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Goran Garellick - One of the best experts on this subject based on the ideXlab platform.
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is the use of antidepressants associated with patient reported outcomes following total Hip Replacement Surgery
Acta Orthopaedica, 2016Co-Authors: Meridith E Greene, Ola Rolfson, Henrik Malchau, Max Gordon, Kristina Annerbrink, Goran GarellickAbstract:Background and purpose - Patients with anxiety and/or depression tend to report less pain reduction and less satisfaction with surgical treatment. We hypothesized that the use of antidepressants would be correlated to patient-reported outcomes (PROs) 1 year after total Hip Replacement (THR), where increased dosage or discontinuation would be associated with worse outcomes. Patients and methods - THR cases with pre- and postoperative patient-reported outcome measures (PROMs) were selected from the Swedish Hip Arthroplasty Register (n = 9,092; women: n = 5,106). The PROMs were EQ-5D, visual analog scale (VAS) for pain, Charnley class, and VAS for satisfaction after Surgery. These cases were merged with a national database of prescription purchases to determine the prevalence of antidepressant purchases. Regression analyses were performed where PROs were dependent variables and sex, age, Charnley class, preoperative pain, preoperative health-related quality of life (HRQoL), patient-reported anxiety/depression, and antidepressant use were independent variables. Results - Antidepressants were used by 10% of the cases (n = 943). Patients using antidepressants had poorer HRQoL and higher levels of pain before and after Surgery and they experienced less satisfaction. Preoperative antidepressant use was independently associated with PROs 1 year after THR regardless of patient-reported anxiety/depression. Interpretation - Antidepressant usage before Surgery was associated with reduced PROs after THR. Cases at risk of poorer outcomes may be identified through review of the patient's medical record. Clinicians are encouraged to screen for antidepressant use preoperatively, because their use may be associated with PROs after THR.
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internet based follow up questionnaire for measuring patient reported outcome after total Hip Replacement Surgery reliability and response rate
Value in Health, 2011Co-Authors: Ola Rolfson, Leif Dahlberg, Roger Salomonsson, Goran GarellickAbstract:Abstract Objective This randomized methodologic study sought to test the reliability of an Internet questionnaire and investigate the differences in response rates between traditional pen-and-paper questionnaires and Internet questionnaires for measuring patient-reported outcome after total Hip Replacement Surgery. Methods From the Swedish Hip Arthroplasty Register, 2400 patients were chosen at random but stratified by age, sex, and diagnosis for inclusion in a 4-year follow-up using the health-related quality of life tool EQ-5D and visual analogue scales for pain and satisfaction. The patients were randomized to answer the follow-up model protocol either via a password-protected Internet questionnaire or via a mailed pen-and-paper questionnaire. Results A reliability test for the Internet follow-up instrument showed adequate correlation. However, the Internet group and the pen-and-paper group differed significantly (P Conclusions The patient-administered Internet questionnaire alone does not give a sufficient response rate in the total Hip Replacement population to replace the pen-and-paper questionnaire. However, the system is reliable and could be used for measuring patient-reported outcome if supplemented with traditional pen-and-paper questionnaires for Internet nonrespondents. It is expected that this answer procedure will soon predominate in view of the general development of Internet functions. Register work may then become less resource-consuming and the results may be analyzed in real time.
