporates the content of the CDCG into the theoretical and operational framework of the Information Motivation and Behavioral Skills (IMB) model of health-related behavior. The development process included elicitation research and incorporation of feedback from providers and PWH; testing is being conducted via an adaptive feasibility clinical trial. The results of this process will form the basis of a large, well-powered clinical trial to test the effectiveness of TOWER in promoting CDCG-adherent opioid prescribing practices and improving outcomes for PWH with chronic pain. Keywords: Chronic pain, Opioids, HIV

The mechanisms underlying the transition from acute to chronic pain remain unclear. Here, we sought to characterize the transcriptome associated with chronic low back pain as well as the transcriptome of the transition from acute to chronic low back pain. For the analysis, we compared the whole blood transcriptome of: (a) patients at the onset of low back pain who no longer had pain within 6 weeks after onset (acute) with patients who developed chronic low back pain at 6 months (chronic T5); and, (b) patients at the onset of low back pain (chronic T1) who developed chronic pain at 6 months with healthy pain-free (normal) controls. The majority of differentially expressed genes were protein coding. We illustrate a unique chronic low back pain transcriptome characterized by significant enrichment for known pain genes, extracellular matrix genes, and genes from the extended major histocompatibility complex (MHC) genomic locus. The transcriptome of the transition from acute to chronic low back pain was characterized by significant upregulation of antigen presentation pathway (MHC class I and II) genes and downregulation of mitochondrial genes associated with oxidative phosphorylation, suggesting a unique genomic signature of vulnerability to low back pain chronicity.

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.

Background: Every year, an estimated 15 million babies are born preterm (Purpose: To identify stress biomarkers that have been studied in preterm infants at different time points in the NICU and as long-term outcome measures. Method/search Strategy: Systematic searches were conducted of PubMed, CINAHL, SCOPUS, and PsychInfo databases. Findings/results: Twenty-one studies met inclusion criteria for this review. Several putative biomarkers were identified, including cortisol levels, epigenetic markers, brain microstructure, markers of oxidative stress, and the brain–gut–microbiome axis. Conclusion: The interaction of disease with therapeutic interventions may inadvertently increase infant allostatic load. In addition to human studies, future research should leverage newly available large data sets to conduct additional analyses.

Both back pain and heart failure (HF) have negative influence on all aspects of life. Little is known about the impact of back pain on older adults with HF. We include 1295 older adults who had data collected in the 11th year (2007-2008) of the Health, Aging and Body Composition (Health ABC) study to evaluate the effect of back pain on health status among older adults with and without HF. The participants aged 79-91, 54.8% were female and 34.8% were African American. Among 94 participants with HF, 63 (67.0%) had back pain; among 1201 participants without HF, 649 (54.0%) had back pain. Females reporting back pain had 4.76 (95% CI: 1.83, 12.37) times the odds of having HF compared to those without back pain. Male with back pain, compared to those without back pain, had 1.14 times (95% CI: 0.65, 2.02) the odds of having HF. Depressive symptoms were measured by the Center for Epidemiological Studies-Depression (CES-D) scale. Performance and functions were measured by the Established Populations for Epidemiologic Studies in the Elderly (EPESE) performance score, the Health ABC performance battery score and self-reported difficulty with functional tasks. These symptom and performance measures were significantly associated with both back pain and HF, but not the interaction terms of back pain and HF after adjusting demographic variables including gender, race, smoking status and BMI category. The high incidence and negative impact of back pain highlighted the needs of developing strategies in pain management among older adults with and without HF.

