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Biomedical subjects

Victor F Tapson

Publications and source records attributed to Victor F Tapson.

At least 37 records · Page 2Linked to original sources

Gender differences in the administration of prophylaxis to prevent deep venous thrombosis.

We investigated gender differences in the prescription of prophylaxis against deep vein thrombosis (DVT) in 2,619 patients who developed acute DVT while being hospitalized for reasons other than DVT or were diagnosed with acute DVT as outpatients but who had been hospitalized within 30 days prior to DVT diagnosis. Men were 21% more likely than women to receive prophylaxis (OR 1.21, 95% CI 1.03-1.43; p=0.021) after adjusting for DVT risk factors, including surgery, trauma, prior DVT, age, and cancer.

Acute Disease↗

Risk factors associated with symptomatic pulmonary embolism in a large cohort of deep vein thrombosis patients.

In patients with deep vein thrombosis (DVT), the factors which predispose to concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT, we analyzed 4,211 patients with a known status for presence (n=639) or absence (n=3572) of symptomatic PE. Age and gender were similar in DVT plus PE (63.7+/-15.6 years; 49% men) and DVT patients (63.4+/-17.3 years; 46% men). Body mass index (BMI) was higher in patients with DVT plus PE (median 29.0, range 15.4-67.0 kg/m2) than in patients with DVT (median 26.8, range 9.7-64.4 kg/m2; p<0.001). Chronic lung disease (17% vs. 12%; p<0.001), a personal history of PE (11% vs. 6%; p<0.001), and a family history of DVT or PE (8% vs. 4%; p<0.001) were more frequent in DVT plus PE patients. Twenty-seven percent of DVT plus PE patients received prophylaxis prior to the thromboembolic event compared with 32% of DVT patients (p=0.002). Proximal DVT (OR 1.84, 95% CI 1.39-2.43), prior PE (OR 1.68, 95% CI 1.20-2.35), obesity (BMI >30 kg/m2) (OR 1.65, 95% CI 1.33-2.04), chronic lung disease (OR 1.51, 95% CI 1.13-2.01), as well as omission of prophylaxis (OR 1.30, 95% CI 1.04-1.64) emerged as independent predictors of concomitant symptomatic PE.

Aged↗

High utilization rate of vena cava filters in deep vein thrombosis.

The objective was to investigate newly diagnosed patients with deep vein thrombosis (DVT) who received inferior vena cava filters (IVCFs). A prospective registry enrolled 5451 patients from 183 US study sites. In all patients, examination by venous duplex ultrasound confirmed the diagnosis of DVT. We collected and analyzed data on 781 patients who received an IVCF. The most frequently prescribed treatments were low-molecular-weight heparin and unfractionated heparin, which were used as a bridge to warfarin in 39% (n=2143) and 35% (n=1926) of patients, respectively. Of the total population, 781 (14%) (235 outpatients, 546 inpatients) underwent IVCF placement. The most common reasons for IVCF placement were contraindication to anticoagulation (n = 271), prophylaxis (n = 259), major bleeding related to anticoagulation therapy (n = 92), and anticoagulation failure (n = 73). Multivariate analysis revealed that patients were more likely to undergo IVCF insertion with multiple system organ failure (odds ratio [OR], 3.6; 95% CI, 1.48-8.60), previous stroke (OR,3.2;95% CI,2.11-4.74), or history of pulmonary embolism (OR,2.4; 95% CI, 1.95-2.91). In conclusion, a surprisingly high 14% (781) of patients with confirmed DVT received an IVCF. Many of these patients may have warranted less invasive methods of venous thromboembolism prophylaxis. Improved physician education regarding mechanical and pharmacologic prophylaxis alternatives might reduce the use of IVCFs.

Aged↗

Few predictors of massive deep vein thrombosis.

