| 1. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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An open-label study of the pharmacokinetics and pharmacodynamics of dabigatran etexilate 150 mg once daily in Caucasian patients with moderate renal impairment undergoing primary unilateral elective total knee or hip replacement surgery
- 2016
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 144, s. 158-164
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Tidskriftsartikel (refereegranskat)abstract
- Background: In adults with moderate renal impairment (creatinine clearance [CrCl] 30-50 mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150 mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. Methods: Single-arm, open-label phase 4 study (NCT01184989) in Caucasian patients receiving dabigatran etexilate 75 mg 1-4 h after surgery and 150 mg qd on days 2-10 (TKR) or days 2-35 (THR). Plasma total dabigatran concentrations (day 6 +/- 1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot (R) Thrombin Inhibitors). Results: Of 112 patients (mean CrCl 42.5mL/min, age 79.1 years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5 ng/mL (10th-90th percentile 19.7-120) and 166 ng/mL (49.1-364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50-500 ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of +/- 15%. Conclusions: These findings in Caucasians with moderate renal impairment undergoing THR or TKR support the use of the 150 mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful. (C) 2016 Published by Elsevier Ltd.
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| 2. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development
- 2009
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Ingår i: Clin Pharmacokinet. - 0312-5963. ; 48:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- For the past five decades, there has been little progress in the development of oral anticoagulants, with the choices being limited to the vitamin K antagonists (VKAs). The situation is changing with the development of orally active small molecules that directly target thrombin or activated factor X (FXa). The two agents in the most advanced stages of development are dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively. Both are approved in the EU and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents in the early stages of development include several FXa inhibitors (apixaban, DU 176b, LY 517717, YM 150, betrixaban, eribaxaban [PD 0348292] and TAK 442) and one thrombin inhibitor (AZD 0837). With a predictable anticoagulant response and low potential for drug-drug interactions, these new agents can be given in fixed doses without coagulation monitoring. This renders them more convenient than VKAs. While the anticoagulant effect of the new thrombin and FXa inhibitors is similar, differences in the pharmacokinetic and pharmacodynamic parameters may influence their use in clinical practice. Here, we compare the pharmacokinetic and pharmacodynamic features of these new oral agents.
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| 3. |
- Liesenfeld, K. H., et al.
(författare)
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Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis
- 2006
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Ingår i: Br J Clin Pharmacol. - 0306-5251. ; 62:5, s. 527-37
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To describe the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD responses. METHODS: BISTRO I patients received oral dabigatran etexilate postsurgery for 6-10 days. Dabigatran plasma concentrations and aPTT/ECT were measured on the day of surgery, on subsequent days and at steady state. PK-PD characteristics of the dabigatran-aPTT/ECT relationships were evaluated using NONMEM V. RESULTS: The dabigatran concentration-aPTT relationship was described combining a linear and an E(max) model. Mean baseline aPTT was 33.4 s and E(max) (maximum increase in aPTT contributed by the E(max) model) was 26.9 s. The dabigatran concentration needed to attain 50% of maximum effect (EC(50)) was 94.7 ng ml(-1) and the mean slope of the linear concentration-response relationship (SLOP) was 0.0509 s ng(-1) ml(-1). Baseline aPTT and E(max) were highest following surgery and declined with time. The dabigatran concentration-ECT relationship fitted a linear model. Mean baseline ECT was 28 s and decreased with time; 50% of the maximum effect was observed after 2.9 days. SLOP decreased from 0.38 to 0.27 s ng(-1) ml(-1) with a half-life of 1.1 day, indicating greater PD effects on the day of surgery. Interindividual and residual variability was low. Covariates could not explain variability of this model. CONCLUSIONS: aPTT and ECT prolongation were directly correlated with dabigatran concentrations. Blood coagulation prolongation was most pronounced following surgery. Data suggest that ECT provides a more precise description of the anticoagulant effect than aPTT.
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| 4. |
- Raskob, G., et al.
