***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: Mycophenolate mofetil ( MMF ) was developed with cyclosporine as a fixed‐dose immunosuppressant . More recent data indicate a relationship between mycophenolic acid ( MPA ) exposure in individuals and clinical endpoints of rejection and toxicity . This 2‐year , open‐label , r and omized , multicenter trial compared the efficacy and safety of concentration‐controlled MMF ( MMFCC ) dosing with a fixed‐dose regimen in 720 kidney recipients . Patients received either ( A ) MMFCC and reduced‐level calcineurin inhibitor ( MMFCC/CNIRL ) ; ( B ) MMFCC and st and ard‐level CNI ( MMFCC/CNISL ) ; or ( C ) fixed‐dose MMF and CNISL ( MMFFD/CNISL ) . Antibody induction and steroid use were according to center practice . The primary endpoint was noninferiority ( α= 0.05 ) of group A versus group C for treatment failure ( including biopsy‐proven acute rejection [ BPAR ] , graft loss and death ) at 1 year . Although mean CNI trough levels in group A did not reach the prespecified targets , they were statistically lower than those in groups B and C ( p ≤ 0.01 for each comparison ) . BPAR rates ( 8.5 % ) were low across groups . Group A had 19 % fewer treatment failures ( 23 % vs. 28 % , p = 0.18 ) . MMF doses were highest ( p < 0.05 ) , with withdrawals for adverse events the fewest ( p = 0.02 ) , in group A. Of the 80 % of subjects taking tacrolimus ( Tac ) , those with higher MPA exposure had significantly less rejection ( p < 0.001 ) and diarrhea correlated with Tac , but not with MPA levels . Thus , MMFCC with low‐dose CNI result ed in outcomes not inferior to those with st and ard CNI exposure and MMFFD , indicating potential utility of MMFCC in CNI‐sparing regimens BACKGROUND Mycophenolate mofetil ( MMF ) is widely used for immunosuppressive therapy in renal transplantation , but comparative data regarding efficacy and safety in paediatric vs. adult kidney allograft recipients in one and the same study are lacking . METHODS We therefore performed this subgroup analysis of the FDCC trial , a 12-month , prospect i ve , r and omised study , comparing fixed-dose ( FD ) with concentration-controlled ( CC ) MMF dosing in paediatric and adult renal transplant recipients . Sixty-two paediatric and 839 adult de novo patients in 19 countries were r and omised 1:1 to receive fixed-dose or concentration-controlled MMF therapy in combination with calcineurin inhibitors and corticosteroids . RESULTS Both patient and allograft survival proved to be excellent in paediatric patients ( 98.4 % and 90.3 % ) and adults ( 96.8 % and 95.0 % ) . The rates of biopsy-proven acute rejections ( BPAR ) and treated acute rejection episodes ( ARE ) were comparable between paediatric ( 12.9 % and 17.7 % ) and adult patients ( 15.5 % and 20.7 % ) . Transplant function at 12 months post-transplant was similar in paediatric ( 67.8 ± 45.6 mL/min/1.73 m2 ; ) and adult recipients ( 64.7 ± 23.3 mL/min/1.73 m2 ; ) . Children < 6 years ( n = 10 ) exhibited a numerically higher frequency of leucocytopaenia ( 20 % ) , diarrhoea ( 40 % ) and weight loss ( 10 % ) than older children ( 6 - 18 years ; 5.8 % , 28.8 % and 1.9 % ) and adults ( 16.1 % , 24.7 % and 1.5 % ) . On the whole , the percentage of patients who experienced adverse events causing interruption of MMF therapy were numerically lower in children ( 4.8 % ) than in adults ( 12.5 % ) . Conclusions . The overall efficacy and tolerability of MMF appear to be comparable between paediatric and adult patients . Further studies are needed to vali date these results In 1978 , the renowned Archie Cochrane in an essay on the future of medicine said “ It is surely a great criticism of our profession that we have not organized a critical summary , by specialty or subspecialty , adapted periodically , of all relevant r and omized controlled trials . ” This did of course eventually result in the creation of the Cochrane collaboration and the Cochrane library of r and omized controlled trial ( RCT ) , but this is large ( more than half a million references ) , it is not organized by specialty , and one does need some more sophisticated search skills to get what you want . Thus , the Transplant Library , where minimal search skills are required , is the first such specialized library that Cochrane identified as being a necessity some 40 yr ago . In the Transplant Library , all the work has been performed for you in that the trials are classified by the organ concerned , and furthermore , it includes references from conference proceedings to RCTs , which are not available in Medline . The Transplant Library contains some 7500 references to RCTs and includes more than 3500 references to abstract s of RCTs in conference proceedings , many of which do not ever come to be published . Another aspect of the Library is that from January 2004 all trials are grade d for the quality of the methodology using allocation concealment , intention to treat analysis , and the Jadad score , which takes into account appropriate methods of r and omization , blinding , and follow-up . From January 2008 , selected good quality systematic review s and meta-analyses have also been added to the Library . The Library is up date d every 2 weeks for RCTs and lists many trials that are published electronically ahead of print , whereas the addition of selected systematic review s is performed on a monthly basis . The Library is an incredibly useful tool for the transplant clinician or healthcare worker in transplantation as it enables one to see what is available in level 1 and level 2 evidence quickly without any sophisticated search knowledge . In the following pages , there is a guide to the use of the Library , and we hope you will find this useful . Please contact us if you have any questions . Journal subscribers have