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 Administration of ferric pyrophosphate citrate ( FPC , Triferic ™ ) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses . FPC donates iron directly to transferrin , bypassing the reticuloendothelial system and avoiding iron sequestration . Methods Two identical Phase 3 , r and omized , placebo-controlled trials ( CRUISE 1 and 2 ) were conducted in 599 iron-replete chronic hemodialysis patients . Patients were dialyzed with dialysate containing 2 µM FPC-iron or st and ard dialysate ( placebo ) for up to 48 weeks . Oral or intravenous iron supplementation was prohibited , and doses of erythropoiesis-stimulating agents were held constant . The primary efficacy end point was the change in hemoglobin ( Hgb ) concentration from baseline to end of treatment ( EoT ) . Secondary end points included reticulocyte hemoglobin content ( CHr ) and serum ferritin . Results In both trials , Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group ( P < 0.001 , combined results ; 95 % confidence interval [ CI ] 0.2–0.6 ) . Placebo treatment result ed in significantly larger mean decreases from baseline in CHr ( −0.9 pg versus −0.4 pg , P < 0.001 ) and serum ferritin ( −133.1 µg/L versus −69.7 µg/L , P < 0.001 ) than FPC treatment . The proportions of patients with adverse and serious adverse events were similar in both treatment groups . Conclusions FPC delivered via dialysate during hemodialysis replaces iron losses , maintains Hgb concentrations , does not increase iron stores and exhibits a safety profile similar to placebo . FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents ( ESA ) , r and omized , controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis ( PD ) patients . In a multicenter trial , patients who had anemia , PD-dependent chronic kidney disease , stable ESA therapy , and a broad range of iron status ( ferritin < or = 500 ng/ml , transferrin saturation < or = 25 % ) were r and omly assigned to receive either 1 g of iron sucrose intravenously in three divided doses ( 300 mg over 1.5 h on days 1 and 15 , 400 mg over 2.5 h on day 29 ) or no supplemental iron . No serious adverse drug events occurred after intravenous iron administration . The primary end point , peak hemoglobin increase , was higher ( 1.3 + /- 1.1 versus 0.7 + /- 1.1 , mean + /- SD ; P = 0.0028 ) , and anemia intervention ( transfusion , increase in ESA dose , or intravenous iron therapy not called for in protocol ) occurred later ( P = 0.0137 ) and less often in intravenous iron-treated patients compared with untreated control subjects ( one of 66 [ 1.3 % ] versus five of 30 [ 16.7 % ] ) . Among patients who did not require intervention , iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects . Baseline iron status did not predict responsiveness to intravenous iron therapy . Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy Although functional iron deficiency ( FID ) may be present in hemodialysis ( HD ) patients with high serum ferritin levels ( > 800 ng/mL ) , current protocol s often preclude the use of intravenous ( IV ) iron in these patients . However , it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin ( Hb ) levels in patients with high serum ferritin . This report describes the hematologic efficacy and safety of ferric gluconate ( FG ) therapy in patients with serum ferritin > 800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31 , 2003 . Patients classified as having high ferritin levels ( serum ferritin > 800 ng/mL on at least 66 % of routine monthly measurements and transferrin saturation [ TSAT ] < 25 % on at least 1 occasion ) were stratified as follows : patients in Group I were suspected of having FID and received FG ≥250 mg IV over a 3‐month period when Hb was < 11 g/dL , and patients in Group II were thought not to have FID and received < 250 mg FG over a 3‐month period . Both groups received st and ard recombinant human erythropoietin therapy as per the unit 's protocol . Of 496 patients , 95 exhibited high ferritin and of these , 39 patients had sufficient data for analysis . Group I patients ( n=14 ) showed a significant increase in Hb levels compared with Group II ( n=25 ) . There was no increase in ferritin levels in response to iron administration . No significant differences in hospitalizations or infections were observed between groups . Hemodialysis patients with high ferritin levels may have FID , and IV iron therapy safely improves FID in some patients . A larger r and omized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted Background Anemia management protocol s in hemodialysis ( HD ) units differ conspicuously regarding optimal intravenous ( IV ) iron dosing ; consequently , patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents ( ESAs ) . Complementary to IV iron safety studies , our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb , TSAT , ferritin , and ESA dose in common clinical practice . Methods 9,471 HD patients ( 11 countries , 2009 - 2011 ) in the DOPPS , a prospect i ve cohort study , were analyzed . Associations of IV iron dose ( 3-month average , categorized as 0 , < 300 , ≥300 mg/month ) with 3-month change in Hgb , TSAT , ferritin , and ESA dose were evaluated using adjusted GEE models . Results Relative change : Monotonically positive associations between IV iron dose and Hgb , TSAT , and ferritin change , and inverse