Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

OBJECTIVE: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. DESIGN: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. SETTING: The prospective Swedish Heart Failure Registry. SUBJECTS: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. MAIN OUTCOME MEASURES: Comorbidities, risk factors and mortality. RESULTS: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p < 0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF ≥50% 26.1 vs. 13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. CONCLUSION: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group. KEY POINTS 97% of heart failure patients with an ejection fraction of more than or equal to 40% managed at primary care based out-patient clinics had any comorbidity. Patients in primary care had partly other independent risk factors than those in hospital care. All-cause mortality during mean follow-up of almost 4 years was higher in primary care compared to hospital care. In matched HF-patients RAS-antagonists, beta-blockers as well as the combination of the two drugs were more seldom prescribed when managed in primary care compared with hospital care.

Recovery of calf muscle endurance 3 months after an Achilles tendon rupture.

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.

Increased mortality rate and suicide in Swedish former elite male athletes in power sports.

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

The effects of rivaroxaban on the complications of surgery after total hip or knee replacement: results from the RECORD programme.

Post-operative complications after total hip or knee replacement can delay recovery, prolong hospitalisation, increase rates of re-admission and, in the most severe cases, lead to long-term disability or even death. In this analysis of pooled data from four large, randomised, phase III clinical trials that compared the oral, direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement (n = 12,729), the incidence of complications, including bleeding and adverse events related to surgery (such as wound infection, wound dehiscence and haemarthrosis) are reported. Interventions and procedures relating to surgery are also compared between the groups. Bleeding events, including excessive wound haematoma and surgical-site bleeding, occurred at similar rates in the rivaroxaban and enoxaparin groups. Over the total study duration, adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement (2.26% vs. 2.69%, respectively) and total hip replacement (1.48% vs. 1.65%, respectively). Blood loss, wound drainage and transfusion requirements were also similar between the two groups. This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin.

Impact of stage 3B chronic kidney disease on thrombosis and bleeding outcomes after orthopedic surgery in patients treated with desirudin or enoxaparin: insights from a randomized trial.

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 randomized, 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 randomized 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.

Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2).

BACKGROUND: Anticoagulant prophylaxis substantially reduces the risk of venous thromboembolism (VTE) after major orthopedic surgery. The direct factor Xa inhibitor YM150 is currently under investigation for the prevention of VTE, stroke and ischemic vascular events in patients after orthopedic surgery, with atrial fibrillation and with acute coronary syndrome, respectively. OBJECTIVES: To investigate the efficacy and safety of YM150 for the prevention of VTE following elective total hip arthroplasty. PATIENTS/METHODS: Patients were randomized to postoperative, once-daily, oral YM150 (5, 10, 30, 60 or 120 mg) (double-blind) or preoperative subcutaneous (open label) enoxaparin (40 mg) for 5 weeks. The primary efficacy endpoint comprised VTE diagnosed by mandatory bilateral venography or verified symptomatic deep vein thrombosis (DVT) plus all deaths up to 9 days after surgery. The primary safety outcome was major bleeding up to 9 days after surgery. RESULTS: Primary efficacy endpoint: of 1017 patients randomized, 960 patients were evaluable for safety and 729 patients for efficacy. A dose-related decrease in VTE incidence from YM150 5 to 60 mg (P = 0.0005) and from 5 to 120 mg (P = 0.0002) was found. The VTE incidence was 27.4%, 31.7%, 19.3%, 13.3% and 14.5% for 5, 10, 30, 60 and 120 mg YM150, respectively, and 18.9% for enoxaparin. Primary safety endpoint: there was one major bleed with YM150 (60 mg) and one with enoxaparin. CONCLUSIONS: The oral direct FXa inhibitor YM150 demonstrated a significant dose response regarding efficacy. Doses from 30 to 120 mg had comparable efficacy to enoxaparin, without compromising safety regarding major bleeding events.

Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.

The definition of major bleeding varies between studies on surgical patients, particularly regarding the criteria for surgical wound-related bleeding. This diversity contributes to the difficulties in comparing data between trials. The Scientific and Standardization Committee (SSC), through its subcommittee on Control of Anticoagulation, of the International Society on Thrombosis and Haemostasis has previously published a recommendation for a harmonized definition of major bleeding in non-surgical studies. That definition has been adopted by the European Medicines Agency and is currently used in several non-surgical trials. A preliminary proposal for a parallel definition for surgical studies was presented at the 54(th) Annual Meeting of the SSC in Vienna, July 2008. Based on those discussions and further consultations with European and North American surgeons with experience from clinical trials a definition has been developed that should be applicable to all agents that interfere with hemostasis. The definition and the text that follows have been reviewed and approved by relevant co-chairs of the subcommittee and by the Executive Committee of the SSC. The intention is to seek approval of this definition from the regulatory authorities to enhance its incorporation into future clinical trial protocols.

Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement.

A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding.

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran.

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.

Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.

Self-efficacy of knee function as a pre-operative predictor of outcome 1 year after anterior cruciate ligament reconstruction.

