human
***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: Aim The aim of this study was to evaluate the benefits and safety of long-term i.v . iron therapy in iron-deficient patients with heart failure ( HF ) . Methods and results CONFIRM-HF was a multi-centre , double-blind , placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction ≤45 % , elevated natriuretic peptides , and iron deficiency ( ferritin < 100 ng/mL or 100–300 ng/mL if transferrin saturation < 20 % ) . Patients were r and omized 1 : 1 to treatment with i.v . iron , as ferric carboxymaltose ( FCM , n = 152 ) or placebo ( saline , n = 152 ) for 52 weeks . The primary end-point was the change in 6-min-walk-test ( 6MWT ) distance from baseline to Week 24 . Secondary end-points included changes in New York Heart Association ( NYHA ) class , Patient Global Assessment ( PGA ) , 6MWT distance , health-related quality of life ( QoL ) , Fatigue Score at Weeks 6 , 12 , 24 , 36 , and 52 and the effect of FCM on the rate of hospitalization for worsening HF . Treatment with FCM significantly prolonged 6MWT distance at Week 24 ( difference FCM vs. placebo : 33 ± 11 m , P = 0.002 ) . The treatment effect of FCM was consistent in all subgroups and was sustained to Week 52 ( difference FCM vs. placebo : 36 ± 11 m , P < 0.001 ) . Throughout the study , an improvement in NYHA class , PGA , QoL , and Fatigue Score in patients treated with FCM was detected with statistical significance observed from Week 24 onwards . Treatment with FCM was associated with a significant reduction in the risk of hospitalizations for worsening HF [ hazard ratio ( 95 % confidence interval ) : 0.39 ( 0.19–0.82 ) , P = 0.009 ] . The number of deaths ( FCM : 12 , placebo : 14 deaths ) and the incidence of adverse events were comparable between both groups . Conclusion Treatment of symptomatic , iron-deficient HF patients  with FCM over a 1-year period result ed in sustainable improvement in functional capacity , symptoms , and QoL and may be associated with risk reduction of hospitalization for worsening HF ( Clinical Trials.gov number NCT01453608 ) Aims Therapy with i.v . iron in patients with chronic heart failure ( CHF ) and iron deficiency ( ID ) improves symptoms , functional capacity , and quality of life . We sought to investigate whether these beneficial outcomes are independent of anaemia . Methods and results FAIR-HF r and omized 459 patients with CHF [ NYHA class II or III , LVEF ≤40 % ( NYHA II ) or ≤45 % ( NYHA III ) ] and ID to i.v . iron as ferric carboxymaltose ( FCM ) or placebo in a 2:1 ratio . We analysed the efficacy and safety according to the presence or absence of anaemia ( haemoglobin ≤120 g/L ) at baseline . Of 459 patients , 232 had anaemia at baseline ( 51 % ) . The effect of FCM on the primary endpoints of self-reported Patient Global Assessment ( PGA ) and NYHA class at week 24 was similar in patients with and without anaemia [ odds ratio ( OR ) for improvement , 2.48 vs. 2.60 , P = 0.97 for PGA and 1.90 vs. 3.39 , P = 0.51 for NYHA ) . Results were also similar for the secondary endpoints , including PGA and NYHA at weeks 4 and 12 , 6 min walk test distance , Kansas City Cardiomyopathy Question naire overall score , and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points . Regarding safety , no differences were noticed in the rates of death or first hospitalization  between FCM and placebo both in anaemic and in non-anaemic patients . Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia . Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) Abstract Aims Iron deficiency is highly prevalent in Southeast Asians with heart failure ( HF ) and associated with worse outcomes . This trial aim ed to assess the effect of intravenous iron in Southeast Asians hospitalized with decompensated HF . Methods and results Fifty patients hospitalized for acute decompensated HF , regardless of ejection fraction , with iron deficiency ( defined as serum ferritin < 300 ng/mL if transferrin saturation is < 20 % ) were r and omized to receive either one dose of intravenous ferric carboxymaltose ( FCM ) 1000 mg or placebo ( 0.9 % saline ) following HF stabilization and before discharge in two Singapore tertiary centres . The primary endpoint was difference in 6‐min walk test ( 6MWT ) distance over 12 weeks , while secondary endpoints were quality of life assessed using vali date d Kansas City Cardiomyopathy Question naire ( KCCQ ) and Visual Analogue Scale ( VAS ) . Improvement in 6MWT distance at Week 12 was observed in both FCM and