***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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    ***EXAMPLES*** 
    Input: BACKGROUND In this r and omized clinical trial , we aim ed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass , self-reported physical health , and other intermediate outcomes among patients undergoing maintenance hemodialysis . METHODS Patients were r and omly assigned to undergo hemodialysis six times per week  ( frequent hemodialysis , 125 patients ) or three times per week  ( conventional hemodialysis , 120 patients ) for 12 months . The two co primary composite outcomes were death or change ( from baseline to 12 months ) in left ventricular mass , as assessed by cardiac magnetic resonance imaging , and death or change in the physical-health composite score of the R AND 36-item health survey . Secondary outcomes included cognitive performance ; self-reported depression ; laboratory markers of nutrition , mineral metabolism , and anemia ; blood pressure ; and rates of hospitalization and of interventions related to vascular access . RESULTS Patients in the frequent-hemodialysis group averaged 5.2 sessions per week ; the weekly st and ard Kt/V(urea ) ( the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea ) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group ( 3.54±0.56 vs. 2.49±0.27 ) . Frequent hemodialysis was associated with significant benefits with respect to both co primary composite outcomes ( hazard ratio for death or increase in left ventricular mass , 0.61 ; 95 % confidence interval [ CI ] , 0.46 to 0.82 ; hazard ratio for death or a decrease in the physical-health composite score , 0.70 ; 95 % CI , 0.53 to 0.92 ) . Patients r and omly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis ( hazard ratio , 1.71 ; 95 % CI , 1.08 to 2.73 ) . Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia . There were no significant effects of frequent hemodialysis  on cognitive performance , self-reported depression , serum albumin concentration , or use of erythropoiesis-stimulating agents . CONCLUSIONS Frequent hemodialysis , as compared with conventional hemodialysis , was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00264758 . ) In the r and omized Hemodialysis ( HEMO ) Study , chronic high-flux dialysis , as defined by higher beta-2 microglobulin ( beta(2)M ) clearance , compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients . This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality . In a multivariable regression model that examined 1704 patients , baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up , with regression coefficients of -7.21 ( + /-0.69 SE ) mg/L per ml/min per 35 L urea volume ( P < 0.0001 ) and -1.94 ( + /-0.30 ) mg/L per ml/min ( P < 0.0001),respectively . In addition , black race and baseline years on dialysis correlated positively whereas age , diabetes , serum albumin , and body mass index correlated negatively with serum beta(2)M levels ( P < 0.05 ) . In time-dependent Cox regression models , mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality ( relative risk = 1.11 per 10-mg/L increase in beta(2)M level ; 95 % confidence interval 1.05 to 1.19 ; P = 0.001 ) , after adjustment for residual kidney urea clearance and number of pre study years on dialysis . This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy Some of the morbidity associated with  chronic hemodialysis  is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis . Hemodiafiltration combines convective and diffusive solute removal in a single therapy . The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospect i ve , r and omized clinical trial . Patients were r and omized to either on-line postdilution hemodiafiltration or high-flux hemodialysis .  The groups did not differ in body size , treatment time , blood flow rate , or net fluid removal . The filtration volume in hemodiafiltration was 21 + /-1 L. Therapy prescriptions were unchanged for a 12-mo study period . Removal of both small ( urea and creatinine ) and large ( ss(2)-microglobulin and complement factor D ) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis . The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group . Pretreatment plasma beta(2)-microglobulin concentrations decreased with time ( P < 0.001 ) ; however , the decrease was similar for both therapies ( P = 0.317 ) . Pretreatment plasma complement factor D concentrations also decreased with time ( P<0.001 ) , and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis ( P = 0.010 ) . The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range . The improved removal may not result in lower pretreatment plasma concentrations , however , possibly because of limitations in mass transfer rates within the body In patients with ESRD , the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear . In this prospect i ve study , we r and omly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration  ( n=358 ) or to continue low-flux hemodialysis  ( n=356 ) . The primary outcome measure was all-cause mortality . The main secondary endpoint was a composite of major cardiovascular events , including death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , therapeutic coronary intervention , therapeutic carotid intervention , vascular intervention , or amputation . After a mean 3.0 years of follow-up ( range , 0.4 - 6.6 years ) , we did not detect a significant difference between treatment groups with regard to all-cause mortality ( 121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups , respectively ; hazard ratio , 0.95 ; 95 % confidence interval , 0.75 - 1.20 ) . The incidences of cardiovascular events were 127 and 116 per 1000 person-years , respectively ( hazard ratio , 1.07 ; 95 % confidence interval , 0.83 - 1.39 ) . Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality , a finding that persisted after adjusting for potential confounders and dialysis facility . In conclusion , this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis . On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration , although this subgroup finding requires confirmation Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments . To study this further , we r and omized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week , all with single-use high-flux dialyzers . The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea ) , a 1.74-fold higher average number of treatments per week , and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm . We did not find a significant effect of nocturnal hemodialysis for either of the two co primary outcomes ( death or left ventricular mass ( measured by MRI ) with a hazard ratio of 0.68 , or of death or R AND Physical Health Composite with a hazard ratio of 0.91 ) . Possible explanations for the left ventricular mass result include limited sample size and patient characteristics . Secondary outcomes included cognitive performance , self-reported depression , laboratory markers of nutrition , mineral metabolism and anemia , blood pressure and rates of hospitalization , and vascular access interventions . Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension , but no significant benefit among the other main secondary outcomes . There was a trend for increased vascular access events in the nocturnal arm . Thus , we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either co primary outcome BACKGROUND Convective dialysis strategies are superior in the removal of protein-bound uraemic retention solutes . Mid-dilution and mixed-dilution haemodiafiltration ( HDF ) , both combining pre-dilution and post-dilution , are promising options to further improve removal capacity and have been shown of additional benefit for large middle molecules . In this study , we compared the removal of small water-soluble and protein-bound solutes in post-dilution versus mid-dilution HDF . METHODS Fourteen chronic haemodialysis ( HD ) patients were included in this crossover study . Patients were kept for 4 weeks on high-flux HD . On the mid-week session of Weeks 3 and 4 , either post-dilution or reversed mid-dilution HDF were applied , in r and om order . Blood and dialysate flows were maintained at 300 and 800 mL/min , while the substitution flow was 75 mL/min in post-dilution and 150 mL/min in mid-dilution HDF . Based on the data collected during the sessions under study , extraction ratio ( ER ) and reduction ratio ( RR ) of small water-soluble and protein-bound solutes were calculated , as well as total solute removal ( TSR ) based on spent dialysate . RESULTS No differences were observed for TSR , ER and RR for protein-bound solutes . For small water-soluble solutes , ER in post-dilution HDF was significantly higher than in mid-dilution HDF : 0.92 ± 0.02 versus 0.87 ± 0.04 for urea ( P < 0.001 ) , 0.92 ± 0.02 versus 0.88 ± 0.02 for creatinine ( P < 0.001 ) and 0.84 ± 0.02 versus 0.82 ± 0.03 for uric acid ( P = 0.009 ) . TSR and RR were , however , not different due to the lower inlet concentrations with post-dilution HDF . CONCLUSIONS TSR of mid-dilution and post-dilution HDF was not different for both small water-soluble and protein-bound compounds . Both strategies in the setting as applied in this study are as adequate for the removal of these solutes Current guidelines recommend obtaining an ankle – brachial index ( ABI ) to screen for peripheral artery disease ( PAD ) in subjects at risk . Previous work demonstrated that a combination of β2-microglobulin , cystatin C , high-sensitivity C-reactive protein and glucose was associated with PAD . This study evaluated the ability of these biomarkers combined with clinical parameters to predict PAD in at-risk subjects . This study enrolled 1025 subjects from 99 primary care clinics who were smokers and /or diabetics ≥ 50 years or any individual ≥ 70 years . Consented subjects underwent a clinical assessment , fasting blood draw , and an ABI measurement with PAD defined as an ABI < 0.90 in either leg . The biomarkers and their interactions were evaluated using logistic regression and performance was evaluated at a cut point of the biomarker panel selected to maximize sensitivity while minimizing the false positive rate of the test . Of the 1025 subjects enrolled , 46 did not meet the ABI or other criteria for inclusion in the analysis . Among the evaluable subjects ( n = 979 )  , PAD was detected in 83 ( 8.5 % ) . The model had a C-statistic of 0.73 ( 95 % CI 0.67–0.79 ) . There were 20 patients with PAD who were judged to be at low to moderate risk for cardiovascular events by clinical assessment ; the model correctly 
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In large scale ( N = 10,000 ) simulations of individuals drawn from the population of β2 M kinetic parameters , we found that , higher dialytic removal material ly affects β2 M exposures only when RRF ( renal clearance of β2 M ) was below 2 ml/min .
In patients initiating  conventional  HF hemodialysis , total loss of RRF was predicted to be associated with a RR of death of more than 20 % .
Hemodiafiltration and daily dialysis may decrease the high risk of death of anuric patients by 10 % relative to conventional , thrice weekly HF dialysis .
Only daily long sessions of hemodialysis consistently reduced mortality risk between 7 - 19 % across the range of β2 M generation rate .