***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 
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    Input: In the Physicians ' Health Study , a r and omized , placebo-controlled , double-blind trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in decreasing cancer incidence , 33,223 subjects were eligible and willing to enter the trial . Instead of r and omizing this group immediately , all participants received identical calendar packs that contained active aspirin and beta-carotene placebo . Following an 18-week run-in , only 22,071 subjects who remained eligible and willing and had taken at least 2/3 of their pills were r and omized . We estimated the effect of the run-in as follows : pill taking compliance increased 20 - 41 per cent ; sample size decreased 34 per cent ; duration of follow-up decreased 7 per cent which result ed in a 7 per cent decrease in the expected event rate for the placebo group . To estimate these changes , we made assumptions about compliance and outcome risk for those excluded by the run-in . Our conclusion , however , about the net effect of the run-in on the power of the study remains constant across variations in a number of those assumptions . The power with the run-in , with 22,071 good compliers was typically higher , and never more than negligibly lower , than the power without the run-in , with 33,223 good and poor compliers . In addition , savings from enrolling 11,152 fewer subjects in the trial result ed from the use of the run-in Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant  treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training BACKGROUND Even though dietary fiber has been hypothesized to reduce the risk of coronary heart disease , few large epidemiological studies have examined this relation with good methodology . METHODS AND RESULTS The Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study was a r and omized , double-blind , placebo-controlled trial with daily supplementation of alpha-tocopherol and /or beta-carotene . Of the participants , 21930 smoking men aged 50 to 69 years who were free of diagnosed cardiovascular disease and had completed a vali date d dietary question naire at baseline were followed for 6.1 years . We monitored the incidence of major coronary events ( a combination of first nonfatal myocardial infa rct ion and coronary heart disease death ; n = 1399 ) and mortality from coronary heart disease ( n = 635 ) . Both entities had a significant inverse association with  dietary fiber  , but the association was stronger for coronary death . For men in the highest quintile of total dietary fiber intake ( median , 34.8 g/d ) , the relative risk for coronary death was 0.69 ( 95 % confidence interval , 0.54 to 0.88 ; P < .001 for trend ) compared with men in the lowest quintile of intake ( median , 16.1 g/d ) . With an adjustment for known cardiovascular risk factors , intake of saturated fatty acids , beta-carotene , vitamin C , and vitamin E did not material ly change the result . Water-soluble fiber was slightly more strongly associated with reduced coronary death than water-insoluble fiber , and cereal fiber also had a stronger association than vegetable or fruit fiber . CONCLUSIONS These findings suggest that independent of other risk factors , greater intake of foods rich in fiber can substantially reduce the risk of coronary heart disease , and particularly coronary death , in middle-aged , smoking men Although administration of zinc to human subjects has been reported to interfere with lymphocyte function , this single report has never been confirmed or refuted . We have developed zinc as a lifelong therapy for patients with Wilson 's disease . Interference with lymphocyte function occurring as a side effect of zinc therapy could produce serious problems in our patients . We evaluated lymphocyte mitogenic response and natural killer cell activity in patients with Wilson 's disease treated for 5 years or longer with zinc  , in comparison with normal controls , and found no differences . In a second study , we evaluated these same parameters in patients with Wilson 's disease before and after 1 year of zinc therapy , and again found no significant differences . We have seen no indications of immune suppression or increased susceptibility to infections in our patients , who have now been treated with zinc for up to 15 years . We conclude that any side effects from compromised lymphocyte function caused by administration of zinc are not of concern to patients with Wilson 's disease The purpose of this study was to evaluate the effect of selenium ( Se ) in the prevention of  human primary liver cancer .  