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APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.

ContextMost of the reviews on the biological basis for symptom clusters suggest that inflammatory processes are involved in the development and maintenance of the symptom clusters. However, no studies have evaluated for associations between genetic polymorphisms and common symptom clusters (e.g., mood disturbance, sickness behavior).ObjectivesExamine the associations between cytokine gene polymorphisms and the severity of three distinct symptom clusters (i.e., mood-cognitive, sickness-behavior, treatment-related) in a sample of patients with breast and prostate cancer (n = 157) at the completion of radiation therapy.MethodsSymptom severity was assessed using the Memorial Symptom Assessment Scale. Symptom clusters were created using exploratory factor analysis. The associations between cytokine gene polymorphisms and the symptom cluster severity scores were evaluated using regression analyses.ResultsPolymorphisms in C-X-C motif chemokine ligand 8 (CXCL8), interleukin (IL13), and nuclear factor kappa beta 2 (NFKB2) were associated with severity scores for the mood-cognitive symptom cluster. In addition to interferon gamma (IFNG1), the same polymorphism in NFKB2 (i.e., rs1056890) that was associated with the mood-cognitive symptom cluster score was associated with the sickness-behavior symptom cluster. Polymorphisms in interleukin 1 receptor 1 (IL1R1), IL6, and NFKB1 were associated with severity factor scores for the treatment-related symptom cluster.ConclusionOur findings support the hypotheses that symptoms that cluster together have a common underlying mechanism and the most common symptom clusters in oncology patients are associated polymorphisms in genes involved in a variety of inflammatory processes.

ContextAlthough physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX).ObjectivesIdentify subgroups of older patients based on changes in their level of physical function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality-of-life (QOL) outcomes.MethodsLatent profile analysis was used to identify groups of older oncology patients (n = 363) with distinct physical function profiles. Patients were assessed six times over two cycles of CTX using the Physical Component Summary score from the Short Form 12. Differences, among the groups, in demographic and clinical characteristics and QOL outcomes were evaluated using parametric and nonparametric tests.ResultsThree groups of older oncology patients with distinct functional profiles were identified: Well Below (20.4%), Below (43.8%), and Above (35.8%) normative Physical Component Summary scores. Characteristics associated with membership in the Well Below class included the following: lower annual income, a higher level of comorbidity, being diagnosed with depression and back pain, and lack of regular exercise. Compared with the Above class, patients in the other two classes had significantly poorer QOL outcomes.ConclusionAlmost 65% of older oncology patients reported significant decrements in physical function that persisted over two cycles of CTX. Clinicians can assess for those characteristics associated with poorer functional status to identify high-risk patients and initiate appropriate interventions.

ContextAn important question in symptom clusters research is whether the number and types of symptom clusters vary based on the specific dimension of the symptom experience used to create the clusters.ObjectivesGiven that lung cancer patients undergoing chemotherapy (CTX) report an average of 14 co-occurring symptoms and studies of symptom clusters in these patients are limited, the purpose of this study, in lung cancer patients undergoing CTX (n = 145), was to identify whether the number and types of symptom clusters differed based on whether symptom occurrence rates or symptom severity ratings were used to create the clusters.MethodsA modified version of the Memorial Symptom Assessment Scale was used to assess for the occurrence and severity of 38 symptoms, one week after the administration of CTX. Exploratory factor analysis was used to extract the symptom clusters.ResultsBoth the number and types of symptom clusters were relatively similar using symptom occurrence rates or symptom severity ratings. Five symptom clusters were identified using both symptom occurrence rates and severity ratings (i.e., sickness behavior, lung cancer specific, psychological, nutritional, and epithelial). Across these two dimensions, the specific symptoms within each of the symptom clusters were relatively similar.ConclusionsIdentification of symptom clusters in patients with lung cancer may assist with the development of more targeted symptom management interventions. Future studies are warranted to determine if symptom clusters change over a cycle of CTX in patients with lung cancer.

ContextEvidence suggests that chemotherapy-induced neuropathy (CIN) is a significant problem for cancer survivors. However, a detailed phenotypic characterization of CIN in cancer survivors is not available.ObjectivesTo evaluate between-group differences in demographic and clinical characteristics, as well as in measures of sensation, function, and postural control, in a sample of cancer survivors who received a platinum and/or a taxane-based CTX regimen and did (n = 426) and did not (n = 197) develop CIN.MethodsSurvivors completed self-report questionnaires and underwent objective testing (i.e., light touch, pain sensation, cold sensation, vibration, muscle strength, grip strength, Purdue Pegboard test, Timed Get Up and Go test, Fullerton Advanced Balance test). Parametric and nonparametric statistics were used to compare between-group differences in study outcomes.ResultsOf the 426 survivors with CIN, 4.9% had CIN only in their upper extremities, 27.0% only in their lower extremities, and 68.1% in both their upper and lower extremities. Demographic and clinical characteristics associated with CIN included the following: older age, lower annual income, higher body mass index, a higher level of comorbidity, being born prematurely, receipt of a higher cumulative dose of chemotherapy, and a poorer functional status. Survivors with CIN had worse outcomes for all of the following objective measures: light touch, pain, temperature, vibration, upper and lower extremity function, and balance.ConclusionsThis study is the first to provide a detailed phenotypic characterization of CIN in cancer survivors who received a platinum and/or a taxane compound. These data can serve as a benchmark for future studies of CIN in cancer survivors.

