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Biomedical subjects

R D Hull

Publications and source records attributed to R D Hull.

At least 37 records · Page 2Linked to original sources
PubMed2000

Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group.

BACKGROUND: Pulmonary embolism (PE) occurs in 50% or more of patients with proximal deep-vein thrombosis. Low-molecular-weight heparin treatment is effective and safe in patients with deep vein thrombosis and may also be so in patients with PE. Recent rigorous clinical trials have established objective criteria for determining a high probability of PE by perfusion lung scanning. OBJECTIVE: To compare low-molecular-weight heparin with intravenous heparin for the treatment of patients with objectively documented PE and underlying proximal deep vein thrombosis. METHODS: In a multicenter, double-blind, randomized trial, we compared fixed-dose subcutaneous low-molecular-weight heparin (tinzaparin sodium) given once daily with dose-adjusted intravenous heparin given by continuous infusion using objective documentation of clinical outcomes. Pulmonary embolism at study entry was documented by the presence of high-probability lung scan findings. RESULTS: Of 200 patients with high-probability lung scan findings at study entry, none of the 97 who received low-molecular-weight heparin had new episodes of venous thromboembolism compared with 7 (6.8%) of 103 patients who received intravenous heparin (95% confidence interval for the difference, 1.9%-11.7%; P = .01). Major bleeding associated with initial therapy occurred in 1 patient (1.0%) who was given low-molecular-weight heparin and in 2 patients (1.9%) given intravenous heparin (95% confidence interval for the difference, -2.4% to 4.3%). CONCLUSIONS: Low-molecular-weight heparin administered once daily subcutaneously was no less effective and probably more effective than use of dose-adjusted intravenous unfractionated heparin for preventing recurrent venous thromboembolism in patients with PE and associated proximal deep vein thrombosis. Our findings extend the use of low-molecular-weight heparin without anticoagulant monitoring to patients with submassive PE.

Adolescent↗
PubMed2000

Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests.

PURPOSE: Patients who have nonmassive acute pulmonary embolism and a high risk of bleeding or contraindication to anticoagulants, such recent surgery or gastrointestinal bleeding, present a clinical dilemma. We sought to estimate whether such patients could be safely left untreated if serial compression ultrasound or serial impedance plethysmography were negative and cardiorespiratory reserve was adequate. SUBJECTS AND METHODS: The frequency of recurrent pulmonary embolism among patients with nonmassive acute pulmonary embolism and negative serial noninvasive leg tests who were not treated was estimated from two prospective studies of the noninvasive management of patients with suspected pulmonary embolism. One of the studies used serial impedance plethysmography of the lower extremities; the other used serial compression ultrasound. The prevalence of pulmonary embolism in patients with nondiagnostic ventilation/perfusion lung scans was determined from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). RESULTS: The estimated frequency of fatal recurrent pulmonary embolism was 1% [95% confidence interval (CI), 0% to 5%) among untreated patients with nonmassive pulmonary embolism who had negative serial impedance plethysmograms and 0% (95% CI, 0% to 4%) among those with negative serial compression ultrasonograms. The frequency of nonfatal recurrent pulmonary embolism among untreated patients was 3%, regardless of whether they had negative serial impedance plethysmograms or negative serial compression ultrasonograms. These results were comparable with the frequency of recurrent pulmonary embolism among patients treated with anticoagulants or with inferior vena cava filters. CONCLUSION: Withholding treatment of nonmassive acute pulmonary embolism, if serial impedance plethysmograms or serial venous ultrasonograms are negative and cardiopulmonary reserve is adequate, is a possible strategy for the management of patients with a high risk of bleeding or other contraindication to anticoagulants. This strategy may be associated with fewer adverse events than treatment with anticoagulants or an inferior vena cava filter. Prospective trials comparing alternative treatments are needed.

Acute Disease↗
PubMed2000

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

The low-molecular-weight heparins (LMWHs) have been evaluated in the prevention and treatment of deep-vein thrombosis and pulmonary embolism. LMWHs have been found to be safe and effective in this clinical setting and have advantages over unfractionated heparin. These advantages include less serious and less frequent therapeutic complications. The favorable pharmacokinetic profile of LMWHs compared with heparin has allowed for safe, effective, and convenient treatment of patients with venous thromboembolism. Use of LMWHs ultimately results in considerable cost savings for the health care system.

Antifibrinolytic Agents↗
PubMed2000

New insights into extended prophylaxis after orthopaedic surgery - the North American Fragmin Trial experience.

