***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 Compared with World Health Organization-defined acute myeloid leukaemia ( AML ) not otherwise specified , patients with AML with myelodysplasia-related changes ( AML-MRC ) are generally older and more likely to have poor-risk cytogenetics , leading to poor response and prognosis . More than one-half of all older ( ≥65 years ) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC . Methods We compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens ( CCR ; induction chemotherapy , low-dose cytarabine , or supportive care only ) overall and within patient subgroups defined by cytogenetic risk ( intermediate or poor ) and age ( 65–74 years or ≥75 years ) . The same analyses were used to compare azacitidine with low-dose cytarabine in patients who had been preselected to low-dose cytarabine before they were r and omized to receive azacitidine or CCR ( ie , low-dose cytarabine ) . Results Median overall survival was significantly prolonged with azacitidine ( n = 129 ) versus CCR ( n = 133 ) : 8.9 versus 4.9 months ( hazard ratio 0.74 , [ 95%CI 0.57 , 0.97 ] ) . Among patients with intermediate-risk cytogenetics , median overall survival  with azacitidine was 16.4 months , and with CCR was 8.9 months ( hazard ratio 0.73 [ 95%CI 0.48 , 1.10 ] ) . Median overall survival was significantly improved for patients ages 65–74 years treated with azacitidine compared with those who received CCR ( 14.2 versus 7.3 months , respectively ; hazard ratio 0.64 [ 95%CI 0.42 , 0.97 ] ) . Within the subgroup of patients preselected to low-dose cytarabine before r and omization , median overall survival  with azacitidine was 9.5 months versus 4.6 months with low-dose cytarabine ( hazard ratio 0.77 [ 95%CI 0.55 , 1.09 ] ) . Within the low-dose cytarabine pre selection group , patients with intermediate-risk cytogenetics who received azacitidine had a median overall survival of 14.1 months versus 6.4 months with low-dose cytarabine , and patients aged 65–74 years had median survival of 14.9 months versus 5.2 months , respectively . Overall response rates were similar with azacitidine and CCR ( 24.8 % and 17.3 % , respectively ) , but higher with azacitidine versus low-dose cytarabine ( 27.2 % and 13.9 % ) . Adverse events were generally comparable between the treatment arms . Conclusions Azacitidine may be the preferred treatment for patients with AML-MRC who are not c and i date s for intensive chemotherapy , particularly patients ages 65–74 years and those with intermediate-risk cytogenetics . Trial registration This study was registered at clinical Trials.gov on February 16 , 2010 ( NCT01074047 ) PURPOSE This multicenter , r and omized , open-label , phase III trial compared the efficacy and safety of decitabine with treatment choice ( TC ) in older patients with newly diagnosed acute myeloid leukemia ( AML ) and poor- or intermediate-risk cytogenetics . PATIENTS AND METHODS Patients ( N = 485 ) age ≥ 65 years were r and omly assigned 1:1 to receive decitabine 20 mg/m(2 ) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC ( supportive care or cytarabine 20 mg/m(2 ) per day as a subcutaneous injection for 10 consecutive days every 4 weeks ) . The primary end point was overall survival ( OS ) ; the secondary end point was the complete remission ( CR ) rate plus the CR rate without platelet recovery ( CRp ) . Adverse events ( AEs ) were recorded . RESULTS The primary analysis with 396 deaths ( 81.6 % ) showed a nonsignificant increase in median OS with decitabine ( 7.7 months ; 95 % CI , 6.2 to 9.2 ) versus TC ( 5.0 months ; 95 % CI , 4.3 to 6.3 ; P = .108 ; hazard ratio [ HR ] , 0.85 ; 95 % CI , 0.69 to 1.04 ) . An unplanned analysis with 446 deaths ( 92 % ) indicated the same median OS ( HR , 0.82 ; 95 % CI , 0.68 to 0.99 ; nominal P = .037 ) . The CR rate plus CRp was 17.8 % with decitabine versus 7.8 % with TC ( odds ratio , 2.5 ; 95 % CI , 1.4 to 4.8 ; P = .001 ) . AEs were similar for decitabine and cytarabine , although patients received a median of four cycles of decitabine versus two cycles of TC . The most common drug-related AEs with decitabine were thrombocytopenia ( 27 % ) and neutropenia ( 24 % ) . CONCLUSION In older patients with AML  , decitabine improved response rates compared with st and ard therapies without