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Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.

Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

OBJECTIVES Numbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (ie, severity of numbness) and objective (ie, loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIPN, n=426) and breast cancer patients with persistent postsurgical pain (n=80). MATERIAL AND METHODS For both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale. Loss of light touch sensations in the hands and feet of patients with CIPN and in the upper arm of patients at 5 and 6 months following breast cancer surgery were assessed using Semmes Weinstein monofilaments. Loss of vibration in the hands and feet of patients with CIPN was assessed using a biothesiometer. Pearson Product Moment correlation coefficients were calculated between average pain and the number or percentage of sites with loss of light touch sensations, mean vibration thresholds, and the severity of numbness. RESULTS For both pain conditions, average pain scores were significantly correlated with objective measures of large fiber function (r=0.12 to 0.34; all P

PURPOSE: While attentional function is an extremely important patient outcome for older adults, research on changes in function in this group is extremely limited. The purposes of this study were to: identify subgroups of older patients (i.e., latent growth classes) based on changes in their level of self-reported attentional function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality of life (QOL) outcomes. METHODS: Older oncology outpatients (n=365) who were assessed for changes in attention and working memory using the Attentional Function Index a total of six times over two cycles of chemotherapy (CTX). QOL was assessed using the Medical Outcomes Study-Short Form 12 and the QOL-Patient Version Scale. Latent profile analysis (LPA) was used to identify subgroups of older adults with distinct attentional function profiles. RESULTS: Three distinct attentional functional profiles were identified (i.e., low, moderate, and high attentional function). Compared to the high class, older adults in the low and moderate attentional function classes had lower functional status scores, a worse comorbidity profile and were more likely to be diagnosed with depression. In addition, QOL scores followed an expected pattern (low class < moderate class < high attentional function class). CONCLUSIONS: Three distinct attentional function profiles were identified among a relatively large sample of older adults undergoing CTX. The phenotypic characteristics associated with membership in the low and moderate latent classes can be used by clinicians to identify high risk patients.

Given the paucity of information on local tissue water (LTW) in the upper extremity and trunk of women after breast cancer surgery, the purpose of this study was to compare tissue dielectric constant (TDC) values between the affected and unaffected sides of breast cancer survivors with and without upper extremity lymphoedema (LE). Differences in LTW were assessed using the TDC method for three sites in the upper limbs, three sites in the lateral thorax and two sites on the back. Additional measures included demographic and clinical characteristics, arm circumference and bioimpedance analysis. For the 112 survivors without LE, no differences in TDC values were found between the affected and unaffected sides for the first dorsal web space, ventral forearm and upper arm, and upper and lower back. Compared to the unaffected side, TDC values were significantly higher on the affected side for the upper, mid and lower lateral thorax. For the 78 survivors with LE, compared to the unaffected side, TDC was significantly higher on the affected side for all of the sites evaluated except the hand web space. Our findings support the use of the TDC method to detect differences in upper extremity and truncal oedema in survivors with LE following breast cancer treatment. Measurement of LTW may provide a useful method to determine truncal as well as extremity LE. The ability to detect early signs of truncal oedema may lead to pre-emptive interventions in breast cancer survivors.

CONTEXT:The most common adverse effects from neurotoxic chemotherapy are chemotherapy-induced neuropathy (CIPN), hearing loss, and tinnitus. Although associations between perceived stress and persistent pain, hearing loss, and tinnitus are documented, no studies have examined these associations in cancer survivors who received neurotoxic chemotherapy. OBJECTIVES:In this cross-sectional study, we evaluated for associations between perceived stress and the occurrence of CIPN, hearing loss, and tinnitus, in 623 adult cancer survivors who received platinum and/or taxane compounds. METHODS:Survivors completed self-report measures of hearing loss, tinnitus, and perceived stress (i.e., Impact of Events Scale-Revised [IES-R]). Separate logistic regression analyses were done for each neurotoxicity to evaluate whether each of the IES-R subscale (i.e., intrusion, avoidance, hyperarousal) and total scores made a significant independent contribution to neurotoxicity group membership. RESULTS:Of the 623 survivors in this study, 68.4% had CIPN, 34.5% reported hearing loss, and 31.0% reported tinnitus. Older age, higher body mass index, poorer functional status, being born prematurely, cancer diagnosis, and higher intrusion (P=0.013), hyperarousal (P=0.014), and total (P=0.047) IES-R scores were associated with CIPN. Older age, being male, poorer functional status, a worse comorbidity profile, and a higher IES-R hyperarousal (P=0.007) score were associated with hearing loss. Being male, having less education, a worse comorbidity profile, and a higher IES-R hyperarousal (P=0.029) score were associated with tinnitus. CONCLUSION:These findings suggest that increased levels of perceived stress are associated with the most common chemotherapy-induced neurotoxicities.

PURPOSE:Limited information is available on the impact of chemotherapy (CTX)-induced neurotoxicity on adult survivors' symptom experience and quality of life (QOL). Purposes were to describe occurrence of hearing loss and tinnitus and evaluate for differences in phenotypic characteristics and measures of sensation, balance, perceived stress, symptom burden, and QOL between survivors who received neurotoxic CTX and did (i.e., neurotoxicity group) and did not (i.e., no neurotoxicity group) develop neurotoxicity. Neurotoxicity was defined as the presence of chemotherapy-induced neuropathy (CIN), hearing loss, and tinnitus. Survivors in the no neurotoxicity group had none of these conditions. METHODS:Survivors (n = 609) completed questionnaires that evaluated hearing loss, tinnitus, stress, symptoms, and QOL. Objective measures of sensation and balance were evaluated. RESULTS:Of the 609 survivors evaluated, 68.6% did and 31.4% did not have CIN. Of the survivors without CIN, 42.4% reported either hearing loss and/or tinnitus and 48.1% of the survivors with CIN reported some form of ototoxicity. Compared to the no neurotoxicity group (n = 110), survivors in the neurotoxicity group (n = 85) were older, were less likely to be employed, had a higher comorbidity burden, and a higher symptom burden, higher levels of perceived stress, and poorer QOL (all p

