Neurophysiological evidence of impaired attention and working memory in untreated hematologic cancer patients.

OBJECTIVE: Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. METHODS: Hematologic cancer patients (19-80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. RESULTS: Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p < .05; Cohen's d > 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen's d = 1.1) but not controls (p = .64). CONCLUSIONS: Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. SIGNIFICANCE: Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

An explanatory model of fatigue in women receiving adjuvant breast cancer chemotherapy.

BACKGROUND: Fatigue is the most common and disturbing complaint reported by women during adjuvant breast cancer chemotherapy, but little is known about the mechanisms influencing it. OBJECTIVES: To test an explanatory model of variables influencing fatigue in women during the first three cycles of adjuvant breast cancer chemotherapy and to determine the extent to which model variables explain fatigue at treatments and predict fatigue at cycle midpoints. METHODS: A prospective, correlational design with repeated measures was used. The sample included 60 women who received chemotherapy after surgery for Stage I or II breast cancer. Fatigue was measured by the Piper Fatigue Scale. Predictor variables and measures were health and functional status (MOS SF-36), chemotherapy protocol, health-promoting lifestyle behaviors (HPLPII), nutritional status (hematocrit [Hct] and body mass index [BMI]), symptom distress (MSDS), and initial reaction to the diagnosis of cancer (RDCQ). Multiple regression was used for path analyses. RESULTS: Trimmed models of influences on fatigue were identified. At treatments, direct influences on fatigue were symptom distress (beta = 0.45-0.76, p = 0.002-0.001), chemotherapy protocol (beta = 0.26, p = 0.02), and interpersonal relations (IPR) behaviors (beta = -0.28, p = 0.02); indirect influences were confronting reaction to the diagnosis through IPR behaviors and through symptom distress. At cycle midpoints, direct influences on fatigue were symptom distress from the previous treatment (beta = 0.36-0.43, p = 0.004-0.001), physical and social function (beta = -0.31-0.50, p = 0.02-0.001), and IPR behaviors (beta = -22, p = 0.05); an indirect influence was confronting reaction to the diagnosis (through IPR behaviors). Variance explained in fatigue ranged from 42% to 62% at treatments and from 40% to 56% at cycle midpoints. CONCLUSIONS: Further testing of the model is warranted. Findings suggest that interventions to reduce symptom distress and promote health and functional status need to be developed and evaluated for effectiveness in modifying fatigue during adjuvant breast cancer chemotherapy.

Correlates of fatigue during and following adjuvant breast cancer chemotherapy: a pilot study.

PURPOSE/OBJECTIVES: To examine patterns of and relationships between activity, sleep, symptom distress, health status, and fatigue during and following adjuvant breast cancer chemotherapy with doxorubicin and cyclophosphamide. DESIGN: Prospective, descriptive, repeated measures. SETTING: Midwestern, urban, oncology clinics. SAMPLE: 14 women, ages 32-69 (X = 52.4), with stage I or II breast cancer receiving four cycles of chemotherapy. METHODS: Wrist actigraph, modified Morin Sleep Diary, Symptom Experience Scale, Medical Outcomes Study-Short Form 36, and Piper Fatigue Scale were used to collect data two days prior to and during the 21-day cycle 3, and for three days at three weeks and two months following treatment 4. MAIN RESEARCH VARIABLES: Activity, sleep, symptom distress, health status, and fatigue. FINDINGS: Fluctuating patterns of lowered activity, disturbed sleep, mild-to-moderate symptom distress, and moderate fatigue were identified. Mean activity levels ranged from 65%-80% of norms during and following treatments. Patterns of sleep (total rest, sleep latency, wake after sleep onset, and sleep efficiency) differed from established norms. Patients experienced the highest levels of fatigue and symptom distress during the first four days after treatment 3. Correlates of fatigue were greater symptom distress, lower activity, and poorer physical and social health status; variables representing disturbed sleep trended toward associations with fatigue. CONCLUSION: Activity, sleep, symptom distress, and health status cluster in patterns associated with either lower or higher fatigue. IMPLICATIONS FOR NURSING PRACTICE: Efforts to manage symptoms, remain active, and obtain quality sleep, especially in women with poorer health status, may assist in modifying fatigue.

The influence of daytime inactivity and nighttime restlessness on cancer-related fatigue.

PURPOSE/OBJECTIVES: To identify indicators involving circadian activity/rest cycles associated with higher levels of cancer-related fatigue (CRF) during the first three chemotherapy cycles after surgery for stage I/II breast cancer. DESIGN: Prospective, descriptive, repeated measures. SETTING: Midwestern oncology clinics and subjects' homes. SAMPLE: 72 women, ages 33-69 and free of unstable chronic illnesses, entered the study. Complete data were obtained from 30-47 subjects at each time. METHODS: CRF was measured using the Piper Fatigue Scale at the start and midpoint of each chemotherapy cycle. Circadian activity/rest indicators were obtained using Mini-Motionlogger wrist actigraphs for 96 hours at the start of each treatment and for 72 hours at the midpoint of each chemotherapy cycle. MAIN RESEARCH VARIABLES: Fatigue and circadian activity/rest indicators. FINDINGS: Women who were less active and had increased night awakenings reported higher CRF levels at all three cycle midpoints, with the strongest association being number of night awakenings. During the third chemotherapy cycle, women who were less active during the day, took more naps, and spent more time resting during a 24-hour period experienced higher CRF. CONCLUSIONS: Women whose sleep is disrupted at cycle midpoints are at risk for CRF. The cumulative effects of less daytime activity, more daytime sleep, and night awakenings are associated with higher CRF levels. IMPLICATIONS FOR NURSING PRACTICE: Assessment of CRF and night awakenings at the midpoints of each chemotherapy cycle and development of nursing interventions to promote daytime activity and nighttime rest are key to managing fatigue and preventing loss of biologic rhythmicity.