(författare)
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Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study
- 2010
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 104:3, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- Edoxaban is a new oral direct factor Xa inhibitor. The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing elective total hip replacement. A total of 903 patients were randomised to oral edoxaban 15, 30, 60 or 90 mg once daily or subcutaneous dalteparin once daily (initial dose 2,500 IU, subsequent doses 5,000 IU). Both drugs were begun 6-8 hours postoperatively and continued for 7-10 days, when bilateral venography was performed. The primary efficacy endpoint was the incidence of total VTE, which included proximal and/or distal deep-vein thrombosis (DVT) by venography or symptomatic, objectively confirmed DVT or pulmonary embolism during the treatment period. The primary safety outcome was the incidence of the composite of major and clinically relevant non-major bleeding. All venograms and bleeding events were reviewed by a central independent adjudication committee blinded as to treatment allocation. Of the 903 patients randomised, 776 were evaluable for the primary efficacy analysis. The incidences of VTE were 28.2%, 21.2%, 15.2%, and 10.6% in patients receiving edoxaban 15, 30, 60 and 90 mg, respectively, compared with 43.8% in the dalteparin group (p<0.005 ). There was a statistically significant (p<0.001) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE. The incidence of clinically relevant bleeding was low and similar across the groups. Oral edoxaban once daily is effective for preventing VTE after total hip replacement.
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| 5. |
- Weitz, J. I., et al.
(författare)
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A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery
- 2010
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 104:6, s. 1150-1157
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Tidskriftsartikel (refereegranskat)abstract
- This multicentre dose-finding study compared TAK-442, an oral factor Xa inhibitor, with enoxaparin for thromboprophylaxis after knee arthroplasty. In this parallel group study, patients were randomised to oral TAK-442 (40 or 80 mg once-daily [QD] or 10, 20, 40, or 80 mg twice-daily [BID] started 6-8 hours postoperatively), which was blinded as to dose, or to open-label subcutaneous enoxaparin (30 mg BID starting 12-24 hours postoperatively) for 10 days. Treatments were continued until bilateral venography was performed (maximum of 14 days). The primary efficacy endpoint was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism or all-cause mortality, while the primary safety endpoint was major bleeding. Of 1,038 patients randomised who received at least one dose of study drug, 949 completed the study and 730 (76.9%) were evaluable for the primary efficacy analysis. Recruitment into the 10 and 20 mg BID dose groups was stopped early because the incidences of the primary efficacy endpoint were significantly higher than that with enoxaparin. The primary efficacy endpoint occurred in 22.0% of patients given enoxaparin and in 39.0%, 38.4%, 23.5%, 21.4%, 26.8%, and 14.3% of those receiving TAK-442 10 mg BID, 20 mg BID, 40 mg QD, 40 mg BID, 80 mg QD, and 80 mg BID, respectively. The incidences of major and clinically relevant non-major bleeding with TAK-442 were not dose-dependent or different from that with enoxaparin. All TAK-442 doses except 10 and 20 mg BID displayed similar efficacy and safety profiles to enoxaparin.
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| 6. |
- Andernord, Daniel, et al.
(författare)
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Surgical Predictors of Early Revision Surgery After Anterior Cruciate Ligament Reconstruction: Results From the Swedish National Knee Ligament Register on 13,102 Patients.