PurposeIn a sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer who received at least two cycles of chemotherapy (CTX), the purposes were to evaluate for inter-individual differences in the severity of sleep disturbance and determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of sleep disturbance.MethodsA total of 1331 patients completed study questionnaires in their homes, at six time points over two cycles of CTX (prior to CTX administration, approximately 1 week after CTX administration, and approximately 2 weeks after CTX administration). Questionnaires included demographic, clinical, and symptom assessments (i.e., General Sleep Disturbance Scale, Lee Fatigue Scale, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventories, Attentional Function Index). Hierarchical linear modeling based on full maximum likelihood estimation was performed.ResultsCharacteristics associated with higher initial levels of sleep disturbance included higher body mass index, poorer functional status, higher trait anxiety, higher depressive symptoms, and higher evening fatigue. Characteristics associated with the worse trajectories of sleep disturbance were higher levels of education and higher sleep disturbance at enrollment. Characteristics associated with both higher initial levels and worse trajectories of sleep disturbance were higher morning fatigue and worse attentional function.ConclusionsA large amount of inter-individual variability exists in sleep disturbance during CTX. The modifiable and non-modifiable characteristics found in this study can be used to identify higher risk patients and provide earlier interventions to reduce sleep disturbance.

PurposeFew studies have examined interindividual variability in the symptom experience of lung cancer patients. We aimed to identify the most prevalent, severe, and distressing symptoms, and risk factors associated with increased symptom burden.MethodsLung cancer patients (n = 145) reported occurrence, severity, and distress for 38 symptoms on the Memorial Symptom Assessment Scale 1 week after chemotherapy. Using multidimensional subscales, risk factors for higher global distress, physical, and psychological symptoms were evaluated using simultaneous linear regression.ResultsMean age was 64.0 years and 56.6% were female. Mean Karnofsky Performance Status score was 79.1 (SD 14.6) and mean Self-Administered Comorbidity Questionnaire score was 7.3 (SD 3.9). The most distressing and prevalent symptom was fatigue. Problems with sexual interest/activity had the highest mean severity rating. Patients with lower functional status (p = 0.001) and higher comorbidity (p = 0.02) reported higher global distress. Similarly, lower functional status (p = 0.003) and higher comorbidity (p = 0.04) were associated with a higher physical symptom burden along with lower body mass index (p = 0.02). Higher psychology symptom burden was associated with lower functional status (p = 0.01), younger age (p = 0.02), non-metastatic disease (p = 0.03), higher number of prior treatments (p = 0.04), and income (p = 0.03).ConclusionsFatigue was the most distressing and prevalent symptom among lung cancer patients receiving chemotherapy. Lower functional status was associated with a higher burden of global distress, physical, and psychological symptoms. Younger age and non-metastatic disease were additional risk factors for increased psychological symptoms. Together, these risk factors can help clinicians identify lung cancer patients at increased need for aggressive symptom management.

PurposeOne of the unanswered questions in symptom clusters research is whether the number and types of symptom clusters vary based on the dimension of the symptom experience used to create the clusters. Given that patients with breast cancer receiving chemotherapy (CTX), report between 10 and 32 concurrent symptoms and studies of symptom clusters in these patients are limited, the purpose of this study, in breast cancer patients undergoing CTX (n = 515), was to identify whether the number and types of symptom clusters differed based on whether symptom occurrence rates or symptom severity ratings were used to create the clusters.MethodsA modified version of the Memorial Symptom Assessment Scale was used to assess for the occurrence and severity of 38 symptoms, one week after the administration of CTX. Exploratory factor analysis was used to extract the symptom clusters.ResultsBoth the number and types of symptom clusters were similar using symptom occurrence rates or symptom severity ratings. Five symptom clusters were identified using symptom occurrence rates (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial). Six symptom clusters (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial, chemotherapy neuropathy) were identified using symptom severity ratings. Across the two dimensions, the specific symptoms within each of the symptom clusters were similar.ConclusionsIdentification of symptom clusters in patients with breast cancer may be useful in guiding symptom management interventions. Future studies are warranted to determine if symptom clusters remain stable over a cycle of CTX in patients with breast cancer.

Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue. Patients completed the Lee Fatigue Scale to determine morning and evening fatigue severity a total of six times over two cycles of CTX. Using a whole exome array, 309 single nucleotide polymorphisms SNPs among the 64 candidate genes that passed all quality control filters were evaluated using hierarchical linear modeling (HLM). Based on the results of the HLM analyses, the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/signal transducers and activators of transcription (JAK/STAT, 10 genes); mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms in six genes from the cytokine (2 genes); inflammasome (2 genes); and NFkB (2 genes) pathways were associated with both morning and evening fatigue. Polymorphisms in six genes from the inflammasome (1 gene); JAK/STAT (1 gene); and NFkB (4 genes) pathways were associated with only morning fatigue. Polymorphisms in three genes from the inflammasome (2 genes) and the NFkB (1 gene) pathways were associated with only evening fatigue. Taken together, these findings add to the growing body of evidence that suggests that morning and evening fatigue are distinct symptoms.

BackgroundPotassium (K) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K channel candidate genes and the development of secondary lymphedema (LE).ObjectiveThe study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K channel genes.MethodsUpper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics.ResultsPatients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K channel gene (KCNA1 rs4766311), four in two inward-rectifying K channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K channel gene (KCNK3 rs1662988) were associated with LE.DiscussionThese preliminary findings suggest that K channel genes play a role in the development of secondary LE.

BackgroundApproximately 28% of patients with gastrointestinal (GI) cancers will receive targeted therapy (TT) because of the associated increases in survival. Only four studies have examined the symptom experience of these patients. To date, no studies have evaluated for differences in symptom occurrence, severity, and distress between patients who received chemotherapy (CTX) alone (n=304) or CTX with TT (n=93).MethodsPatients completed self-report questionnaires, approximately one week after they received CTX. A modified version of the Memorial Symptom Assessment Scale (MSAS) was used to obtain data on symptom occurrence, severity, and distress. Binary logistic regression analyses were used to test for differences in symptom occurrence rates between the two treatment groups. Ordinal logistic regression analyses were used to test for differences in severity and distress ratings between the two treatment groups.ResultsPatients who received CTX with TT were significantly younger (P=0.009); were diagnosed with cancer longer (P=0.004); had a higher number of prior treatments (P=0.024); had metastatic disease, specifically to the liver (P

ObjectiveTotal knee arthroplasty is a painful procedure. No studies have evaluated modifiable predictors of acute postoperative pain trajectories during hospitalization.MethodsConsecutive patients (N = 188) were enrolled in a longitudinal cohort study and completed a demographic questionnaire, as well as the Brief Pain Inventory, Hospital Depression and Anxiety Scale, Lee Fatigue Scale, Fatigue Severity Scale, and Brief Illness Perception Questionnaire on the day before surgery. Clinical data were extracted from medical records.Setting and patientsEach patient completed a pain diary that assessed pain at rest and with activity, and hours per day in pain every evening from day of surgery until postoperative day 3. Using hierarchical linear modeling, we investigated which demographic, clinical, symptom, and psychological characteristics predicted initial levels as well as the trajectories of acute pain at rest and with activity, and hours per day in pain.ResultsHigher levels of all three acute pain characteristics on the day of surgery resulted in worse trajectories. Higher pain scores with rest and with activity on the day of surgery were associated with more days with femoral block, higher average dose of opioids, and higher emotional response to osteoarthritis. Higher number of comorbidities, higher average dose of opioids, and lower perceived control predicted more hours per day in pain on the day of surgery.ConclusionsThis study identified several potentially modifiable predictors of worsening pain trajectories following total knee arthroplasty. Optimal pain management warrants identification of these high-risk patients and treatment of modifiable risk factors.

BackgroundFatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability.PurposeStudy purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics.MethodsOutpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles.ResultsFour distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment.ConclusionsFindings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions.

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10–15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2–4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low LPS on LTP involve the oxysterol, 25-hydroxycholesterol, akin to high LPS. Effects of high LPS on LTP are blocked by inhibiting synthesis of 5α-reduced neurosteroids, indicating that neurosteroids mediate LTP inhibition. 5α-Neurosteroids also have anti-inflammatory effects, and we found that exogenous allopregnanolone (AlloP), a key 5α-reduced steroid, prevented effects of low but not high LPS on LTP. We also found that activation of TLR2, TLR3 and TLR7 inhibited LTP and that AlloP prevented the effects of TLR2 and TLR7, but not TLR3. The enantiomer of AlloP, a steroid that has anti-inflammatory actions but low activity at GABAA receptors, prevented LTP inhibition by TLR2, TLR3 and TLR7. In vivo, both AlloP enantiomers prevented LPS-induced learning defects. These studies indicate that neurosteroids play complex roles in network effects of acute neuroinflammation and have potential importance for development of AlloP analogues as therapeutic agents. [ABSTRACT FROM AUTHOR]

