***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 see whether combined treatment with oral tacrine ( tetrahydroaminoacridine ; THA ) and lecithin improves the symptoms of patients with Alzheimer 's disease . DESIGN --Multicentre double blind , placebo controlled , r and om order crossover trial with individual determination of maximum tolerated dosage and four month follow up . SETTING --Outpatient departments at six university neurological centres . PATIENTS --67 Out patients ( 24 men , 43 women ) aged 53 - 81 ( mean 66 ( SD 7.3 ) ) selected according to the following criteria : probable Alzheimer 's disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer 's Disease and Related Disorders Association ; absence of mood disorder ; mini mental state score lower than 26 ; availability of a close relative able to complete question naires ; and informed consent of the patient or his or her closest relative , or both . INTERVENTIONS --Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover . MAIN OUTCOME MEASURES --Cognitive state as assessed by Folstein 's mini mental state rating scale , behavioural state as assessed by the Stockton geriatric rating scale , and overall state as assessed with a visual analogue scale rated by both the relative and the physician . RESULTS --Compared with placebo tacrine did not improve either the mini mental state score ( mean 14.9 ( SD 7.3 ) v 14.8 ( 7.3 ) ) or the Stockton geriatric score ( 28.2 ( 15.7 ) v 28.7 ( 17.8 ) ) , but a slight and statistically significant improvement occurred in the physician 's score on the visual analogue scale ( 6.3 ( 10.2 ) v 11.6 ( 17.9 ) ) . Seven patients dropped out . Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment . Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study . Twenty patients complained of gastrointestinal side effects . CONCLUSIONS --Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer 's disease . Moreover , these dosages may induce hepatitis ( nine of 67 patients in this series ) We treated 17 patients who had moderate to severe Alzheimer 's disease with oral tetrahydroaminoacridine ( THA ) , a central ly active anticholinesterase , in a three-phase study . In the nonblinded first phase of the study , significant improvement occurred in subjects who received the drug , as compared with their pretreatment status , on the global assessment ( P = 0.001 ) , the Orientation Test ( P = 0.001 ) , and the more sophisticated Names Learning Test ( P = 0.001 ) . During the second phase , the subjects served as their own controls in a double-blind , placebo-controlled , cross-over study in which the order of administration of the drug and placebo was r and omly assigned . Among the 14 subjects completing Phase II , THA treatment produced significantly better results than placebo on the global assessment ( P = 0.003 ) , the Orientation Test ( P = 0.004 ) , the Alzheimer 's Deficit Scale ( P = 0.003 ) , and the Names Learning Test ( P = 0.001 ) . Twelve subjects have entered Phase III , which involves long-term administration of oral THA . The average duration of treatment in these subjects at present is 12.6 months ; symptomatic improvements have occurred , and no serious side effects attributable to THA have been observed . These encouraging initial results suggest that THA may be at least temporarily useful in the long-term palliative treatment of patients with Alzheimer 's disease . We stress that further observations will be required before a clear assessment of the role of this agent can be made Objective : To assess the possible association between tacrine ( Cognex , manufactured by Parke-Davis , Morris Plains , NJ ) dose and likelihood of nursing home placement ( NHP ) or death in patients with AD . Design : A 30-week , r and omized , double-blind , placebo-controlled , parallel-group multicenter clinical trial involving 663 patients , after which patients were treated openly and followed up a minimum of 2 years later . Patients : At baseline , out patients were at least 50 years of age , met criteria for probable AD , with baseline Mini-Mental State Examination scores between 10 and 26 ( inclusive ) , were otherwise healthy , and had a caregiver who could provide assessment s and ensure medication compliance . Interventions : R and omized assignment to placebo or one of three ascending dosage regimens of tacrine over 30 weeks , followed by open label treatment for all patients who began the double-blind trial . Outcome Measures : NHP and death were examined using logistic regression . Results : Patients who remained on tacrine and were receiving doses > 80 mg/d or > 120 mg/d were less likely to have entered a nursing home than patients on lower doses ( odds ratios > 2.7 , 2.8 , respectively . ) There was a trend for lower mortality for patients receiving > 120 mg/d ( p = 0.063 ) . Conclusions : Treatment with tacrine at doses > 80 mg/d was associated with a reduced likelihood of NHP . These data demonstrate that tacrine 's 30-week effects on cognitive function and clinicians ' global ratings may generalize to effects on a major milestone of AD . Future studies should attempt to replicate these findings prospect ively . NEUROLOGY 1996;47 : 166 - Quantitative electroencephalography ( EEG ) was performed on eight of ten Alzheimer patients in a double-blind , inpatient-outpatient  tetrahydroaminoacridine ( THA ) and lecithin trial . Neuropsychological measures were related to EEG activity . Patient baseline dominant parietal rhythms ( DPRs ) and power spectral distributions differed significantly from controls . Severity of cognitive impairment was related to the degree of parietal slowing . Inpatient THA treatment result ed in increased DPR frequency in six of eight patients . Four of eight in patients demonstrated reduced power in the delta and theta b and s. During the outpatient long-term treatment phase , six of the patients were able to continue . Three of these improved significantly on tests of cognition . Two of these improved patients demonstrated DPRs with increased fre quency . One of these patients also showed a decrease in slow-wave activity . Thus , THA may accelerate DPRs while re ducing power in the slower EEG b and s. However , there appears to be only a tentative coupling between individual quantitative EEG measures and cognitive performance associated with THA administration ( J Geriatr Psychiatry Neurol 1991;4:127 - 133 ) OBJECTIVE To characterize the hepatic effects of tacrine treatment in patients with Alzheimer 's disease . DESIGN Controlled trials of tacrine therapy consisting of two blinded , parallel-group trials ; three blinded , enrichment- design trials ; and their respective