It is well-known that peri-operative and post-operative venous thrombosis are common. Trials in Europe have shown that extended out-of-hospital prophylaxis with a low-molecular-weight heparin reduces the rate of deep vein thrombosis in patients undergoing elective hip surgery. North American investigators of limited-outcome descriptive studies, however, have suggested that out-of-hospital prophylaxis is not necessary. To resolve this uncertainty, NAFT (North American Fragmin Trial) was conducted, the results of which are summarized in this paper. The findings of NAFT support the favourable findings of the European studies on extended prophylaxis. Furthermore, European data have shown extended out-of-hospital prophylaxis to be cost-effective. On the basis of the aggregate data, it is felt that the A2 recommendation made by the Fifth American College of Chest Physicians consensus conference for extended prophylaxis should be changed to an A1 recommendation.

Anticoagulants↗
PubMed1999

Effectiveness of the Quick Medical Reference as a diagnostic tool.

A number of computer-based systems with diagnostic capabilities have been developed for internal medicine. Quick Medical Reference (QMR) is one such program. The authors describe key features of QMR and report on their study of its effectiveness as a diagnostic tool. They investigated how frequently the correct diagnosis would appear among the 5 highest ranked diagnoses generated by QMR. The charts of 1144 consecutive patients admitted to a teaching unit were retrospectively screened. Eligible cases included those referred for investigation of an undiagnosed illness with an objectively proven final diagnosis (n = 154). Two physicians familiar with, but not experts in, the use of QMR entered clinical information abstracted from the patients' charts into the program. Physician A obtained the correct diagnosis in 62 (40%) of the 154 cases, and physician B was successful in 56 (36%) of the cases. The authors use study cases to illustrate QMR's strengths and weaknesses.

Diagnosis, Computer-Assisted↗
PubMed1999

Preoperative vs postoperative initiation of low-molecular-weight heparin prophylaxis against venous thromboembolism in patients undergoing elective hip replacement.

BACKGROUND: Although preoperative and postoperative initiation of prophylaxis for deep vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) are effective, the relative effectiveness and safety of these approaches is unknown. In the absence of a published definitive level 1 trial addressing this question, a meta-analysis is appropriate. OBJECTIVE: To report a meta-analysis comparing preoperative with postoperative initiation of prophylaxis of DVT in patients undergoing elective hip replacement. METHODS: Relevant trials were identified, and potential biases in the meta-analysis were minimized by analyzing all rigorously performed randomized trials that met all of the following criteria for conduct of the trial: (1) double-blind design, (2) objective documentation of the frequencies of DVT by ascending contrast venography, (3) venography performed before or at the time of discharge from the hospital, (4) initiation of the same LMWH preoperatively or postoperatively in dosages shown to be effective, (5) compliance with the criteria for a level 1 trial, and (6) objective documentation of major and minor bleeding according to strict criteria. RESULTS: Treatment with LMWH initiated preoperatively was associated with a DVT frequency of 10.0% compared with a frequency of 15.3% when the LMWH was initiated postoperatively (P = .02, Fisher exact test). Major bleeding was less frequent in patients receiving preoperatively initiated LMWH than in patients receiving postoperatively initiated LMWH (0.9%, vs. 3.5%; P = .01, Fisher exact test). CONCLUSIONS: Our findings support the need for a randomized comparison of preoperative and postoperative initiation of pharmacological prophylaxis of DVT. Such a trial would resolve the divergent practices for DVT prophylaxis between Europe and the North American countries, the United States and Canada, and would affect the treatment for thousands of patients on both continents.

Anticoagulants↗
PubMed1999

Diagnosis of pulmonary embolism.

The patient with suspected pulmonary embolism presents a challenging diagnostic problem. The symptoms and signs are nonspecific, and objective testing is required to establish or exclude the presence of pulmonary embolism. Lung scanning continues to be a first-line test, but in 40% to 70% of all patients, the results do not definitively provide indication for either giving or withholding anticoagulant treatment even when combined with the clinical assessment. Pulmonary angiography is the reference standard, but it is invasive and may not be available in all clinical settings. Pulmonary embolism is strongly associated with proximal deep-vein thrombosis of the legs (popliteal, femoral, or iliac vein thrombosis). Objective testing for proximal deep-vein thrombosis is useful in patients with suspected pulmonary embolism. A positive result from such testing provides an indication for anticoagulant treatment. Serial testing for proximal deep-vein thrombosis is a safe and effective alternative to pulmonary angiography in patients with adequate cardiorespiratory reserve. The assay for plasma D-dimer using either a rapid enzyme-linked immunospecific assay technique or a bedside whole-blood agglutination technique is promising as a test for excluding venous thromboembolism. A positive result by spiral CT imaging is useful for ruling in a diagnosis of pulmonary embolism, but the safety of withholding treatment in patients with negative spiral CT results remains uncertain. Pulmonary angiography continues to have an important role in selected patients in whom it is critical to definitively confirm or exclude the presence of pulmonary embolism.