ContextLittle is known about the phenotypic and molecular characteristics associated with changes over time in fatigue and lack of energy in patients with breast cancer.ObjectivesThe aim of this study was to identify subgroups (i.e., latent classes) of women with distinct fatigue and energy trajectories; evaluate for differences in phenotypic characteristics between the latent classes for fatigue and energy; and evaluate for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators and latent class membership.MethodsPatients were enrolled before and followed for six months after breast cancer surgery. Latent class analyses were done to identify subgroups of patients with distinct fatigue and energy trajectories. Candidate gene analyses were done to identify cytokine genes associated with these two symptoms.ResultsFor both fatigue and lack of energy, two distinct latent classes were identified. Phenotypic characteristics associated with the higher fatigue class were younger age, higher education, lower Karnofsky Performance Status score, higher comorbidity, higher number of lymph nodes removed, and receipt of chemotherapy (CTX). Polymorphisms in interleukin (IL) 1β and IL10 were associated with membership in the higher fatigue class. Phenotypic characteristics associated with the lower energy class included: a lower Karnofsky Performance Status score and a higher comorbidity score. A polymorphism in IL1R1 was associated with membership in the lower energy class.ConclusionWithin each latent class, the severity of fatigue and decrements in energy were relatively stable over the first six months after breast cancer surgery. Distinct phenotypic characteristics and genetic polymorphisms were associated with membership in the higher fatigue and lower energy classes.

PurposeNot all oncology patients and their family caregivers (FCs) experience the same quality of life (QOL). The purposes of this study were to identify latent classes of oncology patients (n = 168) and their FCs (n = 85) with distinct physical, psychological, social, and spiritual well-being trajectories from prior to through 4 months after the completion of radiation therapy and to evaluate for demographic, clinical, and genetic characteristics that distinguished between these latent classes.MethodsUsing growth mixture modeling, two latent classes were found for three (i.e., physical, psychological, and social well-being) of the four QOL domains evaluated.ResultsAcross these three domains, the largest percentage of participants reported relatively high well-being scores across the 6 months of the study. Across these three QOL domains, patients and FCs who were younger, female, belonged to an ethnic minority group, had children at home, had multiple comorbid conditions, or had a lower functional status, were more likely to be classified in the lower QOL class. The social well-being domain was the only domain that had a polymorphism in nuclear factor kappa beta 2 (NFKB2) associated with latent class membership. Carrying one or two doses of the rare allele for rs7897947 was associated with a 54 % decrease in the odds of belonging to the lower social well-being class [OR (95 % CI) = .46 (.21, .99), p = .049].ConclusionsThese findings suggest that a number of phenotypic and molecular characteristics contribute to differences in QOL in oncology patients and their FCs.

ObjectiveThe purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment.DesignProspective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function.ResultsWomen had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments.ConclusionSome of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women.

ObjectiveThe number of older adults with cancer is increasing. Given the limited amount of research and the inconsistent findings regarding age differences in common physical symptoms associated with cancer and its treatments, the purposes of this study, in a sample of oncology outpatients receiving chemotherapy (CTX), were to evaluate for age differences in demographic and clinical characteristics, as well as in occurrence rates of and severity ratings for fatigue, decrements in energy, and sleep disturbance. In addition, using regression analysis techniques, within and across age groups, demographic and clinical characteristics associated with the severity of each symptom were evaluated.MethodsPatients (n = 1343) were dichotomized into younger (

Haplodeficiency of the microglia gene TREM2 increases risk for late-onset Alzheimer's disease (AD) but the mechanisms remain uncertain. To investigate this, we used high-resolution confocal and super-resolution (STORM) microscopy in AD-like mice and human AD tissue. We found that microglia processes, rich in TREM2, tightly surround early amyloid fibrils and plaques promoting their compaction and insulation. In Trem2- or DAP12-haplodeficient mice and in humans with R47H TREM2 mutations, microglia had a markedly reduced ability to envelop amyloid deposits. This led to an increase in less compact plaques with longer and branched amyloid fibrils resulting in greater surface exposure to adjacent neurites. This was associated with more severe neuritic tau hyperphosphorylation and axonal dystrophy around amyloid deposits. Thus, TREM2 deficiency may disrupt the formation of a neuroprotective microglia barrier that regulates amyloid compaction and insulation. Pharmacological modulation of this barrier could be a novel therapeutic strategy for AD.

PurposePurposes of this study were to identify subgroups of patients with distinct trajectories for morning and evening fatigue, evaluate for differences in demographic and clinical characteristics among these subgroups, and compare and contrast the predictors of subgroup membership for morning and evening fatigue.MethodsOutpatients with breast, gastrointestinal, gynecological, or lung cancer (n = 582) completed questionnaires, a total of six times over two cycles of chemotherapy (CTX). Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups.ResultsThree latent classes were identified for morning fatigue (i.e., low (31.8 %), high (51.4 %), and very high (16.8 %)) and for evening fatigue (i.e., moderate (20.0 %), high (21.8 %), and very high (58.2 %)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the low class, patients in the high and very high morning fatigue classes were younger, had a lower functional status, and higher level of comorbidity. Compared to the moderate class, patients in the very high evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity.ConclusionLPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms.