placebo groups ( from 252 ± 123 to 334 ± 128 m and from 243 ± 67 to 301 ± 83 m , respectively ) . Unadjusted analysis showed 6MWT distance for FCM exceeded that for placebo , but adjustment for baseline covariates and time attenuated this effect { adjusted mean difference between groups : 0.88 m [ 95 % confidence interval ( CI ) −30.2 to 32.0 , P = 0.956]}. KCCQ overall summary and VAS were similar in both groups [ adjusted mean difference : KCCQ −1.48 ( 95 % CI −8.27 to 5.31 , P = 0.670 ) and VAS 0.26 ( 95 % CI −0.33 to 0.86 , P =  0.386  ) ] . FCM  was well tolerated with no serious treatment‐related adverse events . Conclusions Intravenous FCM administered pre‐discharge in Southeast Asians hospitalized with decompensated HF is clinical ly feasible . Changes in 6MWT distance should be measured beyond Week 12 to account for background therapy effects Objective Iron supplementation in iron-deficiency anaemia is st and ard practice , but the benefits of iron supplementation in iron-deficient non-anaemic ( IDNA ) individuals remains controversial . Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults . Design Systematic review and meta- analysis of r and omised controlled trials ( RCTs ) . Setting Primary care . Participants Adults ( ≥18 years ) who were iron deficient but non-anaemic . Interventions Oral , intramuscular or intravenous iron supplementation ; all therapy doses , frequencies and duration s were included . Comparators Placebo or active therapy . Results We identified RCTs in Medline , Embase , Cochrane Central Register of Controlled Trials , Cumulative Index of Nursing and Allied Health , SportD iscus and CAB Abstract s from inception to 31 October 2016 . We search ed the WHO ’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward search es of included trials and relevant review s in Web of Science . We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment , Development and Evaluation methodology . From 11 580 citations , we included 18 unique trials and 2 companion papers enrolling 1170 patients . Using a Mantel-Haenszel r and om-effects model , iron supplementation was associated with reduced self-reported fatigue ( st and ardised mean difference ( SMD ) −0.38 ; 95 % CI −0.52 to −0.23 ; I2 0 % ; 4 trials ; 714 participants ) but was not associated with differences in objective measures of physical capacity , including maximal oxygen consumption ( SMD 0.11 ; 95 % CI −0.15 to 0.37 ; I2 0 % ; 9 trials ; 235 participants ) and timed methods of exercise testing  . Iron supplementation significantly increased serum haemoglobin concentration ( MD 4.01 g/L ; 95 % CI 1.22 to 6.81 ; I2 48 % ; 12 trials ; 298 participants ) and serum ferritin ( MD 9.23 µmol/L ; 95 % CI 6.48 to 11.97 ; I2 58 % ; 14 trials ; 616 participants ) . Conclusion In IDNA adults , iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity . Given the global prevalence of both iron deficiency and fatigue , patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia . PROSPERO registration number CRD42014007085 Purpose To determine the effect of intravenous iron supplementation on performance , fatigue and overall mood in runners without clinical iron deficiency . Methods Fourteen distance runners with serum ferritin 30–100 µg·L−1 were r and omly assigned to receive three blinded injections of intravenous ferric-carboxymaltose ( 2 ml , 100 mg , IRON ) or normal saline ( PLACEBO ) over four weeks ( weeks 0 , 2 , 4 ) . Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection . Hemoglobin mass ( Hbmass ) was assessed via carbon monoxide rebreathing at weeks 0 and 6 . Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score ( TFS ) and Total Mood Disturbance ( TMD ) using the Brief Fatigue Inventory and Brunel Mood Scale . Data were analyzed using magnitude-based inferences , based on the unequal variances t-statistic and Cohen 's Effect sizes ( ES ) . Results Serum ferritin increased in IRON only ( Week 0 : 62.8±21.9 , Week 4 : 128.1±46.6 µg·L−1 ; p = 0.002 ) and remained elevated two weeks after the final injection ( 127.0±66.3 µg·L−1 , p = 0.01 ) , without significant changes in Hbmass . Supplementation had a moderate effect on T 
    Output:
    
agent
Quality -of-life scores ( Piper Fatigue Scale MD 0.73 , 95 % CI 0.29 to 1.18 ; I2 = 0 % ; studies = 3 ) and peak oxygen consumption ( MD 2.77 mL/kg/min , 95 % CI -0.89 to 6.43 ; I2 = 36 % ; 2 studies , 32 participants ) were associated with very low- quality evidence , and we remain uncertain about the role of intravenous iron for these metrics .