Objective To evaluate the efficacy of negative pressure massage treatment (NPMT) compared with manual lymphatic drainage (MLD) in women with chronic breast cancer–related lymphedema (LE). We hypothesized that NPMT would result in greater improvements in LE and upper limb function. Design Pilot single-blinded randomized controlled trial. Setting Health sciences university. Participants Of 64 women screened, 28 met eligibility requirements (ie, >18y of age; completed active treatment for breast cancer; had unilateral arm LE for ≥1y; were not receiving LE care; had stable LE) and were randomized to the NPMT (n=15) and control groups (n=13). Interventions The intervention group received NPMT and the control group received MLD; both received twelve 60-minute sessions over 4-6 weeks. Main Outcome Measures Bioimpedance (lymphedema index [L-Dex] units]), limb volume (mL) calculated from limb circumference, and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) score. Results Outcomes were analyzed for 28 women. Compared to the MLD group, the NPMT group demonstrated greater improvement with a large effect size in L-Dex scores (P=.001; standardized mean difference [SMD]=−1.15; 95% confidence interval, −1.96 to −0.35) and interlimb volume differences (P=.038; SMD=−0.83; 95% confidence interval, −1.60 to −0.05). Differences in DASH scores were not statistically significant (P=.067). Conclusions Compared to MLD, treatment with NPMT resulted in greater improvement in L-Dex scores and interlimb volume differences in women with a duration of unilateral upper limb LE of >1 year. Our findings need to be confirmed in a larger randomized controlled trial.

Context Although physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX). Objectives Identify 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. Methods Latent 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. Results Three 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. Conclusion Almost 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.

Objective Oncology patients are increasingly encouraged to play an active role in treatment decision making. While previous studies have evaluated relationships between demographic characteristics and decision-making roles, less is known about the association of symptoms and psychological adjustment characteristics (eg, coping styles and personality traits) and decision-making roles. Methods As part of a larger study of symptom clusters, patients (n = 765) receiving chemotherapy for breast, gastrointestinal, gynecological, or lung cancer provided information on demographic, clinical, symptom, and psychological adjustment characteristics. Patient-reported treatment decision-making roles (ie, preferred role and role actually played) were assessed using the Control Preferences Scale. Differences among patients, who were classified as passive, collaborative, or active, were evaluated using χ2 analyses and analyses of variance. Results Over half (56.3%) of the patients reported that they both preferred and actually played a collaborative role. Among those patients with concordant roles, those who were older, those with less education and lower income, and those who were less resilient were more likely to prefer a passive role. Several psychological adjustment characteristics were associated with decision-making role, including coping style, personality, and fatalism. Conclusions Oncology patients' preferences for involvement in treatment decision making are associated with demographic characteristics as well as with symptoms and psychological adjustment characteristics, such as coping style and personality. These results reaffirm the complexities of predicting patients' preferences for involvement in decision making. Further study is needed to determine if role or coping style may be influenced by interventions designed to teach adaptive coping skills.

Moderate to severe fatigue occurs in 14% to 96% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n=19) and high (n=25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as up-regulated and eleven genes were identified to be down-regulated in the high evening fatigue group. Gene set analysis found 24 down-regulated and 94 simultaneously up and down perturbed pathways between the two fatigue groups. Transcript Origin Analysis found that differential expression originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar differential expression profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise, pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multi-factorial.

PurposeApproximately 20% of patients develop lymphedema (LE) following breast cancer (BC) surgery. An evaluation of distinct trajectories of volume change may improve our ability to diagnose LE sooner. The purposes of this study were to identify subgroups of women with distinct trajectories of limb volume changes following BC surgery and to evaluate for phenotypic differences among these classes.MethodsIn this prospective longitudinal study, 380 women were enrolled prior to unilateral BC surgery. Upper limb bioimpedance was measured preoperatively and serially for 1year postoperatively. Resistance ratios (RRs) were calculated. A RR of >1 indicates affected limb volume > unaffected limb volume. Latent class growth analysis (LCGA) was used to identify classes of women with distinct postoperative RR trajectories. Differences among classes were evaluated using analyses of variance and chi-square analyses.ResultsThree distinct classes were identified as follows: RR 1.05 (15.3%). Patients in the RR >1.05 class were more likely to have diabetes (p = 0.036), were more likely to have BC on their dominant side (p

Author(s): Mazor, Melissa; Cataldo, Janine K; Lee, Kathryn; Dhruva, Anand; Paul, Steven M; Smoot, Betty J; Dunn, Laura B; Levine, Jon D; Mastick, Judy; Conley, Yvette P; Miaskowski, Christine | Abstract: BackgroundBreast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery.ObjectiveThe purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery.MethodsA total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms.ResultsOf the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040).ConclusionRegardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age.Implications for practiceAs part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.

PURPOSE:The purpose of this study was to evaluate for differences in demographic, clinical, and pain characteristics, as well as measures of sensation, balance, perceived stress, symptom burden, and quality of life (QOL) among survivors who received neurotoxic chemotherapy (CTX) and who reported only chemotherapy-induced neuropathy (CIN, n=217), CIN and hearing loss (CIN/HL, n=69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n=85). We hypothesized that as the number of neurotoxicities increased, survivors would have worse outcomes. METHODS:Survivors were recruited from throughout the San Francisco Bay area. Survivors completed self-report questionnaires for pain and other symptoms, stress and QOL. Objective measures were assessed at an in person visit. RESULTS:Compared to survivors with only CIN, survivors with all three neurotoxicities were less likely to be female and less likely to report child care responsibilities. In addition, survivors with all three neurtoxicities had higher worst pain scores, greater loss of protective sensation, and worse timed get up and go scores. These survivors reported higher state anxiety and depression and poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported balance problems), significantly worse outcomes were found for the survivors with CIN/HL and CIN/HL/TIN compared to those with only CIN. CONCLUSIONS:Our findings suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are at increased risk for the most severe symptom burden, significant problems associated with sensory loss and changes in balance, as well as significant decrements in all aspects of QOL.

