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Biomedical subjects

R D Hull

Publications and source records attributed to R D Hull.

At least 91 records · Page 5Linked to original sources
PubMed1994

Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism. Consideration of noninvasive management.

OBJECTIVE: To assess the relative risks for bleeding with thrombolytic therapy in patients who are managed using pulmonary angiograms compared with those managed using noninvasive tests, primarily the ventilation-perfusion lung scan. DESIGN: A decision analysis based on data from other studies. METHODS: The risk for major bleeding in patients with pulmonary embolism who receive thrombolytic therapy after a noninvasive diagnosis was assessed from complications of thrombolytic therapy in patients with myocardial infarction, assuming that the same risk ratio for major bleeding when comparing an invasive with a noninvasive approach applied to patients with pulmonary embolism. The risk ratio was 3.3 (95% CI, 1.5 to 9.8) for major bleeding in patients with myocardial infarction. One or more major complications of pulmonary angiography occurred in 1.3% of patients (CI, 0.6% to 1.9%). RESULTS: The average reported risk was 14% (18 of 129 patients) (CI, 7.9% to 20.1%) for major bleeding in patients who had pulmonary angiography before receiving tissue plasminogen activator (tPA). The estimated risk was 4.2% (estimated CI, 1.4% to 9.3%) for major bleeding with tPA after a noninvasive diagnosis of pulmonary embolism. Assuming a risk of 1.3% for major complications from pulmonary angiography, a risk for major hemorrhage of 14.0% for an invasive diagnosis, and a risk of 4.2% for a noninvasive diagnosis, fewer complications would occur with noninvasive management if the prevalence of pulmonary embolism exceeded 21%. CONCLUSION: Among patients with suspected pulmonary embolism who are candidates for thrombolytic therapy, it is safer to use noninvasive diagnostic tests in many patients.

Acute Disease↗
PubMed1994

Physician-guided treatment compared with a heparin protocol for deep vein thrombosis.

BACKGROUND: Effective heparin therapy, defined by therapeutic prolongation of the activated partial thromboplastin time (APTT), decreases the risk of recurrent venous thromboembolism. Achieving therapeutic prolongation of the APTT within 24 hours of the start of heparin therapy has proved difficult. We hypothesized that a protocol that delivered high initial heparin infusions to patients without identifiable risk for bleeding complications would decrease the time to achieve a therapeutic anticoagulant effect without increasing the incidence of major bleeding complications. METHODS: To test this hypothesis, we studied concurrent patient cohorts. We defined a therapeutic anticoagulant effect (APTT > 55 seconds) to be an APTT more than 1.5 times the upper limit of normal. Twenty patients with acute symptomatic deep vein thrombosis received a 5000-U heparin bolus, followed by 1680 U/h (low risk to bleed) or 1240 U/h (high risk to bleed), adjusted by protocol-directed response to APTT results. Forty-eight patients with deep vein thrombosis were treated by their physicians. The Kaplan-Meier method was used to examine the proportion of patients who achieved an APTT greater than 55 seconds as a function of time. RESULTS: The two study cohorts did not differ with respect to age, weight, or risk factors for venous thromboembolism. Analysis of Kaplan-Meier curves showed that the heparin protocol decreased the time to achieve a therapeutic anticoagulant effect (P = .025). Ten (91%) of 11 patients (95% confidence interval, 59% to 100%) without risks to bleed who were treated by the heparin protocol and 29 (60%) of 48 patients (95% confidence interval, 45% to 74%) not treated by the protocol had an initial therapeutic APTT (P = .006). CONCLUSION: A protocol that delivers higher initial heparin infusions to patients without identifiable risks for bleeding decreases the time needed to achieve therapeutic prolongation of APTT, when compared with nonprotocol physician management.

Aged↗
PubMed1994

A noninvasive strategy for the treatment of patients with suspected pulmonary embolism.

