***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND The risk of deep-vein thrombosis ( DVT ) and pulmonary embolism after total hip replacement ( THR ) surgery may persist after hospital discharge , but the extent of the risk is not known . We carried out a single-centre , prospect i ve , r and omised , double-blind trial with the aims of quantifying this risk and assessing the efficacy of continued prophylactic treatment . METHODS At hospital discharge 13 - 15 days after surgery , we recruited 179 consecutive THR patients who had no DVT visible on bilateral ascending venography of the legs . The patients were r and omly assigned subcutaneous enoxaparin ( 40 mg , once daily ; n = 90 ) or placebo ( n = 89 ) for 21 ( 19 - 23 ) days . The primary endpoint was the occurrence of DVT or pulmonary embolism . Venography was repeated at the end of 21 days ' treatment or earlier if necessary . FINDINGS There were no deaths and no symptomatic pulmonary embolisms during the study or follow-up periods . Of 173 patients with evaluable venograms , intention-to-treat analysis of efficacy showed that the rate of DVT at day 21 after discharge was significantly lower in the enoxaparin group than in the placebo group ( 6 [ 7.1 % ] vs 17 [ 19.3 % ] , p = 0.018 ) . Distal DVT was detected in one ( 1.2 % ) patient in the enoxaparin group and in ten ( 11.4 % ) patients in the placebo group ( p = 0.006 ) . Proximal DVT was observed in five ( 5.9 % ) patients in the enoxaparin group and in seven ( 7.9 % ) patients in the placebo group ( p = 0.592 ) . A per protocol analysis of efficacy in 155 patients confirmed these findings . Safety was good ; three minor bleeding episodes occurred in the enoxaparin group and one in the placebo group , but none of these episodes necessitated withdrawal from the study . INTERPRETATION In patients who have undergone THR surgery , are without venogram-proven DVT at hospital discharge , and do not receive antithrombotic prophylaxis after discharge , the risk of late-occurring DVT remains high at least until day 35 after surgery . Continued prophylaxis with enoxaparin is effective and safe in reducing this risk We studied the safety of combining the postoperative use of a non-steroidal anti-inflammatory drug with low-dose heparin . In a double-blind , placebo-controlled clinical trial we review ed the complications in 235 patients after total hip replacement , all treated with low-dose heparin and either indomethacin or a placebo .  The incidence and type of complications in the two groups were nearly equal ; indomethacin-treated patients had no increase in complications related to bleeding . Postoperative bleeding into drains was marginally greater in the indomethacin group , although the difference was not statistically significant . We conclude that treatment with indomethacin and low-dose heparin after hip replacement does not significantly increase the bleeding or other complications . We also found that patients receiving indomethacin were mobilised an average of one day before those on placebo Are meta-analyses the brave new world , or are the critics of such combined analyses right to say that the biases inherent in clinical trials make them uncombinable ? Negative trials are often unreported , and hence can be missed by meta-analysts . And how much heterogeneity between trials is acceptable ? A recent major criticism is that large r and omised trials do not always agree with a prior meta- analysis . Neither individual trials nor meta-analyses , reporting as they do on population effects , tell how to treat the individual patient . Here we take a more rounded approach to meta-analyses , arguing that their strengths outweigh their weaknesses , although the latter must not be brushed aside The peri- and postsurgical thromboembolic prophylaxis with low molecular weight heparins is a well established therapy regimen , but the optimum duration of prophylaxis after surgery still remains uncertain . A few studies have pointed to the fact that the thromboembolic risk of high-risk patients persists longer than the in-hospital period correlating with respective hypercoagulatory conditions . The aim of the present study was to test if a prolongation of thromboprophylaxis with the low molecular weight heparin Certoparin further reduces the rate of thromboembolism in high-risk patients after orthopedic surgery . The " Long-term Thromboprophylaxis"- Study was a multicenter , r and omized , double-blind , placebo-controlled trial . 