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.

Context Fatigue 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. Objectives To determine whether demographic, clinical, and symptom characteristics were associated with initial levels and the trajectories of evening fatigue. Methods A 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. Results A 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. Conclusion This 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.

The purposes of this study, in a sample of women with breast cancer receiving chemotherapy (CTX), were to identify subgroups of women with distinct experiences with the symptom cluster of pain, fatigue, sleep disturbance, and depressive symptoms and evaluate differences in demographic and clinical characteristics, differences in psychological symptoms, and differences in pain characteristics among these subgroups.Patients completed symptom questionnaires in the week following CTX administration. Latent class profile analysis (LCPA) was used to determine the patient subgroups.Three subgroups were identified: 140 patients (35.8 %) in the "low," 189 patients (48.3 %) in the "moderate," and 62 patients (15.9 %) in the "all high" latent class. Patients in the all high class had a lower functional status, a higher comorbidity profile, a higher symptom burden, and a poorer quality of life.Study findings provide evidence of the utility of LCPA to explain inter-individual variability in the symptom experience of patients undergoing CTX. The ability to characterize subgroups of patients with distinct symptom experiences allows for the identification of high-risk patients and may guide the design of targeted interventions that are tailored to an individual's symptom profile.

Context Most 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). Objectives Examine 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. Methods Symptom 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. Results Polymorphisms 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. Conclusion Our 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.

BACKGROUND A large amount of interindividual variability exists in the occurrence of symptoms in patients receiving chemotherapy (CTX). The purposes of the current study, which was performed in a sample of 582 oncology outpatients who were receiving CTX, were to identify subgroups of patients based on their distinct experiences with 25 commonly occurring symptoms and to identify demographic and clinical characteristics associated with subgroup membership. In addition, differences in quality of life outcomes were evaluated. METHODS Oncology outpatients with breast, gastrointestinal, gynecological, or lung cancer completed the Memorial Symptom Assessment Scale before their next cycle of CTX. Latent class analysis was used to identify subgroups of patients with distinct symptom experiences. RESULTS Three distinct subgroups of patients were identified (ie, 36.1% in Low class; 50.0% in Moderate class, and 13.9% in All High class). Patients in the All High class were significantly younger and more likely to be female and nonwhite, and had lower levels of social support, lower socioeconomic status, poorer functional status, and a higher level of comorbidity. CONCLUSIONS Findings from the current study support the clinical observation that some oncology patients experience a differentially higher symptom burden during CTX. These high-risk patients experience significant decrements in quality of life. Cancer 2014;120:2371–2378. © 2014 American Cancer Society.

Aberrant psychological and behavioral symptoms are common in patients with dementia. These symptoms have negative consequences for family caregivers, causing stress and burden. Frontotemporal dementia (FTD) symptoms cause more pronounced stress and burden on caregivers than those associated with Alzheimer dementia. In this randomized, attention control pilot study, we delivered 5-weekly, one-on-one, positive affect intervention sessions to family caregivers of people with FTD. The program, Life Enhancing Activities for Family Caregivers: LEAF was conducted in-person or by videoconference with caregivers across the United States. Measures of affect, caregiver mood, stress, distress, and caregiver burden were assessed at baseline, end of sessions, and 1 month after completion. Twenty-four caregivers (12 intervention and 12 attention control) participated. At the end of the intervention, scores on positive affect, negative affect, burden, and stress all improved in the intervention compared with the control group. These scores continued to show improvement at the assessment done 1 month after intervention. Subjects were receptive to the skills and the delivery methods. The positive emotion skill-building intervention proved feasible especially in the internet videoconference delivery format. The intervention promoted positive affect and improved psychological outcomes for family caregivers of people with FTD.

PURPOSE: Fatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue in oncology patients may identify new therapeutic targets. The objectives of this study were to evaluate the relationships between gene expression and perturbations in biological pathways and evening fatigue severity in oncology patients who received chemotherapy (CTX). METHODS: The Lee Fatigue Scale (LFS) and latent class analysis were used to identify evening fatigue phenotypes. We measured 47,214 ribonucleic acid transcripts from whole blood collected prior to a cycle of CTX. Perturbations in biological pathways associated with differential gene expression were identified from public datasets (i.e., Kyoto Encyclopedia Gene and Genomes, BioCarta). RESULTS: Patients were classified into Moderate (n=65, mean LFS score 3.1) or Very High (n=195, mean LFS score 6.4) evening fatigue groups. Compared to patients with Moderate fatigue, patients with Very High fatigue exhibited differential expression of 29 genes. A number of the perturbed pathways identified validated prior mechanistic hypotheses for fatigue, including alterations in: immune function, inflammation, neurotransmission, energy metabolism, and circadian rhythms. Based on our findings, energy metabolism was further divided into alterations in carbohydrate metabolism and skeletal muscle energy. Alterations in renal function-related pathways were identified as a potential new mechanism. CONCLUSIONS: This study identified differential gene expression and perturbed biological pathways that provide new insights into the multiple and likely inter-related mechanisms associated with evening fatigue in oncology patients.