BACKGROUND: Pulmonary embolism has historically presented a formidable diagnostic problem because of the nonspecificity of the clinical findings associated with this disorder and the diagnostic uncertainties and challenges presented by both ventilation-perfusion lung scanning and pulmonary angiography. We have reported previously that serial noninvasive leg testing provides a practical noninvasive alternative to pulmonary angiography in patients with non-high probability (nondiagnostic) lung scans and adequate cardiorespiratory reserve. We have reevaluated this observation prospectively to (1) confirm or refute our original observation in an independent cohort and (2) to increase the numbers sufficiently to provide narrow confidence limits for the observed outcomes. METHODS: A prospective comparative study in 1564 consecutive patients with suspected pulmonary embolism who underwent ventilation-perfusion lung scanning and objective testing for proximal-vein thrombosis. RESULTS: On long-term follow-up of 627 patients with the following characteristics: (1) abnormal, nondiagnostic lung scans, (2) not taking anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 12 patients (1.9%; 95% confidence limits, 0.8% to 3.0%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in four (0.7%) of 586 patients (95% confidence limits, 0.02% to 1.3%) with normal lung scans in whom anticoagulant therapy was withheld and in eight (5.5%) of 145 patients (95% confidence limits, 1.8% to 9.2%) with high probability lung scans who received anticoagulant therapy. CONCLUSIONS: Our findings indicate that the clinician has a practical noninvasive strategy in patients with adequate cardiorespiratory reserve and nondiagnostic lung scans that (1) avoids pulmonary angiography, (2) identifies patients with proximal-vein thrombosis who require treatment, and (3) avoids the need for treatment and further investigation in the majority of patients.

Adolescent↗
PubMed1994

Prophylaxis of venous thromboembolism in brain tumor patients.

Thromboembolism is a common problem in patients with brain tumors. Within this population are subpopulations of patients at varying but substantial risk for deep vein thrombosis and pulmonary embolism. Prophylactic strategies can be applied to these various risk groups that will dramatically reduce the incidence of thromboembolism, and these should be applied on a routine basis. The standard prophylactic methods for thromboembolic prophylaxis include mechanical devices (e.g., graduated leg stockings; external pneumatic calf compression) and pharmacological agents (e.g., low dose heparin). In addition, a basic knowledge of low molecular weight heparins and heparinoids is essential because these new agents have a potentially promising role in the prophylaxis of neurological disease in certain patients. The principles concerning the prophylaxis of venous thromboembolic disease in patients with brain tumors are addressed in this review.

Brain Neoplasms↗
PubMed1994

Therapeutic use of low molecular weight heparins: knowledge to date and their application to therapy.

Indeed, the accumulating evidence indicates that certain LMW heparins administered subcutaneously may replace classic intravenous heparin therapy. Certain of these subcutaneously administered LMW heparins do not require monitoring. The simplified care offered by LMW heparin therapy offers the possibility of transferring care from in to out of hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW heparin therapy will likely prove to be highly cost effective. It is uncertain at present whether the findings associated with an individual LMW heparin preparation can be extrapolated to a different LMW heparins. For this reason, the findings of clinical trials apply only to the particular LMW heparin evaluated and cannot be generalized to the LMW heparins at large.

Animals↗
PubMed1994

Venous thromboembolism in neurosurgery and neurology patients: a review.

Thromboembolism is a common problem in neurosurgery and neurology patients. Within this diverse population are subpopulations of patients with varying degrees of thromboembolic risk: low, moderate, and high. Patients at substantial risk for deep vein thrombosis and pulmonary embolism include those with spinal cord injury, brain tumor, subarachnoid hemorrhage, head trauma, stroke, and patients undergoing a neurosurgical operation. There are prophylactic strategies that can be applied to these various risk groups that will dramatically reduce the incidence of thromboembolism. The risk of pulmonary embolism or fatal pulmonary embolism typically exceeds the risk of severe or fatal bleeding from adequate prophylaxis, and these techniques should be applied on a routine basis. To adequately care for patients with deep venous thrombosis and pulmonary embolism, the physician requires a thorough understanding of the methods of diagnosis, the pharmacokinetics of heparin and warfarin, and a knowledge of their role in the treatment strategies that have proven efficacy and safety. In addition, an awareness of the low molecular weight heparins and heparinoids is becoming essential. These new agents have a potentially promising role in both the prophylaxis and treatment of patients with neurological disease. The principles concerning the prophylaxis, diagnosis, and clinical management of venous thromboembolic disease in neurosurgery and neurology patients are dealt with in this review.

