***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 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 Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients . An open-label , r and omized , pilot trial examined both the general and differential efficacy of 4 weeks of methylpheni date ( MPH ) and modafinil ( MOD ) in 24 brain tumor patients . Participants completed cognitive tests and self-report measures of fatigue , sleep disturbance , mood and quality of life at baseline and after 4 weeks . Following stimulant treatment , there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention . Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy . Inconsistent , differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD . There was also evidence of a general beneficial effect on patient-reported measures of fatigue , mood , and quality of life , with no statistically significant differences between treatment arms in these measures over time . The results from this small pilot study should be interpreted with caution , but appear to warrant additional research , in larger study sample s , targeting fatigue , processing speed and executive function , and exploring different doses of stimulants . Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment BACKGROUND Fatigue , cognitive deficits , and depression are frequently reported but often undertreated symptoms that can profoundly affect daily life in patients with primary brain tumors ( PBTs ) . To evaluate the effects of the psychostimulant modafinil on fatigue , depression , health-related quality of life ( HRQOL ) , and cognitive functioning in PBT patients , we performed a multicenter , double-blind placebo-controlled crossover trial . METHODS Patients r and omly received either 6 weeks of treatment with modafinil ( up to 400 mg/day ) or 6 weeks with placebo . After a 1-week washout period , the opposite treatment was provided . Assessment s took place at baseline and immediately after the first and second condition . Patients completed self-report question naires on fatigue ( Checklist Individual Strength [ CIS ] ) , depression ( Center for Epidemiologic Studies Depression Scale [ CES-D ] ) , HRQOL ( Short-Form Health Survey [ SF-36 ] ) , and self-perceived cognitive functioning ( Medical Outcomes Study [ MOS ] ) . They also underwent comprehensive neurocognitive testing . RESULTS In total , 37 patients participated . Relative to baseline , patients reported lower fatigue severity ( CIS ) and better motivation ( CIS ) in both the modafinil ( P = .010 and P = .021 , respectively ) and the placebo condition ( P < .001 and P = .027 , respectively ) . The same held for physical health ( SF-36 Physical Component Summary score ; P = .001 and P = .008 , respectively ) , working memory ( P = .040 and P = .043 ) , and information processing capacity ( P = .036 and P = .040 ) . No improvement in depressive symptoms was found in either condition . CONCLUSIONS Modafinil did not exceed the effects of placebo with respect to symptom management . Patient accrual was slow , and relatively many patients dropped out during the trial , due mostly to side effects . Other , preferably nonpharmacologic intervention studies should be considered to improve symptom management of PBT patients 1503 Background : Patients with brain cancer develop neurobehavioral dysfunction and fatigue that compromise their performance of daily activities . We report results from evaluating the efficacy and safety of modafinil treatment for tumor/therapy sequelae in this medically fragile patient population . METHODS Patients : 21 - 65 years old with primary malignant disease or nonmalignant cerebral tumors treated with neurosurgical resection , radiotherapy , and /or chemotherapy .  Clinical Global Impression of Severity ratings of mild to severe attention/memory impairment and /or fatigue . MEASURES Trail Making ( TM ) A and B , Symbol Digit Modalities ( SDM ) , Verbal Fluency ( VF ) , Hamilton Depression Scale ( HAM-D ) , Fatigue Severity Scale ( FSS ) , Visual Analogue Fatigue Scale ( VAFS ) , Modified Fatigue Impact Scale ( MFIS ) . DESIGN Double-blind dose-controlled r and omization ( 200 or 400 mg/day modafinil in divided doses ) 3 wks ; Washout 1wk ; Open label extension 8 wks . STATISTICAL ANALYSES Changes from baseline at scheduled visits ( 1 , 3 , 4 , 8 , 12 wks ) using paired t-tests or Wilcoxon Signed Rank tests as appropriate . RESULTS Thirty patients , 63 % male , mean age ( SD ) = 45.3 ( 11.7 ) yrs were accrued from 6/03 - 10/05 .  Illness severity : moderate 3 ( 10 % ) , marked 13 ( 43 % ) , severe 14 ( 47 % ) . Tumor histology : glioblastoma multiforme 8 ( 27 % ) , anaplastic glioma 10 ( 33 % ) , low grade glioma 10 ( 33 % ) , meningioma 1 ( 3 % ) , CNS lymphoma 1 ( 3 % ) . TREATMENT neurosurgical resection 93 % , radiotherapy 87 % , chemotherapy 70 % . The table shows relationships of nine variables at baseline and 8 and 12 weeks after initiation of modafinil . Adverse events reported by ≥4 patients : headache 13 ( 42 % ) ; insomnia 8 ( 26 % ) ; dizziness 7 ( 23 % ) ; dry mouth 7 ( 23 % ) ; depressed consciousness 5 ( 16 % ) ; nausea 4 ( 13 % ) . CONCLUSIONS Results show improvement across cognitive , mood , and fatigue outcome measures . Modafinil was generally well tolerated , with a low incidence of adverse events . Greatest improvements in outcomes were observed 8 wks after baseline . [ Table : see text ] [ Table : see text ] Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients . We conducted a prospect i ve , observational study . The aim of this study was to investigate the efficacy and tolerability of topiramate ( TPM ) in brain tumor associated epilepsy . We studied 47 patients with brain tumors and epilepsy . The entire group was administered AEDs . TPM was the first therapeutic choice in 14 patients , while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug . Follow-up ranged from 3 to 48 months ( mean 16.5 months ) . Considering the final follow-up of each patient who assumed TPM for at least 3 months , we observed 45 patients : 25 were seizure free ( 55.6 % ) , 9 had a reduction of seizure frequency ( SF ) higher than 50 % ( 20 % ) and 11 were stable ( 24.4 % ) . TPM responder rate was 75.6 % . Three patients ( 6.4 % ) discontinued TPM for severe side effects ( 1 after 4 months and 2 after 1 month ) and 4 ( 8.5 % ) had mild and reversible side effects . In the group of patients who had been in therapy with other AEDs prior to entering the study ( n = 33 ) , 19 patients had side effects ( 57.6 % ) . During follow-up , the haematological parameters were in the normative ranges . Tumor-related seizures are difficult to control with AEDs ; the precise reasons for this difficulty are not yet clear . Using TPM , we obtained good seizure control with a low incidence of side effects PURPOSE Patients with gliomas often experience cognitive deficits , including problems with attention and memory . This r and omized , controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program ( CRP ) on cognitive functioning and selected quality -of-life domains in patients with gliomas . PATIENTS AND METHODS One hundred forty adult patients with low- grade and anaplastic gliomas , favorable prognostic factors , and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherl and s. Patients were r and omly assigned to an intervention group or to a waiting-list control group . The intervention incorporated both computer-based attention retraining and compensatory skills training of attention , memory , and executive functioning . Participants completed a battery of  neuropsychological  ( NP ) tests and self-report question naires on cognitive functioning , fatigue , mental health-related quality of life , and community integration at baseline , after completion of the CRP , and at 6-month follow-up . RESULTS At the immediate post-treatment evaluation , statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures . At the 6-month follow-up , the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue . Group differences in other subjective outcomes were not significant at 6 months . CONCLUSION The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue . Additional research is needed to identify which elements of the intervention are most effective Summary Endocrine functions were studied in long-term survivors of low- grade glioma treated with radiotherapy .  Hypothalamic-pituitary dysfunction has recently been reported to occur more frequently than generally considered . Because endocrine dysfunction is a treatable condition , careful testing and , if necessary , supplementary treatment may enhance quality of life . Thirteen adult patients treated with radiotherapy because of supratentorial low- grade glioma at least one year before ( range 1–11.5 years ) were tested .  Focal brain radiotherapy ( 45–61.2 Gy ) , with calculated dose to the hypothalamic-pituitary area ranging from 0 to 50 Gy ( mean 36.1 ) had been applied to all patients . Serum levels of pituitary hormones , cortisol and thyroid hormone were determined before and after stimulation with hypothalamic hormones . In 10 out of 13 patients one or more hormonal values were out of the normal range . Most disturbances were demonstrated in the pituitary-adrenal axis ( 8 patients ) and the GH-axis ( 4 patients ) . None of the patients had clinical symptomatology of adrenal , thyroid or gonadal dysfunction . Careful endocrine testing after cranial radiotherapy may reveal ( sub clinical ) hypothalamic-pituitary dysfunction in long-term survivors . Follow-up testing in these patients seems warranted PURPOSE This study was undertaken to further underst and the symptom experience and the impact of symptoms in daily life in people treated for brain tumours . METHODS A qualitative prospect i ve longitudinal design was used with 9 people who were interviewed over 4 time points ( soon after diagnosis , 3 months , 6 months and 12-months post-diagnosis ) , providing 21 interviews in total . RESULTS Key issues for these participants were ongoing fatigue , memory loss and inability to drive . Fatalistic views about the outcomes of their disease were the norm . Participants made adjustments to their lives to accommo date their functional limitations . These included making home alterations , introducing regular exercise to their lives and using complementary therapies . Their expectations did not always match with the reality of the situation , which made several participants angry and dissatisfied with health care professionals . CONCLUSIONS Iss 
    Output:
    
Although this study found a significant improvement over time in the primary outcome of fatigue , the improvement occurred after both modafinil and placebo with no significant difference in response between the two groups .
There was insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT .
More research is needed on how best to treat people with brain tumours with high fatigue