Taxol is a common chemotherapy (CTX) drug that is associated with the development of neuropathy. Paclitaxel-induced peripheral neuropathy (PIPN) is the dose limiting toxicity of this CTX drug. Paclitaxel exerts its therapeutic effect by binding to β-tubulin, which interferes with microtubule dynamics and results in microtubule stabilization, mitotic arrest, and apoptosis of cancer cells. However, microtubules are critical for axonal function and for the transport of essential organelles to distal nerve endings. Disruption of axonal transport (AT) can lead to axonal degeneration and neuropathy. The purpose of this pilot study was to evaluate for differential expression (DE) and perturbations in AT related genes and pathways between breast cancer (BC) survivors who did (n=25) and did not (n=25) develop PIPN. Gene expression in peripheral blood was assayed using RNA-seq. BC survivors with PIPN were significantly older; more likely to be unemployed; reported lower alcohol use; had a higher BMI and a poorer functional status; and had a higher number of lower extremity sites with loss of light touch, cold, and pain sensations, and higher vibration thresholds. No between group differences were found in the cumulative dose of paclitaxel received or in the percentage of patients who had a dose reduction or delay due to PIPN. Three candidate paclitaxel metabolizing genes were DE (i.e., TUBB4B, TUBB2A, RFX2) and two pathways associated with AT were significantly perturbed (i.e., axon guidance, regulation of actin cytoskeleton). This study is the first to provide molecular evidence that a number of axonal transport mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors with persistent PIPN and suggest genes for validation and as potential therapeutic targets.

Context Although paclitaxel is one of the most commonly used drugs to treat breast, ovarian, and lung cancers, little is known about the impact of paclitaxel-induced peripheral neuropathy (PIPN) on cancer survivors. Objectives The purposes of this study were to evaluate for differences in demographic and clinical characteristics as well as measures of sensation, balance, upper extremity function, perceived stress, symptom burden, and quality of life (QOL) between survivors who received paclitaxel and did (n = 153) and did not (n = 58) develop PIPN. Methods Pain characteristics associated with PIPN are described in detail. Both subjective and objective measures were used to evaluate the impact of PIPN. Results Survivors with PIPN were significantly older, had a higher body mass index, and a worse comorbidity profile. The duration of PIPN was almost four years, and pain scores were in the moderate range. Compared with survivors without PIPN, survivors with PIPN had a higher number of upper and lower extremity sites that had lost light touch, cold, and pain sensations. Survivors with PIPN had worse upper extremity function, more problems with balance, a higher symptom burden, and higher levels of perceived stress. In addition, survivors with PIPN had worse QOL scores particularly in the domain of physical functioning. Conclusion The findings from this large descriptive study are the first to document the impact of PIPN on survivors' symptom burden, functional status, and QOL.

Context Studies on physical function trajectories in older adults during chemotherapy remain limited. Objectives The objective of this study was to determine demographic, clinical, and symptom characteristics associated with initial levels as well as trajectories of physical function over two cycles of chemotherapy in adults aged ≥65 years with breast, gastrointestinal, gynecological, or lung cancer. Methods Older adults with cancer (n = 363) who had received chemotherapy within the preceding four weeks were assessed six times over two cycles of chemotherapy using the Short Form-12 Physical Component Summary (PCS) score. Hierarchical linear modeling was used to evaluate for interindividual variability in initial levels and trajectories of PCS scores. Results Mean age was 71.4 years (SD 5.5). Mean PCS score at enrollment was 40.5 (SD .45). On average, PCS scores decreased slightly (i.e., 0.21 points) at each subsequent assessment. Lower PCS scores at enrollment were associated with older age, greater comorbidity, being unemployed, lack of regular exercise, higher morning fatigue, lower evening energy, occurrence of pain, lower trait anxiety, and lower attentional function. Only higher morning fatigue and lower enrollment PCS scores were associated with decrements in physical function over time. Conclusion While several symptoms were associated with decrements in PCS scores at enrollment in older adults with cancer receiving chemotherapy, morning fatigue was the only symptom associated with decreases in physical function over time. Regular assessments of symptoms and implementation of evidence-based interventions should be considered to maintain physical function in older adults during chemotherapy.

Decreased postural stability in people with Parkinson's disease (PD) is a major component of disability. Rehabilitation interventions are therefore targeted to improve balance, mobility, and strength. Virtual environment and gaming platforms can encourage therapeutic activity in the home and be challenging and fun. The aims of the project were to demonstrate the technical feasibility of adapting a classroom-based gait-and-balance training program to a video game platform. Ease of use, appeal, and safety of the proposed games were tested for both clinic and in-home use.This cross-sectional observational study was carried out in three phases. Modifications in the game platform were made in an iterative fashion based on feedback from subjects and the observations of clinical and design team members. The first two phases of testing were performed in a laboratory setting, and the final phase was carried out in subjects' homes.Subjects (n=20) scored the primary "Rail Runner" game 3.6 for ease of use (1=hard, 5=easy) and 3.9 for appeal (1=did not like at all, 5=liked very much). There were no safety issues encountered, and the games performed without technical flaws in the final phase of testing.A computer-based video game that incorporates therapeutic movements to improve gait and balance for people with PD was appealing to subjects and feasible for home use.

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.

Oncology patients are increasingly encouraged to play an active role in treatment decision making. While previous studies have evaluated relationships between demographic characteristics and decision-making roles, less is known about the association of symptoms and psychological adjustment characteristics (eg, coping styles and personality traits) and decision-making roles.As part of a larger study of symptom clusters, patients (n = 765) receiving chemotherapy for breast, gastrointestinal, gynecological, or lung cancer provided information on demographic, clinical, symptom, and psychological adjustment characteristics. Patient-reported treatment decision-making roles (ie, preferred role and role actually played) were assessed using the Control Preferences Scale. Differences among patients, who were classified as passive, collaborative, or active, were evaluated using χOver half (56.3%) of the patients reported that they both preferred and actually played a collaborative role. Among those patients with concordant roles, those who were older, those with less education and lower income, and those who were less resilient were more likely to prefer a passive role. Several psychological adjustment characteristics were associated with decision-making role, including coping style, personality, and fatalism.Oncology patients' preferences for involvement in treatment decision making are associated with demographic characteristics as well as with symptoms and psychological adjustment characteristics, such as coping style and personality. These results reaffirm the complexities of predicting patients' preferences for involvement in decision making. Further study is needed to determine if role or coping style may be influenced by interventions designed to teach adaptive coping skills.