Anticoagulants↗
PubMed1994

Relative risks of anticoagulant treatment of acute pulmonary embolism based on an angiographic diagnosis vs a ventilation/perfusion scan diagnosis.

The purpose of this investigation was to assess the relative risks of antithrombotic treatment following pulmonary angiography vs no angiography in patients with acute pulmonary embolism (PE). Comparisons of risks of diagnosis and therapy were made among patients treated on the basis of a pulmonary angiographic diagnosis vs patients treated on the basis of a ventilation/perfusion (V/Q) scan combined with clinical assessment in the presence of a single negative test for deep venous thrombosis. Calculations of risks assumed major complications of pulmonary angiography equal to 1.3 percent, major bleeding with heparin equal to 4.9 percent (1.1 percent among patients with a low risk of bleeding and 10.8 percent among patients with a high risk of bleeding), and major bleeding with warfarin (international normalized ratio 2 to 3) equal to 1.7 percent. Among patients with a risk of major bleeding from heparin followed by warfarin of 6.6 percent, if the estimated probability of PE was greater than about 80 percent, fewer major complications of diagnosis and treatment would occur if treatment was initiated on the basis of the V/Q scan. If the probability of PE in such patients was less than 80 percent, fewer major complications of diagnosis and treatment would occur if the diagnosis was established by pulmonary angiography. Among patients with a high (12.5 percent) risk of major bleeding, it was shown to be safer to treat on the basis of an angiographic diagnosis if the estimated probability of PE was less than 90 percent. If the patients, however, were at low (2.8 percent) risk of major bleeding, fewer major complications would occur if angiography was reserved for patients with an estimated risk of PE less than about 50 percent. Serial studies of the leg veins may eliminate the need for angiography in such patients.

Acute Disease↗
PubMed1993

Therapeutic use of low-molecular-weight heparins.

Accumulating evidence indicates that certain low-molecular-weight (LMW) heparins administered subcutaneously may replace classic intravenous heparin therapy. LMW heparins do not require monitoring and may be safer and more effective than unfractionated heparin. The decreased mortality rate, evident in two randomized trials, which was particularly striking in patients with metastatic carcinoma, requires confirmation. The simplified care offered by LMW heparin therapy raises the possibility of transferring care from in-hospital to out of hospital in uncomplicated patients with deep-vein thrombosis [Salzman EW: Low-molecular weight heparin and other new antithrombotic drugs. N Engl J Med 1992;326: 1017-1019]. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW heparin therapy will likely prove to be highly cost-effective. It is uncertain at present whether the findings associated with an individual LMW heparin preparation can be extrapolated to a different LMW heparin. For this reason the findings of clinical trials apply only to the particular LMW heparin evaluated and cannot be generalized to the LMW heparins at large.

Animals↗
PubMed1993

Strategy for diagnosis of patients with suspected acute pulmonary embolism.