360 patients who underwent endoprothetic joint replacement or osteo synthesis of the lower limb were initially enrolled , all of them received prophylactically 3000 U anti-Xa of Certoparin once daily for 14 days followed by r and omization to prolonged Certoparin application or to placebo up to day 42 . Patients were screened for deep vein thrombosis by sonography every week . Coagulation markers ( fibrin monomers and D-dimers ) were determined during the course of the study . Venous thromboembolism during the prolongation period was observed in 18 patients receiving placebo versus 8 patients of the prolonged Certoparin group ( 12.1 % versus 5.0 % , intention-to-treat sample ) . The analysis revealed a statistically significant difference in favor of Certoparin ( p=0.020 ) , which was confirmed by per- protocol analysis ( 14.2 % versus 5.5 % , p=0.012 ) . The differences remained significant , if analyses considered only clinical ly symptomatic thromboembolic events ( p=0.040 ) . Patients who developed a thrombosis showed a strong increase of coagulation markers as compared to patients without subsequent thrombosis . The respective differentiation started around 18 days before diagnosis of thrombosis . Only one minor bleeding complication was observed during prolonged Certoparin prophylaxis . The present study shows that patients after joint replacement or osteo synthesis of the lower extremities have a persisting risk to develop thromboembolic complications beyond the routine duration of thromboprophylaxis . Extended prophylaxis with Certoparin result ed in a significantly lower rate of thromboembolism and should be strongly recommended BACKGROUND The optimal duration of thromboprophylaxis after major orthopedic surgery is controversial . Although oral anticoagulants are still widely used for the prevention of venous thromboembolism after hip replacement , to our knowledge no study has assessed the benefit of prolonging anticoagulation beyond the hospital stay . METHODS Consecutive patients who had received warfarin sodium prophylaxis after total hip arthroplasty were r and omized to stop taking the drug at the time of hospital discharge or to continue taking it for 4 more weeks . The rate of symptomatic and asymptomatic venous thromboembolic events ( as shown by compression ultrasonography of the proximal-vein system ) occurring during the study period was compared between the 2 groups . The study was prematurely terminated after the inclusion of the first 360 patients because a statistically significant and clinical ly relevant superiority of extended over short-term thromboprophylaxis was observed . RESULTS Objective ly confirmed venous thromboembolic complications were recorded in 10 patients : 9 ( 5.1 % ) in the group of 176 control patients , and 1 ( 0.5 % ) in the group of 184 patients who continued the warfarin treatment . The absolute difference in the incidence of events was 4.57 % ( 95 % confidence interval [ CI ] , 1.15 - 7.99 ) . The relative risk of venous thromboembolism developing in control patients compared with patients assigned to extended thromboprophylaxis was 9.4 ( 95 % CI , 1.2 - 73.5 ) . The number needed to treat was 22 . Major bleeding developed in 1 patient who was r and omized to the extended prophylaxis group ( 0.5 % ; 95 % CI , 0.02 - 3.0 ) compared with none in the control group . CONCLUSION Extending prophylaxis with warfarin for a few more weeks beyond the hospital stay has the potential to considerably improve the outcome of patients who undergo hip arthroplasty Deep venous thrombosis and pulmonary embolism are common complications after total hip or knee arthroplasty [ 1 , 2 ] . Antithrombotic prophylaxis reduces the rate of postoperative thromboembolic complications , and consensus guidelines strongly recommend its use [ 3 ] . Despite the use of effective prophylaxis , however , many patients who have joint arthroplasty still develop asymptomatic deep venous thrombosis that can be reliably detected only with screening tests [ 1 , 3 ] . Concern about the potential risk for pulmonary embolism as a result of asymptomatic deep venous thrombosis has led clinicians to consider extending the duration of postoperative prophylaxis for up to 3 months or performing routine screening tests to diagnose asymptomatic venous thrombosis before hospital discharge [ 1 , 4 - 7 ] . Compression ultrasonography is the most accurate noninvasive test for diagnosing proximal deep venous thrombosis [ 8 ] . Although compression ultrasonography is less sensitive than venography as a screening test for asymptomatic deep venous thrombosis , most of the proximal thrombi not detected by