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variables determining outcome in total Hip Replacement Surgery
Orthopaedic Proceedings, 2010Co-Authors: Ola Rolfson, Leif Dahlberg, Janake Nilsson, Henrik Malchau, Goran GarellickAbstract:Objective: The Charnley grading system (A, B, C) has previously been shown to be a valid predictor concerning outcome after joint Replacement Surgery. In this study we hypothesized that anxiety/depression, one of five dimensions in the health related quality of life measurement tool EQ-5D, could predict the outcome after total Hip Replacement Surgery. Methods: Data from the Swedish Hip Arthroplasty Register including 6 158 patients with primary osteoarthritis were analysed. To examine the association of anxiety with respect to the outcome of pain (VAS) and satisfaction (VAS) a general linear regression model was used. A subgroup of 481 patients in the Western Region of Sweden with complete data on individual CPP (cost per patient) was selected for the health economic analysis. Results: The preoperative EQ-5D anxiety/depression dimension was a strong predictor for pain relief, patient satisfaction, and cost-effectiveness with Surgery. Patients with comorbidity (Charnley category C) had a significant worse outcome with regards to pain relief, satisfaction and EQ-5D index scores than patients in Charnley category A and B (p Conclusion: Orthopaedic surgeons involved with the care of patients eligible for THR Surgery should be alert to the fact that mental health may influence pain-experience and HRQoL outcome. Appropriate assessment of mental health may enable us to modify the approach in which we manage these patients, in order to optimize the outcome following joint Replacement Surgery.
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variables determining outcome in total Hip Replacement Surgery
Journal of Bone and Joint Surgery-british Volume, 2009Co-Authors: Ola Rolfson, Leif Dahlberg, Janake Nilsson, Henrik Malchau, Goran GarellickAbstract:In this study we hypothesised that anxiety/depression, one of five dimensions in the health-related quality of life (HRQoL) measurement tool EQ-5D, could predict outcome after total Hip Replacement Surgery. Pre-operative and one-year post-operative data from the Swedish Hip Arthroplasty Register, including 6158 patients with primary osteoarthritis of the Hip, were analysed. In order to examine the association between anxiety and outcome with respect to pain and satisfaction an analysis of covariance was used. The pre-operative EQ-5D anxiety/depression dimension was a strong predictor for pain relief and patient satisfaction (p < 0.001). Orthopaedic surgeons involved in the care of patients eligible for total Hip Replacement Surgery should be aware that mental health may influence post-operative pain and HRQoL. An appropriate assessment of mental health may enable a modification in the way these patients are managed in order to optimise the outcome after joint Replacement Surgery.
Ola E. Dahl - One of the best experts on this subject based on the ideXlab platform.
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dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total Hip Replacement a randomised double blind non inferiority trial
The Lancet, 2007Co-Authors: Bengt I Eriksson, Ola E. Dahl, Martin H Prins, Nadia Rosencher, Andreas A Kurth, Niek C Van Dijk, Simon P Frostick, Rohan Hettiarachchi, Stefan Hantel, Janet SchneeAbstract:Summary Background After Hip Replacement Surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis. Methods In this double-blind study, we randomised 3494 patients undergoing total Hip Replacement to treatment for 28–35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1–4 h after Surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before Surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7·7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818. Findings Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6·7%) of 897 individuals in the enoxaparin group versus 53 (6·0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference −0·7%, 95% CI −2·9 to 1·6%) and 75 (8·6%) of 874 people in the 150 mg group (1·9%, −0·6 to 4·4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0·44 for 220 mg, p=0·60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups. Interpretation Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total Hip Replacement Surgery, with a similar safety profile.
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dose escalation study of rivaroxaban bay 59 7939 an oral direct factor xa inhibitor for the prevention of venous thromboembolism in patients undergoing total Hip Replacement
Thrombosis Research, 2007Co-Authors: Bengt I Eriksson, Ola E. Dahl, Frank Misselwitz, Lars C Borris, Sylvia Haas, Menno V Huisman, Ajay K Kakkar, Eva Muehlhofer, Peter KaleboAbstract:Abstract Introduction Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban. Materials and methods This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total Hip Replacement Surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6–8 h after Surgery) or enoxaparin (40 mg od starting the evening before Surgery). Therapy continued until mandatory bilateral venography was performed 5–9 days after Surgery. Results A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint – deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality – occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationsHip with rivaroxaban for the primary efficacy endpoint was not statistically significant ( p = 0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban ( p = 0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban ( p = 0.0008), occurring in 0–10.8% of patients, compared with 0% in patients receiving enoxaparin. Conclusions This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total Hip Replacement Surgery.