The knee self-efficacy scale (K-SES) has been shown to have good reliability, validity and responsiveness during rehabilitation for patients' perceived self-efficacy of knee function. Determinants of self-efficacy of knee function 1 year after ACL reconstruction have been found to be the patients' internal locus of control and knee symptoms in sports and recreation. The predictive ability of perceived self-efficacy of knee function measured by the K-SES has not been studied in terms of patient outcome after an ACL reconstruction. The purpose of this study was to explore the potential for pre-operative self-efficacy of knee function measured by the K-SES to predict patient outcome in terms of physical activity, knee symptoms and muscle function 1 year after an ACL reconstruction. Thirty-eight patients were evaluated for outcome in terms of physical activity with the Tegner activity scale and the physical activity scale (PAS), knee symptoms with the Lysholm knee scoring scale and the knee injury and osteoarthritis outcome score (KOOS) and knee function with ability tests for muscle function 1 year after ACL reconstruction. Multiple regression and logistic multiple regression analysis were used to evaluate the K-SES as a possible predictor of outcome. The patients' present perceived self-efficacy of knee function (K-SES(Present)) pre-operatively was a significant predictor (P = 0.016) of the patients returning to their intensity and frequency of physical activity (PAS) 1 year after ACL reconstruction, when adjusted for age, gender and pre-injury physical activity level (Tegner(Pre-injury)) (odds ratio = 2.1). The patients' perceived future self-efficacy of knee function (K-SES(Future)) pre-operatively was a significant predictor (P = 0.045) of their self-rated knee function in sports/recreational activities (KOOS(Sports/recreation)) at the 1-year follow-up, when adjusted for age, gender and Tegner(Pre-injury )(R (2 )=0.25). The pre-operative K-SES(Future) was also a significant predictor (P = 0.023) of the patients' knee-related quality of life (KOOS(Qol)), at the 1-year follow-up, when adjusted for age, gender and Tegner(Pre-injury) (R (2 )=0.23). The pre-operative K-SES(Future) was furthermore a significant predictor of an acceptable outcome 1 year after surgery, on the Lysholm knee scoring scale (P = 0.003, odds ratio = 1.7), as well as on KOOS(Sports/recreation) (P = 0.002, odds ratio = 1.6) and knee-related quality of life (KOOS(Qol)) (P = 0.037, odds ratio = 1.4), when adjusted for age, gender and Tegner(Pre-injury). The pre-operative K-SES(Future) was also a significant predictor (P = 0.04) of an acceptable outcome 1 year after surgery, on the one-leg hop for distance (odds ratio = 2.2), when adjusted for age, gender and Tegner(Pre-injury). In conclusion, this study indicates that patients' perceived self-efficacy of knee function pre-operatively is of predictive value for their return to acceptable levels of physical activity, symptoms and muscle function 1 year after ACL reconstruction.

Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study.

BACKGROUND: Inhibitors of factor (F) IXa show potent antithrombotic activity with a low risk of bleeding in preclinical models. We investigated the anticoagulant potential of oral TTP889, a small molecule that inhibits up to 90% of FIXa activity at therapeutic doses, using a clinical model of extended prophylaxis in hip fracture surgery (HFS). METHODS: In this multicenter, randomized, double-blind study, 261 patients received oral TTP889 (300 mg once daily) or placebo starting 6-10 days after HFS, and standard thromboprophylaxis for 5-9 days. Treatment was continued for 3 weeks and all patients then underwent mandatory bilateral venography. The primary efficacy outcome was venous thromboembolism (VTE; venographic or symptomatic deep vein thrombosis or pulmonary embolism) during treatment, and it was evaluated centrally by an independent adjudication panel. The main safety outcome was bleeding (major, clinically relevant non-major, and minor events). RESULTS: Two hundred and twelve patients with an evaluable venogram were included in the efficacy analysis. The primary efficacy outcome occurred in 32.1% (35/109) of patients who had been allocated TTP889, and 28.2% (29/103) of patients on placebo (P = 0.58). There were no major bleeding events, and only two clinically relevant non-major bleeding events with TTP889. CONCLUSION: Partial FIXa inhibition with TTP889 300 mg daily was not effective for extended prevention of VTE after standard prophylaxis for up to 9 days. Coupled with the low incidence of bleeding episodes, this suggests a lack of antithrombotic potential. Further investigation of TTP889 in different clinical settings is needed. (Clinical trial registration information URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119457).

Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial.

BACKGROUND: Oral anticoagulants, such as dabigatran etexilate, an oral, direct thrombin inhibitor, that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism (VTE) after total knee replacement surgery. METHODS: In this randomized, double-blind study, 2076 patients undergoing total knee replacement received dabigatran etexilate, 150 mg or 220 mg once-daily, starting with a half-dose 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery, for 6-10 days. Patients were followed-up for 3 months. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and mortality during treatment, and the primary safety outcome was the incidence of bleeding events. RESULTS: The primary efficacy outcome occurred in 37.7% (193 of 512) of the enoxaparin group versus 36.4% (183 of 503) of the dabigatran etexilate 220 mg group (absolute difference, -1.3%; 95% CI, -7.3 to 4.6) and 40.5% (213 of 526) of the 150 mg group (2.8%; 95% CI, -3.1 to 8.7). Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion. The incidence of major bleeding did not differ significantly between the three groups (1.3% versus 1.5% and 1.3% respectively). No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up. CONCLUSIONS: Dabigatran etexilate (220 mg or 150 mg) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery.