Three intervention trials were conducted among the residents at high risk to primary liver cancer ( PLC ) in Qidong county , Jiang-su province , the People ’s Republic of China . This area has the second highest rate of PLC in China . One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite ( Se-salt ) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt . The second trial was undertaken among hepatitis B virus surface antigen carriers ( HBVsAg+ ) receiving supplement of 200 μg Se in form of selenized , yeast ( Se-yeast ) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence  using Se-yeast ( 200 μg of Se daily ) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly Purpose The high concentration of carotenoids in the macula , plus evidence linking oxidative stress to age-related macular degeneration ( AMD ) and carotenoids to antioxidation , generated the hypothesis that higher antioxidant intakes can prevent AMD . The aim of this study was to determine whether nutritional supplementation with a targeted nutritional supplement improves visual acuity and visual function in AMD . Methods In this multicenter , prospect i ve open-label r and omized study , 145 patients were r and omly assigned to 2 different treatment groups . Interventions were lutein ( 10 mg ) , zeaxanthin ( 1 mg ) , astaxanthin ( 4 mg ; AZYR SIFI , Catania , Italy ) , and antioxidants/vitamins supplementation formula or no dietary supplementation for 2 years . Primary outcome was mean changes in visual acuity ( VA ) at 12 and 24 months . Other measures included contrast sensitivity ( CS ) and National Eye Institute visual function question naire ( NEI VFQ-25 ) scores at 12 and 24 months . Results Patients in the treated group showed stabilization of VA with significantly ( p=0.003 ) better VA scores ( 81.4±7.2 ) compared to the nontreated group ( 76.8±8.9 ) at 24-month follow-up . An improvement in CS ( p=0.001 ) and final mean NEI VFQ-25 composite scores at 12 and 24 months higher in treated group compared to nontreated group were also shown ( p<0.001 ) . Conclusions Patients treated with lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report clinical ly meaningful stabilization/improvements in VA , CS , and visual function through 24 months compared with nontreated subjects . Further studies are needed with more patients and for longer periods of time Ageing is associated with impaired immune responses and increased infection-related morbidity . This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness .  96 independently living , healthy elderly individuals were r and omly assigned to receive nutrient supplementation or placebo .  Nutrient status and immunological variables were assessed at baseline and at 12 months , and the frequency of illness due to infection was ascertained . Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells , enhanced proliferation response to mitogen , increased interleukin-2 production , and higher antibody response and natural killer cell activity . These subjects were less likely than those in the placebo group to have illness due to infections ( mean [ SD ] 23 [ 5 ] vs 48 [ 7 ] days per year , p = 0.002 ) . Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age OBJECTIVE To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa . DESIGN R and omized , controlled , double-masked trial with 2 x 2 factorial design and duration of 4 to 6 years . Electroretinograms , visual field area , and visual acuity were measured annually . SETTING Clinical research facility . PATIENTS 601 patients aged 18 through 49 years with retinitis pigmentosa meeting preset eligibility criteria . Ninety-five percent of the patients completed the study . There were no adverse reactions . INTERVENTION Patients were assigned to one of four treatment groups receiving 15,000 IU/d of vitamin A , 15,000 IU/d of vitamin A plus 400 IU/d of vitamin E , trace amounts of both vitamins , or 400 IU/d of vitamin E. MAIN OUTCOME MEASURE Cone electroretinogram amplitude . RESULTS The two groups receiving 15,000 IU/d of vitamin A had on average a slower rate of decline of retinal function than the two groups not receiving this dosage ( P = .01 ) . Among 354 patients with higher initial amplitudes , the two groups receiving 15,000 IU/d of vitamin A were 32 % less likely to have a decline in amplitude of 50 % or more from baseline in a given year than those not receiving this dosage ( P = .01 ) , while the two groups receiving 400 IU/d of vitamin E were 42 % more likely to have a decline in amplitude of 50 % or more from baseline than those not receiving this dosage ( P = .03 ) . While not statistically significant , similar trends were observed for rates of decline of visual field area . Visual acuity declined about 1 letter per year in all groups . CONCLUSIONS These results support a beneficial effect of 15,000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa BACKGROUND Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months .  Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chron 
    Output:
    
Adverse effects were not reported but there was possible increased risk of skin rashes in the multivitamin group .
Adverse effects were not consistently reported in these eye studies , but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke or who have been exposed to asbestos .
None of the studies reported quality of life or re source use and costs .
AUTHORS ' CONCLUSIONS Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD .
There is no evidence with respect to other antioxidant supplements , such as lutein and zeaxanthin .
Although generally regarded as safe , vitamin supplements may have harmful effects , and clear evidence of benefit is needed before they can be recommended .