***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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    Input: Subcutaneous treatment with erythropoietin ( epoetin ) in patients undergoing continuous ambulatory peritoneal dialysis ( CAPD ) is convenient , but the optimal injection frequency is under discussion . Epoetin was given subcutaneously to 22 stable anaemic CAPD patients in doses that adjust haemoglobin to 7.2+/-0.3 mmol/l during a correction period . During the maintenance period the frequency of injections in four r and omized groups of patients was changed r and omly to once , twice or three times a week or daily . Each period lasted more than 8 weeks . During the maintenance period the epoetin dose was almost unchanged , whether the patients were treated once , twice or thrice weekly . In 15 patients treated with daily injections , the overall dose reduction was 22 % . These 15 patients were grouped arbitrarily into 7 patients with a skin-fold of more than 20 mm at the injection site , and 8 patients with a skin-fold of less than 20 mm at the injection site . The dose reduction correlated with skin-fold thickness ; the reduction was seen only in the patients with skin-folds of less than 20 mm . Seven of the eight patients experienced an average dose reduction of 36+/-8 % BACKGROUND The ability to reduce the administration frequency of subcutaneous ( SC ) epoetin could provide benefits . This multicenter open-label study investigated the therapeutic equivalence of SC epoetin beta once-weekly and thrice-weekly administration regimens in maintaining anemia correction in stable hemodialysis ( HD ) patients . METHODS One hundred seventy-three patients were r and omly assigned to either once-weekly epoetin beta ( n = 84 ) or their original thrice-weekly regimen ( n = 89 ) for 24 weeks . All patients were administered intravenous iron supplementation , as required . RESULTS The per- protocol analysis included 134 patients ( 69 patients , once-weekly group ; 65 patients , thrice-weekly group ) . Mean hematocrits in both groups remained stable throughout the study . The difference in mean time-adjusted area under the curve for hematocrits between the once-weekly and thrice-weekly groups ( -0.54 vol% ) and 90 % confidence intervals ( -1.27 to 0.19 ) were within the prespecified equivalence range ( -2 to + 2 vol% ) . There was no significant change in  epoetin beta dose during the study . The ratio of mean weekly epoetin beta doses in the once-weekly and thrice-weekly groups ( 1.11 ) and 90 % confidence interval ( 0.99 to 1.23 ) also remained within the prespecified range ( 0.8 to 1.25 ) . Intention-to-treat analysis results were similar to per- protocol analysis results . Both regimens were well tolerated . CONCLUSION Once-weekly and thrice-weekly SC epoetin beta administrations are statistically equivalent in terms of maintaining both stable hematocrits and  epoetin beta dose requirements  in HD patients . These findings may improve compliance among patients Optimal route and frequency of administration of recombinant human erythropoietin ( rHuEPO ) have not yet been determined . There is some evidence to suggest that subcutaneous administration of rHuEPO may be more effective than the intravenous route in reversing renal anemia . It is also unclear whether rHuEPO is more effective when given by a large intermittent dose or by more frequent multiple divided doses . We have compared the effect of twice weekly versus once weekly subcutaneous administration of rHuEPO in two groups of haemodialysis patients . At the end of 12 weeks of treatment with rHuEPO , the mean haemoglobin levels had risen from 6.9 + /- ( SD ) 0.7 to 8.9 + /- 1.3 g/dl in the once weekly group and from 7.2 + /- 1.0 to 9.3 + /- 1.6 g/dl in the twice weekly group . The average doses of rHuEPO  used during the study were 127 + /- 6 and 115 + /- 18 U/kg body weight/week for the once weekly and twice weekly groups , respectively . Subcutaneous administration of low-dose rHuEPO is effective in reversing renal anaemia . Similar responses were obtained with once weekly and twice weekly regimens BACKGROUND Several studies have suggested that if recombinant human erythropoietin ( epoetin ) is administered subcutaneously rather than intravenously , a lower dose may be sufficient to maintain the hematocrit at a given level . METHODS In a r and omized , unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers , we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin .  The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks . We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration . RESULTS For the 107 patients treated by the subcutaneous route , the average weekly dose of epoetin  during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route ( mean [ + /-SD ] , 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week ; P<0.001 ) . Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site , and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild . CONCLUSIONS In patients receiving hemodialysis , subcutaneous administration of epoetin can maintain the hematocrit in a desired target range , with an average weekly dose of epoetin that is lower than with intravenous administration Abstract A prospect i ve r and omized study of the use of recombinant human erythropoietin ( rHuEPO ) in children with chronic renal disease was conducted to assess dosing requirements and side effects . Forty-four children with chronic renal failure , aged 4 months to 21 years , were studied . Twenty-five patients were pre dialysis , 10 on peritoneal dialysis , and 9 on hemodialysis .  Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin ( Hb ) was attained . Dose was then adjusted to maintain a normal Hb . Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks ( mean±SD ) ; 95 % of patients in the high-dose group and 66 % in the low-dose group reached target Hb within 12 weeks . The overall median rHuEPO dose at target Hb was 150 U/kg per week . Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb ( median 250 U/kg per week ) . Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks . Iron deficiency and /or hypertension occurred in 30 % of children . In conclusion , rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease Several studies have compared the efficacy of once-weekly subcutaneous ( s.c . ) epoetin treatment with two or three times weekly treatment in renal anaemia .  