Humans↗
PubMed1999

Thrombin inhibitors as anticoagulant agents.

Hirudin and its analogues and the synthetic antithrombin agents are interesting new antithrombotic agents that have been studied in a number of well-designed randomized clinical trials and further studies are underway. These agents offer certain advantages over heparin and low-molecular-weight heparin, and at least one agent is orally bioavailable. Studies have shown that the specific thrombin inhibitors can significantly decrease the incidence of composite cardiac endpoints in acute ischemic syndromes (following thrombolysis for myocardial infarction, unstable angina, and non-Q wave myocardial infarction and coronary angioplasty), but it is disappointing that the benefits obtained during short-term treatment are not sustained in the long term. Recent data are reviewed here from clinical trials supporting the use of the specific antithrombin agents in the treatment of acute cardiac ischemic syndromes, the prevention and treatment of venous thromboembolism, and the management of heparin-induced thrombocytopenia.

Anticoagulants↗
PubMed1999

The role of newer diagnostic techniques in the diagnosis of pulmonary embolism.

Among the evolving techniques for the diagnosis of acute pulmonary embolism, contrast enhanced spiral CT takes a particularly prominent role because it is available at most centers, it images the pulmonary embolism directly, and it is minimally invasive. It has not yet been fully evaluated, however. Magnetic resonance angiography also has appeal for similar reasons. Few patients have been studied, however. Magnetic resonance angiography for pulmonary embolism is still in the early testing phase. Transesophageal echocardiography can image pulmonary embolism in central pulmonary arteries, but preliminary tests suggest that it has a low negative predictive value and cannot be used to exclude pulmonary embolism. Finally, it seems that a rapid and sensitive technique for measuring d-dimer may now be available, which may assist in eliminating the diagnosis of acute pulmonary embolism in a significant percentage of patients in whom the diagnosis is suspected.

Acute Disease↗
PubMed1999

Extended prophylaxis against venous thromboembolism following total hip and knee replacement.

The recently reported reductions in the incidence of post-operative venous thromboembolism (VTE) are related to the widespread use of prophylactic anticoagulants. Many uncertainties remain with regard to the most effective ways to use thromboprophylaxis, however. The trend towards shorter hospital stays means that patients may receive less than the recommended 7-10 days of prophylaxis. Prolonged periods of thromboprophylaxis may be beneficial for patients at high risk of post-operative VTE, such as those undergoing major orthopaedic surgery. The relative rarity of symptomatic deep vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 28-35 days of prophylaxis with low-molecular-weight heparin to be more effective than 10-14 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.

Anticoagulants↗
PubMed1999

Long term outpatient prophylaxis for venous thromboembolism.

Recent reductions in the incidence of postoperative venous thromboembolism are related to the widespread use of prophylactic anticoagulants, but many uncertainties about the most effective ways to use thromboprophylaxis remain. Orthopedic patients are at high risk of thromboembolism, and the trend towards shorter hospital stays means that they may receive less than the recommended 7 to 10 days of prophylaxis. Longer periods of thromboprophylaxis may be beneficial for high risk patients. The relative rarity of symptomatic deep-vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 30 days of prophylaxis with low molecular weight heparin (LMWH) to be more effective than 7 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.

Ambulatory Care↗
PubMed1998

Immunologic findings among lead-exposed workers.

A comprehensive panel of immune parameters was evaluated among 145 lead-exposed workers with a median blood lead level (BLL) of 39 micrograms/dL (range: 15-55 micrograms/dL) and 84 unexposed workers. After adjusting for covariates, we found no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells, B cells, or NK cells between lead-exposed and unexposed workers, although the association between lead exposure and the number of CD4+ T cells was modified by age. We also found no differences between exposed and unexposed workers in serum immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative responses. However, among exposed workers, the percentage and number of B cells were positively associated with current BLL, serum IgG was negatively associated with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+ cells were positively associated with cumulative lead exposure. We found no evidence of a marked immunotoxic effect of lead at the exposure levels studied, although some subtle differences in immunologic parameters were noted.

Adult↗