The purposes of this study, in oncology outpatients receiving chemotherapy (CTX, n=926), were to: describe the occurrence of different types of pain (i.e., no pain, only non-cancer pain (NCP), only cancer pain (CP), or both CP and NCP) and evaluate for differences in demographic, clinical, and symptom characteristics, and quality of life (QOL) among the four groups. Patients completed self-report questionnaires on demographic and symptom characteristics and QOL. Patients who had pain were asked to indicate if it was or was not related to their cancer or its treatment. Medical records were reviewed for information on cancer and its treatments. In this study, 72.5% of the patients reported pain. Of the 671 who reported pain, 21.5% reported only NCP, 37.0% only CP, and 41.5% both CP and NCP. Across the three pain groups, worst pain scores were in the moderate to severe range. Compared to the no pain group, patients with both CP and NCP were significantly younger, more likely to be female, have a higher level of comorbidity and a poorer functional status. In addition, these patients reported: higher levels of depression, anxiety, fatigue, and sleep disturbance; lower levels of energy and attentional function; and poorer QOL. Patients with only NCP were significantly older than the other three groups. The most common comorbidities in the NCP group were back pain, hypertension, osteoarthritis, and depression. Unrelieved CP and NCP continue to be significant problems. Oncology outpatients need to be assessed for both CP and NCP conditions.

e22022Background: Older age is associated with an increased risk of CIN, which can precipitate falls and functional decline. However, among cancer survivors with CIN, it is unknown if patient-repor...

Context Little is known about the phenotypic and molecular characteristics associated with various domains of quality of life (QOL) in women following breast cancer surgery. Objectives In a sample of women with breast cancer (n= 398), purposes were: to identify latent classes with distinct trajectories of QOL from prior to through six months following surgery and to evaluate for differences in demographic and clinical characteristics, as well as for polymorphisms in cytokine genes, between these latent classes. Methods Latent class analyses were done to identify subgroups of patients with distinct QOL outcomes. Candidate gene analyses were done to identify cytokine gene polymorphisms associated with various domains of QOL (i.e., physical, psychological, spiritual, social). Results One latent class was identified for the psychological and spiritual domains. Two latent classes were identified for the social domain and overall QOL scores. Three latent classes were identified for the physical domain. For the physical and social domains, as well as for the overall QOL scores, distinct phenotypic characteristics (i.e., younger age, poorer functional status, higher body mass index, and receipt of adjuvant chemotherapy) and a number of cytokine gene polymorphisms (CXCL8, NFKB2, TNFSF, IL1B, IL13, and NFKB1) were associated with membership in the lower QOL classes. Conclusions Findings suggest that women experience distinctly different physical well-being, social well-being, and total QOL outcomes during and following breast cancer surgery. The genetic associations identified suggest that cytokine dysregulation influences QOL outcomes. However, specific QOL domains may be impacted by different cytokines. Key words quality of life; cytokine genes; breast cancer; polymorphism; growth mixture modelling

The neurological deterioration in dementia is associated with disturbances in circadian rhythms and rest-activity patterns. These disruptions have been documented in Alzheimer's disease (AD) and dementia with Lewy bodies but little is known about rest-activity patterns in patients with frontotemporal dementia (FTD). We report longitudinal (2 year) actigraphy results for a patient who met diagnostic criteria for FTD and his family caregiver. The subject and his family caregiver wore Actiwatches continuously for 2-weeks at 1-year intervals. The findings suggest that with disease progression there is worsening in multiple areas of rest-activity measures for the patient and a negative impact on sleep quality for the family caregiver.