PurposeLittle is known about the prevalence of combined anxiety and depressive symptoms (CADS) in breast cancer patients. Purpose was to evaluate for differences in demographic and clinical characteristics and quality of life (QOL) prior to breast cancer surgery among women classified into one of four distinct anxiety and/or depressive symptom groups.MethodsA total of 335 patients completed measures of anxiety and depressive symptoms and QOL prior to and for 6 months following breast cancer surgery. Growth Mixture Modelling (GMM) was used to identify subgroups of women with distinct trajectories of anxiety and depressive symptoms. These results were used to create four distinct anxiety and/or depressive symptom groups. Differences in demographic, clinical, and symptom characteristics, among these groups were evaluated using analyses of variance and Chi square analyses.ResultsA total of 44.5% of patients were categorized with CADS. Women with CADS were younger, non-white, had lower performance status, received neoadjuvant or adjuvant chemotherapy, had greater difficulty dealing with their disease and treatment, and reported less support from others to meet their needs. These women had lower physical, psychological, social well-being, and total QOL scores. Higher levels of anxiety with or without subsyndromal depressive symptoms were associated with increased fears of recurrence, hopelessness, uncertainty, loss of control, and a decrease in life satisfaction.ConclusionsFindings suggest that CADS occurs in a high percentage of women following breast cancer surgery and results in a poorer QOL. Assessments of anxiety and depressive symptoms are warranted prior to surgery for breast cancer.

BackgroundThe etiology of cognitive impairment in heart failure (HF) is controversial and likely multifactorial. Physicians may hesitate to prescribe evidence-based HF medication because of concerns related to potential negative changes in cognition among a population that is already frequently impaired. We conducted a study to determine if prescription of evidence-based HF medications (specifically, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blocking agents, diuretics, and aldosterone inhibitors) was associated with cognition in a large HF sample.MethodsA total of 612 patients completed baseline data collection for the Rural Education to Improve Outcomes in Heart Failure clinical trial, including information about medications. Global cognition was evaluated using the Mini-Cog.ResultsThe sample mean (SD) age was 66 (13) years, 58% were men, and 89% were white. Global cognitive impairment was identified in 206 (34%) of the 612 patients. Prescription of evidence-based HF medications was not related to global cognitive impairment in this sample. This relationship was maintained even after adjusting for potential confounders (eg, age, education, and comorbid burden).ConclusionPrescription of evidence-based HF medications is not related to low scores on a measure of global cognitive function in rural patients with HF.

ObjectivesUnrelieved postoperative pain after total knee arthroplasty (TKA) is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA.MethodsPrior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD) 0 to 4. Clinical data were extracted from medical records.ResultsSeveral factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA) were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery.DiscussionPatients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients' perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes.

ContextLittle is known about energy levels in oncology patients and their family caregivers.ObjectivesThis study sought to identify latent classes of participants, based on self-reported energy levels and evaluate for differences in phenotypic and genotypic characteristics between these classes.MethodsEnergy subscale scores from the Lee Fatigue Scale were used to determine latent class membership. Morning and evening energy scores were obtained just before, during, and for four months after the completion of radiation therapy. Genetic associations were evaluated for 15 proinflammatory and anti-inflammatory cytokine genes.ResultsTwo latent classes with distinct morning energy trajectories were identified. Participants who were younger, female, not married/partnered, black, and had more comorbidities, and a lower functional status were more likely to be in the low morning energy class. Two polymorphisms (IL2 rs1479923 and NFKB1 rs4648110) were associated with morning energy latent class membership. Two latent classes with distinct evening energy trajectories were identified. Participants who were younger and male and who had more comorbidities, decreased body weight, and a lower functional status were more likely to be in the moderate evening energy class. Five different polymorphisms (IL1R2 rs4141134, IL6 rs4719714, IL17A rs8193036, NFKB2 rs1056890, and TNFA rs1800683) were associated with evening energy latent class membership.ConclusionThis study provides preliminary evidence that decrements in morning and evening energy are associated with different phenotypic risk factors and cytokine gene variations.

Purpose/objectivesTo evaluate gender differences in quality of life (QOL), demographic, clinical, and symptom characteristics.
DesignProspective, observational.
SettingTwo radiation oncology departments in northern California.
Sample185 patients before initiation of radiation therapy (RT).
MethodsAt their RT simulation visit, patients completed a demographic questionnaire, a measure of QOL, and symptom-specific scales. Backward elimination regression analyses were conducted to determine the significant predictors of QOL
.Main research variablesQOL, gender, and 20 potential predictors
.FindingsIn women, depressive symptoms, functional status, age, and having children at home explained 64% of the variance in QOL. In men, depressive symptoms, state anxiety, number of comorbidities, being a member of a racial or ethnic minority, and age explained 70% of the variance in QOL
.ConclusionsPredictors of QOL differed by gender. Depressive symptom score was the greatest contributor to QOL in both genders.
.Implications for nursingNurses need to assess for QOL and depression at the initiation of RT. Knowledge of the different predictors of QOL may be useful in the design of gender-specific interventions to improve QOL.