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investment in prolonged thromboprophylaxis with dalteparin improves clinical outcomes after Hip Replacement
Journal of Thrombosis and Haemostasis, 2003Co-Authors: Ola E. Dahl, A M PleilAbstract:Summary. Clinical guidelines recommend the use of extended out-of-hospital thromboprophylaxis in patients who have had major arthroplasty. However, the cost-effectiveness of prolonging pharmacological thromboprophylaxis into the out-of-hospital phase following Hip Replacement Surgery remains the subject of considerable debate. This debate centers on the clinical relevance of the ‘surrogate’ venographic endpoints that have been used in most clinical trials and used to generate some of the cost analyses of thromboprophylaxis. The objective of this study was to estimate, from the payer perspective, the direct medical costs of prolonging the duration of thromboprophylaxis with dalteparin from 1 week to 28–35 days in patients undergoing Hip Replacement, and to compare these to the costs associated with using ‘standard’ in-hospital thromboprophylaxis with low-molecular-weight heparin (LMWH) or warfarin. To derive ‘best’ estimates for rates of clinically and economically relevant thromboembolism associated with Hip Replacement Surgery (i.e. those that would in reality incur management costs), we used data on the prevalence of both symptomatic and asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). These estimates were used in conjunction with diagnostic-related groups (DRG) reimbursement rates and a dalteparin cost model, which assumed home-based self-administration for prolonged thromboprophylaxis, to calculate overall direct medical costs of prolonged vs. in-hospital thromboprophylaxis. The management costs of the strategies evaluated were, to the nearest 1000 Euros: 465 000 Euros for in-hospital prophylaxis with LMWH; 339 000 Euros for in-hospital prophylaxis with warfarin; and 368 000 Euros for prolonged prophylaxis with dalteparin. For every 1000 patients treated, prolonging thromboprophylaxis with dalteparin from 1 to 4–5 weeks will avoid 30 clinical DVTs and 18 PEs at a saving of 2000 Euros per clinical event. Compared with in-hospital warfarin, prolonged thromboprophylaxis with dalteparin will avoid 28 DVTs and four PEs at an incremental cost-effectiveness ratio of 900 Euros per clinical event avoided. We consider that investment in prolonged thromboprophylaxis with dalteparin is justified for the improvement in clinical outcomes produced.
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prolonged thromboprophylaxis following Hip Replacement Surgery results of a double blind prospective randomised placebo controlled study with dalteparin fragmin
Thrombosis and Haemostasis, 1997Co-Authors: Ola E. Dahl, G Andreassen, Trude Aspelin, Patrick Mathiesen, S Nyhus, J H Solhaug, Carl Muller, Michael Abdelnoor, Harald ArnesenAbstract:Discontinuation of thromboprophylaxis a few days after Surgery may unmask delayed hypercoagulability and contribute to late formation of deep venous thrombosis (DVT). To investigate whether thromboprophylaxis should be prolonged beyond the hospital stay, a prospective, double-blind randomised study was conducted in 308 patients. All patients received initial thromboprophylaxis with dalteparin, dextran and graded elastic stockings. On day 7, patients were randomised to receive dalteparin (Fragmin) 5000 i.u. once daily, or placebo, for 4 weeks. All patients were subjected to bilateral venography, perfusion ventilation scintigraphy and chest X-ray on days 7 and 35. Patients with venographically verified proximal DVT on day 7 were withdrawn from the randomised study to receive anticoagulant treatment. The overall prevalence of DVT on day 7 was 15.9%. On day 35, the prevalence of DVT was 31.7% in placebo-treated patients compared with 19.3% in dalteparin-treated patients (p = 0.034). The incidence of DVT from day 7 to day 35 was 25.8% in the placebo-treated group versus 11.8% in the dalteparin-treated group (p = 0.017). The incidence of symptomatic pulmonary embolism (PE) from day 7 to day 35 was 2.8% in the placebo-treated group compared with zero in the dalteparin-treated group. This included one patient who died from PE. No patients experienced serious complications related to the injections of dalteparin or placebo. This study shows that prolonged thromboprophylaxis with dalteparin. 5000 IU, once daily for 35 days significantly reduces the frequency of DVT and should be recommended for 5 weeks after Hip Replacement Surgery.
