human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Maintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue . Tumor necrosis factor ( TNF ) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies . We used etanercept ( TNF-decoy receptor ) to maintain dose-intensity of weekly docetaxel . PATIENTS AND METHODS Initially , 12 patients with advanced malignancies were r and omly assigned to either docetaxel 43 mg/m2 weekly alone ( cohort A ) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly ( cohort B ) . Subsequently , higher doses of docetaxel in combination with etanercept were evaluated . Pharmacokinetics ( PKs ) , nuclear factor-kappa B ( NF-kappaB ) activation , and intracellular cytokines levels were measured . Patients completed weekly question naires quantifying asthenia/fatigue . RESULTS Twenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A , and 35 of 36 doses were delivered in cohort B ( P = .055 ) . Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity , whereas no patients from cohort A received additional cycles . Escalation to docetaxel 52 mg/m2 weekly with etanercept result ed in neutropenia , not fatigue , as the limiting adverse effect , and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients . Patients r and omly selected to receive etanercept/docetaxel self-reported less fatigue ( P < .001 ) , and docetaxel PKs show no relevant influence of etanercept . NF-kappaB activation and increased expression of TNF-alpha were associated with increments in docetaxel dose . Antitumor activity was noticed exclusively in patients receiving etanercept . CONCLUSION The addition of etanercept is safe and had no impact on docetaxel concentrations . The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies BACKGROUND Flu-like symptoms are common , early transient side effects of paclitaxel chemotherapy . We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment . The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , IL-12 , and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms . METHODS Ninety patients with breast cancer were included ; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC ( 5-FU , doxorubicin , cyclophosphamide ) chemotherapy . Fifteen healthy volunteers were included as controls .  Cytokines and symptoms were measured before starting therapy , on day 3 and on the last day of one treatment cycle . RESULTS At baseline , all subjects had measurable levels of IL-8 but only 49 % had IL-12 , 45 % had IL-10 , 32 % had IL-6 , and 21 % had IL-1beta or TNF-alpha in their plasma . There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers . Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients . In the every 3-week paclitaxel group , IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline . Fatigue and flu-like symptoms were also worse on day 3 . In the weekly paclitaxel group , increase in IL-10 level correlated positively with joint pain ( p=0.003 ) . In the every 3-week paclitaxel group , increase in IL-8 level correlated positively with flu-like symptom ( p=0.008 ) . In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly . CONCLUSIONS Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma . These changes correlate with joint pain and flu-like symptoms PURPOSE To evaluate yoga 's impact on inflammation , mood , and fatigue . PATIENTS AND METHODS A r and omized controlled 3-month trial was conducted with two post-treatment assessment s of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control . The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and interleukin-1β ( IL-1β ) , and scores on the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) , the vitality scale from the Medical Outcomes Study 36-item Short Form ( SF-36 ) , and the Center for Epidemiological Studies -Depression ( CES-D ) scale . RESULTS Immediately post-treatment , fatigue was not lower ( P > .05 ) but vitality was higher ( P = .01 ) in the yoga group compared with the control group . At 3 months post-treatment , fatigue was lower in the yoga group ( P = .002 ) , vitality was higher ( P = .01 ) , and IL-6 ( P = .027 ) , TNF-α ( P = .027 ) , and IL-1β ( P = .037 ) were lower for yoga participants compared with the control group . Groups did not differ on depression at either time ( P > .2 ) . Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits ( P = .019 ; P < .001 ) , as well as vitality ( P = .016 ; P = .0045 ) , but not depression ( P > .05 ) than simple group assignment ; more frequent practice produced larger changes . At 3 months post-treatment , increasing yoga practice also led to a decrease in IL-6 ( P = .01 ) and IL-1β ( P = .03 ) production but not in TNF-α production ( P > .05 ) . CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability . If yoga dampens or limits both fatigue and inflammation , then regular practice could have substantial health benefits Background : The aim of this longitudinal study was to determine age- and sex-st and ardised prevalence rates of cancer-related fatigue in different groups of patients . Methods : This was a prospect i ve study in a cohort of N=1494 cancer patients investigating fatigue at three time points t1–t3 ( t1 : admission to hospital , t2 : discharge , t3 : half a year after t1 ) .  