Factors that predispose to thrombus propagation from the femoropopliteal veins to the pelvic veins are poorly understood. Our goal was to determine whether there are characteristics that identify patients with massive deep vein thrombosis (DVT). We compared the 122 (2.5%) patients presenting with massive DVT (pelvic plus lower-extremity DVT) to the 4,674 (97.5%) patients with isolated lower-extremity DVT from a prospective United States multicenter DVT registry. Patients with massive DVT were younger (59.4+/-18.9 years vs. 64.3+/-16.8 years; p<0.01), less likely to have hypertension (40% vs. 51%; p=0.02), and more likely to smoke (21% vs. 13%; p=0.02) and have ongoing radiation therapy (7% vs. 3%; p=0.02). The massive DVT group more commonly presented with extremity edema (80% vs. 69%; p<0.01) and erythema (21% vs. 12%; p<0.01) than the isolated lower-extremity DVT group. However, after multivariable logistic regression analysis, extremity erythema (adjusted odds ratio 1.86; 95% CI 1.13-3.04) was the only independent sequela of massive DVT and younger age (adjusted odds ratio 1.17 per decreasing decade of age; 95% confidence interval: 1.02-1.34) was the only independent predictor of massive DVT. Thrombus propagation from the femoropopliteal system cannot be reliably predicted using demographic or clinical characteristics.

Adult↗

The role of smoking in coagulation and thromboembolism in chronic obstructive pulmonary disease.

Pulmonary embolism and deep vein thrombosis both account for many deaths in stable patients with chronic obstructive pulmonary disease (COPD), and the frequency of these events is higher during COPD exacerbations. The morbidity and mortality from deep vein thrombosis and pulmonary embolism in patients with COPD is not surprising given the reduced mobility associated with this disorder, in addition to the presence of coagulation abnormalities in smokers. The potential influence of inflammation on coagulation offers further potential to contribute to thrombogenesis in all smokers. Plasma fibrinogen levels are elevated in smokers and are further elevated during acute COPD exacerbation. Oral contraceptives cause significant increases in fibrinogen levels in smokers and nonsmokers, but only the latter appear to have a compensatory increase in antithrombin III activity. Factor XIII, which stabilizes fibrin clots, is increased in smokers. Quantitative exposure to passive smoke has been positively correlated with blood coagulation activity. Exposure to nicotine may also increase plasminogen activator inhibitor-1 (a major regulator of fibrinolysis), although the extent to which nicotine enhances coagulation is unresolved. Venous thromboembolism is a frequent and potentially fatal complication of patients with COPD. The interrelationship between smoking, COPD, and coagulation is intriguing and awaits further characterization.

Blood Coagulation Disorders↗

Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients.

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk of VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.

Acute Disease↗

Upper-extremity deep vein thrombosis: a prospective registry of 592 patients.

BACKGROUND: Upper-extremity deep vein thrombosis (UEDVT) occurs spontaneously or sometimes develops as a complication of pacemaker use, long-term use of a central venous catheter (CVC), or cancer. METHODS AND RESULTS: To improve our understanding of UEDVT, we compared the demographics, symptoms, risk factors, prophylaxis, and initial management of 324 (6%) patients with central venous catheter (CVC)-associated UEDVT, 268 (5%) patients with non-CVC-associated UEDVT, and 4796 (89%) patients with lower-extremity DVT from a prospective US multicenter DVT registry. The non-CVC-associated UEDVT patients were younger (59.2+/-18.2 versus 64.2+/-16.9 years old; P<0.0001), less often white (65% versus 73%; P<0.01), leaner (body mass index [BMI] 26.8+/-7.1 versus 28.5+/-7.3 kg/m2; P<0.001), and more likely to smoke (19% versus 13%; P=0.02) than the lower-extremity DVT patients. By way of propensity analysis and multivariable logistic regression analysis, we determined that an indwelling CVC was the strongest independent predictor of UEDVT (odds ratio [OR], 7.3; 95% confidence interval [CI], 5.8 to 9.2). An age of <67 years, a BMI of <25 kg/m2, and hospitalization were the independent predictors of non-CVC-associated UEDVT. Most (68%) UEDVT patients were evaluated while they were inpatients. Only 20% of the 378 UEDVT patients who did not have an obvious contraindication to anticoagulation received prophylaxis at the time of diagnosis. CONCLUSIONS: UEDVT risk factors differ from the conventional risk factors for lower-extremity DVT. Our findings identify deficiencies in our current understanding and the prophylaxis of UEDVT and generate hypotheses for future research efforts.

Adolescent↗

End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives.

To date, randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity, usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments, it is likely that the focus will shift toward trials of longer duration, involving patients with less advanced disease, and that different drugs and drug-combination regimens will be compared. In such trials, it is possible that a composite of markers indicating clinical deterioration (e.g., hospitalization for right heart failure, the requirement for the introduction of an alternative treatment, and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however, appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition, hemodynamics will likely remain valuable as secondary end points, but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally, cardiopulmonary exercise testing, echocardiographic studies, and biochemical parameters, such as brain natriuretic peptide or troponin T, may also prove useful as secondary end points in the future.

Clinical Trials as Topic↗

A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.

We enrolled 5,451 patients with ultrasound-confirmed deep vein thrombosis (DVT), including 2,892 women and 2,559 men, from 183 United States sites in our prospective registry. The 5 most frequent co-morbidities were hypertension (50%), surgery within 3 months (38%), immobility within 30 days (34%), cancer (32%), and obesity (27%). Of the 2,726 patients who had their DVT diagnosed while in the hospital, only 1,147 (42%) received prophylaxis within 30 days before diagnosis.

Comorbidity↗

Acute pulmonary embolism.

Deep vein thrombosis (DVT) and, therefore, pulmonary embolism (PE) are often preventable. Because of the lack of specificity of symptoms and signs, DVT and PE are frequently clinically unsuspected, leading to substantial diagnostic and therapeutic delays and resulting in considerable morbidity and mortality. Furthermore, prophylaxis continues to be dramatically underused. The incidence of venous thromboembolism is high in hospitalized patients, and both surgical as well as medical patients are at risk.

Acute Disease↗

Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy.

Pulmonary arterial hypertension (PAH) is a rare debilitating disease characterized by an increase in pulmonary vascular resistance and progressive right ventricular failure. PAH may be primary or associated with other conditions such as collagen vascular disease, portal hypertension, and HIV. Intravenous epoprostenol improves the survival, exercise tolerance, hemodynamics, and quality of life in patients with PAH and is believed to work through multiple pathways including vasodilation, opposition of smooth-muscle hypertrophy, and inhibition of platelet aggregation. Common dose-limiting side effects are flushing, jaw pain, arthralgias, myalgias, and headache, which are attributed to the vasodilatory effects of epoprostenol. In clinical practice, patients often develop persistent rash that is distinct from the flushing associated with epoprostenol. The specific findings both on physical examination and on dermatopathology have not, however, been well described. This report describes the cutaneous and dermatopathologic findings of 12 patients who developed persistent rash while receiving long-term prostacyclin for PAH.

Adult↗

Sitaxsentan therapy for pulmonary arterial hypertension.

Sitaxsentan may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictor effects of endothelin-A while maintaining the vasodilator/clearance functions of endothelin-B receptors. Patients with pulmonary arterial hypertension that was idiopathic, related to connective tissue disease or congenital heart disease, were randomized to receive placebo (n = 60), sitaxsentan 100 mg (n = 55), or sitaxsentan 300 mg (n = 63) orally once daily for 12 weeks. The primary endpoint was change in peak VO(2) at Week 12. Secondary endpoints included 6-minute walk, New York Heart Association class, VO(2) at anaerobic threshold, VE per carbon dioxide production at anaerobic threshold, hemodynamics, quality of life, and time to clinical worsening. Although the 300-mg group increased peak VO(2) compared with placebo (+3.1%, p < 0.01), none of the other endpoints derived from cardiopulmonary exercise testing were met. However, both the 100-mg dose and the 300-mg dose, compared with placebo, increased 6-minute walk distance (100 mg: +35 m, p < 0.01; 300 mg: +33 m, p < 0.01); functional class, cardiac index, and pulmonary vascular resistance also improved (p < 0.02 for each parameter at both doses). The incidence of elevated aminotransferase values (> three times normal) was 3% for the placebo group, 0% for the 100-mg group, and 10% for the 300-mg group.

Adolescent↗

Venous thromboembolism in intensive care patients.

Venous thromboembolism frequently complicates the management of patients with severe medical and surgical illnesses. Because the diagnosis of VTE is especially challenging in critically ill patients, the focus of intensivists should be on characterization of risk factors and the appropriate choice of VTE prophylaxis. LDUH or LMHW is the preferred choice for VTE prophylaxis in ICU patients. Mechanical methods of prophylaxis should be reserved for patients with a high risk for bleeding. The effectiveness of mechanical methods and of combined strategies of prevention and the clinically important outcomes of therapy need to be explored further in critically ill patients. Few diagnostic strategies have been assessed in ICU patients with suspected PE. Ventilation-perfusion lung scans remain a pivotal diagnostic test but retain the same limitations in critically ill patients as seen in other patient populations. Newer noninvasive techniques, such as spiral CT associated with imaging of the extremities, are gaining more wide-spread use, but, thus far, pulmonary angiography remains the most reliable technique to confirm or exclude PE in patients with respiratory failure. A consensus must be reached regarding the most appropriate combination of tests for adequate and cost-effective diagnosis of VTE. Further investigation of diagnostic strategies that include adequate consideration of clinical diagnosis using standardized models and noninvasive imaging are warranted.

Anticoagulants↗

Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension.

Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials. In the first trial, intravenous epoprostenol and intravenous treprostinil were compared. In the second trial, intravenous treprostinil and subcutaneous treprostinil were compared. In the third trial, subcutaneous treprostinil was compared with placebo infusion during an 8-week period. Intravenous epoprostenol and intravenous treprostinil resulted in a similar reduction in pulmonary vascular resistance acutely (22% and 20%, respectively). Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance (23% and 28%, respectively). The placebo-controlled 8-week trial demonstrated a mean improvement of 37 +/- 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 +/- 28 m reduction in those receiving placebo. There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group. Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term. Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.

Adolescent↗

Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study.

STUDY OBJECTIVES: We report on the long-term safety and efficacy of bosentan treatment in patients with pulmonary arterial hypertension (PAH). BACKGROUND: In a preceding study, bosentan was well tolerated and significantly improved the exercise capacity and hemodynamics of patients with PAH after 12 weeks of treatment. DESIGN: The present study was an open-label extension to the preceding double-blind, placebo-controlled study of 32 patients with PAH (primary or associated with scleroderma) who received bosentan or placebo at 125 mg bid for 3 to 7 months. PATIENTS: Twenty-nine of the original 32 patients received bosentan for an additional year (62.5 mg bid for 4 weeks and then 125 mg bid). INTERVENTIONS: Study end points included long-term safety, 6-min walk distance at week 4, modified New York Heart Association (NYHA) functional class of PAH at month 12, and the occurrence of withdrawal due to clinical worsening. Additional exploratory analyses included a walk test at month 6 for 19 patients and hemodynamic assessment at month 12 for 11 patients. RESULTS: At month 6, assessed patients continuing bosentan treatment maintained the improvement in walk distance observed at the end of the previous study (mean +/- SEM, 60 +/- 11 m), and patients starting bosentan treatment improved their walk distance by 45 +/- 13 m. Long-term treatment with bosentan for > 1 year was associated with an improvement in hemodynamic parameters and modified NYHA functional class. Overall, bosentan treatment was well tolerated. No patient underwent transplantation or died. CONCLUSIONS: Long-term treatment with bosentan is safe and has sustained benefits on exercise capacity and hemodynamics in patients with PAH.

Adult↗