With Alzheimer’s disease (AD), nighttime sleep is severely fragmented, and daytime activity is disrupted by multiple naps. Leading theories that suggest possible etiologies for the rest–activity disruption include neurological deterioration that underlies the AD process and decreased exposure to external zeitgebers that influence circadian rhythms (e.g., bright light).1 Pharmacological treatments for nighttime sleep disruption have proven only minimally effective and are often associated with unacceptable side effects that are particularly problematic in AD, because sedative medications worsen cognition and contribute to fall risk.1,2 Disturbances in the rest–activity rhythm negatively affect quality of life and are one of the primary reasons caregivers seek institutionalization of patients with AD.3,4 Patients with socially unacceptable rest–activity rhythms (i.e., active during the night and asleep during the day) pose challenges for professional and lay care providers. In an institutional environment, patients experiencing rest–activity disruption can disturb other residents at night. Daytime somnolence also prevents participation in activities and social interaction.5 Exposure of the eyes to light of sufficient intensity and duration at the appropriate time of day can have profound effects on the quality, duration, and timing of sleep. The retinohypothalamic tract mediates the effect of light on the brain, and the daily light–dark cycle is the primary synchronizer responsible for entrainment of circadian rhythms to the 24-hour day. In an institutional environment, where light levels tend to be low, residents may not be exposed to sufficient bright light to entrain to the 24-hour day.6 Therapeutic exposure to bright light has been shown to alter rest–activity rhythms. Results from earlier phases of this study indicated that morning bright-light exposure (9:30–10:30 a.m.) for 10 weeks did not induce an overall improvement in measures of sleep or rest–activity rhythm, although subjects with aberrant timing of their rest–activity rhythm showed significant improvement in rhythm stability and amplitude.7 Subjects who received morning (9:30–10:30 a.m.) or afternoon (3:30–4:30 p.m.) bright-light exposure for 10 weeks were subsequently compared with a control group, and significant stabilization of the rest–activity rhythm acrophase was found in subjects who received bright light.8 Other investigators have reported positive effects of bright light on nighttime sleep time and circadian rhythm variables in subjects with dementia.9–14 In summary, although the appropriate intensity, duration, and timing of exposure to light has not been established, research results indicate that bright light can be an effective treatment strategy for rest–activity disruption in subjects with AD. Retinal neurons respond to stimuli from the light–dark cycle and project, through the retinohypothalamic tract, to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, which acts as a pacemaker. The light–dark cycle entrains the pacemaker and its outputs, including melatonin secretion.13,15 The pacemaker thus regulates the pineal gland’s timed secretion of the neurohormone melatonin, which in turn feeds back on melatonin receptors in the SCN. This feedback may be attenuated with older age because of a reduction in serum melatonin concentration and a shift in the melatonin secretion rhythm.15–17 Melatonin secretion is even lower in patients with AD, and this decrease is evident in the early stages of the disease.16,18–20 A further attenuation of the functional feedback signal of melatonin to the SCN in AD may result from the decrease in SCN melatonin receptors.21 Exogenous administration of melatonin in the morning delays circadian rhythms, and administration in the evening advances circadian rhythms.15 Nighttime melatonin administration has also been shown to act as a soporific, increasing sleep propensity, sleep efficiency, and daytime alertness and decreasing sleep onset latency and number of nighttime awakenings.22,23 In patients with dementia, exogenous melatonin administration has been shown to improve sleep in some studies but not in others. In two community-based studies using doses of 2.5 and 10 mg of melatonin and 6 mg of slow-release melatonin, there were no significant effects on nighttime sleep variables.24,25 In nursing home subjects, 6-mg melatonin treatment resulted in better sleep and less sundowning,26 and 1 to 3 mg melatonin resulted in less daytime sleepiness and sundowning but no improvement in nighttime sleep.27 Melatonin is considered to be a safe and nontoxic molecule. In healthy elderly people, low doses (0.2–2 mg) reportedly did not produce improvement in sleep measures, but a higher dose (50 mg) produced a sleep benefit with no adverse effects.24 One study found that 5 mg administered over 1 week trended toward improving sleep in subjects with Parkinson’s disease.28 Few side effects have been observed with low-dose melatonin (≤10 mg). None were noted during the pilot study (n = 8)28 or the subsequent larger study (n = 40).29 Another study24 found in its large sample (n = 157) no difference between tolerability of melatonin and that of placebo. Long-term side effects or interactions of melatonin with other drugs are not known.30 Possible effects of exogenous melatonin in humans include antioxidant properties, drowsiness, reduced glucose tolerance, an increase in peripheral but not cerebral blood flow, and reduction in blood pressure.31–34 Treatment with simultaneous bright light and melatonin in subjects with dementia has also been studied. One study35 reported on motor restless behavior in institutionalized subjects who received bright-light therapy in combination with 2.5 mg of melatonin and bright-light therapy in combination with placebo. Subjects who received melatonin became more aggressive and exhibited more disturbed behavior than subjects who received the placebo, who exhibited less restlessness and better cooperation. In summary, the results of previous studies on the effects of light and melatonin treatments for sleep disruption in dementia have been equivocal, and treatment durations have been short (a few weeks) and sample sizes small. The purpose of this study was to investigate the effects of bright light and bright light plus melatonin as zeitgebers to strengthen input to the circadian system on actigraphic estimates of night sleep time, daytime activity, day:night sleep ratio, and rest–activity rhythm.

Context Approximately 30% of the women report pain in the affected breast before breast cancer surgery. Objectives The 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. Methods Differences 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. Results Between-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. Conclusion Investigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high-risk group, are needed.

s The Journal of Pain S5 (116) Assessment of anxiety as mediator of the relationship between sleep disturbance and pain catastrophizing in chronic pain (118) Differentiating among veterans who evidence clinically meaningful improvement in pain and those who don’t: a longitudinal analysis M Chahal, C Taub, B Darnall, M Kao, and S Mackey; Stanford University, Stanford, CA M Driscoll, A Burger, R Kerns, D Higgins, J Goulet, A Heapy, C Brandt, and S Haskell; VA Connecticut Healthcare System, West Haven, CT One of the most commonly reported issues of chronic pain sufferers is sleep disturbance, which causes decreases in productivity and quality of life for 70- 88% of the chronic pain population. 3 These patients also often suffer from anx- iety and pain catastrophizing (PC), a negative emotional and cognitive state regarding actual or anticipated pain; however, it is unclear how these psycho- logical conditions contribute to their disrupted sleep. Thus, we conducted the largest known retrospective review of sleep disturbance, anxiety, and PC scores using the Stanford-NIH Collaborative Health Outcomes Measurement Informa- tion Registry (CHOIR), 1 including measures from the Patient Reported Out- comes Measurement Information System (PROMIS). Data were obtained for 637 chronic pain patients who were seeking new medical evaluation at a ter- tiary pain clinic (390 females, 247 males, mean age=48.8). Anxiety is known to highly correlate with PC 4 and with sleep disturbance 2 thus, we hypothesized a significant relationship between patients’ sleep disturbance and PC scores and that anxiety would specifically mediate this relationship because psycho- logical and physiological responses to anxiety are known to disrupt sleep. Uni- variate analysis showed a significant direct relationship between sleep disturbance scores and PC scores (p

Context Fatigue 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. Objectives An 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. Methods A 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. Results A 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. Conclusion The 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.

Background: Disturbances in rest–activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to enable the circadian clock to entrain to the 24-hour day. The purpose of this randomized, placebo-controlled, clinical trial was to test the effectiveness of morning bright light therapy in reducing rest–activity (circadian) disruption in institutionalized patients with severe AD.Method: Subjects (n=46, mean age 84 years) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke – the Alzheimer's Disease and Related Disorders Association) AD diagnostic criteria were recruited from two large, skilled nursing facilities in San Francisco, California. The experimental group received one hour (09:30–10:30) of bright light exposure (≥2500lux in gaze direction) Monday through Friday for 10weeks. The control group received usual indoor light (150–200lux). Nighttime sleep efficiency, sleep time, wake time and number of awakenings and daytime wake time were assessed using actigraphy. Circadian rhythm parameters were also determined from the actigraphic data using cosinor analysis and nonparametric techniques. Repeated measures analysis of variance (ANOVA) was used to test the primary study hypotheses.Results and conclusion: Although significant improvements were found in subjects with aberrant timing of their rest–activity rhythm, morning bright light exposure did not induce an overall improvement in measures of sleep or the rest–activity in all treated as compared to control subjects. The results indicate that only subjects with the most impaired rest–activity rhythm respond significantly and positively to a brief (one hour) light intervention.