Fatigue was measured with the  Multidimensional Fatigue Inventory . Age- and sex-adjusted norms were derived from a representative community sample of N=2037 , using a cutoff at the 75th percentile . Results : At admission to the hospital , 32 % of the patients were classified as fatigued . At discharge , the overall prevalence rate was 40 % , and at half a year after t1 , prevalence was 34 % . Fatigue prevalence rates differed according to tumour stage , site , age , and sex of the patients . Conclusion : The prevalence rates provided by this study can be used for the planning of research and clinical routine PURPOSE / OBJECTIVES To determine the relationship between fatigue and physical activity in older patients with cancer . DESIGN Targeted analysis using data from a prospect i ve longitudinal study . SETTING A cancer care facility in southeastern Ontario , Canada . SAMPLE 440 patients , aged 65 years and older , seeking consultation for cancer treatment at a regional cancer clinic for lymphoma or leukemia or lung , breast , genitourinary , head or neck , gastrointestinal , or skin cancers . METHODS Self-report question naires were mailed to consenting participants and completed at baseline and three and six months after consultation for cancer treatment . MAIN RESEARCH VARIABLES Participants rated fatigue and physical activity and reported comorbidities and personal demographic characteristics . Clinical measures of disease and treatment factors were obtained through chart abstract ion . FINDINGS Fatigue was the most prevalent symptom reported . Higher fatigue was associated with lower physical activity levels . Physical activity level significantly predicted fatigue level , regardless of age . CONCLUSIONS Physical activity level is a modifiable factor significantly predicting cancer-related fatigue at three and six months following consultation for cancer treatment . The results suggest that physical activity may reduce fatigue in older patients with cancer . IMPLICATION S FOR NURSING Physical activity interventions should be developed and tested in older patients with cancer Background : Pain and fatigue are 2 of the most common symptoms experienced by individuals undergoing treatment for cancer . It has been hypothesized that older adults experience lower levels of severity and interference from pain and fatigue when compared with younger adults . Objective : The purpose of this study was to identify how pain and fatigue , severity , and interference may vary between younger and older adults undergoing cancer treatment over time . Methods : This study is a secondary analysis of data of 2 different r and omized controlled trials that examined the symptom experience in adults undergoing treatment for cancer .  A linear mixed model analysis was used to determine the differences based on age across 6 contacts over 8 weeks . Results : Results indicate that pain severity is significantly ( P < .01 ) related to age . Age was not found to be significantly related to the level of interference associated with pain or the severity or interference associated with fatigue . Conclusion : Symptoms of pain and fatigue are prevalent across age groups and will vary across time . Older and younger adults do not necessarily experience symptoms differently . Interference associated with pain and fatigue impacts all age groups ; interference may not be directly related to the level of severity . Implication s for Practice : This study highlights the importance of assessing both severity and interference associated with symptoms in all adults undergoing treatment for cancer . Further research is needed to better underst and the relationship between age and symptoms in individuals undergoing treatment for cancer Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging ( MRI ) studies of breast cancer patients after cancer treatment . Here we report the first prospect i ve MRI study of women undergoing treatment for breast cancer , with or without chemotherapy , as well as healthy controls . We hypothesized that chemotherapy-associated changes in gray matter density would be detectable 1 month after treatment , with partial recovery 1 year later . Participants included breast cancer patients treated with ( CTx+ , N = 17 ) or without ( CTx− , N = 12 ) chemotherapy and matched healthy controls ( N = 18 ) .  MRI scans were acquired at baseline ( after surgery but before radiation , chemotherapy , and /or anti-estrogen treatment ) , 1 month after completion of chemotherapy ( M1 ) , and 1 year later ( Y1 ) . Voxel-based morphometry ( VBM ) was used to evaluate gray matter density differences between groups and over time . There were no between-group gray matter differences at baseline . Group-by-time interactions showed declines from baseline to M1 in both cancer groups relative to controls . Within-group analyses indicated that at M1 relative to baseline the CTx+ group had decreased gray matter density in bilateral frontal , temporal , and cerebellar regions and right thalamus . Recovery was seen at Y1 in some regions , although persistent decreases were also apparent . No significant within-group changes were found in the CTx− or control groups . Findings were not attributable to recency of cancer surgery , disease stage , psychiatric symptoms , psychotropic medication use , or hormonal treatment status . This study is the first to use a prospect i ve , longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time . These gray matter alterations appear primarily related to the effects of chemotherapy , rather than solely reflecting host factors , the cancer disease process , or effects of other cancer treatments PURPOSE Cancer-related fatigue ( CRF ) is the most common symptom in patients with advanced cancer . The primary objective of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF . PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms ( ie , fatigue , pain , nausea , loss of appetite , depression , anxiety , or sleep disturbance ) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale ( ESAS ) were eligible . Patients were r and omly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days . The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue ( FACIT-F ) subscale from baseline to day 15 . Secondary outcomes included anorexia , anxiety , depression , and symptom distress scores . RESULTS A total of 84 patients were evaluable  ( dexamethasone , 43 ; placebo , 41 ) . Mean ( ± st and ard deviation ) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group ( 9 [ ± 10.3 ] v 3.1 [ ± 9.59 ] ; P = .008 ) . The improvement in FACIT-F total quality -of-life scores was also significantly better for the dexamethasone group at day 15 ( P = .0 