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Biomedical subjects

A S Gallus

Publications and source records attributed to A S Gallus.

At least 37 records · Page 2Linked to original sources
PubMed1998

Replacing inpatient care by outpatient care in the treatment of deep venous thrombosis--an economic evaluation. TASMAN Study Group.

Two clinical trials in patients with acute deep venous thrombosis have indicated that the outpatient management with fixed-dose, subcutaneous low-molecular-weight heparin is at least as effective and safe as inpatient treatment with unfractionated intravenous heparin with respect to recurrent venous thromboembolism and major bleeding. We performed an economic evaluation alongside one of these trials to assess the cost consequences of the outpatient management strategy. Data were collected through case record forms, complemented by a prospective questionnaire in 78 consecutive patients, interviews with health care providers, and hospital data bases. Our study demonstrated that seventy-five percent of patients allocated to low-molecular-weight heparin received treatment either entirely at home or after a brief hospital stay. Fifteen percent of these patients required professional domiciliary care. Within-centre comparisons of resource utilisation in terms of natural units showed that outpatient management with low-molecular-weight heparin reduced the average number of hospital days in the initial treatment period in nine centres by 59 percent (95% CI: 43 to 71 percent) accompanied by a limited increase in outpatient and professional domiciliary care. The average reduction in hospital days at the end of follow up was 40 percent (95% CI: 25 to 54 percent). A cost-minimisation analysis, focusing on resource utilisation directly related to the treatment of deep venous thrombosis and associated costs in one centre demonstrated a cost reduction of 64 percent (95% CI: 56 to 72 percent) with the outpatient management with low-molecular-weight heparin. These data suggest that outpatient management of patients with proximal venous thrombosis using low-molecular-weight heparin reduces resource utilisation and total treatment cost. Implementation should be preceded by a cautious evaluation of a potential cost shifting and organisational prerequisites.

Administration, Cutaneous↗
PubMed1997

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

BACKGROUND: Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis. However, its application to pulmonary embolism or previous episodes of thromboembolism has not been studied. METHODS: We randomly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose, subcutaneous low-molecular-weight heparin (reviparin sodium) or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks. Approximately one third of the patients had associated pulmonary embolism. The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism, major bleeding, and death. We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism. RESULTS: Twenty-seven of the 510 patients assigned to low-molecular-weight heparin (5.3 percent) had recurrent thromboembolic events, as compared with 25 of the 511 patients assigned to unfractionated heparin (4.9 percent). The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence. Sixteen patients assigned to low-molecular-weight heparin (3.1 percent) and 12 patients assigned to unfractionated heparin (2.3 percent) had episodes of major bleeding (P= 0.63), and the mortality rates in the two groups were 7.1 percent and 7.6 percent, respectively (P=0.89). CONCLUSIONS: Fixed-dose, subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose, intravenous unfractionated heparin for the initial management of venous thromboembolism, regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism.

Anticoagulants↗
PubMed1996

Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group.

BACKGROUND: An intravenous course of standard (unfractionated) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the standard initial in-hospital treatment for patients with deep-vein thrombosis, but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe. Because the latter treatment can be given on an outpatient basis, we compared the two treatments in symptomatic outpatients with proximal-vein thrombosis but no signs of pulmonary embolism. METHODS: We randomly assigned patients to adjusted-dose intravenous standard heparin administered in the hospital (198 patients) or fixed-dose subcutaneous low-molecular-weight heparin administered at home, when feasible (202 patients). We compared the treatments with respect to recurrent venous thromboembolism, major bleeding, quality of life, and costs. RESULTS: Seventeen of the 198 patients who received standard heparin (8.6 percent) and 14 of the 202 patients who received low-molecular-weight heparin (6.9 percent) had recurrent thromboembolism (difference, 1.7 percentage points; 95 percent confidence interval, -3.6 to 6.9). Major bleeding occurred in four patients assigned to standard heparin (2.0 percent) and one patient assigned to low-molecular-weight heparin (0.5 percent; difference, 1.5 percentage points; 95 percent confidence interval, -0.7 to 2.7). Quality of life improved in both groups. Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin. Among the patients in that group, 35 percent were never admitted to the hospital at all, and 40 percent were discharged early. This treatment was associated with a mean reduction in hospital days of 67 percent, ranging from 29 percent to 86 percent in the various study centers. CONCLUSIONS: In patients with proximal-vein thrombosis, treatment with low-molecular-weight heparin at home is feasible, effective, and safe.