157 Background: CIN is the most prevalent neurologic complication of cancer treatment. Inter-individual variability exists in survivors’ reports of the factors that aggravate CIN in their hands. The purpose of this study was to identify groups of survivors with CIN in their hands based on distinct aggravating factors and evaluate for differences in demographic, clinical, symptom characteristics and quality of life (QOL) based on group membership. Methods: Cancer survivors (n = 307) who received a platinum and/or a taxane and rated their altered sensation/pain in their hands at > 3 on 0-10 scale were enrolled and completed study questionnaires, including a list of 22 factors that could make pain worse. Medical records were reviewed and sensory and motor tests were done. Latent class analysis was used to identify groups of survivors based on the occurrence rates for aggravating factors. Differences among the groups were evaluated using parametric and nonparametric statistics. Results: Three groups were identified based on occurrence rates for aggravating factors in the hands (i.e., Activity and Temperature (41.0%), Activity (8.7%), Few Factors (52.2%)). No differences were found among the groups in demographic characteristics, or sensory (light touch, temperature, pain, vibration) and motor (grip strength, pegboard) tests. Compared to the Few Factors group, the Activity and Temperature group had more comorbidities, poorer sleep, greater fatigue, and more anxious and depressive symptoms. Survivors who received a platinum compound were more likely to be in the Activity and Temperature group. Those who received a taxane compound were more likely to be in the Few Factors or Activity groups. Conclusions: Survivors who reported a higher occurrence of aggravating factors had a higher symptom burden and poorer QOL. Most differences were found between the Few Factors group and the Activity and Temperature group which may be due to the small sample size of the Activity group. Objective measures did not differ among the groups. Findings suggest that subgroups of survivors can be identified based on their reports of CIN aggravating factors.

151 Background: CIN is the most prevalent neurologic complication of cancer treatment. Inter-individual variability exists in survivors’ reports of the factors that aggravate CIN in their feet. The purpose of this study was to identify groups of survivors with CIN in their feet based on distinct aggravating factors and evaluate for differences in demographic, clinical, symptom characteristics and quality of life (QOL) based on group membership. Methods: Cancer survivors (n = 403) who received a platinum and/or a taxane and rated their altered sensation/pain in their feet at > 3 on 0-10 scale were enrolled and completed study questionnaires, including a list of 22 factors that could make pain worse. Medical records were reviewed and sensory and motor tests were done. Latent class analysis was used to identify groups of survivors based on the occurrence rates for aggravating factors. Differences among the groups were evaluated using parametric and nonparametric statistics. Results: Three groups were identified based on occurrence rates for aggravating factors in the feet (i.e., Activity and Temperature (40.2%), Activity (25.8%), Few Factors (34.0%)). No differences were found among the groups in demographic characteristics, or sensory (light touch, temperature, pain, vibration) and motor (Timed Up and Go, Fullerton Assessment of Balance) tests. Compared to the Few Factors group, the other two groups had higher BMI, worse foot pain, poorer functional status and sleep, more depressive symptoms, and lower QOL. Survivors who received a platinum compound were more likely to be in the Activity and Temperature group. Those that received a taxane compound were more likely to be in the Few Factors or Activity groups. Conclusions: Survivors who reported a higher occurrence of aggravating factors had a higher symptom burden and poorer QOL. Objective measures did not differ among the groups. Aggravating factors associated with the CTX received supports previous work in that the survivors who received platinum drugs noted cold temperatures aggravated their CIN. Findings suggest that subgroups of survivors can be identified based on their reports of CIN aggravating factors.

Context Fatigue is a common problem in oncology patients. Less is known about decrements in energy levels and the mechanisms that underlie both fatigue and energy. Objectives In patients with breast cancer, variations in neurotransmitter genes between lower and higher fatigue latent classes and between the higher and lower energy latent classes were evaluated. Methods Patients completed assessments before and monthly for six months after surgery. Growth mixture modeling was used to identify distinct latent classes for fatigue severity and energy levels. Thirty candidate genes involved in various aspects of neurotransmission were evaluated. Results Eleven single-nucleotide polymorphisms or haplotypes (i.e., ADRB2 rs1042718, BDNF rs6265, COMT rs9332377, CYP3A4 rs4646437, GALR1 rs949060, GCH1 rs3783642, NOS1 rs9658498, NOS1 rs2293052, NPY1R Haplotype A04, SLC6A2 rs17841327, and 5HTTLPR + rs25531 in SLC6A4 ) were associated with latent class membership for fatigue. Seven single-nucleotide polymorphisms or haplotypes (i.e., NOS1 rs471871, SLC6A1 rs2675163, SLC6A1 Haplotype D01, SLC6A2 rs36027, SLC6A3 rs37022, SLC6A4 rs2020942, and TAC1 rs2072100) were associated with latent class membership for energy. Three of 13 genes (i.e., NOS1 , SLC6A2 , and SLC6A4 ) were associated with latent class membership for both fatigue and energy. Conclusions Molecular findings support the hypothesis that fatigue and energy are distinct, yet related symptoms. Results suggest that a large number of neurotransmitters play a role in the development and maintenance of fatigue and energy levels in breast cancer patients.