Current evidence is insufficient to show benefit of intravenous iron preparations for the treatment of non-anaemic iron deficiency across a variety of patient population s , beyond stating that it may result in a small , clinical ly insignificant increase in haemoglobin concentration .
***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: Aim The aim of this study was to evaluate the benefits and safety of long-term i.v . iron therapy in iron-deficient patients with heart failure ( HF ) . Methods and results CONFIRM-HF was a multi-centre , double-blind , placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction ≤45 % , elevated natriuretic peptides , and iron deficiency ( ferritin < 100 ng/mL or 100–300 ng/mL if transferrin saturation < 20 % ) . Patients were r and omized 1 : 1 to treatment with i.v . iron , as ferric carboxymaltose ( FCM , n = 152 ) or placebo ( saline , n = 152 ) for 52 weeks . The primary end-point was the change in 6-min-walk-test ( 6MWT ) distance from baseline to Week 24 . Secondary end-points included changes in New York Heart Association ( NYHA ) class , Patient Global Assessment ( PGA ) , 6MWT distance , health-related quality of life ( QoL ) , Fatigue Score at Weeks 6 , 12 , 24 , 36 , and 52 and the effect of FCM on the rate of hospitalization for worsening HF . Treatment with FCM significantly prolonged 6MWT distance at Week 24 ( difference FCM vs. placebo : 33 ± 11 m , P = 0.002 ) . The treatment effect of FCM was consistent in all subgroups and was sustained to Week 52 ( difference FCM vs. placebo : 36 ± 11 m , P < 0.001 ) . Throughout the study , an improvement in NYHA class , PGA , QoL , and Fatigue Score in patients treated with FCM was detected with statistical significance observed from Week 24 onwards . Treatment with FCM was associated with a significant reduction in the risk of hospitalizations for worsening HF [ hazard ratio ( 95 % confidence interval ) : 0.39 ( 0.19–0.82 ) , P = 0.009 ] . The number of deaths ( FCM : 12 , placebo : 14 deaths ) and the incidence of adverse events were comparable between both groups . Conclusion Treatment of symptomatic , iron-deficient HF patients  with FCM over a 1-year period result ed in sustainable improvement in functional capacity , symptoms , and QoL and may be associated with risk reduction of hospitalization for worsening HF ( Clinical Trials.gov number NCT01453608 ) Aims Therapy with i.v . iron in patients with chronic heart failure ( CHF ) and iron deficiency ( ID ) improves symptoms , functional capacity , and quality of life . We sought to investigate whether these beneficial outcomes are independent of anaemia . Methods and results FAIR-HF r and omized 459 patients with CHF [ NYHA class II or III , LVEF ≤40 % ( NYHA II ) or ≤45 % ( NYHA III ) ] and ID to i.v . iron as ferric carboxymaltose ( FCM ) or placebo in a 2:1 ratio . We analysed the efficacy and safety according to the presence or absence of anaemia ( haemoglobin ≤120 g/L ) at baseline . Of 459 patients , 232 had anaemia at baseline ( 51 % ) . The effect of FCM on the primary endpoints of self-reported Patient Global Assessment ( PGA ) and NYHA class at week 24 was similar in patients with and without anaemia [ odds ratio ( OR ) for improvement , 2.48 vs. 2.60 , P = 0.97 for PGA and 1.90 vs. 3.39 , P = 0.51 for NYHA ) . Results were also similar for the secondary endpoints , including PGA and NYHA at weeks 4 and 12 , 6 min walk test distance , Kansas City Cardiomyopathy Question naire overall score , and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points . Regarding safety , no differences were noticed in the rates of death or first hospitalization  between FCM and placebo both in anaemic and in non-anaemic patients . Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia . Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) Abstract Aims Iron deficiency is highly prevalent in Southeast Asians with heart failure ( HF ) and associated with worse outcomes . This trial aim ed to assess the effect of intravenous iron in Southeast Asians hospitalized with decompensated HF . Methods and results Fifty patients hospitalized for acute decompensated HF , regardless of ejection fraction , with iron deficiency ( defined as serum ferritin < 300 ng/mL if transferrin saturation is < 20 % ) were r and omized to receive either one dose of intravenous ferric carboxymaltose ( FCM ) 1000 mg or placebo ( 0.9 % saline ) following HF stabilization and before discharge in two Singapore tertiary centres . The primary endpoint was difference in 6‐min walk test ( 6MWT ) distance over 12 weeks , while secondary endpoints were quality of life assessed using vali date d Kansas City Cardiomyopathy Question naire ( KCCQ ) and Visual Analogue Scale ( VAS ) . Improvement in 6MWT distance at Week 12 was observed in both FCM and placebo groups ( from 252 ± 123 to 334 ± 128 m and from 243 ± 67 to 301 ± 83 m , respectively ) . Unadjusted analysis showed 6MWT distance for FCM exceeded that for placebo , but adjustment for baseline covariates and time attenuated this effect { adjusted mean difference between groups : 0.88 m [ 95 % confidence interval ( CI ) −30.2 to 32.0 , P = 0.956]}. KCCQ overall summary and VAS were similar in both groups [ adjusted mean difference : KCCQ −1.48 ( 95 % CI −8.27 to 5.31 , P = 0.670 ) and VAS 0.26 ( 95 % CI −0.33 to 0.86 , P =  0.386  ) ] . FCM  was well tolerated with no serious treatment‐related adverse events . Conclusions Intravenous FCM administered pre‐discharge in Southeast Asians hospitalized with decompensated HF is clinical ly feasible . Changes in 6MWT distance should be measured beyond Week 12 to account for background therapy effects Objective Iron supplementation in iron-deficiency anaemia is st and ard practice , but the benefits of iron supplementation in iron-deficient non-anaemic ( IDNA ) individuals remains controversial . Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults . Design Systematic review and meta- analysis of r and omised controlled trials ( RCTs ) . Setting Primary care . Participants Adults ( ≥18 years ) who were iron deficient but non-anaemic . Interventions Oral , intramuscular or intravenous iron supplementation ; all therapy doses , frequencies and duration s were included . Comparators Placebo or active therapy . Results We identified RCTs in Medline , Embase , Cochrane Central Register of Controlled Trials , Cumulative Index of Nursing and Allied Health , SportD iscus and CAB Abstract s from inception to 31 October 2016 . We search ed the WHO ’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward search es of included trials and relevant review s in Web of Science . We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment , Development and Evaluation methodology . From 11 580 citations , we included 18 unique trials and 2 companion papers enrolling 1170 patients . Using a Mantel-Haenszel r and om-effects model , iron supplementation was associated with reduced self-reported fatigue ( st and ardised mean difference ( SMD ) −0.38 ; 95 % CI −0.52 to −0.23 ; I2 0 % ; 4 trials ; 714 participants ) but was not associated with differences in objective measures of physical capacity , including maximal oxygen consumption ( SMD 0.11 ; 95 % CI −0.15 to 0.37 ; I2 0 % ; 9 trials ; 235 participants ) and timed methods of exercise testing  . Iron supplementation significantly increased serum haemoglobin concentration ( MD 4.01 g/L ; 95 % CI 1.22 to 6.81 ; I2 48 % ; 12 trials ; 298 participants ) and serum ferritin ( MD 9.23 µmol/L ; 95 % CI 6.48 to 11.97 ; I2 58 % ; 14 trials ; 616 participants ) . Conclusion In IDNA adults , iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity . Given the global prevalence of both iron deficiency and fatigue , patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia . PROSPERO registration number CRD42014007085 Purpose To determine the effect of intravenous iron supplementation on performance , fatigue and overall mood in runners without clinical iron deficiency . Methods Fourteen distance runners with serum ferritin 30–100 µg·L−1 were r and omly assigned to receive three blinded injections of intravenous ferric-carboxymaltose ( 2 ml , 100 mg , IRON ) or normal saline ( PLACEBO ) over four weeks ( weeks 0 , 2 , 4 ) . Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection . Hemoglobin mass ( Hbmass ) was assessed via carbon monoxide rebreathing at weeks 0 and 6 . Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score ( TFS ) and Total Mood Disturbance ( TMD ) using the Brief Fatigue Inventory and Brunel Mood Scale . Data were analyzed using magnitude-based inferences , based on the unequal variances t-statistic and Cohen 's Effect sizes ( ES ) . Results Serum ferritin increased in IRON only ( Week 0 : 62.8±21.9 , Week 4 : 128.1±46.6 µg·L−1 ; p = 0.002 ) and remained elevated two weeks after the final injection ( 127.0±66.3 µg·L−1 , p = 0.01 ) , without significant changes in Hbmass . Supplementation had a moderate effect on T 
    Output:
    