ContextFatigue is the most common symptom in oncology patients during chemotherapy. Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients.ObjectivesAn evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue.MethodsA sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (n = 586) completed demographic and symptom questionnaires a total of six times over two cycles of chemotherapy. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling was used to answer the study objectives.ResultsA large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index, who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance, and depressive symptoms reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients' ethnicity and younger age.ConclusionThe modifiable risk factors that were associated with only morning fatigue were body mass index, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors.

ContextFatigue is a distressing persistent sense of physical tiredness that is not proportional to a person's recent activity. Fatigue impacts patients' treatment decisions and can limit their self-care activities. Although significant interindividual variability in fatigue severity has been noted, little is known about predictors of interindividual variability in initial levels and trajectories of evening fatigue severity in oncology patients receiving chemotherapy.ObjectivesTo determine whether demographic, clinical, and symptom characteristics were associated with initial levels and the trajectories of evening fatigue.MethodsA sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N = 586) completed demographic and symptom questionnaires a total of six times over two cycles of chemotherapy. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling was used to answer the study objectives.ResultsA large amount of interindividual variability was found in the evening fatigue trajectories. A piecewise model fit the data best. Patients who were white, diagnosed with breast, gynecological, or lung cancer, and who had more years of education, childcare responsibilities, lower functional status, and higher levels of sleep disturbance and depression reported higher levels of evening fatigue at enrollment.ConclusionThis study identified both nonmodifiable (e.g., ethnicity) and modifiable (e.g., childcare responsibilities, depressive symptoms, sleep disturbance) risk factors for more severe evening fatigue. Using this information, clinicians can identify patients at higher risk for more severe evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors.

PurposeAlthough fear of recurrence (FCR) is common among cancer survivors, it remains unclear what factors predict initial levels (e.g., prior to surgery) or changes in FCR in the post-treatment period. Among women treated for breast cancer, this study evaluated the effects of demographic, clinical, symptom, and psychosocial adjustment characteristics on the initial (preoperative) levels of FCR and trajectories of FCR over 6 months following surgery.MethodsPrior to and for 6 months following breast cancer surgery, 396 women were assessed for demographic and clinical (disease and treatment) characteristics, symptoms, psychological adjustment characteristics, and quality of life (QOL). FCR was assessed using a four-item subscale from the QOL instrument. Hierarchical linear modeling was used to examine changes in FCR scores and to identify predictors of inter-individual differences in preoperative FCR levels and trajectories over 6 months.ResultsFrom before surgery to 6 months post-operatively, women with breast cancer showed a high degree of inter-individual variability in FCR. Preoperatively, women who lived with someone, experienced greater changes in spiritual life, had higher state anxiety, had more difficulty coping, or experienced more distress due to diagnosis or distress to family members reported higher FCR scores. Patients who reported better overall physical health and higher FCR scores at enrollment demonstrated a steeper decrease in FCR scores over time.ConclusionsThese findings highlight inter-individual heterogeneity in initial levels and changes in FCR over time among women undergoing breast cancer surgery. Further work is needed to identify and provide interventions for women experiencing FCR during and after breast cancer treatment.

ContextCancer patients experience a broad range of physical and psychological symptoms as a result of their disease and its treatment. On average, these patients report 10 unrelieved and co-occurring symptoms.ObjectivesThe aims were to determine if subgroups of oncology outpatients receiving active treatment (n = 582) could be identified based on their distinct experience with 13 commonly occurring symptoms; to determine whether these subgroups differed on select demographic and clinical characteristics; and to determine if these subgroups differed on quality of life (QOL) outcomes.MethodsDemographic, clinical, and symptom data from one Australian and two U.S. studies were combined. Latent class analysis was used to identify patient subgroups with distinct symptom experiences based on self-report data on symptom occurrence using the Memorial Symptom Assessment Scale.ResultsFour distinct latent classes were identified (i.e., all low [28.0%], moderate physical and lower psych [26.3%], moderate physical and higher psych [25.4%], and all high [20.3%]). Age, gender, education, cancer diagnosis, and presence of metastatic disease differentiated among the latent classes. Patients in the all high class had the worst QOL scores.ConclusionFindings from this study confirm the large amount of interindividual variability in the symptom experience of oncology patients. The identification of demographic and clinical characteristics that place patients at risk for a higher symptom burden can be used to guide more aggressive and individualized symptom management interventions.

ContextApproximately 30% of the women report pain in the affected breast before breast cancer surgery.ObjectivesThe purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain.MethodsDifferences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time.ResultsBetween-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast before surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. The LME modeling revealed significant group effects for most outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain.ConclusionInvestigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high-risk group, are needed.

