***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: Numerous epidemiologic studies have evaluated the association of statin use and cataracts but the results have been inconsistent . Statins , or 3-hydroxy-3methylglutaryl-coenzyme A reductase inhibitors , are currently the most common lipid-lowering class of drugs . The Age-Related Eye Diseases Study 2 ( AREDS2 ) was a prospect i ve , multicenter , clinical trial that evaluated the progression of  age-related macular degeneration ( AMD ) and cataract in participants aged 50 to 85 with at least intermediate AMD . In this report , we investigated the association of statin use with cataract progression or cataract surgery in AREDS2 . The AREDS2 , sponsored by the National Eye Institute , evaluated the safety and efficacy of adding lutein and zeaxanthin and / or omega-3 long-chain polyunsaturated fatty acids to the AREDS supplements in reducing the primary outcome of progression of AMD and the secondary outcome of cataract progression . As reported , the supplementation had no effect on lens opacity progression .  The study enrolled 4203 participants aged 50 through 85 between 2006 and 2008 at 82 clinical centers in the United States . The study concluded in October 2012 with a median follow-up of 5 years . Institutional review board approval was obtained at each clinical site , and participants signed informed consent for the study . Participants included in these analyses were bilaterally phakic at baseline and had cortical and posterior subcapsular ( PSC ) lens opacities involving < 5 % of the area in the central 5 mm diameter zone of the lens as documented on red reflex lens photographs . Progression to 5 % was considered an outcome for both cortical and PSC opacities . Cataract surgery was used as a surrogate of moderate to severe lens opacity of unspecified type . Slit-lamp examination at annual study visits documented the presence of pseudophakia and an interim history of cataract surgery was obtained during study telephone calls that occurred every 6 months between the study visits . Statin use was self-reported at baseline . The propensity score approach can be used to reduce or eliminate the effects of confounding when using observational data ( e.g. , statin use ) to estimate treatment effects . We used logistic regression to estimate propensity scores , which range from 0 to 1 and indicate the probability that a participant is a statin user , based on the risk factors at baseline . Values closer to 1 indicate a greater likelihood of a participant using statins . We then conducted age and sex-adjusted Cox regression using the propensity score , with and without matching of these scores , to evaluate the association of statin use with progression of lens opacities in either eye . Finally , adjustment was made for the competing risk of death . The unit of analysis is by person . Of the 2771 participants who were bilaterally phakic at baseline with < 5 % center subfield cortical or PSC opacity , 1184 ( 42.7 % ) were statin users . Table 1 ( available at www.aaojournal.org ) displays the baseline characteristics of these 2 groups . Statin users tended to be older , male , former or current smokers , and to have a history of diabetes and aspirin use . Statin users were also more likely to have a history of hypertension , congestive heart failure , coronary heart disease , angina , myocardial infa rct ion , and stroke . The progression rates at 5 years were 18.0 % ( 499/2771 ) for cataract surgery , 42.6 % ( 1111/2609 ) cortical lens opacities , and 30.6 % ( 819/2673 ) PSC lens opacities . In age and sex-adjusted analyses that included propensity scores , statin users had an increased risk of cataract surgery ( hazard ratio [ HR ] , 1.90 ; 95 % CI , 1.17e3.10 ) , cortical lens opacity progression ( HR , 1.52 ; 95 % CI , 1.08e2.12 ) , and PSC lens opacity progression ( HR , 1.84 ; 95 % CI , 1.25e2.71 ; Table 2 ) . Female statin users had an increased risk of cataract progression and cataract surgery . Statin users under the age of 75 years also had an increased risk of PSC lens opacity progression and cataract surgery . Matching statin users and nonusers by propensity scores result ed in 904 matched pairs . Differences in the covariates were then no longer significantly different ( Table 1 ) . However , the age difference between each propensity-matched pair could still range between 0 and 30 years , despite the matching . The analyses of the propensity-matched cohort were adjusted for age in the subsequent Cox regression analysis . Results for the matched analyses and the competing risks analysis were similar to those seen for the unmatched analyses ( Table 3 , available at www.aaojournal.org ) . The use of  statins in AREDS2 participants was associated with cataract surgery and progression of both cortical and PSC lens opacities . Risk of these outcomes seemed to be greater for women and patients < 75 years who used statins .  The current study has limitations . Although propensity matching is design ed to decrease bias by balancing the covariates between those choosing and not choosing to take statins , the propensity technique can adjust only for factors that were measured in AREDS2 . Whether unknown or unmeasured factors influenced our findings or the findings of previously conducted observational studies can not be determined . Of particular concern , given the widespread use of statins in patients with cardiovascular disease , is incomplete adjustment for risk factors associated with both CVD and cataract . Our study was subject to potential recall bias because statin use was self-reported . Both statin dosage and duration of use were not ascertained , but 86 % of participants who reported using statins at baseline continued to report statin use at their close-out visit . Our study results are not necessarily generalizable because our study cohort was a select population of patients with intermediate to late AMD . Important strengths of this study include its longitudinal prospect i ve nature , large sample size , st and ardized examinations , and the central ized grading of the lens photographs . An additional strength of the study was the collection and analyses of data on a large number of potentially important covariates . Our study raises important questions about some of the most commonly used drugs in the population . Additional studies in other population s are needed to determine whether use of statins increases the risk of cataract and whether cataract outcomes with statin use are influenced by sex or age group . Currently , Given the substantially increasing geriatric population , the need for evidence -based strategies to address the medical and societal consequences of these demographic trends has never been greater . In this context , statins for primary prevention of atherosclerotic cardiovascular disease ( ASCVD ) provide substantial potential social value by improving health and survival . However , using statins for primary prevention in older adults presents a clinical dilemma . Even though compelling evidence exists supporting statins for