William A Hanson - One of the best experts on this subject based on the ideXlab platform.
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an image directed robotic system for precise orthopaedic Surgery
International Conference on Robotics and Automation, 1994Co-Authors: Russell H Taylor, H A Paul, Bela Musits, Peter Kazanzides, Joel Zuhars, Bill Williamson, William A Hanson, B D Mittelstadt, Edward GlassmanAbstract:The authors have developed an image-directed robotic system to augment the performance of human surgeons in precise bone machining procedures in orthopaedic Surgery, initially targeted at cementless total Hip Replacement Surgery. The total system consists of an interactive CT-based presurgical planning component and a surgical system consisting of a robot, redundant motion monitoring, and man-machine interface components. In vitro experiments conducted with this system have demonstrated an order-of-magnitude improvement in implant fit and placement accuracy, compared to standard manual preparation techniques. The first generation system described in this paper was used in a successful veterinary clinical trial on 26 dogs needing Hip Replacement Surgery. It was the basis for subsequent development of a second-generation system that is now in human clinical trials. >
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a surgical robot for total Hip Replacement Surgery
International Conference on Robotics and Automation, 1992Co-Authors: H A Paul, Russell H Taylor, B Mittlestadt, William L Bargar, Bela Musits, Peter Kazanzides, Joel Zuhars, Bill Williamson, William A HansonAbstract:The authors describe a robotic surgical system that has been designed to create femoral cavities that are precisely shaped and positioned for implantation of uncemented prostheses. This robotics system creates cavities with a dimensional accuracy more than 50 times greater than broached cavities, exceeds the tolerances to which implants are manufactured, and does not produce gaps that prevent bone ingrowth. A canine study was undertaken to evaluate the prosthesis fit and placement achieved by employing a surgical robot to prepare the femur. This study compared the results achieved on 15 dogs undergoing total Hip Replacement with manual broaching techniques and 25 dogs undergoing robotically assisted Surgery. Among the 25 dogs, which ranged in age from 2/sup 1///sub 2/ to 11 years, there were no deaths, no infections, and no intraoperative complications. Human applications of this technique are also considered. >
Ola Rolfson - One of the best experts on this subject based on the ideXlab platform.
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is the use of antidepressants associated with patient reported outcomes following total Hip Replacement Surgery
Acta Orthopaedica, 2016Co-Authors: Meridith E Greene, Ola Rolfson, Henrik Malchau, Max Gordon, Kristina Annerbrink, Goran GarellickAbstract:Background and purpose - Patients with anxiety and/or depression tend to report less pain reduction and less satisfaction with surgical treatment. We hypothesized that the use of antidepressants would be correlated to patient-reported outcomes (PROs) 1 year after total Hip Replacement (THR), where increased dosage or discontinuation would be associated with worse outcomes. Patients and methods - THR cases with pre- and postoperative patient-reported outcome measures (PROMs) were selected from the Swedish Hip Arthroplasty Register (n = 9,092; women: n = 5,106). The PROMs were EQ-5D, visual analog scale (VAS) for pain, Charnley class, and VAS for satisfaction after Surgery. These cases were merged with a national database of prescription purchases to determine the prevalence of antidepressant purchases. Regression analyses were performed where PROs were dependent variables and sex, age, Charnley class, preoperative pain, preoperative health-related quality of life (HRQoL), patient-reported anxiety/depression, and antidepressant use were independent variables. Results - Antidepressants were used by 10% of the cases (n = 943). Patients using antidepressants had poorer HRQoL and higher levels of pain before and after Surgery and they experienced less satisfaction. Preoperative antidepressant use was independently associated with PROs 1 year after THR regardless of patient-reported anxiety/depression. Interpretation - Antidepressant usage before Surgery was associated with reduced PROs after THR. Cases at risk of poorer outcomes may be identified through review of the patient's medical record. Clinicians are encouraged to screen for antidepressant use preoperatively, because their use may be associated with PROs after THR.