Introduction Chronic pain is a global public health problem, which impairs the physical, mental and social well-being of afflicted individuals. Distraction-based interventions have been posited as one approach to divert attention away from noxious stimulation and thereby modulate the severity of pain. The current review aimed to identify studies that explicitly used distraction-based interventions for patients with chronic pain. Methods The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Databases including PubMED, EMBASE, PsychINFO, and CINAHL were searched using combinations of keywords. Studies from the last decade (2005–2015) were included if they (a) were published in English, (b) used experimental or quasi-experimental designs, (c) explicitly used distraction as an intervention for pain, and, (d) evaluated measures of pain pre-post intervention. Results A total of 12 studies that examined distraction-based interventions for chronic pain were included in this review. Most interventions were evaluated in adults with chronic pain conditions, such as fibromyalgia, and involved a combination of activities including internal and external distraction techniques. There was wide variation in the implementation of interventions, particularly in the use of practice sessions, dose frequency and duration. Conclusion Distraction was not sufficiently elaborated upon in the theoretical frameworks. Directions for future research are discussed including the use of standardized pain, symptom, and outcome measures and tailored intervention approaches based on the individual’s level of distractibility. Strategies to target the individual’s distraction threshold could lead to greater precision in delivery of effective interventions to reduce pain.

The aim of the present study was to explore clusters of psychoneurological symptoms and inflammation (levels of C-reactive protein) over time in a cohort of women with early-stage breast cancer. Specifically, we examined the relationships among affective symptoms (depression, anxiety, fatigue, sleep disturbances, pain, and perceived stress), domains of cognitive performance, and levels of peripheral C-reactive over a period of 2 years. This was a prospective, longitudinal study of 77 women diagnosed with early-stage breast cancer. Data collection, including symptom questionnaires, performance-based cognitive testing, and blood draws, took place at 5 time points: prior to initiating adjuvant chemotherapy, prior to the fourth chemotherapy treatment, and at 6, 12, and 24 months after the initiation of chemotherapy. Exploratory factor analysis with varimax orthogonal rotation was used to examine the covariance among symptoms at each visit. Using the factor scores and weighted sums, three clusters were identified: global cognition, affective symptoms, and cognitive efficiency. Peripheral levels of C-reactive protein were inversely correlated with the cognitive efficiency factor across time. The findings suggest that objectively measured domains of cognitive function occur independently of other affective symptoms that are commonly reported by women with breast cancer in long-term survivorship. The cognitive efficiency symptom cluster may be amenable to interventions targeted to biological influences that reduce levels of C-reactive protein.

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.

Cognitive dysfunction in women with breast cancer continues to be an area of intense research interest. The prevalence, severity, timing, and cognitive domains that are most affected, as well as the contribution of cancer and its treatments to cognition, remain unresolved. Thus, longitudinal studies are needed that examine cognitive function during different stages of breast cancer treatment and survivorship. This longitudinal trial followed women with early-stage breast cancer, prior to chemotherapy through 2 years survivorship.In women with early-stage breast cancer (N = -75), performance-based assessment of nine cognitive domains was performed at five time points beginning prior to chemotherapy and finishing 24 months after initial chemotherapy. Linear mixed effects models were used to examine the temporal changes in cognitive performance domains, while adjusting for cofactors, including those related to individuals, tumor attributes, chemotherapy (adjuvant or neoadjuvant), radiation, endocrine therapy, and concurrent symptoms.At baseline, scores on reaction time, complex attention, cognitive flexibility, executive function, and visual memory were lower than 90. At 2 years, all domains improved except for the memory domains (verbal, visual, and composite). Scores on six domains (psychomotor speed, reaction time, complex attention, cognitive flexibility, and visual memory) remained lower than 100 at 2 years. Neoadjuvant chemotherapy and fatigue had strong inverse relationship with cognitive functioning at multiple time points.The low performance-based cognitive scores at baseline and over time warrant further study. Although most scores improved over time, memory did not improve. In all, the level of cognitive function is lower than expected for a majority college-educated sample. Thus, future studies are warranted to replicate these findings and to develop methods for identifying women with cognitive dysfunction pretreatment and into survivorship.

It is well established that the environment contributes to health. However, few studies have evaluated environmental exposures in women that may influence future health of their offspring. Knowledge gained may inform nursing how to better advocate for patients and families; and provide individualized interventions and education. Therefore, a more comprehensive investigation of the maternal exposome to uncover mechanistic insight into complex disease in offspring is warranted. To advance understanding of biological mechanisms that contribute to high-risk birth outcomes and offspring predisposition to disease, it will be necessary to measure a range of exposures and biomarkers before and during pregnancy.