***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 evaluate the efficacy and safety of donepezil , an acetylcholinesterase inhibitor , as a treatment for cognitive impairment and dementia in patients with Parkinson ' s disease ( PD ) . METHODS Using a r and omized , double-blind , placebo-controlled design , nine patients received placebo and seven patients received donepezil ( 2.5 - 10 mg/day ) for a mean ( SD ) duration of 15.2 ( 3.4 ) weeks . The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory , attention , psychomotor speed , and visuospatial and executive functions . Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings . Primary safety measures were motor signs and assessment s of adverse effects . RESULTS Patients on donepezil showed selective and significant ( p<0.05 ) improvement on the memory subscale of the Dementia Rating Scale . There was also a trend toward improvement on a measure of psychomotor speed and attention . There were no group differences in psychiatric status , motor function , or activities of daily living as measured at baseline or end-point . Adverse effects result ed in premature withdrawal of four patients on donepezil , two for peripheral cholinergic effects and one for increased parkinsonism . Side effects were associated with dosage increases . CONCLUSION Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment . However , variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD , especially with dosage increases BACKGROUND Vascular dementia is the second commonest form of dementia , and vascular factors contribute to the development of dementia in many patients with Alzheimer 's disease .  Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors . It has shown broad , sustained benefits in patients with Alzheimer 's disease . We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer 's disease combined with cerebrovascular disease . METHODS Eligible patients were r and omly assigned galantamine 24 mg/day ( n=396 ) or placebo ( n=196 ) in a multicentre , double-blind , 6-month trial . Primary endpoints were cognition ( Alzheimer 's disease assessment scale , cognitive subscale [ ADAS-cog ] ) and global functioning ( clinician 's interview-based impression of change plus caregiver input [ CIBIC-plus ] ) . Secondary endpoints included assessment s of activities of daily living and behavioural symptoms . Patients were monitored for adverse events . Analyses were on the basis of observed case or last observation carried forward . FINDINGS Galantamine showed greater efficacy than placebo on ADAS-cog ( galantamine change -1.7 [ SE 0.4 ] vs placebo 1.0 [ 0.5 ] ; treatment effect 2.7 points ; p<0.0001 ) and CIBIC-plus ( 213 [ 74 % ] vs 95 [ 59 % ] patients remained stable or improved , p=0.0001 ) . Activities of daily living and behavioural symptoms were also significantly improved compared with placebo ( p=0.002 and p=0.016 , respectively ) . Galantamine was well tolerated . INTERPRETATION Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients BACKGROUND Cholinergic deficits are prominent in patients who have dementia associated with Parkinson 's disease . We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients . METHODS Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson 's disease were r and omly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks . Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-cog ) and Alzheimer 's Disease Cooperative Study -Clinician 's Global Impression of Change ( ADCS-CGIC ) . Secondary clinical outcomes were the scores for the Alzheimer 's Disease Cooperative Study -Activities of Daily Living , the 10-item Neuropsychiatric Inventory , the Mini-Mental State Examination , Cognitive Drug Research power of attention tests , the Verbal Fluency test , and the Ten Point Clock-Drawing test . RESULTS A total of 541 patients were enrolled , and 410 completed the study . The outcomes were better among patients treated with rivastigmine than among those who received placebo ; however , the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer 's disease . Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog , from a baseline score of 23.8 , as compared with a 0.7-point worsening in the placebo group , from a baseline score of 24.3 ( P<0.001 ) . Clinical ly meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group , and clinical ly meaningful worsening was observed in 13.0 percent and 23.1 percent , respectively ( mean score at 24 weeks , 3.8 and 4.3 , respectively ; P=0.007 ) . Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables . The most frequent adverse events were nausea ( affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group , P<0.001 ) , vomiting ( 16.6 and 1.7 percent , P<0.001 ) , and tremor ( 10.2 and 3.9 percent , P=0.01 ) . CONCLUSIONS In this placebo-controlled study , rivastigmine was associated with moderate improvements in dementia associated with Parkinson 's disease but also with higher rates of nausea , vomiting , and tremor The efficacy of a central ly active cholinesterase inhibitor , rivastigmine tartrate ( ENA 713 ) , in patients with advanced moderate Alzheimer ’s disease ( AD ) was evaluated in a 12-month placebo-controlled study . We aim ed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease . These patients were compared with matched controls . In this study , 24 patients with advanced moderate AD received rivastigmine for 12 months . Another 20 patients received placebo . Mean daily doses of rivastigmine in the higher-dose group at 3 , 6 , 9 , and 12 months were 6.1 ± 1.0 , 8.3 ± 1.2 , 8.9 ± 1.3 , and 10.7 ± 1.6 mg/day , respectively . Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale ( ADAS-cog ) . Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog . Conversely , only 18.3 % of patients treated with rivastigmine declined by 4 or more points . Functional disabilities , as assessed using the Disability Assessment for Dementia Scale , remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients . Patients benefited from high-dose rivastigmine treatment on all outcome measures , including the Mini-Mental State Examination , Progressive Deterioration Scale , as well as the Global Deterioration Scale . Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients ( p < 0.001 ) . By 52 weeks , patients originally treated with 6–12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo . Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD OBJECTIVE The objective of this study was to compare the efficacy and safety of the moderate-affinity , uncompetitive N-methyl-d-aspartate receptor antagonist , memantine , versus placebo in patients with mild to moderate Alzheimer disease ( AD ) . METHOD This was a r and omized , double-blind , placebo-controlled clinical trial conducted at 42 U.S. sites . Participants were 403 out patients with mild to moderate AD and Mini-Mental State Examination scores of 10 - 22 r and omized to memantine  ( 20 mg/day ; N=201 ) or placebo ( N=202 ) for 24 weeks . Primary outcomes were change from baseline at 24 weeks on the Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( ADAS-cog ) , a measure of cognition , and on the Clinician 's Interview-Based Impression of Change Plus Caregiver Input ( CIBIC-Plus ) , a global measure . Secondary outcomes included change on the Neuropsychiatric Inventory ( NPI ) and the Alzheimer 's Disease Cooperative Study Activities of Daily Living Inventory ( ADCS-ADL(23 ) ) , measures of behavior and function , respectively . RESULTS Most ( 82.4 % ) participants completed the trial . Memantine result ed in significantly better outcomes than placebo on measures of cognition , global status , and behavior when based on the protocol -specified primary last observation carried forward imputation as well as a mixed-models repeated- measures approach applied to the continuous outcomes . Treatment discontinuations because of adverse events for memantine versus placebo were 19 ( 9.5 % ) and 10 ( 5.0 % ) , respectively . CONCLUSIONS These results support the safety and efficacy of memantine for the treatment of mild to moderate AD OBJECTIVE The authors examined the effect of the acetylcholinesterase inhibitor donepezil on magnetic resonance markers of neurodegeneration in Alzheimer 's disease . METHOD In this r and omized , double-blind , placebo-controlled pilot study , 67 patients with mild to moderate Alzheimer 's disease received 24 weeks of treatment with  donepezil ( 5 mg/day for the first 28 days and 10 mg/day thereafter ) or placebo . Patients were reevaluated at 6-week intervals to measure change from baseline in several outcome measures , including right , left , and total hippocampal volumes , measured with magnetic resonance imaging ; brain concentrations of N-acetylaspartate , measured with proton magnetic resonance spectroscopy ; and cognition , assessed with the Alzheimer 's Disease Assessment Scale cognitive subscale . RESULTS At some interim assessment s , mean normalized measures of N-acetylaspartate concentration tended to be higher in the donepezil-treated patients than in the patients who received placebo , but these differences were not significant at endpoint . At endpoint , the donepezil-treated patients had significantly smaller mean decreases in total and right hippocampal volumes and a smaller , nearly significant mean decrease in left hippocampal volume , compared with the placebo-treated patients . Mean