Virological response to protease inhibitor therapy in an HIV clinic cohort.

OBJECTIVE: New antiretroviral strategies aim to reduce plasma HIV RNA (viral load) to below the limits of detectability of assays with the objective of reducing viral replication in order to stop or reverse the pathogenic process and prevent development of drug resistance. First use of a protease inhibitor might offer the most realistic chance of achieving this aim. Our objective was to study the virological response to protease inhibitors in patients taking them for the first time. METHODS: A total of 901 patients from a large outpatient clinic were followed a mean of 15 months from the time of starting a protease inhibitor until 1 May 1998. Viral load and CD4 cell count measurements were made on average every 34 days. RESULTS: Overall there was a 79% [95% confidence interval (CI), 76-82] probability of the patients achieving a viral load < 500 copies/ml by 24 weeks after starting the protease inhibitor. In a multiple Cox regression model, those with lower initial viral load [relative hazard (RH), 0.72; P < 0.0001], higher CD4 cell count (RH, 1.07; P = 0.002), those starting other new drugs at same time as the protease inhibitor (RH, 1.46 for two versus none; P = 0.003), those who were antiretroviral-naive, and those using indinavir or nelfinavir were more likely to achieve such levels. In those 651 patients achieving viral load < 500 copies/ml within 24 weeks, there was an estimated 53% (95% CI, 51-55) probability of rebound of viral load to > 500 copies/ml by 52 weeks from the first undetectable value. Again, those who had started other new drugs at the same time as the protease inhibitor (RH, 0.57; P = 0.003 for starting two versus none) tended to experience a lower probability of viral load rebound, as did those with higher initial CD4 cell count (RH, 0.87 per 100 x 10(6)/l higher; P = 0.0007). Those who took saquinavir achieved less durable virological responses than those who took other protease inhibitors. CONCLUSIONS: Starting protease inhibitor therapy with two other new antiretroviral drugs simultaneously with protease inhibitor therapy offers a better best chance of achieving sustained viral load < 500 copies/ml than starting fewer new drugs.

Factors influencing oral cavity status during high-dose antineoplastic therapy: a secondary data analysis.

PURPOSE/OBJECTIVES: To identify factors associated with oral cavity status in patients receiving high-dose antineoplastic therapy. DESIGN: Descriptive, correlational secondary analysis. SETTING: Midwestern university oncology special care unit. SAMPLE: 50 males and females, ages 15-69. METHODS: The Oral Assessment Guide (OAG) was used to assess oral cavity status every shift throughout hospitalization. Additional data were collected by chart audit. Correlations and Cox regression analysis were performed. MAIN RESEARCH VARIABLES: Oral cavity status, absolute granulocyte count, blood urea nitrogen (BUN), creatinine, mean OAG score during the preparative regimen (prep-OAG), age, and total body irradiation (TBI). FINDINGS: Elevated BUN and creatinine, higher prep-OAG, older age, and TBI were associated with higher OAG scores. Cox analysis revealed that TBI was predictive of an OAG score > or = 16, and an OAG score > or = 18 was predictive of death by day +20. CONCLUSIONS: Patients who receive TBI and chemotherapy in combination are most likely to experience severely compromised oral cavity status. Those who are older, have poorer oral status, and have decreased renal function are at increased risk. IMPLICATIONS FOR NURSING PRACTICE: High-risk patients must be identified early, and oral assessments and care must be given consistently to decrease morbidity and potential mortality.

Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy.

PURPOSE/OBJECTIVES: To describe the patterns of fatigue and activity and rest and their relationship during adjuvant breast cancer chemotherapy. DESIGN: Prospective, descriptive, repeated measures. SETTING: Midwestern oncology clinics and subjects' homes. SAMPLE: 72 women, ages 30-69, who were receiving chemotherapy after surgery for stage I or II breast cancer. METHODS: The Piper Fatigue Scale was used to measure fatigue 48 hours after each treatment and at treatment cycle midpoints for three cycles. Wrist actigraphs were used to measure activity and rest cycles for 96 hours at each treatment and for 72 hours at each cycle midpoint. MAIN RESEARCH VARIABLES: Fatigue, activity and rest cycles, chemotherapy protocols (doxorubicin- or non-doxorubicin-based protocols). FINDINGS: Total and subscale fatigue scores were significantly different over time, with scores higher at treatments and lower at cycle midpoints. Activity levels were significantly different over time in a mirror-image pattern of fatigue. Fatigue was negatively correlated with activity levels at all times except the cycle 2 midpoint and positively correlated with awakenings at night only at the cycle 2 midpoint. Activity levels were significantly lower in women receiving doxorubicin-based protocols. CONCLUSIONS: Roller-coaster patterns of fatigue and activity have not been previously reported in this patient population. Examination of the inverse relationship between fatigue and activity will assist nurses in the development and testing of interventions to modify fatigue. IMPLICATIONS FOR NURSING PRACTICE: Women should be instructed to monitor the intensity of fatigue and encouraged to maintain activity levels balanced with efficient rest periods. Nurses can inform women that these patterns may be expected to be similar during the first three chemotherapy cycles.