A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgery.

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.

Association between asymptomatic deep vein thrombosis detected by venography and symptomatic venous thromboembolism in patients undergoing elective hip or knee surgery.

BACKGROUND: Venography is commonly used to compare the efficacy of different thromboprophylaxis strategies for preventing deep vein thrombosis (DVT) in patients undergoing total hip replacement (THR) or total knee replacement (TKR). METHODS: We explored the relation between asymptomatic DVT and symptomatic venous thromboembolism (VTE) in patients undergoing THR or TKR treated with standard doses of enoxaparin (30 mg b.i.d. or 40 mg o.d.) by comparing the incidence of asymptomatic DVT in venographic studies with the incidence of symptomatic VTE in studies where venography was not performed. RESULTS: In 10 venographic studies involving 5796 patients, the incidence of asymptomatic DVT after THR was 13.2% [95% CI, 12.2-14.2%] and after TKR was 38.1% (95% CI, 35.5-40.8%). In two studies involving 3500 patients who did not undergo venography, the 90-day incidence of symptomatic VTE after THR was 2.7% (95% CI, 2.1-3.4%) and after TKR was 1.8% (95% CI, 0.9-2.7%). For every symptomatic VTE in THR studies where venography was not performed there were five asymptomatic DVTs in the venographic studies; for TKR, the ratio was 1:21. The incidence of asymptomatic DVT and the symptomatic VTE/asymptomatic DVT ratio was influenced by the venogram reading committee (Gothenburg vs. Hamilton: total DVT after THR, 19.5% vs. 8.7%, P < 0.0001; for TKR, 42.7% vs. 27.2%, P < 0.0001). CONCLUSIONS: Comparisons across trials show a consistent relation between asymptomatic venographic DVT in patients undergoing elective THR or TKR surgery and symptomatic VTE in patients not undergoing venography. Differences exist in the strength of the relation depending on the type of surgery and the venogram reading committee.

Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study.

BACKGROUND: Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. OBJECTIVES: A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. PATIENTS/METHODS: Patients received study drugs until mandatory, bilateral venography was performed 7 +/- 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. RESULTS: A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. CONCLUSIONS: Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.

Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors.

PURPOSE: To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors. MATERIAL AND METHODS: Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome. RESULTS: Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations. CONCLUSION: Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.

Self-efficacy, symptoms and physical activity in patients with an anterior cruciate ligament injury: a prospective study.

Self-efficacy belief may be of major importance for the outcome of rehabilitation after sports-related injuries. A new instrument, the Knee Self-Efficacy Scale (K-SES), was used to evaluate the role of perceived self-efficacy in patients with an anterior cruciate ligament (ACL) injury. The purpose of this prospective exploratory study was to describe the patients' perceived self-efficacy at various times post-injury and surgery, respectively, for responsiveness of the K-SES and to correlate the K-SES score with the patients' subjective symptoms. The purpose was also to describe the influence of gender, age and physical activity on the patients' perceived self-efficacy. Thirty recently injured patients with an ACL-deficient knee and 33 patients who had undergone ACL reconstruction reported their physical activity level and their perceived self-efficacy on four test occasions during a 1-year period. The patients' subjective knee symptoms were documented on two of the test occasions. A significant increase in the K-SES score was seen after injury as well as after surgery, during the course of rehabilitation. Pre-operatively, men's perceived self-efficacy was significantly (P=0.013) higher compared with women's self-efficacy. Patients with a high baseline (pre-injury) physical activity level (Tegner 7-10) perceived their self-efficacy as being significantly (P=0.005) higher pre-operatively compared with patients with a low baseline activity level (Tegner 3-6). "Younger" (age 17-29), recently injured patients, perceived their self-efficacy as being significantly (P=0.034) higher compared with "older" patients (age 30-54). At the 12-month test, 15 of 30 patients with an ACL-deficient knee and 15 of 33 patients who had undergone ACL reconstruction reported that they had returned or nearly returned to their baseline physical activity level. The subjective knee outcome score, as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS), improved significantly (P<0.01) during rehabilitation, apart from the KOOS subscale of "pain" (P=0.077) for patients who had undergone ACL reconstruction. There was a "low" to "strong" correlation (r(s)=0.0-0.7) between the K-SES and the five subscales in the KOOS. We conclude from the present study that K-SES has good responsiveness with significantly increased self-efficacy during the rehabilitation process for patients with an ACL-deficient knee as well as for patients who had undergone ACL reconstruction. The improvement in perceived self-efficacy could, however, only be partly explained by the improvement in subjective symptoms. Furthermore, self-efficacy differed significantly with gender, age and physical activity level early in the rehabilitation process.