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Maintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue . Tumor necrosis factor ( TNF ) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies . We used etanercept ( TNF-decoy receptor ) to maintain dose-intensity of weekly docetaxel . PATIENTS AND METHODS Initially , 12 patients with advanced malignancies were r and omly assigned to either docetaxel 43 mg/m2 weekly alone ( cohort A ) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly ( cohort B ) . Subsequently , higher doses of docetaxel in combination with etanercept were evaluated . Pharmacokinetics ( PKs ) , nuclear factor-kappa B ( NF-kappaB ) activation , and intracellular cytokines levels were measured . Patients completed weekly question naires quantifying asthenia/fatigue . RESULTS Twenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A , and 35 of 36 doses were delivered in cohort B ( P = .055 ) . Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity , whereas no patients from cohort A received additional cycles . Escalation to docetaxel 52 mg/m2 weekly with etanercept result ed in neutropenia , not fatigue , as the limiting adverse effect , and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients . Patients r and omly selected to receive etanercept/docetaxel self-reported less fatigue ( P < .001 ) , and docetaxel PKs show no relevant influence of etanercept . NF-kappaB activation and increased expression of TNF-alpha were associated with increments in docetaxel dose . Antitumor activity was noticed exclusively in patients receiving etanercept . CONCLUSION The addition of etanercept is safe and had no impact on docetaxel concentrations . The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies BACKGROUND Flu-like symptoms are common , early transient side effects of paclitaxel chemotherapy . We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment . The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , IL-12 , and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms . METHODS Ninety patients with breast cancer were included ; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC ( 5-FU , doxorubicin , cyclophosphamide ) chemotherapy . Fifteen healthy volunteers were included as controls .  Cytokines and symptoms were measured before starting therapy , on day 3 and on the last day of one treatment cycle . RESULTS At baseline , all subjects had measurable levels of IL-8 but only 49 % had IL-12 , 45 % had IL-10 , 32 % had IL-6 , and 21 % had IL-1beta or TNF-alpha in their plasma . There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers . Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients . In the every 3-week paclitaxel group , IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline . Fatigue and flu-like symptoms were also worse on day 3 . In the weekly paclitaxel group , increase in IL-10 level correlated positively with joint pain ( p=0.003 ) . In the every 3-week paclitaxel group , increase in IL-8 level correlated positively with flu-like symptom ( p=0.008 ) . In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly . CONCLUSIONS Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma . These changes correlate with joint pain and flu-like symptoms PURPOSE To evaluate yoga 's impact on inflammation , mood , and fatigue . PATIENTS AND METHODS A r and omized controlled 3-month trial was conducted with two post-treatment assessment s of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control . The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and interleukin-1β ( IL-1β ) , and scores on the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) , the vitality scale from the Medical Outcomes Study 36-item Short Form ( SF-36 ) , and the Center for Epidemiological Studies -Depression ( CES-D ) scale . RESULTS Immediately post-treatment , fatigue was not lower ( P > .05 ) but vitality was higher ( P = .01 ) in the yoga group compared with the control group . At 3 months post-treatment , fatigue was lower in the yoga group ( P = .002 ) , vitality was higher ( P = .01 ) , and IL-6 ( P = .027 ) , TNF-α ( P = .027 ) , and IL-1β ( P = .037 ) were lower for yoga participants compared with the control group . Groups did not differ on depression at either time ( P > .2 ) . Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits ( P = .019 ; P < .001 ) , as well as vitality ( P = .016 ; P = .0045 ) , but not depression ( P > .05 ) than simple group assignment ; more frequent practice produced larger changes . At 3 months post-treatment , increasing yoga practice also led to a decrease in IL-6 ( P = .01 ) and IL-1β ( P = .03 ) production but not in TNF-α production ( P > .05 ) . CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability . If yoga dampens or limits both fatigue and inflammation , then regular practice could have substantial health benefits Background : The aim of this longitudinal study was to determine age- and sex-st and ardised prevalence rates of cancer-related fatigue in different groups of patients . Methods : This was a prospect i ve study in a cohort of N=1494 cancer patients investigating fatigue at three time points t1–t3 ( t1 : admission to hospital , t2 : discharge , t3 : half a year after t1 ) .  