Epoetin administration frequency has attracted a high level of attention in recent years , and numerous small-scale studies have shown comparable efficacy and tolerability of once-weekly vs more frequent administration . The results of two large-scale , r and omized , controlled trials of once-weekly administration of epoetin beta became available recently . One of these studies , by Locatelli et al. , was the first to be design ed specifically to demonstrate therapeutic equivalence between once-weekly and three times weekly epoetin beta treatment , using rigorous statistical methods . This was a large , multicentre , r and omized , parallel group , 24-week study in 173 chronic renal failure patients . Treatment regimens were considered equivalent if : ( i ) the 90 % confidence interval ( CI ) of the difference between treatment groups was within + /-2 % for the time-adjusted area under the haematocrit ( Hct ) curve ( AUC ) ; and ( ii ) for mean weekly epoetin beta dose , the 90 % CI of the ratio of the groups was between 0.8 and 1.25 . As recommended by current guidelines for statistical analysis of clinical trial data , multiple analysis population s were examined in order to demonstrate robustness of the results with regard to the population chosen for analysis . Findings from the primary analysis , the per- protocol population , were confirmed by both the intent-to-treat analysis and an exploratory analysis that examined the influence of five patients who received dose increases above the mean . In all three analyses , the 90 % CIs were within the pre-specified equivalence ranges for both the difference between treatment groups for Hct AUC and the ratio of mean weekly epoetin beta dose . In conclusion , once-weekly and three times weekly s.c . epoetin beta treatment regimens are statistically equivalent in terms of maintaining stable Hct levels and dose requirements in haemodialysis patients . The agreement of the three analysis population s provides a convincing demonstration of the robustness of the results . These results confirm that a once-weekly epoetin beta regimen is an effective option for management of renal anaemia that may improve patient convenience and compliance We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis . The recombinant human erythropoietin was given intravenously three times weekly after dialysis , and transfusion requirements , hematocrit , ferrokinetics , and reticulocyte responses were monitored . Over a range of doses between 15 and 500 units per kilogram of body weight , dose-dependent increases in effective erythropoiesis were noted . At 500 units per kilogram , changes in the hematocrit of as much as 10 percentage points were seen within three weeks , and increases in ferrokinetics of three to four times basal values , as measured by erythron transferrin uptake , were observed . Of 18 patients receiving effective doses of recombinant human erythropoietin , 12 who had required transfusions no longer needed them , and in 11 the hematocrit increased to 35 percent or more . Along with the rise in hematocrit , four patients had an increase in blood pressure , and a majority had increases in serum creatinine and potassium levels . No organ dysfunction or other toxic effects were observed , and no antibodies to the recombinant hormone were formed . These results demonstrate that recombinant human erythropoietin is effective , can eliminate the need for transfusions with their risks of immunologic sensitization , infection , and iron overload , and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease Abstract . Hypertension is one of the most important complications of erythropoietin ( rHuEPO ) therapy in dialysis patients . In this study , the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [ BP ] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis ( CAPD ) . Patients were r and omized to receive rHuEPO 50 U/kg , either once a week ( group 1 , 50 U/kg per week ) or three times a week ( group 2 , 150 U/kg per week ) . At the beginning of the study , 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy . In group 1 , the hematocrit increased gradually and significantly from 18.98%±1.79 % to 30.1%±1.62 % after 6 months , while in group 2 it rapidly increased from 19.53%±1.86 % to 32.4%±1.11 % after 3 months . A significant increase in the mean arterial BP was observed in group 2 . Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group . None of the patients in group 1 required a change in antihypertensive medication . We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD , and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension Objective The purpose of the present study was to compare the dosage requirements of recombinant human erythropoietin ( rHuEPO ) administered subcutaneously ( SC ) either one or three times weekly . Design A r and omized , prospect i ve study . . Setting : The patients were recruited from two university hospitals and five county hospitals . Patients Thirty-three anemic patients on continuous ambulatory peritoneal dialysis ( CAPD ) treatment for endstage renal failure completed the study . Interventions Initially , all were treated with rHuEPOSC three times a week until hemoglobin blood levels ( Hb ) remained constant between 105 and 121 g/L for three months . Following r and omization , 17 patients continued the same treatment schedule ( group A ) , while 16 patients received the same dose , but administered only once weekly for three months ( group B ) . Main Outcome Measures The Hb levels and rHuEPO doses at the 
    Output:
    
There was no significant difference in maintaining target haemoglobin for once versus twice weekly administration ( one study , 20 patients : RR 1.00 , 95 % CI 0.42 to 2.40 ) or mean haemoglobin after 12 weeks of therapy between haemodialysis and CAPD patients ( two studies : WMD -0.21 g/dL , 95 % CI -0.98 to 0.56 ) At the end of study for once versus thrice weekly administration ( three studies : SMD -0.31 , 95 % CI -0.67 to 0.06 ) and at the end of maintenance phase ( one study : WMD -0.2 g/dL , 95 % CI -0.65 to 0.25 ) there was no significant difference .
There was no difference in the frequency of adverse events .
AUTHORS ' CONCLUSIONS There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHuEPO .