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Biomedical subjects

Russell D Hull

Publications and source records attributed to Russell D Hull.

At least 19 recordsLinked to original sources
PubMed2007

Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.

PURPOSE: A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis. METHODS: We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months. RESULTS: Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH. CONCLUSION: Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.

Anticoagulants↗
PubMed2006

Multidetector computed tomography for acute pulmonary embolism.

BACKGROUND: The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively. METHODS: The Prospective Investigation of Pulmonary Embolism Diagnosis II trial was a prospective, multicenter investigation of the accuracy of multidetector CTA alone and combined with venous-phase imaging (CTA-CTV) for the diagnosis of acute pulmonary embolism. We used a composite reference test to confirm or rule out the diagnosis of pulmonary embolism. RESULTS: Among 824 patients with a reference diagnosis and a completed CT study, CTA was inconclusive in 51 because of poor image quality. Excluding such inconclusive studies, the sensitivity of CTA was 83 percent and the specificity was 96 percent. Positive predictive values were 96 percent with a concordantly high or low probability on clinical assessment, 92 percent with an intermediate probability on clinical assessment, and nondiagnostic if clinical probability was discordant. CTA-CTV was inconclusive in 87 of 824 patients because the image quality of either CTA or CTV was poor. The sensitivity of CTA-CTV for pulmonary embolism was 90 percent, and specificity was 95 percent. CTA-CTV was also nondiagnostic with a discordant clinical probability. CONCLUSIONS: In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results.

Acute Disease↗
PubMed2006

Extended-duration thromboprophylaxis in acutely ill medical patients with recent reduced mobility: methodology for the EXCLAIM study.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of mortality and morbidity in medical patients. Although thromboprophylaxis with enoxaparin reduces the risk of VTE in these patients, the optimal duration of therapy is not currently known. The EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) study is designed to compare the efficacy and safety of extended-duration thromboprophylaxis using enoxaparin with the standard regimen of enoxaparin in acutely ill medical patients with recent reduced mobility. METHODS: All enrolled acutely ill medical patients receive enoxaparin 40 mg subcutaneously once daily for 10 +/- 4 days. Eligible patients are then randomized in a blinded manner to receive either extended-duration thromboprophylaxis with enoxaparin 40 mg subcutaneously once daily or placebo subcutaneously once daily for an additional 28 +/- 4 days. The primary efficacy endpoint is the incidence of VTE during the 28 +/- 4 days after randomization. This study utilizes a standardized bilateral compression ultrasonography examination protocol that consists of an intensive interrogation of the deep veins of the lower extremities for proximal deep-vein thrombosis. The secondary efficacy endpoints are the rate of symptomatic VTE during the 3 months after randomization and mortality at 3 and 6 months after enrollment. The primary safety endpoint is the incidence of major hemorrhagic complications during the 28 +/- 4 days after randomization. RESULTS: To date, 3,983 patients, with a broad range of medical conditions, have been included in the study. Almost one third of the enrolled patients with reduced mobility are acutely ill due to respiratory insufficiency and one third have infectious diseases. CONCLUSIONS: The EXCLAIM study is designed to show the efficacy and safety of extended-duration thromboprophylaxis using enoxaparin in acutely ill medical patients with recent reduced mobility, which may potentially lead to a reduction in the incidence of late VTE events in these patients. The EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) study, involving 4,726 acutely ill medical patients with recent reduced mobility, is designed to compare the efficacy and safety of extended-duration thromboprophylaxis using 40 mg once daily enoxaparin (38 +/- 4 days) with the standard regimen for enoxaparin (40 mg once daily for 10 +/- 4 days). The objective of this study is to demonstrate that the extended-duration enoxaparin regimen is an effective and safe thromboprophylaxis regimen out of hospital.

Adult↗
PubMed2006

Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer.

PURPOSE: A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding. Low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy. SUBJECTS AND METHODS: Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis. We performed a multi-centre randomized, open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months. Outcomes were assessed at 3 and 12 months. RESULTS: Of 200 patients, 100 received tinzaparin and 100 received usual care. At 12 months, the usual-care group had an excess of recurrent venous thromboembolism; 16 of 100 (16%) versus 7 of 100 (7%) receiving low-molecular-weight heparin (P=.044; risk ratio=.44; absolute difference -9.0; 95% confidence interval [CI], -21.7 to -0.7). Bleeding, largely minor, occurred in 27 patients (27%) receiving tinzaparin and 24 patients (24%) receiving usual care (absolute difference -3.0; 95% CI, -9.1 to 15.1). In patients without additional risk factors for bleeding at the time of randomization, major bleeding occurred in 0 of 51 patients (0%) receiving tinzaparin and 1 of 48 patients (2.1%) receiving usual care. Mortality at 1 year was high, reflecting the severity of the cancers; 47% in each group died. CONCLUSION: Our findings confirm the limited but benchmark data in the literature that long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis.

Adult↗
PubMed2006

Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators.

PURPOSE: To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials. METHODS: Diagnostic management recommendations were formulated based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) and outcome studies. RESULTS: The PIOPED II investigators recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D-dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast-enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary. CONCLUSION: The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances.

Acute Disease↗
PubMed2006

Effective thromboprophytaxis administered close to the time of major orthopedic surgery: a review.

As major orthopedic surgery poses a high risk for venous thromboembolic disease, use of thromboprophylaxis has become routine in this setting. Unfortunately, there is still no consensus regarding optimal time to initiate thromboprophylaxis. Results from several studies indicate the importance of timing to the efficacy and safety of thromboprophylaxis. As thrombogenesis is thought to begin perioperatively, "just-in-time" thromboprophylaxis has been proposed-antithrombotic therapy with low-molecular-weight heparins initiated soon before or soon after surgery. Results from our large clinical trial show the efficacy and safety of a modified dalteparin regimen administered close to the time of total hip arthroplasty.

Dose-Response Relationship, Drug↗
PubMed2005

Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: a systematic review.

PURPOSE: Clot-burden change in patients receiving anticoagulant therapy, by predicting subsequent recurrent venous thromboembolism, may provide a clinically relevant surrogate endpoint of prognostic importance. The validity of this objective measure is yet to be established. METHODS: A PubMed search was performed to retrieve articles published up to December 2003. We identified 11 randomized trials reported from 1990 to 2003 that met our study identification and selection criteria. Anticoagulant therapy subsequently approved by regulatory affairs was assessed by clot-burden change and the validated outcome measure, long-term venous thromboembolism. Two additional randomized trials, partly meeting the inclusion criteria, were included in the sensitivity analysis. RESULTS: Individual studies suggested a predictive relationship between clot-burden change and likelihood of recurrent venous thromboembolism irrespective of the particular anticoagulant. The summary treatment effects strongly favored the therapy under evaluation and were in harmony for improved clot-burden (relative risk 0.82; 95% CI, 0.76-0.88; P <0.001) and for recurrent venous thromboembolism (relative risk 0.56; 95% CI, 0.42-0.76; P <0.001). The aggregate data show a striking predictive correlation for clot-burden change and subsequent recurrent venous thromboembolism using meta-regression analysis; (correlation = 0.81, P = 0.005) validating quantitative clot-burden assessment. CONCLUSION: Clot-burden change predicts long-term outcome, providing clinically relevant, patient-specific prognostic findings that may guide duration of anticoagulant therapy as well as provide a valid surrogate endpoint for clinical trials of innovative antithrombotic therapy, allowing more efficient trials exposing far fewer patients to the hazards of ineffective therapy than is required for outcome studies. Noninvasive assessment (duplex ultrasonography) of clot-burden change is currently being deployed for use in clinical trials.

Anticoagulants↗
PubMed2005

Vitamin K antagonists and direct thrombin inhibitors: present and future.

Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.

Cardiovascular Diseases↗
PubMed2005

Fatal vascular outcomes following major orthopedic surgery.

Major orthopedic surgery is known to be associated with potentially serious arterial and venous vascular complications, although uncertainty exists about current event rates. Using electronic databases and investigator contact, we identified randomized and cohort studies reporting overall mortality and fatal vascular events. Where possible, studies reporting high autopsy rates (>60%) were examined. Pooled incidences were calculated from eligible studies. For Autopsy studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis could not be calculated, while with prophylaxis they were 0.44% (95% confidence interval 0.02 to 0.87%) and 0.43% (0.01 to 0.85%). For patients undergoing hip fracture surgery, the corresponding rates without prophylaxis were 15.9% (14.5 to 17.3%) and 1.9% (1.4 to 2.4%). With prophylaxis, mortality and fatal pulmonary embolismrates were 8.5% (7.3 to 9.7%) and 1.0% (0.6 to 1.5%). Among Cohort studies: Pooled overall mortality and fatal pulmonary embolism for patients undergoing elective hip and knee replacement without prophylaxis were 0.93% (0.57 to 1.29%) and 0.36% (0.14 to 0.59%). For patients receiving prophylaxis (7 to 14 days), mortality and fatal pulmonary embolism were 0.57% (0.51 to 0.62%) and 0.18% (0.14 to 0.21%). Patients undergoing hip fracture surgery receiving prophylaxis hadmortality and fatal pulmonary embolismrates of 3.2% (2.8 to 3.6%) and 0.30% (0 to 0.61%). Vascular events contributed towards approximately 50% of all deaths with similar proportions due to ischemic heart disease, cardiac failure and pulmonary embolism. In conclusion, although prophylaxis results in a reduction in overall mortality and fatal pulmonary embolism, vascular events continue to be a common cause of mortality.

Autopsy↗
PubMed2005

Low-molecular-weight heparin for the treatment of venous thromboembolism in the elderly.

Venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) is a common problem in the elderly population. Indeed, increasing age is a significant risk factor for venous thromboembolism. The treatment of venous thromboembolism in the elderly population presents certain unique problems related to aging, such as decreasing body weight, increasing renal insufficiency and numerous comorbid conditions, which complicate therapy. Treatment of venous thromboembolism in the elderly has been complicated by an increased incidence of bleeding, particularly with the use of warfarin. The risk of bleeding may be substantially reduced by carefully adjusting the warfarin dose to maintain a therapeutic INR and for this purpose anticoagulant management clinics have been shown to be useful. The low-molecular-weight heparins have been shown to be efficacious and safe for the treatment of venous thromboembolism in several clinical trials, including many patients in the older age brackets. Furthermore, these agents can safely be used in the out-of-hospital setting. Long-term use of low-molecular-weight heparin is an alternative to the use of oral anticoagulant therapy, particularly in patients with cancer or recurrent venous thromboembolism.

Aged↗
PubMed2004

Venous thromboembolism according to age: the impact of an aging population.

BACKGROUND: With the aging of the US population, there is concern that the rate of venous thromboembolism will increase, thereby increasing the health burden. In this study we sought to determine trends in the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in the elderly as well as the use of diagnostic tests. METHODS: Data from the National Hospital Discharge Survey were used. These data are abstracted each year from a sample of records of patients discharged from non-federal short-stay hospitals in the entire United States. Main outcome measures were trends in rates of diagnosis of DVT and PE as well as trends in the use of diagnostic tests between 1979 and 1999. RESULTS: The rates of diagnosis of DVT and PE and of the use of diagnostic tests over 21 years were markedly higher in elderly than in younger patients (P<.001). Although the rate of diagnosed DVT in elderly patients strikingly increased over the past decade (P< .001), that of PE has been relatively constant. There was a proportionately greater use of venous ultrasonography, ventilation-perfusion lung scanning, and pulmonary angiography in elderly than in younger patients. CONCLUSIONS: Extensive use of diagnostic tests in elderly patients in the past decade has resulted in an increased diagnostic rate for DVT but not PE. The reason for this disparity is uncertain but may reflect early diagnosis and treatment of DVT. With the aging of the population, DVT will increase the health burden.

Adult↗
PubMed2004

Dalteparin: pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic diseases.

Dalteparin is a low molecular weight heparin (LMWH) with a mean molecular weight of approximately 5,000. As with the other low molecular weight heparins, dalteparin has certain advantages over unfractionated heparin (UFH) most important of which are improved bio-availability by subcutaneous injection, a prolonged antithrombotic activity which is highly correlated with body weight permitting the once daily administration of the drug. Other possible advantages of LMWH including dalteparin include a lower incidence of heparin induced thrombocytopenia and thrombosis and decreased tendency to produce osteopenia on prolonged administration. Dalteparin has been subjected to a large number of well designed randomised clinical trials for the prevention and treatment of venous thromboembolism. Based on data from the randomised clinical trials, dalteparin has been approved internationally for a wide spectrum of clinical indications.

Anticoagulants↗