compression ultrasonography are very small and are of uncertain clinical importance [ 9 , 10 ] . We performed a double-blind , r and omized , controlled trial in patients receiving warfarin prophylaxis after total hip or knee arthroplasty to determine whether performing screening compression ultrasonography to diagnose and guide the treatment of asymptomatic proximal deep venous thrombosis influenced rates of subsequent symptomatic deep venous thrombosis or pulmonary embolism . We also determined the rates of symptomatic venous thromboembolic and major bleeding complications occurring within 90 days of hospital discharge . Methods This trial was conducted at the Victoria General Hospital , Halifax , Nova Scotia , between July 1993 and December 1995 . The research protocol was approved by the hospital 's research review committee . Informed consent was obtained from all patients . Study Sample Consecutive patients undergoing elective total hip or knee arthroplasty who received postoperative warfarin prophylaxis and were expected to be discharged from the hospital within 48 to 72 hours were eligible for the study . Exclusion criteria were 1 ) investigations for symptoms of deep venous thrombosis or pulmonary embolism during warfarin prophylaxis , 2 ) hospitalization for more than 30 days after surgery , 3 ) previous venous thromboembolic disease , 4 ) contraindications to anticoagulant therapy , 5 ) need for long-term anticoagulant therapy , 6 ) acute hip fracture as the indication for arthroplasty , 7 ) use of an anticoagulant other than warfarin for more than 24 hours after surgery , 8) lack of administration of warfarin within 72 hours after surgery , and 9 ) previous enrollment in the study . Within 7 months of the start of recruitment ( after 265 patients had been enrolled ) , metastatic cancer was also made an exclusion criterion to ensure that only patients undergoing elective surgery were included . Prophylaxis and Screening for Deep Venous Thrombosis Patients received 5 mg of sodium warfarin ( Coumadin , Dupont Pharma , Mississauga , Ontario , Canada ) on the night of surgery . The warfarin dose was adjusted to increase the international normalized ratio ( INR ) to more than 1.7 by postoperative day 4 and to maintain it between 1.8 and 2.5 thereafter . Warfarin prophylaxis was continued until hospital discharge . All patients were evaluated daily , as per usual clinical practice by the orthopedic medical staff . Consenting eligible patients were r and omly assigned to undergo either bilateral screening compression ultrasonography or a sham ultrasonography procedure . The r and omization scheme was determined by a computer algorithm . Assignments to the study groups were concealed in sealed envelopes that were opened by an ultrasonographic technologist only after consenting patients arrived in the ultrasonography department . Patients were stratified by type of arthroplasty . Compression ultrasonography was done by using a high-resolution color duplex-doppler scanner with an electronically focused linear array transducer and either 5- or 7.5-MHz probes . The entire proximal deep venous system between the proximal common femoral vein and the trifurcation of the popliteal vein in the calf was evaluated for compressibility at 1-cm intervals . The results of compression ultrasonography  were considered to be positive if a vein or venous segment was not fully compressible [ 11 ] . Patients with positive results underwent confirmatory venography of the involved leg , which was done by using the method of Rabinov and Paulin [ 12 ] . If venography could not be done or if the results of venography were judged to be inadequate because of nonvisualization of the suspected area of thrombosis , the result of screening compression ultrasonography  was considered to be true positive . Patients who received a diagnosis of asymptomatic proximal deep venous thrombosis were treated with unfractionated intravenous heparin for 5 days and had warfarin therapy continued for 3 months with the dose adjusted to maintain the INR between 2.0 and 3.0 . The sham ultrasonography procedure was design ed to mimic the technique of the genuine compression ultrasonography . For both the genuine and the sham procedures , the ultrasonography screen was shielded from patients . Thus , patients , nurses , and physicians did not know whether a patient 
    Output:
    
Moderate quality evidence suggests extended- duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery , although the benefit should be weighed against the increased risk of minor bleeding .