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internet based follow up questionnaire for measuring patient reported outcome after total Hip Replacement Surgery reliability and response rate
Value in Health, 2011Co-Authors: Ola Rolfson, Leif Dahlberg, Roger Salomonsson, Goran GarellickAbstract:Abstract Objective This randomized methodologic study sought to test the reliability of an Internet questionnaire and investigate the differences in response rates between traditional pen-and-paper questionnaires and Internet questionnaires for measuring patient-reported outcome after total Hip Replacement Surgery. Methods From the Swedish Hip Arthroplasty Register, 2400 patients were chosen at random but stratified by age, sex, and diagnosis for inclusion in a 4-year follow-up using the health-related quality of life tool EQ-5D and visual analogue scales for pain and satisfaction. The patients were randomized to answer the follow-up model protocol either via a password-protected Internet questionnaire or via a mailed pen-and-paper questionnaire. Results A reliability test for the Internet follow-up instrument showed adequate correlation. However, the Internet group and the pen-and-paper group differed significantly (P Conclusions The patient-administered Internet questionnaire alone does not give a sufficient response rate in the total Hip Replacement population to replace the pen-and-paper questionnaire. However, the system is reliable and could be used for measuring patient-reported outcome if supplemented with traditional pen-and-paper questionnaires for Internet nonrespondents. It is expected that this answer procedure will soon predominate in view of the general development of Internet functions. Register work may then become less resource-consuming and the results may be analyzed in real time.
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variables determining outcome in total Hip Replacement Surgery
Orthopaedic Proceedings, 2010Co-Authors: Ola Rolfson, Leif Dahlberg, Janake Nilsson, Henrik Malchau, Goran GarellickAbstract:Objective: The Charnley grading system (A, B, C) has previously been shown to be a valid predictor concerning outcome after joint Replacement Surgery. In this study we hypothesized that anxiety/depression, one of five dimensions in the health related quality of life measurement tool EQ-5D, could predict the outcome after total Hip Replacement Surgery. Methods: Data from the Swedish Hip Arthroplasty Register including 6 158 patients with primary osteoarthritis were analysed. To examine the association of anxiety with respect to the outcome of pain (VAS) and satisfaction (VAS) a general linear regression model was used. A subgroup of 481 patients in the Western Region of Sweden with complete data on individual CPP (cost per patient) was selected for the health economic analysis. Results: The preoperative EQ-5D anxiety/depression dimension was a strong predictor for pain relief, patient satisfaction, and cost-effectiveness with Surgery. Patients with comorbidity (Charnley category C) had a significant worse outcome with regards to pain relief, satisfaction and EQ-5D index scores than patients in Charnley category A and B (p Conclusion: Orthopaedic surgeons involved with the care of patients eligible for THR Surgery should be alert to the fact that mental health may influence pain-experience and HRQoL outcome. Appropriate assessment of mental health may enable us to modify the approach in which we manage these patients, in order to optimize the outcome following joint Replacement Surgery.
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variables determining outcome in total Hip Replacement Surgery
Journal of Bone and Joint Surgery-british Volume, 2009Co-Authors: Ola Rolfson, Leif Dahlberg, Janake Nilsson, Henrik Malchau, Goran GarellickAbstract:In this study we hypothesised that anxiety/depression, one of five dimensions in the health-related quality of life (HRQoL) measurement tool EQ-5D, could predict outcome after total Hip Replacement Surgery. Pre-operative and one-year post-operative data from the Swedish Hip Arthroplasty Register, including 6158 patients with primary osteoarthritis of the Hip, were analysed. In order to examine the association between anxiety and outcome with respect to pain and satisfaction an analysis of covariance was used. The pre-operative EQ-5D anxiety/depression dimension was a strong predictor for pain relief and patient satisfaction (p < 0.001). Orthopaedic surgeons involved in the care of patients eligible for total Hip Replacement Surgery should be aware that mental health may influence post-operative pain and HRQoL. An appropriate assessment of mental health may enable a modification in the way these patients are managed in order to optimise the outcome after joint Replacement Surgery.