associations with ESA dose change , were observed across multiple strata of prior Hgb , TSAT , and ferritin levels . Absolute change : TSAT , ferritin , and ESA dose changes were nearest zero with IV iron < 300 mg/month , rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing . Findings were robust to numerous sensitivity analyses . Conclusions Though residual confounding can not be ruled out in this observational study , findings suggest that IV iron dosing < 300 mg/month , as commonly seen with maintenance dosing of 100 - 200 mg/month , may be a more effective approach to support Hgb than the higher IV iron doses ( 300 - 400 mg/month ) often given in many European and North American hemodialysis clinics . Alongside studies supporting the safety of IV iron in 100 - 200 mg/month dose range , these findings help guide the rational dosing of IV iron in anemia management protocol s for everyday hemodialysis practice Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Correction of iron deficiency is critical in chronic hemodialysis patients , and intravenous administration is superior to the oral route in this goal . Recently , concern was raised that intravenous iron administration might promote infection in dialysis patients . METHODS We review ed the data from a recent prospect i ve study of 985 patients in which no link between iron therapy and bacteremia had been found . We tested the potential role of the administration route of the iron ( intravenous vs. oral ) , the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients . RESULTS were 4-fold : in multivariate analysis , neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v . iron-treated patients were significant risk factors for bacteremia ;  iron was not given more frequently intravenously in bacteremic than in non-bacteremic patients ; among patients treated with intravenous iron , the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not ; and in patients receiving i.v . iron , there was an increased risk of bacteremia associated with concurrent administration of erythropoietin , which was not observed in patients receiving iron orally . CONCLUSION This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients . However , there might be a slightly increased risk of bacteremia in patients given high-frequency , high-dose intravenous iron Background In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial . The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron , and of hemoglobin and variables related to iron status . Methods The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York , NY from January 1998 to June , 2007 . A patient-centered , coded , electronic patient record used in patient care enabled retrospective analysis of data collected prospect ively . For survival analysis , patients were censored when transplanted , transferred to hemodialysis at home or elsewhere , peritoneal dialysis . Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox 's regression , using as variables age , race , gender , major co-morbid conditions , epoetin-alfa and intravenous iron administered , and 15 laboratory tests . Results Median age was 59 years , epoetin-alfa ( interquartile range ) 18,162 ( 12,099 , 27,741 ) units/week , intravenous iron 301 ( 202 , 455 ) mg/month , survival 789 ( 354 , 1489 ) days . Median hemoglobin was 116 ( 110 , 120)g/L , transferrin saturation 29.7 ( 24.9 , 35.1)% , serum ferritin 526 ( 247 , 833 ) μg/L , serum albumin 39.0 ( 36.3 , 41.5 ) g/L. Survival was better the higher the hemoglobin , best with > 120 g/L. Epoetin-alfa  effect on survival was weak but had statistically significant interaction with intravenous iron . For intravenous iron , survival was best with 1–202 mg/month , slightly worse with 202–455 mg/month ; it was worst with no intravenous iron , only slightly better with > 455 mg/month . Survival was worst with transferrin saturation ≤ 16 % , serum ferritin ≤ 100 μg/L , best with transferrin saturation > 25 % , serum ferritin > 600 μg/L The effects of each of hemoglobin , intravenous iron , transferrin saturation , and serum ferritin on survival were independently significant and not mediated by other predictors in the model . Conclusion Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level , by moderate intravenous iron administration , and by indicators of iron sufficiency . It was unfavorably influenced by a low hemoglobin level , and by indicators of iron deficiency Ferric pyrophosphate citrate ( FPC ) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin . The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent ( ESA ) use and maintain hemoglobin in hemodialysis patients . This 9-month , r and omized , placebo-controlled , double-blind , multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly . The FPC group received dialysate containing 2 μmol/l of iron . The placebo group received st and ard dialysate . A blinded central anemia management group facilitated ESA dose adjustments . Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l . The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment . Secondary end points included intravenous iron use and safety . At the end of treatment , there was a 
    Output:
    
agent
High-dose parenteral iron does not seem to be associated with higher risk of infection , all-cause mortality , increased hospitalization or increased cardiovascular events on analysis of RCTs .