STUDY PROTOCOL: Two separate groups of clinical investigators have provided new information and divergent approaches to the management of acute pulmonary embolism (PE). In this position paper, investigators from both groups (Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] and Canadian study groups) have utilized the combined scientific database in order to rationalize seemingly polarized diagnostic recommendations into a single practical algorithm. METHODS: An in-depth review established the relative risks of deep venous thrombosis (DVT) and the related accuracy of diagnostic tests. In PIOPED, 640 of 887 patients at risk for PE had either an intermediate probability ventilation/perfusion (V/Q) scan or a V/Q scan probability that was discordant with the prior estimate of probability by clinical assessment. The risk of PE in these patients was 16 to 88 percent (average, 34 percent). In this group, we calculated the probability of PE assuming that tests for DVT had been performed and that 50 percent of patients with PE have detectable proximal DVT. By calculation, 108 in 640 patients of whom the diagnosis of PE was uncertain, would have shown proximal DVT. In 239 of these 640 patients, tests for DVT would have been negative and the risks of PE in these patients is calculated to be less than 10 percent. RESULTS: Therefore, we calculate that in 347 of 640 patients, confident recommendations for treatment or no treatment could have been given without pulmonary angiography. Accordingly, in the PIOPED study group of 887 patients, the need for pulmonary angiography would have been reduced from 640 (72 percent) to 293 patients (33 percent). CONCLUSION: In conclusion, a diagnostic strategy that includes the clinical evaluation, V/Q scan, and evaluation for DVT would decrease the number of patients who require pulmonary angiography from 72 to 33 percent.

Acute Disease↗
PubMed1993

Adverse effects of coumarin anticoagulants.

The biochemistry of vitamin K metabolism and the role of vitamin K-dependent gamma-carboxylation of the vitamin K-dependent coagulation factors are now well understood. Likewise, there is a clear understanding of the role of oral anticoagulants in the inhibition of these coagulation factors. However, the effect of oral anticoagulants on extrahepatic gamma-carboxylated proteins such as osteocalcin and matrix gamma-carboxyglutamate (Gla)-protein (MGP), and the effects of long term anticoagulants on bone mineral metabolism are just now being recognised. The relevance of these observations on mineral metabolism for elderly individuals, and in particular postmenopausal women who are on long term anticoagulants, is still unknown but worthy of continued close observation. The most significant hazard of oral anticoagulants is haemorrhage. Clinical trials continue to demonstrate that less intense (lower dosage) warfarin therapy can significantly decrease this risk of haemorrhage while at the same time providing equal efficacy when compared to more intense warfarin therapy. The more widespread use of the International Normalised Ratio (INR) for the control of anticoagulants will undoubtedly further decrease the risk of haemorrhage, but new innovations such as the use of ultra low-dose warfarin or newer techniques for the continued monitoring of oral anticoagulants are still required, particularly as the indications for oral anticoagulants continue to expand.

Coumarins↗
PubMed1993

Low-molecular-weight heparins for the treatment of venous thromboembolism.

Recent studies have indicated that certain low-molecular-weight heparins given subcutaneously may replace continuous intravenous unfractionated heparin for the treatment of venous thromboembolism. Low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and they do not require laboratory monitoring. These characteristics of low-molecular-weight heparin therapy raise the possibility of treating uncomplicated patients with deep venous thrombosis or pulmonary embolism in the outpatient setting. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient low-molecular-weight heparin will likely prove to be highly cost-effective. At the present time, the finding associated with an individual low-molecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins and each must be evaluated in separate clinical trials. Recent randomized clinical trials indicate that low-molecular-weight heparin may be safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. A decreased mortality rate, which was particularly striking in patients with metastatic carcinoma, was unexpected and requires confirmation in further prospective randomized trials.

Heparin, Low-Molecular-Weight↗
PubMed1993

Therapeutic use of low molecular weight heparins: the knowledge to date as applied to therapy.

Indeed, the accumulating evidence indicates that certain LMWH administered subcutaneously may replace classic intravenous heparin therapy. Certain of these subcutaneously administered LMWH do not require monitoring. The simplified care offered by LMWH therapy presents the possibility of transferring care from in-hospital to out of hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMWH therapy will likely prove to be highly cost-effective. It is uncertain at present whether the findings associated with an individual LMWH preparation can be extrapolated to a different LMWH. For this reason, the findings of clinical trials apply only to the particular LMWH evaluated and cannot be generalized to the LMWH at large.

Animals↗
PubMed1992

Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.

BACKGROUND: Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. METHODS: In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. RESULTS: Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049). CONCLUSIONS: Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.

Double-Blind Method↗
PubMed1992

Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model.

An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper-reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