Purpose of the researchEvaluate for associations between variations in genes involved in catecholaminergic, gamma-aminobutyric acid (GABA)-ergic, and serotonergic mechanisms of neurotransmission and attentional function latent classes.Patients and methodsThis descriptive, longitudinal study was conducted at two radiation therapy departments. The sample included three latent classes of individuals with distinct trajectories of self-reported attentional function during radiation therapy, who were previously identified using growth mixture modeling among 167 oncology patients and 85 of their family caregivers. Multivariable models were used to evaluate for genotypic associations of neurotransmission genes with attentional function latent class membership, after controlling for covariates.ResultsVariations in catecholaminergic (i.e., ADRA1D rs4815675, SLC6A3 rs37022), GABAergic (i.e., SLC6A1 rs2697138), and serotonergic (i.e., HTR2A rs2296972, rs9534496) neurotransmission genes were significant predictors of latent class membership in multivariable models.ConclusionsFindings suggest that variations in genes that encode for three distinct but related neurotransmission systems are involved in alterations in attentional function. Knowledge of both phenotypic and genetic markers associated with alterations in attentional function can be used by clinicians to identify patients and family caregivers who are at higher risk for this symptom. Increased understanding of the genetic markers associated with alterations in attentional function may provide insights into the underlying mechanisms for this significant clinical problem.

ContextOlder oncology patients have unique needs associated with the many physical, psychological, and social changes associated with the aging process. The mechanisms underpinning and the impact of these changes are not well understood. Identification of clusters of symptoms is one approach that has been used to elicit hypotheses about the biological and/or psychological basis for variations in symptom experiences.ObjectivesThe purposes of this study were to identify and compare symptom clusters in younger (

PurposeAnxiety is common among cancer patients and their family caregivers (FCs) and is associated with poorer outcomes. Recently, associations between inflammation and anxiety were identified. However, the relationship between variations in cytokine genes and anxiety warrants investigation. Therefore, phenotypic and genotypic characteristics associated with trait and state anxiety were evaluated in a sample of 167 oncology patients with breast, prostate, lung, or brain cancer and 85 of their FCs.MethodsUsing multiple regression analyses, the associations between participants' demographic and clinical characteristics as well as variations in cytokine genes and trait and state anxiety were evaluated.ResultsIn the bivariate analyses, a number of phenotypic characteristics were associated with both trait and state anxiety (e.g., age, functional status). However, some associations were specific only to trait anxiety (e.g., number of comorbid conditions) or state anxiety (e.g., participation with a FC). Variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety.ConclusionsThese findings suggest that both trait and state anxiety need to be assessed in oncology patients and their FCs. Furthermore, variations in cytokine genes may contribute to higher levels of anxiety in oncology patients and their FCs.

The purpose of this study was to evaluate for differences in variations in pro- and anti-inflammatory cytokine genes between participants who were classified as having low and high levels of morning and evening fatigue and to evaluate for differences in phenotypic characteristics between these two groups. In a sample of 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their family caregivers, growth mixture modeling was used to identify latent classes of individuals based on ratings of morning and evening fatigue obtained prior to, during, and for 4 months following completion of radiation therapy. Differences in single nucleotide polymorphisms and haplotypes in 15 cytokine genes were evaluated between the latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on morning and evening fatigue class membership. Associations were found between morning fatigue and number of comorbidities as well as variations in tumor necrosis factor alpha (TNFA) rs1800629 and rs3093662. Evening fatigue was associated with caring for children at home and variations in interleukin 4 (IL4) rs2243248 and TNFA rs2229094. Younger age and lower performance status were associated with both morning and evening fatigue. These findings suggest that inflammatory mediators are associated with the development of morning and evening fatigue. However, because different phenotypic characteristics and genomic markers are associated with diurnal variations in fatigue, morning and evening fatigue may be distinct but related symptoms.

UnlabelledPersistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility.PerspectiveFor persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women.

UnlabelledInterindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction.PerspectiveSubgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

BackgroundThe diagnosis of breast cancer, in combination with the anticipation of surgery, evokes fear, uncertainty, and anxiety in most women.ObjectiveStudy purposes were to examine in patients who underwent breast cancer surgery how ratings of state anxiety changed from the time of the preoperative assessment to 6 months after surgery and to investigate whether specific demographic, clinical, symptom, and psychosocial adjustment characteristics predicted the preoperative levels of state anxiety and/or characteristics of the trajectories of state anxiety.Interventions/methodsPatients (n = 396) were enrolled preoperatively and completed the Spielberger State Anxiety inventory monthly for 6 months. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of state anxiety.ResultsPatients experienced moderate levels of anxiety before surgery. Higher levels of depressive symptoms and uncertainty about the future, as well as lower levels of life satisfaction, less sense of control, and greater difficulty coping, predicted higher preoperative levels of state anxiety. Higher preoperative state anxiety, poorer physical health, decreased sense of control, and more feelings of isolation predicted higher state anxiety scores over time.ConclusionsModerate levels of anxiety persist in women for 6 months after breast cancer surgery.Implications for practiceClinicians need to implement systematic assessments of anxiety to identify high-risk women who warrant more targeted interventions. In addition, ongoing follow-up is needed to prevent adverse postoperative outcomes and to support women to return to their preoperative levels of function.