Observational studies show increased risk for all-cause mortality , infections and hospitalizations that were not statistically significant and were associated with significant heterogeneity
***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 Administration of ferric pyrophosphate citrate ( FPC , Triferic ™ ) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses . FPC donates iron directly to transferrin , bypassing the reticuloendothelial system and avoiding iron sequestration . Methods Two identical Phase 3 , r and omized , placebo-controlled trials ( CRUISE 1 and 2 ) were conducted in 599 iron-replete chronic hemodialysis patients . Patients were dialyzed with dialysate containing 2 µM FPC-iron or st and ard dialysate ( placebo ) for up to 48 weeks . Oral or intravenous iron supplementation was prohibited , and doses of erythropoiesis-stimulating agents were held constant . The primary efficacy end point was the change in hemoglobin ( Hgb ) concentration from baseline to end of treatment ( EoT ) . Secondary end points included reticulocyte hemoglobin content ( CHr ) and serum ferritin . Results In both trials , Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group ( P < 0.001 , combined results ; 95 % confidence interval [ CI ] 0.2–0.6 ) . Placebo treatment result ed in significantly larger mean decreases from baseline in CHr ( −0.9 pg versus −0.4 pg , P < 0.001 ) and serum ferritin ( −133.1 µg/L versus −69.7 µg/L , P < 0.001 ) than FPC treatment . The proportions of patients with adverse and serious adverse events were similar in both treatment groups . Conclusions FPC delivered via dialysate during hemodialysis replaces iron losses , maintains Hgb concentrations , does not increase iron stores and exhibits a safety profile similar to placebo . FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents ( ESA ) , r and omized , controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis ( PD ) patients . In a multicenter trial , patients who had anemia , PD-dependent chronic kidney disease , stable ESA therapy , and a broad range of iron status ( ferritin < or = 500 ng/ml , transferrin saturation < or = 25 % ) were r and omly assigned to receive either 1 g of iron sucrose intravenously in three divided doses ( 300 mg over 1.5 h on days 1 and 15 , 400 mg over 2.5 h on day 29 ) or no supplemental iron . No serious adverse drug events occurred after intravenous iron administration . The primary end point , peak hemoglobin increase , was higher ( 1.3 + /- 1.1 versus 0.7 + /- 1.1 , mean + /- SD ; P = 0.0028 ) , and anemia intervention ( transfusion , increase in ESA dose , or intravenous iron therapy not called for in protocol ) occurred later ( P = 0.0137 ) and less often in intravenous iron-treated patients compared with untreated control subjects ( one of 66 [ 1.3 % ] versus five of 30 [ 16.7 % ] ) . Among patients who did not require intervention , iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects . Baseline iron status did not predict responsiveness to intravenous iron therapy . Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy Although functional iron deficiency ( FID ) may be present in hemodialysis ( HD ) patients with high serum ferritin levels ( > 800 ng/mL ) , current protocol s often preclude the use of intravenous ( IV ) iron in these patients . However , it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin ( Hb ) levels in patients with high serum ferritin . This report describes the hematologic efficacy and safety of ferric gluconate ( FG ) therapy in patients with serum ferritin > 800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31 , 2003 . Patients classified as having high ferritin levels ( serum ferritin > 800 ng/mL on at least 66 % of routine monthly measurements and transferrin saturation [ TSAT ] < 25 % on at least 1 occasion ) were stratified as follows : patients in Group I were suspected of having FID and received FG ≥250 mg IV over a 3‐month period when Hb was < 11 g/dL , and patients in Group II were thought not to have FID and received < 250 mg FG over a 3‐month period . Both groups received st and ard recombinant human erythropoietin therapy as per the unit 's protocol . Of 496 patients , 95 exhibited high ferritin and of these , 39 patients had sufficient data for analysis . Group I patients ( n=14 ) showed a significant increase in Hb levels compared with Group II ( n=25 ) . There was no increase in ferritin levels in response to iron administration . No significant differences in hospitalizations or infections were observed between groups . Hemodialysis patients with high ferritin levels may have FID , and IV iron therapy safely improves FID in some patients . A larger r and omized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted Background Anemia management protocol s in hemodialysis ( HD ) units differ conspicuously regarding optimal intravenous ( IV ) iron dosing ; consequently , patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents ( ESAs ) . Complementary to IV iron safety studies , our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb , TSAT , ferritin , and ESA dose in common clinical practice . Methods 9,471 HD patients ( 11 countries , 2009 - 2011 ) in the DOPPS , a prospect i ve cohort study , were analyzed . Associations of IV iron dose ( 3-month average , categorized as 0 , < 300 , ≥300 mg/month ) with 3-month change in Hgb , TSAT , ferritin , and ESA dose were evaluated using adjusted GEE models . Results Relative change : Monotonically positive associations between IV iron dose and Hgb , TSAT , and ferritin change , and inverse associations with ESA dose change , were observed across multiple strata of prior Hgb , TSAT , and ferritin levels . Absolute change : TSAT , ferritin , and ESA dose changes were nearest zero with IV iron < 300 mg/month , rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing . Findings were robust to numerous sensitivity analyses . Conclusions Though residual confounding can not be ruled out in this observational study , findings suggest that IV iron dosing < 300 mg/month , as commonly seen with maintenance dosing of 100 - 200 mg/month , may be a more effective approach to support Hgb than the higher IV iron doses ( 300 - 400 mg/month ) often given in many European and North American hemodialysis clinics . Alongside studies supporting the safety of IV iron in 100 - 200 mg/month dose range , these findings help guide the rational dosing of IV iron in anemia management protocol s for everyday hemodialysis practice Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Correction of iron deficiency is critical in chronic hemodialysis patients , and intravenous administration is superior to the oral route in this goal . Recently , concern was raised that intravenous iron administration might promote infection in dialysis patients . METHODS We review ed the data from a recent prospect i ve study of 985 patients in which no link between iron therapy and bacteremia had been found . We tested the potential role of the administration route of the iron ( intravenous vs. oral ) , the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients . RESULTS were 4-fold : in multivariate analysis , neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v . iron-treated patients were significant risk factors for bacteremia ;  iron was not given more frequently intravenously in bacteremic than in non-bacteremic patients ; among patients treated with intravenous iron , the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not ; and in patients receiving i.v . iron , there was an increased risk of bacteremia associated with concurrent administration of erythropoietin , which was not observed in patients receiving iron orally . CONCLUSION This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients . However , there might be a slightly increased risk of bacteremia in patients given high-frequency , high-dose intravenous iron Background In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial . The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron , and of hemoglobin and variables related to iron status . Methods The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York , NY from January 1998 to June , 2007 . A patient-centered , coded , electronic patient record used in patient care enabled retrospective analysis of data collected prospect ively . For survival analysis , patients were censored when transplanted , transferred to hemodialysis at home or elsewhere , peritoneal dialysis . Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox 's regression , using as variables age , race , gender , major co-morbid conditions , epoetin-alfa and intravenous iron administered , and 15 laboratory tests . Results Median age was 59 years , epoetin-alfa ( interquartile range ) 18,162 ( 12,099 , 27,741 ) units/week , intravenous iron 301 ( 202 , 455 ) mg/month , survival 789 ( 354 , 1489 ) days . Median hemoglobin was 116 ( 110 , 120)g/L , transferrin saturation 29.7 ( 24.9 , 35.1)% , serum ferritin 526 ( 247 , 833 ) μg/L , serum albumin 39.0 ( 36.3 , 41.5 ) g/L. Survival was better the higher the hemoglobin , best with > 120 g/L. Epoetin-alfa  effect on survival was weak but had statistically significant interaction with intravenous iron . For intravenous iron , survival was best with 1–202 mg/month , slightly worse with 202–455 mg/month ; it was worst with no intravenous iron , only slightly better with > 455 mg/month . Survival was worst with transferrin saturation ≤ 16 % , serum ferritin ≤ 100 μg/L , best with transferrin saturation > 25 % , serum ferritin > 600 μg/L The effects of each of hemoglobin , intravenous iron , transferrin saturation , and serum ferritin on survival were independently significant and not mediated by other predictors in the model . Conclusion Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level , by moderate intravenous iron administration , and by indicators of iron sufficiency . It was unfavorably influenced by a low hemoglobin level , and by indicators of iron deficiency Ferric pyrophosphate citrate ( FPC ) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin . The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent ( ESA ) use and maintain hemoglobin in hemodialysis patients . This 9-month , r and omized , placebo-controlled , double-blind , multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly . The FPC group received dialysate containing 2 μmol/l of iron . The placebo group received st and ard dialysate . A blinded central anemia management group facilitated ESA dose adjustments . Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l . The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment . Secondary end points included intravenous iron use and safety . At the end of treatment , there was a 
    Output:
    