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: BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia Background . Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents ( ESAs ) in non-dialysis-dependent chronic kidney disease ( ND-CKD ) patients .  Current intravenous iron agents can not be administered in a single high dose because of adverse effects . Ferric carboxymaltose , a non-dextran parenteral iron preparation , can be rapidly administered in high doses . Methods . This open-label trial r and omized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2 , haemoglobin ≤ 11 g/dL , transferrin saturation ≤ 25 % , ferritin ≤ 300 ng/mL , and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min ( with up to two additional doses of 500 mg at 2-week intervals ) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days . Results . In the modified intent-to-treat population , the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4 % with ferric carboxymaltose and 34.7 % with oral iron ( P < 0.001 ) . At Day 42 , mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL ( P = 0.005 ) , mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL ( P < 0.001 ) and mean increase in transferrin saturation was 13.6 ± 11.9 % vs 6.1 ± 8.1 % ( P < 0.001 ) . Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron ( 2.7 % and 26.2 % , respectively ; P < 0.0001 ) . Conclusions . We conclude that 1000 mg ferric carboxymaltose can be rapidly administered , is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL  , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of  iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425 Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin < 50 µg/L and transferrin saturation < 20 % , or ferritin < 15 µg/L ) and normal or borderline hemoglobin ( ≥115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p<0.001 ) . At Day 56 , all FCM-treated patients had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin < 15 µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov Background : Secondary thrombocytosis is a common clinical feature . In patients with cancer , it is a risk factor for venous thromboembolic events . In inflammatory bowel disease ( IBD ) , thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population . Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis . Here , we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis . Methods : We performed a r and omized , single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose ( FCM ) in patients with IBD with secondary thrombocytosis ( platelets > 450 G/L ) . Changes in platelet counts , hemoglobin , iron parameters , disease activity , megakaryopoietic growth factors , erythropoietin , and platelet activity were assessed . Patients received placebo or up to 1500 mg iron as FCM . Endpoints were evaluated at week 6 . Results : A total of 26 patients were included in the study , 15 patients were available for the per protocol analysis . A drop in platelets > 25 % ( primary endpoint ) was observed in 4 of 8 ( 50 % , iron group ) and 1 of 7 patients ( 14 % , placebo group , P = 0.143 ) . Mean platelet counts dropped on FCM but not on placebo ( 536 G/L to 411 G/L versus 580 G/L to 559 G/L ; P = 0.002 ) . Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM . The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression . Conclusion : FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Abstract Objective : Iron deficiency is a common but treatable comorbidity in chronic heart failure ( CHF ) that is associated with impaired health-related quality -of-life ( HRQoL ) . This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose ( FCM ) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective . Methods : A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo . Data on health outcomes and medical re source use were mainly taken from the FAIR-HF trial and combined with Swedish cost data . An incremental cost-effectiveness ratio ( ICER ) was calculated as well as the change in per-patient costs for primary care and hospital care . Results : In the FCM group compared with placebo  , quality -adjusted life years ( QALYs ) are higher ( difference = 0.037 QALYs ) , but so are per-patient costs [ ( difference = SEK 2789 ( € 303 ) ] . Primary care and hospital care equally share the additional costs , but within hospitals there is a major shift of costs from inpatient care to outpatient care . The ICER is SEK 75,389 ( € 8194 ) per QALY . The robustness of the result is supported by sensitivity analyses . Conclusions : Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective . The ICER in the base case scenario is twice as high as previously thought , but noticeably below 
    Output:
    
agent
Conclusions All currently available intravenous iron preparations appear to be safe and effective , but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients
***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: BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia Background . Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents ( ESAs ) in non-dialysis-dependent chronic kidney disease ( ND-CKD ) patients .  Current intravenous iron agents can not be administered in a single high dose because of adverse effects . Ferric carboxymaltose , a non-dextran parenteral iron preparation , can be rapidly administered in high doses . Methods . This open-label trial r and omized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2 , haemoglobin ≤ 11 g/dL , transferrin saturation ≤ 25 % , ferritin ≤ 300 ng/mL , and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min ( with up to two additional doses of 500 mg at 2-week intervals ) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days . Results . In the modified intent-to-treat population , the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4 % with ferric carboxymaltose and 34.7 % with oral iron ( P < 0.001 ) . At Day 42 , mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL ( P = 0.005 ) , mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL ( P < 0.001 ) and mean increase in transferrin saturation was 13.6 ± 11.9 % vs 6.1 ± 8.1 % ( P < 0.001 ) . Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron ( 2.7 % and 26.2 % , respectively ; P < 0.0001 ) . Conclusions . We conclude that 1000 mg ferric carboxymaltose can be rapidly administered , is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL  , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of  iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425 Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin < 50 µg/L and transferrin saturation < 20 % , or ferritin < 15 µg/L ) and normal or borderline hemoglobin ( ≥115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerl and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p<0.001 ) . At Day 56 , all FCM-treated patients had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin < 15 µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov Background : Secondary thrombocytosis is a common clinical feature . In patients with cancer , it is a risk factor for venous thromboembolic events . In inflammatory bowel disease ( IBD ) , thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population . Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis . Here , we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis . Methods : We performed a r and omized , single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose ( FCM ) in patients with IBD with secondary thrombocytosis ( platelets > 450 G/L ) . Changes in platelet counts , hemoglobin , iron parameters , disease activity , megakaryopoietic growth factors , erythropoietin , and platelet activity were assessed . Patients received placebo or up to 1500 mg iron as FCM . Endpoints were evaluated at week 6 . Results : A total of 26 patients were included in the study , 15 patients were available for the per protocol analysis . A drop in platelets > 25 % ( primary endpoint ) was observed in 4 of 8 ( 50 % , iron group ) and 1 of 7 patients ( 14 % , placebo group , P = 0.143 ) . Mean platelet counts dropped on FCM but not on placebo ( 536 G/L to 411 G/L versus 580 G/L to 559 G/L ; P = 0.002 ) . Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM . The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression . Conclusion : FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Abstract Objective : Iron deficiency is a common but treatable comorbidity in chronic heart failure ( CHF ) that is associated with impaired health-related quality -of-life ( HRQoL ) . This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose ( FCM ) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective . Methods : A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo . Data on health outcomes and medical re source use were mainly taken from the FAIR-HF trial and combined with Swedish cost data . An incremental cost-effectiveness ratio ( ICER ) was calculated as well as the change in per-patient costs for primary care and hospital care . Results : In the FCM group compared with placebo  , quality -adjusted life years ( QALYs ) are higher ( difference = 0.037 QALYs ) , but so are per-patient costs [ ( difference = SEK 2789 ( € 303 ) ] . Primary care and hospital care equally share the additional costs , but within hospitals there is a major shift of costs from inpatient care to outpatient care . The ICER is SEK 75,389 ( € 8194 ) per QALY . The robustness of the result is supported by sensitivity analyses . Conclusions : Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective . The ICER in the base case scenario is twice as high as previously thought , but noticeably below 
    Output:
    