Bengt I Eriksson - One of the best experts on this subject based on the ideXlab platform.
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dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total Hip Replacement a randomised double blind non inferiority trial
The Lancet, 2007Co-Authors: Bengt I Eriksson, Ola E. Dahl, Martin H Prins, Nadia Rosencher, Andreas A Kurth, Niek C Van Dijk, Simon P Frostick, Rohan Hettiarachchi, Stefan Hantel, Janet SchneeAbstract:Summary Background After Hip Replacement Surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis. Methods In this double-blind study, we randomised 3494 patients undergoing total Hip Replacement to treatment for 28–35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1–4 h after Surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before Surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7·7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818. Findings Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6·7%) of 897 individuals in the enoxaparin group versus 53 (6·0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference −0·7%, 95% CI −2·9 to 1·6%) and 75 (8·6%) of 874 people in the 150 mg group (1·9%, −0·6 to 4·4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0·44 for 220 mg, p=0·60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups. Interpretation Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total Hip Replacement Surgery, with a similar safety profile.
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a dose escalation study of ym150 an oral direct factor xa inhibitor in the prevention of venous thromboembolism in elective primary Hip Replacement Surgery
Journal of Thrombosis and Haemostasis, 2007Co-Authors: Bengt I Eriksson, Alexander G G Turpie, M R Lassen, Peter Kalebo, Martin H Prins, Giancarlo Agnelli, M L Gaillard, L MeemsAbstract:Summary. Background: YM150, a new oral direct factor Xa inhibitor is used as prophylaxis for venous thromboembolism (VTE), a well-known risk after orthopaedic Surgery. Objectives: To assess the safety and efficacy of thromboprophylaxis with YM150 in a dose escalation study. Patients/methods: Patients (174) undergoing Hip Replacement Surgery were randomized per cohort to oral once daily YM150 or subcutaneous enoxaparin (40 mg daily) in a 4:1 ratio for 7–10 days treatment. The YM150 doses were 3, 10, 30 and 60 mg by sequential four-dose escalation cohorts. The primary endpoint was major and/or clinically relevant non-major bleeding. The incidence of VTE was defined as a composite of verified symptomatic events and/or positive findings at bilateral venography on the last treatment day. An independent adjudication committee evaluated blindly the outcomes of the open-label study. Results: No major and three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI, 0.1–15.1) in the 3 mg and 2 (5.7%; 95% CI, 1.0–18.8) in the 10 mg YM150 dose groups. Of 147 patients (84%) with an evaluable venogram, VTE was observed in 51.9% (95% CI, 31.9–71.4), 38.7% (95% CI, 22.6–57.0), 22.6% (95% CI, 9.7–39.4), and 18.5% (95% CI, 7.5–36.5) in the YM150 dose groups 3, 10, 30 and 60 mg, respectively. A significant YM150 dose-related trend in VTE incidence was found (P=0.006). VTE with enoxaparin was 38.7% (95% CI, 22.6–57.0). Conclusions: YM150, 10–60 mg daily, starting 6–10 h after primary Hip Replacement, was shown to be safe, well tolerated and effective.
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dose escalation study of rivaroxaban bay 59 7939 an oral direct factor xa inhibitor for the prevention of venous thromboembolism in patients undergoing total Hip Replacement
Thrombosis Research, 2007Co-Authors: Bengt I Eriksson, Ola E. Dahl, Frank Misselwitz, Lars C Borris, Sylvia Haas, Menno V Huisman, Ajay K Kakkar, Eva Muehlhofer, Peter KaleboAbstract:Abstract Introduction Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban. Materials and methods This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total Hip Replacement Surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6–8 h after Surgery) or enoxaparin (40 mg od starting the evening before Surgery). Therapy continued until mandatory bilateral venography was performed 5–9 days after Surgery. Results A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint – deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality – occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationsHip with rivaroxaban for the primary efficacy endpoint was not statistically significant ( p = 0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban ( p = 0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban ( p = 0.0008), occurring in 0–10.8% of patients, compared with 0% in patients receiving enoxaparin. Conclusions This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total Hip Replacement Surgery.