major differences in safety . An unplanned survival analysis showed a benefit for decitabine , which was not observed at the time of the primary analysis PURPOSE In a phase III r and omized trial , azacitidine significantly prolonged overall survival ( OS ) compared with conventional care regimens ( CCRs ) in patients with intermediate-2- and high-risk myelodysplastic syndromes . Approximately one third of these patients were classified as having acute myeloid leukemia ( AML ) under current WHO criteria . This analysis compared the effects of azacitidine versus CCR on OS in this subgroup . PATIENTS AND METHODS Patients were r and omly assigned to receive subcutaneous azacitidine 75 mg/m(2)/d or CCR ( best supportive care [ BSC ] only , low-dose cytarabine ( LDAC ) , or intensive chemotherapy [ IC ] ) . RESULTS Of the 113 elderly patients ( median age , 70 years ) r and omly assigned to receive azacitidine ( n = 55 ) or CCR ( n = 58 ; 47 % BSC , 34 % LDAC , 19 % IC ) , 86 % were considered unfit for IC . At a median follow-up of 20.1 months , median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients ( hazard ratio = 0.47 ; 95 % CI , 0.28 to 0.79 ; P = .005 ) , and 2-year OS rates were 50 % and 16 % , respectively ( P = .001 ) . Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC ( P = .0003 ) . Azacitidine was associated with fewer total days in hospital ( P < .0001 ) than CCR . CONCLUSION In older adult patients with low marrow blast count ( 20 % to 30 % ) WHO-defined AML , azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin  and  heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful BACKGROUND Hypomethylating agents , such as decitabine , are the st and ard of care for older patients with newly diagnosed acute myeloid leukaemia . Single-arm studies have suggested that a 10-day schedule of decitabine cycles leads to better outcomes than the usual 5-day schedule . We compared the efficacy and safety of these two schedules . METHODS Eligible patients were aged 60 years or older with acute myeloid leukaemia but unsuitable for intensive chemotherapy ( or < 60 years if unsuitable for intensive chemotherapy with an anthracycline plus cytarabine ) . The first 40 patients were allocated equally to the two treatment groups by computer-generated block r and omisation ( block size 40 ) , after which a response-adaptive r and omisation algorithm used all previous patients ' treatment and response data to decide the allocation of each following patient favouring the group with superior response . Patients were assigned to receive 20 mg/m2 decitabine intravenously for 5 or 10 consecutive days as induction therapy , every 4 - 8 weeks for up to three cycles . Responding patients received decitabine as consolidation therapy on a 5-day schedule for up to 24 cycles . We assessed a composite primary endpoint of complete remission , complete remission with incomplete platelet recovery ( CRp ) , and complete remission with incomplete haematological recovery ( CRi ) achieved at any time and assessed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01786343 . FINDINGS Between Feb 28 , 2013 , and April 12 , 2018 , 71 patients were enrolled . 28 received decitabine for 5 days and 43 for 10 days , and all were assessable for efficacy and safety . The primary endpoint was achieved in similar proportions of patients in the two treatment groups ( 12 [ 43 % ] of 28 in the 5-day schedule group , 95 % credible interval 26 - 60 , and 17 [ 40 % ] of 43 in the 10-day schedule group , 26 - 54 , p=0·78 ; difference 3 % , -21 to 27 ) . Total follow-up was 38·2 months , during which the median duration of overall survival was 5·5 months ( IQR 2·1 - 11·7 ) in the 5-day group and 6·0 months ( 1·9 - 11·7 ) in the 10-day group . 1-year overall survival was 25 % in both groups . Complete remission , CRp , CRi , and overall survival did not differ between groups when stratified by cytogenetics , de-novo versus secondary or therapy-related acute myeloid leukaemia , or TP53mut status . The most common grade 3 - 4 adverse events were neutropenic fever ( seven patients [  
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No statistical significance was found for the other studied outcomes .
Compared to CCR , decitabine and azacitidine can promote studied outcomes in elderly AML patients .