***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  Osteopontin ( OPN ) is an extracellular matrix protein that plays an integral role in myocardial remodelling and has previously been shown to be a valuable biomarker in cardiovascular disease . Because of the concentric myocardial hypertrophy associated with severe , symptomatic aortic stenosis ( AS ) , we hypothesised that OPN expression may have a prognostic value in patients undergoing transcatheter aortic valve implantation ( TAVI ) .  Methods We prospect ively included 217 patients undergoing TAVI between February 2011 and December 2013 with a median follow-up of 349 days . Twenty healthy individuals from the same age range free from structural heart disease served as controls . The primary endpoint for the analysis was survival time . Results Median preprocedural OPN levels ( 675 ng/mL ; IQR 488.5–990.5 ng/mL ) were significantly higher in patients with severe aortic valve stenosis compared with healthy controls ( 386 ng/mL ; IQR 324.5–458 , p<0.001 ) . Patients with increased OPN values showed at baseline a decreased 6 min walk test performance , increased rates of atrial arrhythmia , and an increased risk of death during follow-up ( HR 2.2 ; 95 % CI 1.3 to 3.5 for the comparison of the highest vs lowest OPN quartile ) . Multiple Cox regression analysis demonstrated that OPN improves the prediction of an adverse prognosis further than N-terminal probrain natriuretic peptide . Conclusions  OPN levels at baseline are associated with adverse outcomes in patients with severe , symptomatic AS undergoing TAVI Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers OBJECTIVES This study sought to evaluate whether frailty improves mortality prediction in combination with the conventional scores . BACKGROUND European System for Cardiac Operative Risk Evaluation ( EuroSCORE ) or Society of Thoracic Surgeons ( STS ) score have not been evaluated in combined models with frailty for mortality prediction after transcatheter aortic valve replacement ( TAVR ) . METHODS This prospect i ve cohort comprised 330 consecutive TAVR patients ≥70 years of age .  Conventional scores and a frailty index ( based on assessment of cognition , mobility , nutrition , and activities of daily living ) were evaluated to predict 1-year all-cause mortality using Cox proportional hazards regression ( providing hazard ratios [ HRs ] with confidence intervals [ CIs ] ) and measures of test performance ( providing likelihood ratio [ LR ] chi-square test statistic and C-statistic [ CS ] ) . RESULTS All risk scores were predictive of the outcome ( EuroSCORE , HR : 1.90 [ 95 % CI : 1.45 to 2.48 ] , LR chi-square test statistic 19.29 , C-statistic 0.67 ; STS score , HR : 1.51 [ 95 % CI : 1.21 to 1.88 ] , LR chi-square test statistic 11.05 , C-statistic 0.64 ; frailty index , HR : 3.29 [ 95 % CI : 1.98 to 5.47 ] , LR chi-square test statistic 22.28 , C-statistic 0.66 ) . A combination of the frailty index with either EuroSCORE ( LR chi-square test statistic 38.27 , C-statistic 0.72 ) or STS score ( LR chi-square test statistic 28.71 , C-statistic 0.68 ) improved mortality prediction . The frailty index accounted for 58.2 % and 77.6 % of the predictive information in the combined model with EuroSCORE and STS score , respectively . Net reclassification improvement and integrated discrimination improvement confirmed that the added frailty index improved risk prediction . CONCLUSIONS This is the first study showing that the assessment of frailty significantly enhances prediction of 1-year mortality after TAVR in combined risk models with conventional risk scores and relevantly contributes to this improvement Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information BACKGROUND Few studies have examined the impact of novel indices of comorbidity , frailty , and disability on outcomes after  transcatheter aortic valve replacement ( TAVR ) .  