BackgroundInterventions using mobile health (mHealth) apps have been effective in promoting healthy lifestyle behavior change and hold promise in improving health outcomes to thereby reduce health disparities among diverse racial/ethnic populations, particularly Latino and Asian American subgroups (Filipinos and Koreans) at high risk for diabetes and cardiovascular disease. Latinos and Asian Americans are avid digital technology owners and users. However, limited datasets exist regarding digital technology ownership and use, especially among specific racial/ethnic subgroups. Such information is needed to inform development of culturally tailored mHealth tools for use with lifestyle interventions promoting healthy behaviors for these at-risk racial/ethnic populations.ObjectiveThe intent of the study was to examine (1) digital technology ownership and usage, and (2) factors predicting downloading health apps for Caucasian, Filipino, Korean, and Latino American subgroups.MethodsA cross-sectional survey conducted in August 2013 through December 2013 recruited 904 participants (Caucasians n=172, Filipinos n=250, Koreans n=234, and Latinos n=248), age >18 years, from California community events, clinics, churches, and online. English, Spanish, and Korean surveys were administered via paper or online. Descriptive statistics characterized the sociodemographics and digital technology ownership/usage of the 904 participants. Differences among groups in categorical variables were examined using chi-square statistics. Logistic regression was used to determine factors predicting downloading health apps.ResultsOverall, mean age was 44 years (SD 16.1), with 64.3% (581/904) female. Only 44.7% (404/904) of all participants reported English as their primary language (Caucasian 98.3%, 169/172; Filipino 67.6%, 169/250; Korean 9.4%, 22/234, and Latino 17.7%, 44/248. Overall, mobile phone ownership was 92.8% (839/904). Compared to all groups, Koreans were more likely to own a mobile phone (82.8%, 194/234), computer (91.4%, 214/234), or tablet (55.2%, 129/234), whereas Latinos (67.5%, 167/248; 65.3%, 162/248; 24.4%, 61/248, respectively) were least likely. Internet access via mobile phones (90.5%, 818/904) was higher than computers (78.6%, 711/904). Odds of downloading health apps increased with college (OR 2.62, 95% CI 1.44-4.80) or graduate school (OR 2.93, 95% CI 1.43-6.00) compared to some high school; and family history of heart attack (OR 2.02, 95% CI 1.16-3.51). Odds of downloading health apps were reduced with: race/ethnicity, Latino (OR 0.37, 95% CI 0.20-0.69), and Korean (OR 0.52, 95% CI 0.31-0.88) compared to Caucasians; increasing age (OR 0.96, 95% CI 0.95-0.97); and completing paper surveys (OR 0.50, 95% CI 0.34-0.75).ConclusionsThis survey study uniquely targeted specific racial/ethnic subgroups. Results indicated that despite a narrowing racial/ethnic "digital divide", some disparities still exist, particularly among racial/ethnic groups with less education and whose primary language is not English. Findings will be used to inform development and evaluation of culturally tailored mHealth apps for use with interventions promoting healthy behavior change for Filipinos, Koreans, and Latinos.

BackgroundUnderstanding normal volume asymmetry is essential for accurate assessment of limb volume changes following breast cancer (BC) treatment in which lymphatic function is disrupted. The purposes of this study were to evaluate for differences in dominant and nondominant limb volumes and to evaluate for interactions between the effects of dominance and side of cancer on limb volume.Methods and resultsThis study evaluated preoperative limb volumes of 397 women enrolled in a prospective, longitudinal study of neuropathic pain and lymphedema. Volume was calculated from circumference. Limb resistance was measured with bioimpedance. Women were dichotomized into two groups: those whose cancer was on their dominant side and those whose cancer was on their nondominant side. Analyses of variance were used to evaluate for differences. In 47%, BC occurred on the side of the dominant limb. Except for the 30 to 40 centimeter (cm) limb volume segment, a main effect of dominance was found for all measures. The volume of the dominant limb was significantly greater than that of the nondominant limb. No main effects were found for side of cancer. A statistically significant interaction was found only at the 0 to 10 cm limb volume segment.ConclusionsPrior to BC treatment, the dominant limb demonstrated lower bioimpedance resistance (-2.09%) and greater total limb volume (1.12%) than the nondominant limb. Segmental volume differences were greatest at the proximal forearm segment (2.31%) and least at the proximal arm segment (0.21%). This study provides evidence that preoperative volume assessment is important due to normal variability associated with limb dominance.