secondary prevention in individuals older than 75 years with clinical ASCVD , the same can not be said for primary prevention . In this Viewpoint , we describe existing evidence on the benefits of statins for primary prevention in older adults , uncertainties about risks , and the need for a r and omized trial before non– evidence -based prescribing patterns become irreversibly incorporated into practice Abstract . Simvastatin , a potent blood lipid reducer , has been suspected of inducing cataract in dogs . Twenty‐nine type II hyperlipidemic patients on simvastatin  were followed over 2 years at half‐year intervals . A parallel group of sex‐ and age‐matched normolipidemics were followed over a half year . Patients and controls had similar nuclear and cortical lens opacities , and water clefts . Vacuole number did not differ significantly between right and left eyes , nor between nasal and temporal parts of the lenses . General vacuole index ( total vacuole number in a patient ) for left eyes was analysed further . Controls showed significantly higher indices than patients , for no obvious reason . Indices for controls increased significantly over the half‐year test period , and among patients over each half‐year interval . The speed of this increase did not differ significantly from that of the controls . Furthermore , the increase was judged to be clinical ly insignificant . No deleterious effect  of simvastatin on the lens could be established Purpose The study of the grounds on which data regulatory authorities base their decisions on drug safety evaluations is an important clinical and public health issue . The aim of this study was to review the type and publication status of data sources supporting benefit/risk ratio re-evaluations conducted by the major regulatory authorities on safety issues . Methods A website search was carried out to identify all  safety alerts published by the U.S Food and Drugs Administration , Health Canada , European Medicines Agency and the Australian Therapeutics Goods Administration . Safety alerts were included if the causal relation between a suspected drug exposure and the occurrence of an adverse event was evaluated for the first time between 2010 and 2012 . Type of data sources evaluated by these regulatory authorities , publication status of the data sources and status of the drug label section with respect to updating were evaluated . Results A total of 59 safety alerts were included in this study . Of these , 33 ( 56 % ) were supported by post-marketing spontaneous reports , 24 ( 41 % ) evaluated r and omized clinical trials , 16 evaluated cohort studies ( 27 % ) , 13 were case – control studies ( 22 % ) and 11 evaluated case report/case series ( 17 % ) . Twenty-three safety alerts ( 39 % ) were issued based . on unpublished evidence , corresponding mainly to post-marketing spontaneous reports . The “ Warnings and pre caution s section ” was the drug label section most frequently up date d ( n = 40 ; 68 % ) . Conclusion Despite the different lengths of time taken by the different regulatory authorities to come to similar decisions on the same issues — an issue which would seem to deserve further harmonization — post-marketing spontaneous reports have supported most of the benefit/risk ratio re-evaluations , thereby confirming the value of such re-evaluations in detecting unknown adverse events BACKGROUND AND AIMS We aim ed to assess the association between exposure to statins and hospitalization for cataract . METHODS A population -based , nested case-control study was performed on a cohort of 134,441 patients from Lombardy ( Italy ) , newly treated with statins between 2005 and 2007 . Cases were patients hospitalized for cataract or lens extraction surgery after initial statin prescription until December 31 , 2012 . For each case patient , up to 5 controls were r and omly selected from the cohort and matched by gender , age at cohort entry , and date of index prescription . Logistic regression was used to model the outcome risk associated with low ( proportion of days covered , PDC 25 - 49 % ) , intermediate ( PDC 50 - 74 % ) , and high ( PDC ≥ 75 % ) adherence compared with very-low adherence ( PDC < 25 % ) . RESULTS 1334 case patients were matched to 6601 controls . Mean age ( SD ) of cases and controls was about 70 years ( 9 years ) and 51 % of them were men . There was a slight but continuous trend toward an increased risk of cataract as adherence to statin therapy  increased in the adjusted risk models , with a significant odds ratio of 1.19 ( 95 % CI 1.01 - 1.40 % ) for PDC 50 - 74 % and 1.20 ( 95 % CI 1.02 - 1.40 ) for PDC ≥ 75 % vs. PDC < 25 % , respectively . There was no statistical evidence that the effect of statins on cataract risk differed according to statin potency at starting therapy . CONCLUSIONS Statin therapy was associated with a modestly increased risk of cataract surgery . Nevertheless , in view of the overwhelming benefit of statins for reduction of CV events , clinical practice for statins therapy does not need to change Observational studies have a record of extremely successful contributions to medicine . They are essential for our knowledge about causes and pathogenesis — eg , genetic , environmental , or infectious causes of disease . Additionally , for medical practice we rely on observational studies of prognosis and diagnosis . Nevertheless , over the past years , we have seen recurrent debates about the merit of observational versus r and omised research . The debates have been fuelled recently because of seeming total failures , in which the results of observational studies were completely overturned by r and omised studies . Hormone replacement therapy showed protection from myocardial infa rct ion in observational studies , but a small increase was seen in r and omised trials ; a similar reversal happened for carotene and lung cancer . Such discrepancies raise the question : in what circumstances can observational comparisons be as convincing as r and omised experiments ? To answer that question : I will first recall what is expected from r and omisation . I will then describe two specific issues , adverse effects of drugs and genetic causes of disease , to eluci date under what circumstances evidence from observational research is as good as that from r and omised trials . This description can be generalised to other areas of clinical and epidemiological research , and leads to a proposal for a three-pronged restriction to give observational research the best chance to be as credible as r and omised controlled trials . Benefits of r and omisation Two benefits are expected from r and omisation : unbiased allocation of treatment , because of easier concealment of the allocation scheme , 1 and application of statistical theory on the basis of r and om sampling . Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data 
    Output:
    
Meta-regressions identified an inverse relationship between the risk of cataracts and the proportion of diabetic patients in the studies .
The results point out an increased risk of cataract development  with statins .