OBJECTIVES This study analyzed patients from the Medtronic CoreValve U.S. Pivotal Trial program to develop a simple scoring system that incorporates st and ard and novel predictor variables . METHODS A multidisciplinary heart team used objective criteria , such as The Society of Thoracic Surgeons Predicted Risk of Mortality ( STS PROM ) , and subjective criteria to assess patients ' eligibility for TAVR . The analysis included 3,687 patients r and omly divided ( 2:1 ) into a derivation cohort ( n = 2,482 ) and a validation cohort ( n = 1,205 ) . The study evaluated predictors of all-cause death , which were used to calculate a risk score for each patient . RESULTS The overall mortality rate was 5.8 % at 30 days and 22.8 % at 1 year . Home oxygen use , assisted living , albumin levels < 3.3 g/dl , and age > 85 years predicted death at 30 days . Home oxygen use , albumin levels < 3.3 g/dl , falls in the past 6 months , STS PROM score > 7 % , and severe ( ≥5 ) Charlson comorbidity score predicted death at 1 year . A simple scoring system created on the basis of these multivariable predictors effectively stratified risk at 30 days and 1 year into low-risk , moderate-risk , and high-risk subsets . This score showed a 3-fold difference in mortality rates for the low-risk and high-risk subsets at 30 days ( 3.6 % and 10.9 % , respectively ) and 1 year ( 12.3 % and 36.6 % , respectively ) . The 1-year mortality model was more stable than the 30-day model ( C-statistics : 0.79 vs. 0.75 ) . CONCLUSIONS A simple score dominated by novel predictors of outcome effectively stratified early and late mortality rates in extreme-risk and high-risk patients and may assist in selecting appropriate c and i date s for TAVR . ( Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) BACKGROUND The role of frailty as a prognostic factor in non-selected patients with symptomatic severe aortic stenosis ( SAS ) is still uncertain . This study aims to examine the association between the frailty syndrome and mortality among very old patients with symptomatic SAS , and to assess whether the association varies with the type of SAS treatment . METHODS AND RESULTS Prospect i ve study of 606 patients aged ≥75years with symptomatic SAS , recruited from February 2010 to January 2015 , who were followed up through June 2015 . At baseline , frailty was defined as having at least three of the following five criteria : muscle weakness , slow gait speed , low physical activity , exhaustion , and unintentional weight loss . Statistical analyses were performed with multivariate Cox regression . At baseline , 49.3 % patients were frail . During a mean follow-up of 98weeks , 35.3 % of patients died . The hazard ratio ( 95 % confidence interval ) of mortality among frail versus non-frail patients was 1.83 ( 1.33 - 2.51 ) . The corresponding results were 1.58 ( 1.09 - 2.28 ) among patients under medical treatment , 3.06 ( 1.25 - 7.50 ) in those with transcatheter aortic valve replacement , and 1.97 ( 0.83 - 4.67 ) in those with surgical aortic valve replacement , p for interaction=0.21 . When the frailty criteria were considered separately , mortality was also higher among patients with slow gait speed [ 1.52 ( 1.05 - 2.19 ) ] or low physical activity [ 1.35 ( 1.00 - 1.85 ) ] . CONCLUSIONS Frailty is associated with increased mortality among patients with symptomatic SAS , and this association does not vary with the type of SAS treatment . Future studies evaluating the benefits of different treatments in SAS patients should account for baseline frailty Aims This study aim ed to assess functional course in elderly patients undergoing transcatheter aortic valve implantation ( TAVI )  and to find predictors of functional decline . Methods and results In this prospect i ve cohort , functional course was assessed in patients ≥70 years using basic activities of daily living ( BADL ) before and 6 months after TAVI .  Baseline EuroSCORE , STS score , and a frailty index ( based on assessment of cognition , mobility , nutrition , instrumental and basic activities of daily living ) were evaluated to predict functional decline ( deterioration in BADL ) using logistic regression models . Functional decline was observed in 22 ( 20.8 % ) of 106 surviving patients .  EuroSCORE ( OR per 10 % increase 1.18 , 95 % CI : 0.83 - 1.68 , P = 0.35 ) and STS score ( OR per 5 % increase 1.64 , 95 % CI : 0.87 - 3.09 , P = 0.13 ) weakly predicted functional decline . In contrast , the frailty index strongly predicted functional decline in univariable ( OR per 1 point increase 1.57 , 95 % 
    Output:
    
Chronic lung disease , chronic kidney disease , underweight , hypoalbuminaemia , a low frailty score , anaemia , low gait speed and an ADL deficiency were associated with worse 1‑year outcomes after TAVI