- 2014
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 42:7, s. 1574-1582
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:An important objective of anterior cruciate ligament (ACL) registries is to detect and report early graft failure and revision surgery after ACL reconstruction. PURPOSE:To investigate surgical variables and identify predictors of revision surgery after ACL reconstruction. STUDY DESIGN:Prospective cohort study; Level of evidence, 2. METHODS:This prospective cohort study was based on data from the Swedish National Knee Ligament Register during the years 2005 through 2011. Eight surgical variables were investigated: graft selection, graft width, single-bundle or double-bundle techniques, femoral graft fixation, tibial graft fixation, injury-to-surgery interval, injuries to menisci, and injuries to cartilage. The primary endpoint was the 2-year incidence of revision surgery. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated and adjusted for confounders by use of multivariate statistics. RESULTS:A total of 13,102 patients were included (5541 women [42%] and 7561 men [58%]; P < .001). Hamstring tendon autografts accounted for 90% (11,764 patients) of all reconstructions, of which 96% were performed with a single-bundle technique (11,339 patients). Patellar tendon autografts accounted for the remaining 10% (1338 patients). At index reconstruction, observed injuries to menisci and cartilage were common (40% and 28%, respectively). The overall 2-year incidence of revision surgery was 1.60% (women, 1.57%; men, 1.63%; P = .854). Patients with metal interference screw fixation of a semitendinosus tendon autograft on the tibia had a significantly reduced risk of early revision surgery (RR = 0.32; 95% CI, 0.12-0.90; P = .031). CONCLUSION:Metal interference screw fixation of a semitendinosus tendon autograft on the tibia was an independent predictor of significantly lower 2-year incidence of revision surgery. Graft selection, graft width, a single-bundle or a double-bundle technique, femoral graft fixation, the injury-to-surgery interval, and meniscus injury were not predictors of early revision surgery.
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| 7. |
- Augustsson Ryman, Sofia, 1975, et al.
(författare)
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Performance Enhancement Following a Strength and Injury Prevention Program: A 26-Week Individualized and Supervised Intervention in Adolescent Female Volleyball Players
- 2011
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Ingår i: INTERNATIONAL JOURNAL OF SPORTS SCIENCE & COACHING. - : SAGE Publications. - 1747-9541 .- 2048-397X. ; 6:3, s. 399-417
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The aim of this study was to evaluate the effects of a 26-week individualized and supervised strength and injury prevention program on performance enhancement in young female volleyball players who completed resistance training with either a supervised and individualized training program (experimental group, n=10) or an unsupervised non-individualized training program (control group, n=17). Exposure and injury data were collected during the 2006-2007 season (baseline season) and the 26-week program was conducted during the 2007-2008 season (intervention season). All players were tested for physical performance. At post-test, the players in the experimental group had improved significantly more than the players in the control group for squat (p<0.0001), bench press (p=0.048), push-ups (p=0.02) and sit-ups (p<0.0001) but not for the vertical jump test. Thirty-five percent (6/17) of the players from the control group and 80% (8/10) of the players in the experimental group completed the resistance training with compliance of no less than 50%. The present study shows the importance of individualization and supervision for resistance training in young female athletes when it comes to compliance, strength gains and performance.
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| 8. |
- Brorsson, Annelie, et al.
(författare)
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Development and evaluation of a new seated heel-rise test in the early stages of rehabilitation after an acute Achilles tendon rupture.
- 2014
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Ingår i: 16th ESSKA (European Society of Sports Traumatology, Knee Surgery and Arthroscopy) Congress, 14-17 May 2014, Amsterdam, Netherlands.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The early stages of rehabilitation appear to be of great importance for outcome after an Achilles tendon rupture. It is a challenge to evaluate the patients’ calf muscle endurance at this stage in a safe and adequate way. The aim of our study was to develop a seated heel-rise test suitable for evaluating calf muscle endurance three months after an Achilles tendon rupture. Furthermore we wanted to evaluate how the seated heel-rise test correlated to the ability to perform one-legged standing heel-rise and patient-reported symptoms. Method: Ninety-three patients, 79 men and 14 women, mean age of 40 (20-63) years, were included from a cohort of 100 patients participating in a prospective, randomized controlled trial comparing non-surgical and surgical treatment after Achilles tendon rupture. Forty-seven were treated with surgery and 46 with non-surgery. They were evaluated after 3, 6 and 12 months. Patient reported outcome was evaluated with Achilles Tendon Rupture Score (ATRS) and functional outcome with seated and standing heel-rise test. The seated heel-rise test was performed with the patient sitting with hip and knee in 90°. A leg extension weight-training machine was used to provide load onto the patient’s thigh at 50% body weight. The limb symmetry index (LSI=injured/healthy x 100) was calculated in order to compare the results from the seated and standing heel-rise test. Results: Ninety-one patients out of 93 (98%) could perform the seated heel-rise test. At the 3-month follow-up there was a significant difference (p<0.01) in the seated heel-rise test between the injured and the healthy side. There were no significant differences between the surgical and non-surgical treatment groups. There were significant differences in the seated heel-rise test and in ATRS (p<0.01) when comparing the group who could perform a standing heel-rise test at the 3-months follow-up, with the group who could not. There were significant correlations between the LSI-values in the seated heel-rise height at the 3-month follow-up and the standing heel-rise height at the 6-month (r=0.36, p<0.001, n= 91) and the 12-month follow-up (r=0.35, p=0.001, n=85). There were also significant correlations (r=0.22-0.37, p=<0.04) between the seated heel-rise test and ATRS. Conclusions: The seated heel-rise-test has the capacity to identify differences between the injured and the healthy side three months after injury. This test also correlates with patient reported outcomes and the heel-rise ability at 6 and 12 months. This test appears to be a safe and suitable test for evaluating calf muscle endurance and function in the early stages of rehabilitation after an Achilles tendon rupture.