access to the Transplant Library as part of their subscription . You can access the Transplant Library through the home page of the Journal . It may also be available through your institution or membership of the BTS and ESOT . The Transplant Library is funded in part by Wolters Kluwer Health . Neither author receives a remuneration from Wolters Kluwer Health . Centre for Evidence in Transplantation , Royal College of Surgeons of Engl and , Lincoln ’s Inn Fields , London , United Kingdom . Address correspondence to : Liset Pengel , Ph.D. , Centre for Evidence in Transplantation , Royal College of Surgeons of Engl and , 35 - 43 Lincoln ’s Inn Fields , London WC2A 3PE , UK . E-mail : lpengel@rcseng.ac.uk . Accepted 7 July 2011 . Copyright © 2011 by Lippincott Williams & Wilkins ISSN 0041 - 1337/11/9206 - 613 DOI : Background . Three r and omized-controlled trials have examined the utility of mycophenolic acid ( MPA ) therapeutic drug monitoring in kidney transplant recipients . Each used a different methodology to estimate MPA exposure ( predose concentrations [ C0 ] , multiple regression – derived limited sampling strategies [ LSSs ] , and Bayesian estimation in Opticept , FDCC [ fixed dose versus concentration controlled ] and APOMYGERE [ adaption de Posologie du MMF en Greffe Renale ] trials , respectively ) . Results were conflicting . This study aim ed to compare the ability of these method ologies to predict AUC0–12 in an independent cohort of kidney transplant recipients . Methods . Sixty-nine full AUC ( AUCf ) profiles were collected from 45 subjects .  C0 and AUC0–12 predicted by the LSSs and Bayesian estimation ( AUCp ) were compared with AUCf . Results . Correlation between C0 and AUCf was poor . There was better correlation between LSSs and AUCf , and correlation was higher again between Bayesian estimates and AUCf . Bias and precision associated with the LSS and Bayesian-forecasting methods fell close to the level considered acceptable in clinical studies ( < 15 % ) . However , neither method quite achieved this , and regardless of whether LSSs or Bayesian forecasting were applied , only 45 % to 47 % of AUCp values fell within 15 % of AUCf . Discordance between C0 and AUCp and AUCf occurred in 15 % to 27 % of cases . Conclusions . This study highlights the difficulties of MPA therapeutic drug monitoring . Bayesian estimations showed slight superiority over C0 and LSS predictions , suggesting that this may be the preferable methodology Summary We compared steady-state pharmacokinetics of mycophenolate mofetil ( MMF ) – Myfenax ® ( Teva ) and CellCept ® ( Roche ) – in stable kidney transplant recipients ( KTRs ) . This was an international , multi-centre , r and omized , open-label , two-treatment , two-sequence crossover study with a 3-month follow-up . We included KTRs at least 12 months post-transplantation with stable renal graft function for at least 3 months . The maintenance treatment consisted of MMF in combination with tacrolimus with or without steroids . At the end of the two treatment periods , 6-h or 12-h PK studies of mycophenolic acid ( MPA ) were performed . A total of 43 patients ( mean age : 50.7 ± 13.5 years ; 19 females , 24 males ) were r and omized . Estimates of test to reference ratios ( 90 % CIs ) were 0.959 ( 0.899 ; 1.023 ) h*μg/ml for AUC(0–tau ) and 0.873 ( 0.787 ; 0.968 ) μg/ml for Cmax . Estimates for AUC(0–6h ) were 0.923 ( 0.865 ; 0.984 ) h*μg/ml and 0.985 ( 0.877 ; 1.106 ) μg/ml for Cmin . Thus , AUC(0–tau ) , AUC(0–6h ) , and Cmin of MPA were within the predefined margins . Cmax was somewhat outside of these margins in this set of patients . The numbers and types of adverse events were not different between the two treatments . The steady-state pharmacokinetics of MPA as well as adverse events are comparable for Myfenax ® and CellCept ® in tacrolimus-treated stable KTRs . ( EudraCT-No . : 2009 - 010562 - 31 ; Clinical Trials . Gov number : NCT00991510 Efficacy and safety of mycophenolate mofetil ( MMF ) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite , mycophenolic acid ( MPA ) . In this 12‐month study , 137 renal allograft recipients from 11 French centers receiving basiliximab , cyclosporine A , MMF and corticosteroids  were r and omized to receive either concentration‐controlled doses or fixed‐dose MMF . A novel Bayesian estimator of MPA AUC based on three‐point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1 , 3 and 6 . The primary endpoint was treatment failure ( death , graft loss , acute rejection and MMF discontinuation ) . Data from 65 patients /group were analyzed . At month 12 , the concentration‐controlled group had fewer treatment failures ( p = 0.03 ) and acute rejection episodes ( p = 0.01 ) with no differences in adverse event frequency .  The MMF dose was higher in the concentration‐controlled group at day 14 ( p < 0.0001 ) , month 1 ( p < 0.0001 ) and month 3 ( p < 0.01 ) , as were median AUCs on day 14 ( 33.7 vs. 27.1 mg•h/L ; p = 0.0001 ) and at month 1 ( 45.0 vs. 30.9 mg•h/L ; p < 0.0001 ) . Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown . We conducted a r and omized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus , tacrolimus/mycophenolate mofetil ( MMF ) , and cyclosporine/sirolimus .  All patients received daclizumab induction and maintenance corticosteroids . Median follow-up was 8 yr post-transplant . Acute rejection ( AR ) occurred significantly less often among those treated with tacrolimus/MMF ( 12 % ) than among those treated with tacrolimus/sirolimus ( 30 % ) or cyclosporine/sirolimus ( 28 % ) . Mean estimated GFR was consistently higher in the tacrolimus/MMF arm , especially after controlling for don 
    Output:
    
Based on current evidence , CD MMF administration can not be recommended as routine practice for kidney transplant recipients .