Aged↗
PubMed1995

Sera from patients with systemic lupus erythematosus demonstrate enhanced IgG binding to endothelial cells pretreated with tumour necrosis factor alpha.

Fluorescence flow cytometry and indirect immunofluorescence were used to detect circulating IgG antiendothelial cell antibodies (IgG-AECA) in the sera of patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Pretreatment of endothelial cells with tumour necrosis factor alpha (TNF alpha), but not with interferon gamma (IFN gamma), increased the IgG binding from sera of some patients with active SLE. In contrast, no change in binding activity to cytokine-stimulated endothelial cells was observed in the RA and PSS sera. The results of this study suggested that the enhanced binding of IgG from the sera of patients with SLE to endothelial cells stimulated with TNF alpha may be due to the ability of this cytokine to increase the expression of potential antigens on the surface of these cells. Hence, TNF alpha may play a role in the immune-mediated vascular damage associated with SLE.

Arthritis, Rheumatoid↗
PubMed1992

Apparent lack of synergism between heparin and dihydroergotamine in prevention of deep vein thrombosis after elective hip replacement: a randomised double-blind trial reported in conjunction with an overview of previous results.

We report the results of a double-blind, randomised trial of venous thrombosis (VT) prevention in 117 patients having elective hip replacement where low dose heparin alone (5,000 IU sodium heparin given subcutaneously [sc] 8 hourly until the seventh postoperative day) was compared with low dose heparin plus dihydroergotamine (DHE; 0.5 mg, given 8 hourly by sc injection). The trial end point consisted of VT discovered through bilateral ascending venography done routinely on the seventh postoperative day. VT developed in 34% of patients given heparin/DHE (95% confidence interval = 22% - 47%) compared with 24% in those given low dose heparin alone (95% confidence interval = 14% - 37%; p = 0.34), difference = 10% (95% confidence interval = -7% to +26%). Corresponding figures for the incidence of proximal (above-knee) thrombosis were 17% and 14% (95% confidence intervals = 8% - 29% and 6% - 25% respectively). These results are discussed in the context of a detailed overview of published evidence concerning VT prevention with heparin/DHE after hip replacement and we conclude it is unlikely that heparin/DHE is markedly superior to low dose heparin alone in this clinical setting.

Aged↗
PubMed1991

Standardised initial warfarin treatment: evaluation of initial treatment response and maintenance dose prediction by randomised trial, and risk factors for an excessive warfarin response.

We report a comparison of warfarin treatment outcomes in 172 inpatients in two general hospitals randomly assigned to commence warfarin therapy by one of two methods; the first where warfarin dosage was determined using a flexible dose induction protocol, and the other where dosage was prescribed empirically by resident medical staff. The mean INR for each treatment day, the mean time to reach a therapeutic level of INR, the mean maintenance dose and the mean time to reach maintenance dose were not significantly different between the protocol and empirical treatment groups. Although the mean observations of warfarin effect were similar between the two groups, there were more patients with excessive warfarin effect (INR greater than 4.0) during empirical treatment. In addition, age and identified complicating factors such as interfering drugs, heart failure or alcohol abuse were significant predictors of excessive warfarin effect, regardless of treatment group. The protocol dose administered on day 4 of treatment, which has been used as a determinant of maintenance dose, predicted maintenance dose to within 1 mg in 57/83 patients (69%, 95% confidence interval: 59-79%). We conclude that as a method for safely and effectively initiating warfarin therapy, this protocol at least matches the empirical prescribing skills of medical staff in a teaching hospital.

