***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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    ***EXAMPLES*** 
    Input: We did a prospect i ve study of women with singleton viable pregnancies at 10 - 13 weeks ' gestation who requested first-trimester fetal karyotyping because of advanced maternal age , parental anxiety , or family history of chromosomal abnormality . Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis , early amniocentesis ( EA ) , or chorionic villus sampling ( CVS ) , or r and omisation to EA or CVS at 10 - 13 weeks . EA was done in 731 patients ( 493 by choice and 238 by r and omisation ) and CVS in 570 ( 320 by choice and 250 by r and omisation ) . Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle . The rate of successful sampling was the same for both procedures ( 97.5 % ) . Spontaneous loss ( intrauterine or neonatal death ) was significantly higher after EA ( total group mean = 5.3 % , 95 % CI 3.8 - 7.2 ; r and omised subgroup mean = 5.9 % , 3.3 - 9.7 ) than after CVS ( total group : mean = 2.3 % , 1.2 - 3.9 ; r and omised subgroup : mean = 1.2 % , 0.3 - 3.5 ) . The gestation at delivery and birthweight of the infants after EA and CVS were similar . In the EA group the incidence of talipes equinovarus ( 1.63 % ) , was higher than in the CVS group ( 0.56 % ) , but this difference was not significant 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 OBJECTIVES To compare the clinical - and cost-effectiveness of minimally invasive direct coronary artery bypass grafting ( MIDCAB ) and percutaneous transluminal coronary angioplasty ( PTCA ) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery ( LAD ) . DESIGN Multi-centre r and omised trial without blinding . The computer-generated sequence of r and omised assignments was stratified by centre , allocated participants in blocks and was concealed using a central ised telephone facility . SETTING Four tertiary cardiothoracic surgery centres in Engl and . PARTICIPANTS Patients with ischaemic heart disease with at least 50 % proximal stenosis of the LAD , suitable for either PTCA or MIDCAB , and with no significant disease in another vessel . INTERVENTIONS Patients r and omised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure . Patients r and omised to MIDCAB had general anaesthetic . The chest was opened through an 8 - 10-cm left anterior thoracotomy . The ribs were retracted and the left internal thoracic artery ( LITA ) harvested . The pericardium was opened in the line of the LAD to confirm the feasibility of operation . The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD . All operators were experienced in carrying out MIDCAB . MAIN OUTCOME MEASURES The primary outcome measure was survival free from cardiac-related events . Relevant events were death , myocardial infa rct ion , repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up . Secondary outcome measures were complications , functional outcome , disease-specific and generic quality of life , health and social services re source use and their costs . RESULTS A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001 . Of the 1091 patients with proximal stenosis of the LAD , 127 were eligible and consented to take part ; 100 were r and omised and the remaining 27 consented to follow-up . All r and omised participants were included in an intention-to-treat analysis of survival free from cardiac-related events , which found a non-significant benefit from MIDCAB .  Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2 % for MIDCAB and PTCA , respectively . There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life . The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA , respectively . The costs of re sources used during 1 year of follow-up were 1033 British pounds and 843 British pounds , respectively . CONCLUSIONS The study found no evidence that MIDCAB was more effective than PTCA . The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA . Given these findings , it is unlikely that MIDCAB represents a cost-effective use of re sources in the reference population . Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB . At the same time , cardiologists are treating more patients with multi-vessel disease by PTCA . Future primary research should focus on this comparison . Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review The Emory Angioplasty versus Surgery Trial ( EAST ) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty ( PTCA ) and coronary bypass surgery ( CABG )  had equivalent 3-year outcomes regarding survival , myocardial infa rct ion , and major myocardial ischemia .  Patients eligible for the trial who were not r and omized because of physician or patient refusal were followed in a registry . This study compares the outcomes of the r and omized and registry patients . Of the 842 eligible patients , 450 did not enter the trial . Their baseline features closely resembled those of the r and omized patients and follow up was performed using the same methods . In the registry there was a bias toward selecting CABG in patients with 3-vessel disease ( 84 % ) and PTCA in patients with 2-vessel disease ( 54 % ) . Three-year survival for the registry patients was 96.4 % , which was better than the r and omized patients , 93.4 % ( p = 0.044 ) . Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry ( 12.4 % ) than PTCA r and omized patients ( 19.6 % ) ( p = 0.079 ) . Thus , the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup . Since baseline differences were small , improved survival in the registry may be due to treatment selection . Physician judgment , even in patients judged appropriate for clinical trials , remains a potentially important predictor of outcomes OBJECTIVES This study was done to compare characteristics and outcomes of patients with acute myocardial infa rct ion participating in two thrombolysis trials with those of nontrial patients at study hospitals and external hospitals . BACKGROUND Preferential recruitment of lower risk patients into r and omized trials of thrombolysis has been suggested by earlier studies . However , to date there has not been a definitive population -based comparison of characteristics and outcomes for thrombolysis trial participants and non participants . METHODS Population -based data on hospital admissions and mortality from acute myocardial infa rct ion for all hospitals in Ontario from 1989 to 1992 were linked to data on trial participants in two distinct thrombolysis studies ( GUSTO I and LATE ) . Included were 1,304 patients entered into GUSTO , 12,657 non participants at GUSTO hospitals , 249 patients entered into LATE , 5,997 non participants at LATE hospitals and 12,299 patients at external hospitals . The main outcomes were differences in age , gender , comorbidity scores , coronary revascularization and survival to hospital discharge . RESULTS Patients in both GUSTO and LATE were significantly more likely to be < 70 years old ( odds ratio [ OR ] 2.8 and 3.2 , respectively ) , to be male ( OR 2.0 and 2.1 , respectively ) , to have low comorbidity scores ( OR 2.0 and 2.3 , respectively ) and , for GUSTO alone , to undergo coronary revascularization ( OR 2.4 ) . Nontrial patients were similar between trial hospitals and external hospitals . In-hospital mortality rates for GUSTO and LATE patients were lower ( 6.9 % and 6.6 % , respectively ) than for non participants at study hospitals ( 16.8 % and 19.7 % , respectively ; p<0.001 for both comparisons ) . Survival to hospital discharge remained higher among GUSTO ( OR 1.9 ) and LATE patients ( OR 2.0 ) than non participants at study hospitals even after adjustment for age , gender , revascularization and comorbidity scores . CONCLUSIONS Compared with nontrial patients , thrombolysis trial participants are younger , more often male , undergo more revascularization and have less comorbid disease . Even after adjustment for these factors , participants have a survival advantage over non participants that is larger than expected from thrombolysis alone . These findings are not attributable to inferior care or skewed population s at hospitals that did not join these major trials . Further study of these selection biases may guide future trial design and deepen our underst and ing of why thrombolytics have been underused for high risk patients in routine practice The Coronary Artery Surgery Study ( CASS ) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infa rct ion who were r and omized to either medical or surgical therapy and 1,319 patients who were eligible for r and omization but were not r and omized ( r and omizable patients ) . There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the r and omized and r and omizable patients assigned to the medical ( 79 % versus 80 % ) or surgical ( 82 % versus 81 % ) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction . Cox regression analyses were done with independent variables known to be predictors of survival , including surgical versus medical therapy and r and omized versus r and omizable group , to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment ( r and omized versus r and omizable ) . In no case did the initial group category enter as a significant predictor of survival . The results in the r and omizable group reinforce those in the r and omized group with respect to the medical versus surgical comparison . Two subgroups are identified with a significant surgical advantage : 1 ) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70 % and an ejection fraction less than 0.50 , and 2 ) patients with three vessel coronary artery disease and an ejection fraction less than 0.50 . In both groups , coronary bypass surgery had a statistically significant beneficial effect on survival ( p less than 0.05 ) . After a decade of follow-up 
    Output:
    
This review indicates that participation in RCTs is associated with similar outcomes to receiving the same treatment outside RCTs .