***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: Low-molecular-weight heparins ( LMWHs ) accumulate in patients with impaired renal function . As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination , LMWHs might have different pharmacodynamic profiles . The primary objective was to examine if any accumulation effect of two LMWHs , enoxaparin and tinzaparin , occurred after repeated administration of a prophylactic dose over eight days in elderly patients ( age > 75 years ) with creatinine clearance between 20 and 50 ml/min and body weight < 65Kg . Patients were openly r and omized to two groups ( enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily ) . Anti-Xa was measured on day 1 and day 8 . Blood sample s were taken at 0 , 2 , 4 , 5 , 6 , 9 , 12 , 16 and 24 hours . The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day 1 and day 8 . Fifty-five patients were included ( mean age 87.9 + /- 5.5 ) . The creatinine clearance was 34.7 + /- 11.4 ml/min ; the body weight was 52.3 + /- 8.6 kg . The accumulation factor defined was not significant for tinzaparin ( 1.05 , p = 0.29 ) while it was significantly enhanced for enoxaparin ( 1.22 , p < 0.0001 ) . In this pharmacodynamic study performed in elderly patients with impaired renal function , a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin , which are two LMWHs with different chain lengths . Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations Patients with severe renal insufficiency ( sRI ) have been suggested to be at an increased risk of bleeding with low-molecular-weight heparins ( LMWH ) . We aim ed at assessing the benefits and risks of certoparin in comparison to unfractionated heparin ( UFH ) in these patients . In this subgroup analysis of the CERTIFY trial , acutely ill , non-surgical patients ≥70 years received certoparin 3,000U aXa o.d . or UFH 5,000 IU t.i.d .  One hundred eighty-nine patients had a glomerular filtration rate ( GFR ) ≤30 ml/min/1.73 m2 , 3,050 patients served as controls . Patients with sRI had a mean age of 85.9 ± 6.6 years ( controls 78.4 ± 6.0 ) and were treated for a mean of 9.3 ± 3.7 days ( 9.9 ± 4.3 ) . Thromboembolic event rates were comparable ( 4.55 vs. 4.21 % ; OR1.08 ; 95%CI 0.5 - 2.37 ) but bleeding was increased in sRI ( 9.52 vs. 3.54 % ; OR2.87 ; 95%CI 1.70 - 4.83 ) . The incidence of the combined end-point of proximal DVT , symptomatic non-fatal PE and VTE related death was 6.49 % with certoparin and 2.60 % with UFH ( OR2.60 ; 95%CI 0.49 - 13.85 ) . There was a decrease in total bleeding  with certoparin ( OR0.33 ; 95%CI 0.11 - 0.97 ) , which was non-significant in patients with GFR > 30 ml/min/1.73 m2 . In two multivariable regression models certoparin and immobilisation < 10 days were associated with less bleeding while a GFR ≤30 ml/min/1.73 m2 was associated with increased bleeding . A total of 11.3 % of certoparin- and 18.5 % of UFH-treated patients experienced serious adverse events ( 14.8 in patients with a GFR ≤30 vs. 5.6 % vs. > 30 ml/min/1.73 m2 ) . In conclusion , certoparin 3,000U anti Xa o.d . was as efficacious as 5,000 IU UFH t.i.d . in patients with sRI but had a reduced risk of bleeding OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Enoxaparin is commonly used to prevent venous thromboembolism(VTE ) [ 1,2 ] but has not been well-studied in patients with extreme obesity , a population at high risk for VTE . We prospect ively compared three enoxaparin dosing regimens for the achievement of goal peak anti-Factor Xa levels in medically ill patients ( n 5 31 ) with extreme obesity ( body mass index ( BMI ) ‡ 40 kg/m2 ) . Patients were assigned to receive fixed-dose ( FD ) enoxaparin 40 mg daily ( QDay , n 5 11 ) , weight based , lower-dose ( LD ) enoxaparin 0.4 mg/kg QDay ( n 5 9 ) , or weight based , higher-dose ( HD ) enoxaparin 0.5 mg/kg QDay ( n 5 11 ) . The  average BMI and weight of the entire cohort was 62.1 kg/m2 ( range40.5–82.4 ) and 176 kg ( range 115–256 kg ) and did not differ between  groups . Peak anti-Factor Xa levels were significantly higher in the HD group compared to either LD or FD groups . Patients in the HD group achieved target anti-Factor Xa levels more frequently than the LD and FD groups ( P < 0.05 ) . Peak anti-Factor Xa levels did not correlate with age , weight , BMI , or creatinine clearance , demonstrating the predictability of weight-based enoxaparin dosing . There were no adverse events ( e.g. , bleeding , thrombosis , thrombocytopenia ) . To our knowledge this is the first prospect i ve comparative study demonstrating that in extremely obese , medically ill patients enoxaparin 0.5 mg/kg QDay is superior to FD and LD enoxaparin for the achievement of target anti-Factor Xa levels Patients undergoing total hip or knee arthroplasty should receive anticoagulant therapy because of the high risk of venous thromboembolism . However , many are already taking non-steroidal anti-inflammatory drugs ( NSAIDs ) or acetylsalicylic acid ( ASA ) that can have antihaemostatic effects . We assessed the bleeding risk in patients treated with thromboprophylactic dabigatran etexilate , with and without concomitant NSAID or ASA .  