Aged↗
PubMed1990

Trial of different intensities of anticoagulation in patients with prosthetic heart valves.

We compared the efficacy and complications of anticoagulation with warfarin in 258 patients with prosthetic heart valves treated with regimens of "moderate intensity" (prothrombin-time ratio, 1.5; international normalized ratio, 2.65) or "high intensity" (prothrombin-time ratio, 2.5; international normalized ratio, 9) in a prospective, randomized study. The two patient groups were followed up for 421 patient-years and 436 patient-years, respectively. Eleven patients were lost to follow-up. Thromboembolism occurred with similar frequency in the two groups (4.0 and 3.7 episodes per 100 patient-years, respectively), but there was a total of 6.2 bleeding episodes per 100 patient-years in the moderate-intensity group, as compared with 12.1 episodes in the high-intensity group (P less than 0.002). There were 5.2 episodes of minor bleeding per 100 patient-years in the moderate-intensity group, as compared with 10.1 episodes in the high-intensity group (P less than 0.01). Major bleeding was also more common in the high-intensity group (2.1 episodes per 100 patient-years--including the only two fatal hemorrhages--as compared with 0.95 episode in the moderate-intensity group), but the difference was not statistically significant. We conclude that a moderate anticoagulant effect (prothrombin-time ratio, about 1.5) in patients with a mechanical prosthetic heart valve offers protection equivalent to that of more intensive therapy, but at a significantly lower risk.

Adolescent↗
PubMed1990

IgG and IgM anti-endothelial cell antibodies in patients with collagen-vascular disorders.

A cellular enzyme-linked immunosorbent assay (ELISA) was used to detect circulating anti-endothelial cell antibodies (AECA) in sera of patients suffering from rheumatoid arthritis (RA). Felty's syndrome (FS), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and those with a "lupus anticoagulant" (LA). IgG AECA were detected in RA, FS, SLE and LA sera, while IgM AECA were only detected in RA and FS. AECA were not specific for endothelial cells. However, IgG binding to endothelial cells and dermal fibroblasts was F(ab) mediated while in all other cell types tested, nonspecific binding most likely via the Fc region occurred. In RA and FS rheumatoid factor was shown to augment immunoglobulin binding to endothelial cells. Additional studies revealed that some of these pathological sera also contained cytotoxic IgG autoantibodies which fixed complement and damaged human umbilical vein endothelial cells in vitro. These studies suggest that a group of autoantibodies, present in a variety of collagen vascular disorders, react with endothelial cells and thus may be important aetiopathogenic factors in the vasculopathies associated with these disorders.

Antibodies↗
PubMed1990

Anticoagulants in the prevention of venous thromboembolism.

For 50 years, the key to successfully preventing venous thrombosis (VT) or pulmonary embolism (PE) among high-risk patients has been the judicious use of anticoagulants: first through full doses of oral anticoagulants and more recently through low-dose heparin prophylaxis. Low-dose heparin has become the standard of comparison for other preventive methods, since it is relatively safe and simple, its ability to prevent approximately 65% of the subclinical VT found by leg scanning after elective general surgery is well known, and recent meta-analysis of the many pertinent published clinical trials (large and small) strongly suggests a much greater benefit: a 65% reduction in the risk of postoperative death from major PE. In addition, there are trials that have also found low-dose heparin to be effective in general medical patients, although its value in this clinical setting is much less well documented. Although several effective approaches other than low-dose heparin are available, many of these tend to be either more cumbersome (intermittent external leg compression) or probably less powerful (graded pressure elastic stockings). There are situations where low-dose heparin prophylaxis fails, most obviously after orthopaedic surgery where the use of more complex regimens, including adjusted-dose heparin treatment and various schedules of warfarin prophylaxis, becomes appropriate. Recent progress has come from the intensive clinical exploration of various low molecular weight heparin fractions or fragments which appear to be effective after once daily administration to general surgical patients and show great promise of effectiveness and safety after hip surgery. The level of warfarin effect needed for VT prophylaxis has also been reinvestigated, with trials suggesting a need for less warfarin and a lower prothrombin time effect than was previously thought to be appropriate. Given that any attempts to minimize mortality from PE in hospital patients must rely on the widespread and systematic use of simple, safe, and cost-effective preventive methods, it is hoped that these advances will help move anticoagulant prophylaxis further out of the realm of clinical research and into that of common clinical practice.