Alzheimer 's Disease Assessment Scale cognitive subscale scores were improved after treatment with donepezil , relative to placebo , at weeks 6 , 12 , 18 , and 24 . CONCLUSIONS These preliminary results suggest that donepezil may have a potentially protective effect in Alzheimer 's disease . Larger , longer-term confirmatory studies of the medication 's effects are warranted OBJECTIVE To evaluate the efficacy of donepezil in patients with early-stage Alzheimer disease . DESIGN Multicenter , r and omized , double-blind , 24-week , placebo-controlled study that enrolled patients with early-stage Alzheimer disease . Patients were r and omized in an approximately 2:1 ratio to donepezil , 5 mg/d , for the first 6 weeks , with a forced escalation to 10 mg/d thereafter ( n = 96 ) , or placebo ( n = 57 ) . The primary efficacy measure was the modified Alzheimer Disease Assessment Scale-cognitive subscale . Secondary efficacy measures included the Mini-Mental State Examination , the Computerized Memory Battery Test , the Clinical Dementia Rating Scale-Sum of the Boxes , the Patient Global Assessment Scale , and the Apathy Scale . RESULTS Improvements favoring donepezil on the Alzheimer Disease Assessment Scale-cognitive subscale were found at weeks 12 and 24 and at the end point ( last observation carried forward ) ; treatment differences were 1.9 ( P = .03 ) , 2.3 ( P = .008 ) , and 2.3 ( P = .001 ) points , respectively . Improvements favoring donepezil on the Mini-Mental State Examination were found at weeks 6 , 12 , and 24 and at the end point ( last observation carried forward ) ; treatment differences were 1.4 ( P = .02 ) , 1.2 ( P = .04 ) , 1.4 ( P = .03 ) , and 1.8 ( P = .002 ) points , respectively . Donepezil-treated patients showed greater mean improvement compared with placebo-treated patients on the following Computerized Memory Battery Test subscales : facial recognition ( P = .007 in the intent-to- 
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Consistent evidence demonstrates that LMWH is superior to unfractionated heparin for the initial treatment of DVT , particularly for reducing mortality and reducing the risk for major bleeding during initial therapy .
In addition , trials of unfractionated heparin in pulmonary embolism show that many patients are subtherapeutic or supratherapeutic while receiving unfractionated heparin , whereas LMWH is quickly and consistently therapeutic , an important consideration in the treatment of VTE .
The evidence demonstrated a marked reduction in the incidence and severity of postthrombotic syndrome among patients wearing compression stockings , either over-the-counter stockings or custom-fit stockings , if use was initiated within 1 month diagnosis of proximal DVT .
Recommendation 4 : There is insufficient evidence to make specific recommendations for types of anticoagulation management of VTE in pregnant women .
During pregnancy , women have a 5-fold increased risk for VTE compared with nonpregnant women .
Neither LMWH nor unfractionated heparin crosses the placenta , and neither is associated with embryopathy or fetal bleeding .
While the appropriate duration of anticoagulation for idiopathic or recurrent VTE is not definitively known , there is evidence of substantial benefit for extended- duration therapy .
For VTE secondary to transient risk factors , 3 or 6 months of treatment was associated with similar risks for recurrent VTE .
Evidence from high- quality r and omized trials supports the use of LMWH as comparable to oral anticoagulation for VTE in selected patients .
Low-molecular-weight heparin may be a useful treatment for patients in whom control of the international normalized ratio ( INR ) is difficult and may be more efficacious than oral anticoagulants in patients with cancer .
Evidence Summary Is Heparin or LMWH Safer and More Efficacious for Initial Treatment of VTE ?
Of the 11 review s that pooled the trial results , none demonstrated that unfractionated heparin was superior to LMWH in preventing recurrent DVT .
In addition , heparin-induced thrombocytopenia is a possibility with both therapies , although LMWH is less likely to cause antibody formation for this condition .
In summary , the evidence suggests that LMWH is superior to unfractionated heparin for treating DVT of the lower extremities , particularly for reducing mortality and the risk for major bleeding during initial therapy .
It is at least as safe and effective as unfractionated heparin for patients with pulmonary embolism .
For the initial treatment of VTE , LMWH is either cost-saving or cost-effective compared with unfractionated heparin .
Is Outpatient Treatment of VTE Safe and Effective Compared with Inpatient Treatment ?