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| 9. |
- Brorsson, Annelie, et al.
(författare)
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Long-term follow up after acute Achilles tendon rupture.
- 2015
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Ingår i: Danish Sports Medicine Congress, Copenhagen, January 22-24, 2015. - : Danish Association of Sports Medicine.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is still unknown why many patients never fully recover after an Achilles tendon rupture (ATR). The aim of this study was to perform a long-term follow-up (5-9 years) of patients treated either surgically or non-surgically after an ATR. Furthermore, we wanted to examine if the patients had a tendon elongation on the injured side and evaluate if this correlated to function, symptoms and foot structure. Material and Method Sixty-seven patients (13 women) mean age of 50 years were evaluated 5-9 years after injury. Thirty-five patients were treated with surgery and 32 with non-surgery. Patient reported outcome and activity level, lower leg function, tendon length, and foot-structure were evaluated. Both the healthy and the injured side were examined and the limb symmetry index (LSI=injured/healthy x 100) was calculated. Results There were significant differences between the healthy and injured side in all function tests (p<0.001-0.015) and the tendon was significantly longer on the injured side (p<0.001) independent of treatment. There were no significant correlations between tendon length and patient reported outcome, function or foot structure. The heel-rise height increased significantly (p<0.000) from the 1 year- to the 5-9-years-follow up. The mean Achilles tendon Total Rupture Score (ATRS) was 91/100, indicating minor symptoms. Conclusion: Patients with an Achilles tendon rupture continues to have significant deficits in tendon structure and function 5-9 years after injury. There is, however continued improvement between the 1 and 5-9 year follow-up.
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| 10. |
- Brorsson, Annelie, et al.
(författare)
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Recovery of calf muscle endurance 3 months after an Achilles tendon rupture.
- 2016
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Ingår i: Scandinavian journal of medicine & science in sports. - : Wiley. - 1600-0838 .- 0905-7188. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate calf muscle endurance in a seated position 3 months after an Achilles tendon rupture and to evaluate how the ability to perform standardized seated heel-rises correlated to the single-leg standing heel-rise test and to patient-reported symptoms evaluated with the Achilles tendon Total Rupture Score (ATRS) 3 and 6 months after the injury. Ninety-three patients were included from a cohort of 101 patients participating in a prospective, randomized controlled trial comparing surgical and nonsurgical treatment after Achilles tendon rupture. Forty-seven patients were treated surgically and 46 nonsurgically. Ninety-one patients out of 93 (98%) could perform the standardized seated heel-rises. At the 3-month follow-up, there was a significant difference (P < 0.001) between the injured and the healthy side performing standardized seated heel-rises. There were also significant correlations (r = 0.29-0.37, P = < 0.05) between the standardized seated heel-rises and ATRS 3 and 6 months after injury in the group who could not perform single-leg standing heel-rises. There were no significant differences between the surgical and nonsurgical treatment groups. The evaluation of standardized seated heel-rises appears to be a useful tool to quantify progress and predict future functional performance and patient-reported symptoms.
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