Anticoagulants↗
PubMed1989

Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172.

Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti-Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.

Antigen-Antibody Reactions↗
PubMed1989

Acute phase reaction, fibrinogen level and thrombus size.

The influence of an acute phase reaction on the size, weight, and fibrin content of experimental venous thrombi was examined in 10 pairs of rabbits. Jugular vein thrombosis was provoked by venous stasis plus mechanical injury 36 hours after one member of each pair received 0.5 ml/kg sterile turpentine in olive oil by subcutaneous injection. Fibrinogen level, factor VIII activity, and antithrombin III activity were significantly higher at the time of thrombus formation in turpentine treated rabbits, as were thrombus size (assessed by visual scoring), dry weight of thrombi, and their fibrin content (derived by measuring 125I-fibrinogen incorporation). In addition, the fibrinogen concentration correlated significantly with size, weight, and fibrin content of thrombi when results from turpentine treated and control animals were pooled, suggesting that plasma fibrinogen concentration at the time of thrombus formation may strongly influence the extent of thrombosis. This effect could help explain observations of a "hypercoagulable state" after injury.

Acute-Phase Reaction↗
PubMed1989

Prospective evaluation of a flexible protocol for starting treatment with warfarin and predicting its maintenance dose.

We have evaluated a flexible warfarin dose induction protocol by monitoring its performance in 100 elderly inpatients. The protocol (designed by Fennerty et al., has two aims: (a) to move the prothrombin time (PT) ratio smoothly and quickly into its therapeutic range, and (b) to predict the steady-state warfarin requirement from the PT ratio measured on the fourth treatment day. It proved simple to use and reasonably successful, since after four days, 67/100 patients had achieved a therapeutic level of PT ratio, nine exceeded the therapeutic range, and 24 remained sub-therapeutic, while none had bled due to excessive anticoagulation. Maintenance dose prediction was tested by comparing the predicted and observed maintenance doses in patients within the 'therapeutic range' of PT ratio after various median times of treatment. After ten days, the observed dose was within 1 mg of that predicted in 65/86 patients (76%). This proportion became 57/77 (74%) after 18 days, and 49/79 (62%) after 34 days.

Aged↗
PubMed1988

Long term warfarin treatment in artery disease.

The long-term use of oral anticoagulants like warfarin in artery disease has long been controversial. Possible aims of treatment include the primary or secondary prevention of systemic embolism, preventing recurrence after myocardial infarction or the progression of transient cerebral ischemia to a complete stroke, and the prevention of artery graft occlusion. The value of long-term anticoagulation is generally accepted in the few situations where, as in patients with mechanical heart valve prostheses, mitral valve disease and atrial fibrillation, or idiopathic dilated cardiomyopathy, the risk of arterial thromboembolism without anticoagulation is known to be high and there is good evidence that anticoagulants are effective, so the benefit:risk balance strongly favours their use. In many settings, however, it is hard to justify long-term warfarin treatment as the benefit:risk balance remains unknown; either because the risk of thromboembolism without anticoagulation remains to be clearly defined (as in the case of patients with 'lone' atrial fibrillation), or because possible benefits have not been well documented (as after transient cerebral ischemia or peripheral vascular surgery). Finally, there is the difficult problem of estimating the benefit from long-term anticoagulation after myocardial infarction. It seems that warfarin can reduce the likelihood of non-fatal reinfarction with relative safety in highly selected patients, but whether it reduces mortality, and how its effect compares with that of other, more recent, therapies aimed at preventing reinfarction, remains unknown.

Cerebrovascular Disorders↗