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ym150 an oral direct factor xa inhibitor as prophylaxis for venous thromboembolism in patients with elective primary Hip Replacement Surgery a dose escalation study
Blood, 2005Co-Authors: Bengt I Eriksson, Alexander G G Turpie, M R Lassen, Martin H Prins, Giancarlo Agnelli, M L Gaillard, Bert MeemsAbstract:Activated factor X (FXa) is a pivotal blood coagulation factor positioned at the crossroads of the extrinsic and intrinsic coagulation cascade. Inhibitors of FXa are anticoagulants that could be used in the prevention and treatment of thrombosis and venous thromboembolism (VTE). YM150 is a once daily, orally active FXa inhibitor. A randomized, enoxaparin-controlled, dose escalation study was performed in 174 patients undergoing elective primary Hip Replacement Surgery to assess safety and efficacy of 7–10 days treatment with oral doses of YM150 (3, 10, 30 or 60 mg once daily starting 6–10 h after Surgery) or s.c. enoxaparin (40 mg once daily starting 12 h before Surgery). Safety is defined as major and/or clinically relevant non-major bleeding, and efficacy as venous thromboembolism detected by mandatory bilateral venography on the last treatment day and/or symptomatic VTE. The study was open-label with blinded evaluation of all outcomes by an independent Adjudication Committee. There were no major bleeds. Three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI: 0–16%) in the 3 mg and 2 (5.7%; 1–19%) in the 10 mg YM150 dose groups. No trend was observed in the incidence of minor bleeds with dose of YM150 in the range 10 mg to 60 mg daily. The proportion of patients with minor bleeding events in the enoxaparin group (22%; 95% CI: 10–39%) was similar to that in the YM150, 60 mg daily group (24%; 11–41%). 147 patients (84%) were considered to have an evaluable venogram. The incidences of VTE were 52% (95% CI: 31–72%), 39% (22–57%), 23% (9–40%), and 19% (7–37%) for the respective 3, 10, 30 and 60 mg YM150 once daily dose groups in comparison with 39% (22–57%) for enoxaparin. Logistic regression analysis revealed a statistically significant dose-related trend (p=0.006) for patients reaching the VTE endpoint during YM150 treatment. No trend in any of the measured safety parameters was observed with study treatment (YM150 or enoxaparin) or dose of YM150. Oral, once daily doses of YM150, 10 mg to 60 mg administered 6 to 10 h after primary Hip Replacement, were shown to be safe, well tolerated and effective in this study.
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postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective Hip Replacement Surgery a randomised double blind trial
The Lancet, 2002Co-Authors: Alexander G G Turpie, Kenneth A Bauer, Bengt I Eriksson, M R LassenAbstract:Summary Background Elective Hip-Replacement Surgery carries significant risk of venous thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the pentasaccharide fondaparinux, the first drug of a new class of synthetic antithrombotic agents, could reduce this risk to a greater extent than other available treatments. Methods In a double-blind study, we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective Hip-Replacement Surgery to receive postoperative subcutaneous injections of either 2·5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary efficacy outcome was venous thromboembolism to day 11. The main safety outcomes were bleeding and death. Patients were followed up for 6 weeks. Findings We assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day 11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction in risk was 26·3% (95% CI −10·8 to 52·8, p=0·099). The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding. Interpretation In patients undergoing elective Hip-Replacement Surgery, 2·5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However, the lower risk recorded with fondaparinux than enoxaparin was clinically important, with no increase in clinically relevant bleeding.