Introduction Before and after breast cancer surgery, women have reported varying anxiety levels. Recent evidence has suggested that anxiety has a genetic basis and is associated with inflammation. The purposes of the present study were to identify the subgroups of women with distinct anxiety trajectories; to evaluate for differences in the phenotypic characteristics between these subgroups; and to evaluate for associations between polymorphisms in cytokine genes and subgroup membership. Patients and Methods Patients with breast cancer (n = 398) were recruited before surgery and followed up for 6 months. The patients completed the Spielberger State Anxiety Inventory and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify the subgroups of patients with distinct anxiety trajectories. Results Two distinct anxiety subgroups were identified. The women in the higher anxiety subgroup were younger and had a lower functional status score. Two single nucleotide polymorphisms in tumor necrosis factor-α (rs1799964, rs3093662) were associated with the higher anxiety subgroup. Conclusion The results of the present exploratory study suggest that polymorphisms in cytokine genes could partially explain the interindividual variability in anxiety. The determination of phenotypic and molecular markers associated with greater levels of anxiety can assist clinicians to identify high-risk patients and initiate appropriate interventions.

Background: Dementia is associated with disruptions in sleep and sleep quality for patients and their family caregivers. Little is known about the impact of frontotemporal dementia (FTD) on sleep. Objective: The purpose of this study was to characterize sleep in patients with FTD and their family caregivers. Methods: Twenty-two patient–caregiver dyads were enrolled: Thirteen behavioral variant FTD (bvFTD) and nine semantic dementia (SD). Sleep and sleep quality data were collected for 2 weeks using diaries and Actiwatches. Results: Patients with bvFTD and SD spent more time in bed at night compared to their caregivers. Nighttime behaviors were reported more frequently by caregivers for the bvFTD patients and strongly correlated with caregiver distress. Actigraphy data showed normal sleep efficiency and timing of the nighttime sleep period for both patients and their caregivers. Caregivers of patients with bvFTD reported poorer sleep quality compared to the SD caregivers. A greater number of bvFTD caregivers compared to SD reported negative aspects of sleep quality for themselves and used sleep medications more frequently. Conclusion: The clinical manifestations of bvFTD appear to be associated with different and more distressing impacts on the caregiver sleep quality than SD.

This study characterized daytime activity and apathy in patients with behavioral variant frontotemporal dementia (bvFTD) and semantic dementia (SD) and their family caregivers. Twenty-two patient-caregiver dyads were enrolled: 13 bvFTD and 9 SD. Data were collected on behavior and movement. Patients and caregivers wore Actiwatches for 2 weeks to record activity. We predicted that bvFTD patients would show greater caregiver report of apathy and less daytime activity compared with patients diagnosed with SD. Patients with bvFTD spent 25% of their day immobile, whereas patients with SD spent 16% of their day inactive. BvFTD caregivers spent 11% of their day immobile and SD caregivers were immobile 9% of their day. Apathy was present in all of the patients with bvFTD and in all but one patient with SD; the severity of apathy was greater in bvFTD compared with SD. Apathy correlated with caregiver emotional distress in both groups. In conclusion, apathy has been defined as a condition of diminished motivation that is difficult to operationalize. Among patients with frontotemporal dementia, apathy was associated with lower levels of activity, greater number of bouts of immobility, and longer immobility bout duration. Apathy and diminished daytime activity appeared to have an impact on the caregiver. Objective measures of behavioral output may help in formulation of a more precise definition of apathy.

e21657Background: Lung cancer patients experience a high prevalence and severity of symptoms, which often co-occur to form symptom clusters. Symptom clusters can be identified using different measu...

Some oncology outpatients experience a higher number of and more severe symptoms during chemotherapy (CTX). However, little is known about whether this high risk phenotype persists over time. Latent transition analysis (LTA) was used to examine the probability that patients remained in the same symptom class when assessed prior to the administration of and following their next dose of CTX. For the patients whose class membership remained consistent, differences in demographic and clinical characteristics, and quality of life (QOL) were evaluated. The Memorial Symptom Assessment Scale (MSAS) was used to evaluate symptom burden. LTA was used to identify subgroups of patients with distinct symptom experiences based on the occurrence of the MSAS symptoms. Of the 906 patients evaluated, 83.9% were classified in the same symptom occurrence class at both assessments. Of these 760 patients, 25.0% were classified as Low-Low, 44.1% as Moderate-Moderate and 30.9% as High-High. Compared to the Low-Low class, the other two classes were younger, more likely to be women and to report child care responsibilities, and had a lower functional status and a higher comorbidity scores. The two higher classes reported lower QOL scores. The use of LTA could assist clinicians to identify higher risk patients and initiate more aggressive interventions.

To test whether the addition of melatonin to bright-light therapy enhances the efficacy in treating rest-activity (circadian) disruption in institutionalized patients with Alzheimer's disease (AD).Randomized, controlled trial.Two nursing homes in San Francisco, California.Fifty subjects (mean age 86) with AD.Experimental subjects received 1 hour of morning light exposure (or = 2,500 lux in gaze direction) Monday to Friday for 10 weeks and 5 mg melatonin (LM, n=16) or placebo (LP, n=17) in the evening. Control subjects (n=17) received usual indoor light (150-200 lux).Nighttime sleep variables, day sleep time, day activity, day:night sleep ratio, and rest-activity parameters were determined using actigraphy.Linear mixed models were employed to test the primary study hypotheses. No significant differences in nighttime sleep variables were found between groups. At the end of the intervention, the LM group showed significant improvement in daytime somnolence as indicated by a reduction in the duration of daytime sleep, an increase in daytime activity, and an improvement in day:night sleep ratio. The LM group also evidenced a significant increase in rest-activity rhythm amplitude and goodness of fit to the cosinor model.Light treatment alone did not improve nighttime sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm. Future studies should resolve the question of whether these improvements can be attributed to melatonin or whether the two zeitgebers interact to amplify efficacy.

Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day.The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30-10.30 am) or afternoon (3.30-4.30 pm) bright light exposure (or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses.Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours.One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day.