***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 Acute rejection episodes after renal transplantation are an important clinical challenge , despite use of multidrug immunosuppressive regimens . We did a prospect i ve , multicentre , r and omised , double-blind trial to investigate the impact of the addition of sirolimus , compared with azathioprine , to a cyclosporin and prednisone regimen . METHODS 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were r and omly assigned , after transplantation , sirolimus  2 mg daily ( n=284 ) or 5 mg daily ( n=274 ) , or azathioprine ( n=161 ) . We assessed the primary composite endpoint of efficacy failure , occurrence of biopsy-confirmed acute rejection episodes , graft loss , or death , and various secondary endpoints that characterise these episodes at 6 months and 12 months . Analyses were done by intention to treat . FINDINGS The rate of efficacy failure at 6 months was lower in the two sirolimus groups ( 2 mg 18.7 % , p=0.002 ; 5 mg 16.8 % , p<0.001 ) than in the azathioprine group ( 32.3 % ) . The frequency of biopsy-confirmed acute rejection episodes was also lower ( 2 mg 16.9 % , p=0.002 ; 5 mg 12.0 % , p<0.001 ; azathioprine 29.8 % ) . At 12 months , survival was similar in all groups for grafts ( 97.2 % , 96.0 % , and 98.1 % ) and patients ( 94.7 % , 92.7 % , and 93.8 % ) . Patients on sirolimus  showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grade s of rejection episodes and related antibody treatment , compared with the azathioprine group . Rates of infection and malignant disorders were similar in all groups . INTERPRETATION Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications . Further studies are needed to establish the optimum doses for the combined regimen Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function . The aim of this study was to compare the effects of tacrolimus ( Tac ) and cyclosporine microemulsion ( CsA ) based immunosuppressive protocol s using protocol biopsies from well-functioning renal allografts . 35 consecutive renal transplant patients were r and omized to Tac ( n : 17 ) versus CsA ( n : 18 ) treatment arms . Patient age and sex , donor type and age , histocompatibility , cold ischemia time and prior delayed graft function were similar between the two groups . Treatment protocol consisted of prednisolone , azathioprine and Tac or CsA. Biopsies performed on the third , sixth and twelfth months were blindly evaluated by the same pathologist . The incidences of acute rejection ( AR ) episodes among CsA vs Tac groups were 33 % vs 29 % , respectively ( NS ) . The Creatinine level was lower in Tac than CsA , although it was not significant ( Table ) . Sub clinical AR and sub clinical chronic allograft nephropathy were detected on protocol biopsies in 3 ( 2 CsA , 1 Tac ) and 12 ( 7 CsA , 5 Tac ) patients , respectively . Acute lesion score at the third month PBx was significantly lower in the Tac group ( p < 0.05 ) . Chronic lesion scores in all biopsies were lower in the Tac group , although not significantly . The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group Background No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant ( RTx ) patients . Methods This 12-month , multicenter , open-label study r and omized ( 1:1 ) 122 Japanese de-novo RTx patients to either an everolimus regimen  ( 1.5 mg/day starting dose ( target trough : 3 to 8 ng/ml ) + reduced-dose cyclosporine ) or a mycophenolate mofetil ( MMF ) regimen  ( 2 g/day + st and ard dose cyclosporine ) . All patients received basiliximab and corticosteroids . Key endpoints at month 12 were composite efficacy failure ( treated biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) and renal function ( estimated glomerular filtration rate ; Modification of Diet in Renal Disease-4 ) . Results Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study ( 52 % reduction at month 12 ) . Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF ( 11.5 % vs. 11.5 % ) . The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group ( P = 0.063 ) . Overall , the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments . The everolimus group had a higher incidence of wound healing events and edema , whereas a higher rate of cytomegalovirus infections was reported in the MMF group . Conclusions This study confirmed the efficacy of everolimus 1.5 mg/day ( target trough : 3 to 8 ng/ml ) in Japanese RTx patients for preventing acute rejection , while allowing for substantial cyclosporine sparing . Renal function and safety findings were comparable with previous reports from other RTx population s . Trial registration Clinical Trials.gov number : Background The once-daily ( QD ) , prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily ( BD ) tacrolimus . Treatment nonadherence in transplant recipients has been associated with poor graft outcomes . Methods This open-label , parallel-group study r and omized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day ( Arm 1 ; n=309 ) , QD 0.2 mg/kg per day ( Arm 2 ; n=302 ) , QD 0.3 mg/kg per day ( Arm 3 ; n=304 ) all with mycophenolate mofetil and corticosteroids  ( tapered ) over 24 weeks , or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil , basiliximab , and corticosteroids given only perioperatively ( Arm 4 ; n=283 ) . The primary composite endpoint ( efficacy failure ; per protocol set ) was defined as graft loss , biopsy-confirmed acute rejection , or graft dysfunction at week 24 . Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m2 . The prespecified noninferiority margin was 12.5 % . Results The per protocol set included 976 patients : 237 , 263 , 246 , and 230 patients in Arms 1 to 4 , respectively . Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1 ; Kaplan – Meier estimates of efficacy failure were 42.2 % and 40.6 % , respectively ( difference , −1.6 % ; 95 % confidence interval [ CI ] , −12.2 % to 9.0 % ) . Noninferiority to Arm 1 was not confirmed for Arm 3 ( difference , −3.5 % ; 95 % CI , −13.6 % to 6.6 % ) or Arm 4 ( difference , −7.1 % ; 95 % CI , −16.1 % to 1.9 % ) . Graft dysfunction ( estimated glomerular filtration rate < 40 mL/min/1.73 m2 ) was the main determinant of composite-endpoint efficacy failure across all arms . Conclusions In patients representative of the European kidney transplant population , tacrolimus QD-based immunosuppression ( 0.2 mg/kg/day ) , without induction , showed similar efficacy to 0.2 mg/kg per day tacrolimus BD BACKGROUND The economic impact of therapies has increasingly become part of the clinical decision-making process . Costs associated with kidney transplantation are substantial and economic evaluations are useful in identifying immunosuppressive regimens that yield optimal clinical and economic benefits . METHODS Utilisation of health care re sources during the first 6-months after renal transplantation was examined in 557 kidney transplant recipients participating in a European , multicentre , r and omised , parallel group study that compared the efficacy and safety of a tacrolimus-based regimen versus a cyclosporin-microemulsion-based regimen .  Cost-minimisation and cost-effectiveness analyses were conducted from an Italian hospital perspective , including direct medical costs only ( e.g. medication , hospitalisation ) . RESULTS The incidence of acute rejection was significantly lower in the tacrolimus group than in the cyclosporin microemulsion ( ME ) group ( 32.5 % versus 51.3 % ; p<0.001 ) . Patient and graft survival  were similar in both treatment groups . Renal transplant recipients receiving tacrolimus-based immunosuppression had lower utilisation of health care re sources and lower total costs per patient than cyclosporin-ME treated patients . When surviving patients with a rejection-free graft were analysed , tacrolimus therapy was cost-saving , since it was both more effective ( 18.8 % difference in the incidence of acute rejection ; 95%CI 10.7%-26.8 % ; p<0.001 ) and less costly than cyclosporin-ME based therapy ( cost difference euro9918 ) . The costs per patient with a functioning graft were euro2305 , the costs per surviving patient were euro1892 lower in tacrolimus treated patients . Sensitivity analyses using the key cost-drivers ( hospitalisation , study drug , and concomitant medication ) found the cost advantage of tacrolimus was maintained . CONCLUSION In the first 6 months after renal transplantation , tacrolimus-based therapy was less costly than cyclosporin-ME based therapy . When surviving patients with a rejection-free graft were considered , tacrolimus was the dominant therapy Purpose : We sought to compare directly elicited valuations for EQ-5D health states between the US and UK general adult population s. Methods : We analyzed data from 2 EQ-5D valuation studies where , using similar time trade-off protocol s , values for 42 common health states were elicited from representative sample s of the US and UK general adult population s. First , US and UK population mean valuations were estimated and compared for each health state . Second , r and om-effect models were used to compare the US and UK valuations while adjusting for known predictors of EQ-5D valuations ( ie , age , sex , health state descriptors ) and to investigate whether and how the valuations differ . Results :  Population mean valuations of the 42 health states ranged from −0.38 to 0.88 for the United States and from −0.54 to 0.88 for the United Kingdom , with the US mean scores being numerically higher than the UK for 39 health states ( mean difference : 0.11 ; range : −0.01 to 0.25 ) . After adjusting for the main effects of known predictors , the average difference in valuations was 0.10 ( P < 0.001 ) . The magnitude of the difference in the US and UK valuations was not constant across EQ-5D health states ; greater differences in valuations were present in health states characterized by extreme problems . Conclusions : Meaningful differences exist in directly elicited TTO valuations of EQ-5D health states between the US and UK general population s. Therefore , EQ-5D index scores generated using valuations from the US general population should be used for studies aim ing to reflect health state preferences of the US general public We performed a prospect i ve r and omized trial comparing sirolimus/mycophenolate mofetil (MMF)/prednisone to cyclosporine/MMF/prednisone and selected induction therapy with basiliximab .  Twenty patients received sirolimus ( 10 mg loading dose followed by 3 mg/m body surface area/day , keeping 24-hr trough levels at 10 - 15 ng/mL for six months and 5 - 10 ng/mL thereafter . Twenty-one patients began cyclosporine ( 4 to 8 mg/kg/day , keeping 12-hour trough levels at 150 - 300 ng/mL for 6 months and 100 - 200 ng/mL afterwards ) . Mean follow up was 15.8 months . One-year patient and graft survival was similar in both groups ( > 90 % ) . Acute rejection rate was 16.6 % in the sirolimus group and 5.2 % in the cyclosporine group ( P = NS ) . There were no differences in mean serum creatinine between groups . No patients who 
    Output:
    
No statistically significant differences in key outcomes were found between BAS and placebo/no induction .
BAS plus TAC and AZA was predicted to be cost-effective at £ 20,000 - 30,000 per QALY when all regimens were compared using extrapolated adult evidence .