Fatigue was measured with the  Multidimensional Fatigue Inventory . Age- and sex-adjusted norms were derived from a representative community sample of N=2037 , using a cutoff at the 75th percentile . Results : At admission to the hospital , 32 % of the patients were classified as fatigued . At discharge , the overall prevalence rate was 40 % , and at half a year after t1 , prevalence was 34 % . Fatigue prevalence rates differed according to tumour stage , site , age , and sex of the patients . Conclusion : The prevalence rates provided by this study can be used for the planning of research and clinical routine PURPOSE / OBJECTIVES To determine the relationship between fatigue and physical activity in older patients with cancer . DESIGN Targeted analysis using data from a prospect i ve longitudinal study . SETTING A cancer care facility in southeastern Ontario , Canada . SAMPLE 440 patients , aged 65 years and older , seeking consultation for cancer treatment at a regional cancer clinic for lymphoma or leukemia or lung , breast , genitourinary , head or neck , gastrointestinal , or skin cancers . METHODS Self-report question naires were mailed to consenting participants and completed at baseline and three and six months after consultation for cancer treatment . MAIN RESEARCH VARIABLES Participants rated fatigue and physical activity and reported comorbidities and personal demographic characteristics . Clinical measures of disease and treatment factors were obtained through chart abstract ion . FINDINGS Fatigue was the most prevalent symptom reported . Higher fatigue was associated with lower physical activity levels . Physical activity level significantly predicted fatigue level , regardless of age . CONCLUSIONS Physical activity level is a modifiable factor significantly predicting cancer-related fatigue at three and six months following consultation for cancer treatment . The results suggest that physical activity may reduce fatigue in older patients with cancer . IMPLICATION S FOR NURSING Physical activity interventions should be developed and tested in older patients with cancer Background : Pain and fatigue are 2 of the most common symptoms experienced by individuals undergoing treatment for cancer . It has been hypothesized that older adults experience lower levels of severity and interference from pain and fatigue when compared with younger adults . Objective : The purpose of this study was to identify how pain and fatigue , severity , and interference may vary between younger and older adults undergoing cancer treatment over time . Methods : This study is a secondary analysis of data of 2 different r and omized controlled trials that examined the symptom experience in adults undergoing treatment for cancer .  A linear mixed model analysis was used to determine the differences based on age across 6 contacts over 8 weeks . Results : Results indicate that pain severity is significantly ( P < .01 ) related to age . Age was not found to be significantly related to the level of interference associated with pain or the severity or interference associated with fatigue . Conclusion : Symptoms of pain and fatigue are prevalent across age groups and will vary across time . Older and younger adults do not necessarily experience symptoms differently . Interference associated with pain and fatigue impacts all age groups ; interference may not be directly related to the level of severity . Implication s for Practice : This study highlights the importance of assessing both severity and interference associated with symptoms in all adults undergoing treatment for cancer . Further research is needed to better underst and the relationship between age and symptoms in individuals undergoing treatment for cancer Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging ( MRI ) studies of breast cancer patients after cancer treatment . Here we report the first prospect i ve MRI study of women undergoing treatment for breast cancer , with or without chemotherapy , as well as healthy controls . We hypothesized that chemotherapy-associated changes in gray matter density would be detectable 1 month after treatment , with partial recovery 1 year later . Participants included breast cancer patients treated with ( CTx+ , N = 17 ) or without ( CTx− , N = 12 ) chemotherapy and matched healthy controls ( N = 18 ) .  MRI scans were acquired at baseline ( after surgery but before radiation , chemotherapy , and /or anti-estrogen treatment ) , 1 month after completion of chemotherapy ( M1 ) , and 1 year later ( Y1 ) . Voxel-based morphometry ( VBM ) was used to evaluate gray matter density differences between groups and over time . There were no between-group gray matter differences at baseline . Group-by-time interactions showed declines from baseline to M1 in both cancer groups relative to controls . Within-group analyses indicated that at M1 relative to baseline the CTx+ group had decreased gray matter density in bilateral frontal , temporal , and cerebellar regions and right thalamus . Recovery was seen at Y1 in some regions , although persistent decreases were also apparent . No significant within-group changes were found in the CTx− or control groups . Findings were not attributable to recency of cancer surgery , disease stage , psychiatric symptoms , psychotropic medication use , or hormonal treatment status . This study is the first to use a prospect i ve , longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time . These gray matter alterations appear primarily related to the effects of chemotherapy , rather than solely reflecting host factors , the cancer disease process , or effects of other cancer treatments PURPOSE Cancer-related fatigue ( CRF ) is the most common symptom in patients with advanced cancer . The primary objective of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF . PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms ( ie , fatigue , pain , nausea , loss of appetite , depression , anxiety , or sleep disturbance ) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale ( ESAS ) were eligible . Patients were r and omly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days . The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue ( FACIT-F ) subscale from baseline to day 15 . Secondary outcomes included anorexia , anxiety , depression , and symptom distress scores . RESULTS A total of 84 patients were evaluable  ( dexamethasone , 43 ; placebo , 41 ) . Mean ( ± st and ard deviation ) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group ( 9 [ ± 10.3 ] v 3.1 [ ± 9.59 ] ; P = .008 ) . The improvement in FACIT-F total quality -of-life scores was also significantly better for the dexamethasone group at day 15 ( P = .0 
    Output:
    