A post-hoc analysis was undertaken of the pooled data from trials comparing dabigatran etexilate ( 220 mg and 150 mg once daily ) and enoxaparin .  Major bleeding event ( MBE ) rates were determined and odds ratios ( ORs ) generated for patients who received study treatment plus NSAID ( half-life ≤12 hours ) or ASA ( ≤160 mg/day ) versus study treatment alone . Relative risks were calculated for comparisons between treatments . Overall , 4,405/8,135 patients ( 54.1 % ) received concomitant NSAID and 386/8,135 ( 4.7 % ) received ASA.ORs for the comparison with/without concomitant NSAID were 1.05 ( 95 % confidence interval [ CI ] 0.55 - 2.01 ) for 220 mg dabigatran etexilate ; 1.19 ( 0.55 - 2.55 ) for 150 mg ; and 1.32 ( 0.67 - 2.57 ) for enoxaparin . ORs for the comparison with/without ASA were 1.14 ( 0.26 - 5.03 ) ; 1.64 ( 0.36 - 7.49 ) ; and 2.57 ( 0.83 - 7.94 ) , respectively . For both NSAIDs and ASA there was no significant difference in bleeding between patients with and without concomitant therapy in any treatment arm . Patients concomitantly taking NSAIDs or ASA have a similar risk of MBE to those taking dabigatran etexilate alone . No significant differences in MBE were detected between dabigatran etexilate and enoxaparin within co-medication subgroups , suggesting that no increased major bleeding risk exists when dabigatran etexilate is administered with NSAID or ASA BACKGROUND Venous thromboembolism ( VTE ) remains a significant complication of major orthopedic surgery , and chronic kidney disease ( CKD ) is common among elderly patients undergoing total hip replacement ( THR ) . OBJECTIVES The purpose of this study was to evaluate thrombosis and bleeding outcomes in patients with stage 3B CKD treated with either desirudin or enoxaparin after elective THR . PATIENTS / METHODS This was a post hoc subgroup analysis of a r and omized , multicenter , double-blind study of desirudin vs. enoxaparin in patients undergoing elective THR . RESULTS Patients received either subcutaneous desirudin 15 mg twice daily or subcutaneous enoxaparin 40 mg once daily . Of the 2078 r and omized patients who received study medication , 577 had stage 3B CKD or worse ( 27.8 % ) , and the proportion of these patients who experienced a major VTE in the enoxaparin treatment group was found to be much higher than in the desirudin treatment group ( 11.1 % vs. 3.4 % , model-adjusted odds ratio 3.52 , 95 % confidence interval 1.48 - 8.40 , P=0.004 ) . There was no statistically significant difference between treatment groups in terms of rates of major bleeding , regardless of stage of renal function . CONCLUSIONS CKD has been reported previously to increase the risk of bleeding with anticoagulants , and these findings suggest that CKD may also increase the risk of major VTE for patients treated with enoxaparin , but not for patients treated with desirudin . Clinicians should consider the impact of CKD on the risk of VTE when choosing a prophylaxis agent BACKGROUND We were concerned that a fixed rather than a weight-based dosing regimen of dalteparin sodium to prevent venous thromboembolism ( VTE ) might result in decreased efficacy in obese patients and decreased safety in elderly patients . METHODS We retrospectively performed subgroup analyses using the data base from the Prospect i ve Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients ( PREVENT ) Trial , a study of 3706 hospitalized , medically ill patients r and omized to receive either dalteparin sodium , 5000 U/d , or placebo .  The primary end point was a composite of symptomatic VTE , fatal pulmonary embolism , sudden death , or asymptomatic proximal deep venous thrombosis by day 21 . Obesity was defined as a body mass index ( calculated as weight in kilograms divided by the square of height in meters ) of 30 or greater for men and 28.6 or greater for women . RESULTS 
    Output:
    
The current evidence is insufficient regarding optimal VTE prophylaxis for patients with renal insufficiency , obesity , or those who are on antiplatelet drugs including aspirin .