***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 Cancer patients receiving chemotherapy  are at increased risk of thrombosis .  Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events ( TEs ) by about 50 % in cancer out patients receiving chemotherapy . The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy . Methods Cancer out patients were r and omly assigned to receive subcutaneous injections of nadroparin or placebo . The incidence of symptomatic TEs was assessed according to the type of chemotherapy . Results were reported as risk ratios with associated 95 % CI and two-tailed probability values . Results 769 and 381 patients have been evaluated in the nadroparin and placebo group , respectively . In the absence of thromboprophylaxis , the highest rate of TEs was found in patients receiving gemcitabine- ( 8.1 % ) or cisplatin-based chemotherapy ( 7.0 % ) . The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2 % . Thromboprophylaxis reduced TE risk by 68 % in patients receiving gemcitabine ; with a further decrease to 78 % in those receiving a combination of gemcitabine and platinum . Conclusions This retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine , platinum analogues or their combination are at higher risk of TEs . Our results also suggest that out patients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin . Clinical Trial registration number : NCT Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma ( MM ) but is associated with an increased risk of venous thromboembolism ( VTE ) . This prospect i ve , open-label , r and omized sub study of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin ( ASA ) or low-molecular-weight heparin ( LMWH ) in patients with newly diagnosed MM , treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation . Overall , 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA 100 mg/d ( n = 176 ) or LMWH enoxaparin 40 mg/d ( n = 166 ) . The incidence of VTE was 2.27 % in the ASA group and 1.20 % in the LMWH group . Compared with LMWH , the absolute difference in the proportion of VTE was 1.07 % ( 95 % confidence interval , -1.69 - 3.83 ; P = .452 ) in the ASA group . Pulmonary embolism was observed in 1.70 % of patients in the ASA group and none in the LMWH group . No arterial thrombosis , acute cardiovascular events , or sudden deaths were reported . No major hemorrhagic complications were reported . In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk , ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis PURPOSE Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B ( CALGB ) suggested that the addition of warfarin to chemotherapy might enhance response and /or survival in small-cell lung cancer ( SCLC ) . This r and omized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC . PATIENTS AND METHODS Patients were r and omized to receive warfarin or no warfarin .  All patients received three cycles of doxorubicin , cyclophosphamide , and etoposide ( ACE ) . Cycles 4 and 5 ( cisplatin , cyclophosphamide , and etoposide [ PCE ] ) were given concurrently with radiation therapy . Three cycles of ACE were given after chemoradiation therapy , but were discontinued due to a high rate of pulmonary toxicity . RESULTS There were no significant differences in response rates , survival , failure-free survival , disease-free survival , or patterns of relapse between the warfarin-treated and control groups . In patients treated according to the initial design , an increase in failure-free survival seen with warfarin treatment approached significance ( P = .07 ) . Preamendment results , while not significant , did not have superimposable treatment survival curves . A l and mark analysis at 8 months showed a median survival time after the l and mark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin ( P = .05 ) . Differences between the complete responders in this preamendment population were not significant ( P = .103 ) . CONCLUSION Warfarin does not appear to improve outcome significantly in limited-stage SCLC . However , the differences in some variables between population s before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies PURPOSE Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35  recurrences  and 12  bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy Background Advanced pancreatic cancer , in addition to its high mortality , is characterized by one of the highest rates of venous thromboembolic events ( VTE ) as compared to other types of cancer . Enoxaparin , a low molecular weight heparin ( LMWH ) , has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients . Results of some small studies suggest that this benefit might extend to patients with cancer , however , enoxaparin is not currently indicated for this use . This phase IIb study was design ed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy . Methods The aim of this prospect i ve multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation  in 540 patients . Primary endpoint is the incidence of clinical ly relevant VTE ( symptomatic deep venous thrombosis ( DVT ) of the leg and /or pelvic and /or pulmonary embolism ( PE ) ) within the first 3 months . Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6 , 9 and 12 months as well as remission at 3 , 6 , 9 and 12 months , overall survival and bleeding . Trial registration : is rct n.org identifier CCT-NAPN-16752 , controlled-trials.com identifier : IS RCT N02140505 . Results An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding ( 5 pts vs. 6 pts , Chi2 : 0.763 ) . Conclusion PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer . Its results will lead to a new underst and ing of the role of heparins in the prevention of venous thromboembolism and of their effect on survival , remission rates and toxicity of chemotherapeutic regimens Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVE To study the efficacy of daily low-dose aspirin ( 81 mg orally ) in decreasing the incidence of venous thromboembolic events ( VTEs  ) in patients with multiple myeloma receiving pegylated doxorubicin , vincristine , and decreased-frequency dexamethasone , plus thalidomide ( DVd-T ) . PATIENTS AND METHODS In this phase 2 clinical trial of DVd-T , conducted by the Clevel and Clinic Foundation from August 2001 to October 2003 , 105 patients were enrolled . The first 35 patients experienced increased numbers of VTEs . von Willebr and levels and platelet aggregation to ristocetin before and after treatment with DVd-T increased significantly , suggesting a pathophysiology involving platelet-endothelial interaction . Aspirin was added to the regimen , thus generating 3 patient groups : group 1 received aspirin from the start of DVd-T treatment before the study began ( 58 patients ) , group 2 received aspirin after the start of DVd-T treatment and after the study began ( 26 patients ) , and group 3 did not receive daily low-dose aspirin during the study ( 19 patients ) . Two patients being treated with warfarin for other indications were excluded from the study . The primary end point for this study was the incidence of VTE in the form of either deep venous thrombosis or pulmonary embolism . Secondary end points were the time to the first VTE , time to the composite end point of death or first VTE , and incidence of bleeding complications . RESULTS After a median follow-up of 24 months , on an intent-to-treat basis , 26 posttreatment VTEs occurred after a median of 90 days , with 19 % occurring in group 1 , 15 % in group 2 , and 58 % in group 3 . Following multivariate time-to-event analysis , aspirin use continued to be associated with lower relative risk of VTE ( hazard ratio , 0.22 ; confidence interval , 0.10 - 0.47 ; P<.001 ) and of the composite end point ( hazard ratio , 0.28 ; confidence interval , 0.15 - 0.51 ; P<.001 ) . CONCLUSION Daily low-dose aspirin ( 81 mg orally ) given to patients with newly diagnosed and relapsed/refractory multiple myeloma who were receiving DVd-T reduced the incidence of VTEs without an increase in bleeding complications BACKGROUND Children with acute lymphoblastic leukemia ( ALL ) have a substantial risk for thromboembolism ( TE ) that is related to L-asparaginase-induced antithrombin ( AT ) deficiency and placement of central venous lines . Recent in vitro studies showed that the anticoagulant effects of low-molecular-weight heparin were profoundly affected 
    Output:
    
Antithrombin , evaluated in one study involving paediatric patients , had no significant effect on VTE or on major bleeding when compared with no antithrombin .
AUTHORS ' CONCLUSIONS In this second up date , we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy .
In addition , the uLMWH semuloparin , which is not commercially available , significantly reduced the incidence of symptomatic VTE .