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: Objective : To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS PURPOSE A prospect i ve , open-label phase II study was conducted to determine whether donepezil , a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer 's type dementia , improved cognitive functioning , mood , and quality of life ( QOL ) in irradiated brain tumor patients . PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks , then 10 mg/d for 18 weeks , followed by a washout period of 6 weeks off drug . Outcomes were assessed at baseline , 12 , 24 ( end of treatment ) , and 30 weeks ( end of wash-out ) . All tests were administered by a trained research nurse . RESULTS Of 35 patients who initiated the study , 24 patients ( mean age , 45 years ) remained on study for 24 weeks and completed all outcome assessment s. All 24 patients had a primary brain tumor , mostly low- grade glioma . Scores significantly improved between baseline ( pretreatment ) and week 24 on measures of attention/concentration , verbal memory , and figural memory and a trend for verbal fluency ( all P < .05 ) . Confused mood also improved from baseline to 24 weeks ( P = .004 ) , with a trend for fatigue and anger ( all P < .05 ) . Health-related QOL improved significantly from baseline to 24 weeks , particularly , for brain specific concerns with a trend for improvement in emotional and social functioning ( all P < .05 ) . CONCLUSION Cognitive functioning , mood , and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil .  Toxicities were minimal . We are planning a double blinded , placebo-controlled , phase III trial of donepezil to confirm these favorable results Ifosfamide and cisplatin cause urinary loss of carnitine , which is a fundamental molecule for energy production in mammalian cells . We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients . Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry . Patients were excluded if they had anaemia or other conditions thought to be causing asthenia .  Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life question naire . Treatment consisted of oral levocarnitine 4 g daily , for 7 days . Fifty patients were enrolled ; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients . In the whole group , baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 ( ±6.4 ; st and ard deviation ) and the mean plasma carnitine value was 20.9 μM ( ±6.8 ; st and ard deviation ) . After 1 week , fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 ( ±5.4 ; st and ard deviation ) ( P<.001 ) . All patients achieved normal plasma carnitine levels . Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy . In selected patients , levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue . This compound deserves further investigations in a r and omised , placebo-controlled study & NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG The aim of this study was to evaluate a low-dose regimen of megestrol acetate ( MA ; 320 mg/day ) on appetite in advanced cancer patients . Out- patients with far-advanced non-hormone responsive tumours and loss of appetite were r and omised in a phase III trial , with two consecutive phases : a 14-day double-blind placebo controlled phase ( phase A ) and a 76-day open phase ( phase B ) . During phase A , patients were treated with MA , two 160 mg tablets/day , or placebo . In phase B , the MA dose was titrated to clinical response in both groups . Appetite , food intake , body weight , performance status , mood and quality of life were evaluated with st and ardised measures ; patients ' global judgement about treatment efficacy was also requested . Of 42 patients entering the study , 33 ( 17 MA and 16 placebo ) were evaluable for efficacy . The appetite score improved significantly with MA after 7 days ( P = 0.0023 ) , and this effect was still significant at 14 days ( P = 0.0064 ) . Patients judged the treatment with MA effective in 88.2 % of cases ( 14th day ) , whilst placebo was considered effective by 25 % ( P = 0.0003 ) . None of the other measures showed significant changes during treatment . The remarkable effect on appetite evident after 7 days , without serious side-effects , shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease BACKGROUND Although the underlying pathology is initially confined to the lungs , the associated emotional responses to chronic obstructive pulmonary disease ( COPD ) contribute greatly to the result ing morbidity . The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms . METHODS We conducted a 12-week , r and omized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Question naire ( CRQ ) , an evaluative COPD -specific quality -of-life question naire , was the primary outcome . RESULTS 23 patients were r and omized and 15 completed the trial ( 8 on Paroxetine ; 7 on placebo ) . In the per- protocol analysis , we observed statistically and clinical ly significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ : emotional function ( adjusted mean difference : 1.1 ; 95 % confidence interval [ CI ] : 0.0 - 2.2 ) and mastery ( difference : 1.1 ; CI : 0.4 - 1.8 ) . Dyspnea and fatigue improved , but to an extent that did not reach statistical significance . In the intention-to-treat analysis , none of the differences in CRQ scores was significant . Paroxetine was not associated to any worsening of respiratory symptoms . CONCLUSIONS The results of this small r and omized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present . This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD The effectiveness of an 8-week , 125 mg/day intravenous course of methylprednisolone sodium succinate ( MPSS ) for improving quality of life in patients with preterminal cancer was investigated in a double-blind , placebo-controlled , multicenter study . Quality of life was assessed using the Nurses ' Observational Scale for Inpatient Evaluation ( NOSIE ) , the Linear Analog Self- Assessment Scale ( LASA ) , and the Physicians ' Global Evaluation . A total of 403 patients were enrolled : 207 were treated with MPSS and 196 were treated with placebo . MPSS was significantly more effective than placebo in improving quality of life as judged by the changes from baseline in the NOSIE and LASA total scores . ( P less than 0.05 ) and by the Physicians ' Global Evaluation ( P less than 0.001 ) . The mortality rate was similar between  MPSS-treated males ( 40.2 % ) ,  placebo-treated  males ( 35.5 % ) , and  MPSS-treated  females ( 40.0 % ) . However , the mortality rate of 27.7 % for female placebo-treated females was significantly lower than for their MPSS-treated counterparts . The reason for lower mortality among placebo-treated females is unknown and warrants further study Patients with breast cancer treated with MPA often report an improvement in appetite . Similar appetite stimulation is seen in patients treated with some corticosteroids , but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect . MPA ( 100 mg tds orally ) has therefore been compared with placebo in 60 patients with advanced malignant disease . Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy .  Patients were treated for 6 weeks and were assessed at weeks 0 , 3 and 6 for appetite , energy , mood and pain using visual analogue scales . Nutritional status was assessed by the measurement of serum proteins and anthropometrics . Karnofsky score was recorded as a measure of performance status . There was a significant improvement in appetite in the M 
    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: Objective : To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS PURPOSE A prospect i ve , open-label phase II study was conducted to determine whether donepezil , a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer 's type dementia , improved cognitive functioning , mood , and quality of life ( QOL ) in irradiated brain tumor patients . PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks , then 10 mg/d for 18 weeks , followed by a washout period of 6 weeks off drug . Outcomes were assessed at baseline , 12 , 24 ( end of treatment ) , and 30 weeks ( end of wash-out ) . All tests were administered by a trained research nurse . RESULTS Of 35 patients who initiated the study , 24 patients ( mean age , 45 years ) remained on study for 24 weeks and completed all outcome assessment s. All 24 patients had a primary brain tumor , mostly low- grade glioma . Scores significantly improved between baseline ( pretreatment ) and week 24 on measures of attention/concentration , verbal memory , and figural memory and a trend for verbal fluency ( all P < .05 ) . Confused mood also improved from baseline to 24 weeks ( P = .004 ) , with a trend for fatigue and anger ( all P < .05 ) . Health-related QOL improved significantly from baseline to 24 weeks , particularly , for brain specific concerns with a trend for improvement in emotional and social functioning ( all P < .05 ) . CONCLUSION Cognitive functioning , mood , and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil .  Toxicities were minimal . We are planning a double blinded , placebo-controlled , phase III trial of donepezil to confirm these favorable results Ifosfamide and cisplatin cause urinary loss of carnitine , which is a fundamental molecule for energy production in mammalian cells . We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients . Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry . Patients were excluded if they had anaemia or other conditions thought to be causing asthenia .  Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life question naire . Treatment consisted of oral levocarnitine 4 g daily , for 7 days . Fifty patients were enrolled ; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients . In the whole group , baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 ( ±6.4 ; st and ard deviation ) and the mean plasma carnitine value was 20.9 μM ( ±6.8 ; st and ard deviation ) . After 1 week , fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 ( ±5.4 ; st and ard deviation ) ( P<.001 ) . All patients achieved normal plasma carnitine levels . Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy . In selected patients , levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue . This compound deserves further investigations in a r and omised , placebo-controlled study & NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG The aim of this study was to evaluate a low-dose regimen of megestrol acetate ( MA ; 320 mg/day ) on appetite in advanced cancer patients . Out- patients with far-advanced non-hormone responsive tumours and loss of appetite were r and omised in a phase III trial , with two consecutive phases : a 14-day double-blind placebo controlled phase ( phase A ) and a 76-day open phase ( phase B ) . During phase A , patients were treated with MA , two 160 mg tablets/day , or placebo . In phase B , the MA dose was titrated to clinical response in both groups . Appetite , food intake , body weight , performance status , mood and quality of life were evaluated with st and ardised measures ; patients ' global judgement about treatment efficacy was also requested . Of 42 patients entering the study , 33 ( 17 MA and 16 placebo ) were evaluable for efficacy . The appetite score improved significantly with MA after 7 days ( P = 0.0023 ) , and this effect was still significant at 14 days ( P = 0.0064 ) . Patients judged the treatment with MA effective in 88.2 % of cases ( 14th day ) , whilst placebo was considered effective by 25 % ( P = 0.0003 ) . None of the other measures showed significant changes during treatment . The remarkable effect on appetite evident after 7 days , without serious side-effects , shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease BACKGROUND Although the underlying pathology is initially confined to the lungs , the associated emotional responses to chronic obstructive pulmonary disease ( COPD ) contribute greatly to the result ing morbidity . The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms . METHODS We conducted a 12-week , r and omized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Question naire ( CRQ ) , an evaluative COPD -specific quality -of-life question naire , was the primary outcome . RESULTS 23 patients were r and omized and 15 completed the trial ( 8 on Paroxetine ; 7 on placebo ) . In the per- protocol analysis , we observed statistically and clinical ly significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ : emotional function ( adjusted mean difference : 1.1 ; 95 % confidence interval [ CI ] : 0.0 - 2.2 ) and mastery ( difference : 1.1 ; CI : 0.4 - 1.8 ) . Dyspnea and fatigue improved , but to an extent that did not reach statistical significance . In the intention-to-treat analysis , none of the differences in CRQ scores was significant . Paroxetine was not associated to any worsening of respiratory symptoms . CONCLUSIONS The results of this small r and omized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present . This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD The effectiveness of an 8-week , 125 mg/day intravenous course of methylprednisolone sodium succinate ( MPSS ) for improving quality of life in patients with preterminal cancer was investigated in a double-blind , placebo-controlled , multicenter study . Quality of life was assessed using the Nurses ' Observational Scale for Inpatient Evaluation ( NOSIE ) , the Linear Analog Self- Assessment Scale ( LASA ) , and the Physicians ' Global Evaluation . A total of 403 patients were enrolled : 207 were treated with MPSS and 196 were treated with placebo . MPSS was significantly more effective than placebo in improving quality of life as judged by the changes from baseline in the NOSIE and LASA total scores . ( P less than 0.05 ) and by the Physicians ' Global Evaluation ( P less than 0.001 ) . The mortality rate was similar between  MPSS-treated males ( 40.2 % ) ,  placebo-treated  males ( 35.5 % ) , and  MPSS-treated  females ( 40.0 % ) . However , the mortality rate of 27.7 % for female placebo-treated females was significantly lower than for their MPSS-treated counterparts . The reason for lower mortality among placebo-treated females is unknown and warrants further study Patients with breast cancer treated with MPA often report an improvement in appetite . Similar appetite stimulation is seen in patients treated with some corticosteroids , but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect . MPA ( 100 mg tds orally ) has therefore been compared with placebo in 60 patients with advanced malignant disease . Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy .  Patients were treated for 6 weeks and were assessed at weeks 0 , 3 and 6 for appetite , energy , mood and pain using visual analogue scales . Nutritional status was assessed by the measurement of serum proteins and anthropometrics . Karnofsky score was recorded as a measure of performance status . There was a significant improvement in appetite in the M 
    Output:
    