open-label extensions . SETTING Multicenter clinical trials in the United States , France , and Canada . PATIENTS A total of 2446 men and women at least 50 years of age with a diagnosis of probable Alzheimer 's disease of mild to moderate severity and in good health without significant hepatic , cardiovascular , or renal disease . INTERVENTION Administration of tacrine vs placebo , with weekly measurement of serum hepatic enzymes . MAIN OUTCOME MEASURES Incidence , maximum severity , and timing of event for serum alanine aminotransferase ( ALT ) elevation . RESULTS Among the 2446 patients who received tacrine in clinical trials , ALT levels greater than the upper limit of normal ( ULN ) occurred on at least one occasion in 1203 patients ( 49 % ) , ALT levels greater than three times the ULN occurred in 621 patients ( 25 % ) , and ALT levels greater than 20 times the ULN occurred in 40 patients ( 2 % ) . The elevated ALT levels were generally asymptomatic and occurred more frequently in women than men . The mean time from initiation of tacrine treatment to first ALT level greater than three times the ULN was 50 days , and 90 % of all initial ALT levels greater than three times the ULN occurred during the first 12 weeks of treatment . Of 145 patients who discontinued tacrine treatment because of an ALT level greater than three times the ULN and were rechallenged , 127 ( 88 % ) were able to resume long-term therapy with the drug . In all instances , discontinuing tacrine completely reversed elevations in ALT levels , and no deaths related to hepatotoxicity occurred . CONCLUSIONS These data suggest that the potential for serious hepatic toxicity can be reduced through careful monitoring of ALT levels in patients who may benefit from tacrine therapy Abstract Objective : To assess the method ological quality of approaches to blinding and to h and ling of exclusions as reported in r and omised trials from one medical specialty . Design : Survey of published , parallel group r and omised controlled trials . Data sources : A r and om sample of 110 reports in which allocation was described as r and omised from the 1990 and 1991 volumes of four journals of obstetrics and gynaecology . Main outcome measures : The adequacy of the descriptions of double blinding and exclusions after r and omisation . Results : Though 31 trials reported being double blind , about twice as many could have been . Of the 31 trials only eight ( 26 % ) provided information on the protection of the allocation schedule and only five ( 16 % ) provided some written assurance of successful implemention of double blinding . Of 38 trials in which the authors provided sufficient information for readers to infer that no exclusions after r and omisation had occurred , six ( 16 % ) reported adequate allocation concealment and none stated that an intention to treat analysis had been performed . That compared with 14 ( 27 % ) and six ( 12 % ) , respectively , for the 52 trials that reported exclusions . Conclusions : Investigators could have double blinded more often . When they did double blind , they reported poorly and rarely evaluated it . Paradoxically , trials that reported exclusions seemed generally of a higher method ological st and ard than those that had no apparent exclusions . Exclusions from analysis may have been made in some of the trials in which no exclusions were reported . Editors and readers of reports of r and omised trials should underst and that flawed reporting of exclusions may often provide a misleading impression of the quality of the trial . Key messages Key messages Poor reporting of methods used for double blinding raises concerns about how effective blinding was in many of the studies Some investigators may have excluded some patients from the analysis but not reported these exclusions in their published paper Given the apparent failure to report exclusions , some of the more biased trials may be mistaken as unbiased and vice versa Investigators must pay more attention to executing and reporting their approaches to blinding and the h and ling of OBJECTIVE To determine the efficacy of tetrahydroaminoacridine ( THA ) in Alzheimer 's disease . DESIGN R and omized , double-blind , multiple crossover trial with three treatment periods , each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration . SETTING Referral-based geriatric practice in a community hospital . PATIENTS Thirty-four patients with moderate to severe Alzheimer 's disease . Subjects were included if they had stage 3 to 6 disease ( as determined by the Reisberg scale ) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin . INTERVENTIONS Fifty to 100 mg of THA daily and matched placebo . RESULTS Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study ; however , all 22 who completed the study were able to tolerate at least the minimum dose . For the 22 patients there was no clinical ly or statistically significant effect of THA on cognition , functional status or behaviour . The results for individual patients showed no subgroup of THA-responsive patients . CONCLUSION THA has no clinical ly important benefits in Alzheimer 's disease and is associated with appreciable toxic effects Abstract Objective : To assess the efficacy of tacrine and lecithin in treating Alzheimer 's disease over nine months . Design : Double blind r and omised controlled trial . Setting : Out patients clinic of university department of geriatric medicine . Subjects : 53 subjects ( 26 women , 27 men ) with probable Alzheimer 's disease . 41 completed the dose finding phase and were r and omised to treatment . 32 ( 14 tacrine , 18 placebo ) completed nine months ' treatment . Interventions : Lecithin and tacrine or lecithin and placebo for 36 weeks . Main outcome measures : Scores on neuropsychological tests sensitive to deficits in the cholinergic system ; mini-mental state score ; behaviour change ; mood ; functional state ; and stress in carers . Results - The tacrine and placebo groups were similar except that the tacrine group had a longer duration of disease ( mean 5.4 v 2.5 years in placebo group ; P=0.003 ) . Only 17 of the 32 patients could tolerate the maximum dose of tacrine ( 100 mg ) . No significant difference was found between the groups for any of the tests after nine months ' 
    Output:
    
Adverse events were more frequent at doses of > or = 100 mg/day and disappeared on discontinuation of tacrine treatment .
Tacrine shows a modest degree of efficacy among a small proportion of patients with mild to moderate AD , yet has important adverse effects which limit its clinical usefulness .
It is not known which AD patient subgroup could benefit from the treatment .