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H R Büller

Publications and source records attributed to H R Büller.

At least 73 records · Page 4Linked to original sources
PubMed2001

Outpatient treatment of patients with pulmonary embolism.

Very few treatment studies have included patients with pulmonary embolism (PE) but there have been many enrolling patients with deep vein thrombosis (DVT). Should treatment for PE be different from treatment for DVT? Post-mortem and clinical studies have shown a strong association between PE and the presence of venous thrombosis in the lower limbs but some recent data suggest that certain clinical factors will predict patients at higher risk of death from PE. Unfortunately, it is not clear that identifying patients as high risk will affect outcome. Two large studies recently compared treatment with unfractionated heparin to treatment with low-molecular-weight heparin in patients with PE. Combining the two studies, the rates of recurrent DVT or PE were 2.9% (13/442) in the low-molecular-weight heparin group and 3.2% (14/441) in the unfractionated heparin group, and major hemorrhage occurred in fewer than 3% of patients. The feasibility of providing outpatient care to many patients presenting to tertiary care hospitals with acute PE has become evident. In our institutions, the data suggest about 50% of patients with PE could be treated as outpatients. Until further knowledge is available, it is not unreasonable to perform echocardiography and cardiac troponin T on patients with PE if they are not completely stable or if concern over concomitant cardiopulmonary disease exists. If they meet criteria demonstrated to result in early death, it is of course reasonable not to treat such patients on a solely outpatient basis. Evidence is accumulating that patients with PE as their initial symptom complex of their venous thromboembolic disease have a worse prognosis, specifically, higher risk of recurrence and higher risk of death, but there are no data to suggest outpatient therapy will affect their prognosis. Low-molecular-weight heparin or intravenous unfractionated heparin, followed by oral anticoagulant therapy, provide adequate therapy in most patients with PE, and many can be treated as outpatients.

Acute Disease↗
PubMed2001

Active-control trials: how would a new agent compare with placebo? A method illustrated with clopidogrel, aspirin, and placebo.

BACKGROUND: In an active-control trial with a new treatment and a comparator that has placebo-controlled trials, how might the effect of the new therapy versus placebo be estimated? For many diseases it is not ethically justified to use a placebo-control trial, yet in the United States regulatory efficacy is conceptually defined in comparison with placebo. METHODS: By use of the logarithm of the odds ratio for the active-control trial and for the placebo-controlled trials of the active-control, we estimated the effect of the new agent versus placebo. This "putative placebo" estimate assumes that the odds ratio in the active-control versus placebo trials is the same as would have been obtained had a placebo arm been possible in the trial with the new agent. A formula is given for sample size calculation in such a setting. RESULTS: Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist, and aspirin were compared in the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) Study of patients with recent myocardial infarction, recent ischemic stroke, or symptomatic peripheral arterial disease. The 40 trials comparing aspirin with placebo are summarized by the Antiplatelet Trialists' Collaboration. For the outcome cluster of stroke, myocardial infarction, or vascular mortality, the estimated odds ratio for clopidogrel versus placebo is 0.70 (95% confidence interval 0.64-0.78, P<.000001). The relative risk reduction of approximately 30% represents a clinically meaningful benefit. CONCLUSIONS: For active-control trials use of prior trials of the active-control versus placebo may be usefully used to estimate the effect of the new therapy versus a putative placebo.

Aspirin↗
PubMed2001

Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.

OBJECTIVE: To study the incidence, signs and symptoms, diagnostic tests, risk factors, therapy, and complications of pediatric venous thromboembolism (VTE) in The Netherlands. METHODS: A prospective 2-year registry of VTE in children aged < or = 18 years. RESULTS: Ninety-nine patients were registered. The annual incidence of VTE was 0.14/10,000 children, 35% of whom were symptom free. Almost half of the patients were newborns. Neonatal VTE was almost exclusively catheter related, located in the upper venous system, and asymptomatic. In older children VTE was catheter related in approximately one third and more often was located in the lower venous system. In 85% of all patients, thrombosis developed while the patient was in the hospital. Diagnosis was usually made by ultrasonography. In 98% of all patients, at least 1 risk factor was present. Congenital prothrombotic disorders were more often present in older children (21%) than in neonates (6%). A variety of treatment modalities were used. Morbidity consisted of bleeding (7%) and recurrent thrombosis (7%). Two children died as result of VTE. CONCLUSION: VTE is mostly diagnosed in hospitalized children, especially sick newborns with central venous catheters and older children with a combination of risk factors. Primary prevention, optimal treatment, and long-term outcome of pediatric symptomatic and asymptomatic VTE need to be studied.

Adolescent↗
PubMed2001

Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis.

Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11 049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers.

Adult↗
PubMed2001

Acute pulmonary embolism: impact of selection bias in prospective diagnostic studies. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localization of Pulmonary Embolism.

We evaluated selection bias in a prospective study of 1,162 consecutive patients with suspected pulmonary embolism. Of these, 983 were eligible, and 627 could actually be included. During two months extensive data were collected on all non-included patients. Finally, our patient characteristics were compared with those of the PIOPED study (1990) and the study of Hull et al. (1994). Compared with included patients, the non-included patients had more often non-diagnostic V/Q scans (50% vs. 36%, p <0.01) and were more often already hospitalized (31% vs. 22%, P = 0.04). The subgroup of patients not included due to refusal or inability to give informed consent (IC) was older (mean age 61 vs. 53 years, P <0.01), more often suffered from malignancies (26% vs. 11%, P <0.01) and frequently had non-diagnostic V/Q scans (57%) as compared to included patients. In our study, 54% of all patients screened was eventually included versus 27% in the PIOPED study. In the PIOPED study patients who had contra-indications for pulmonary angiography were excluded, while in the study of Hull et al. those with inadequate cardiorespiratory reserve were excluded. In studies on new diagnostic technologies, patient selection bias does occur. The potential for such a selection bias should be taken into account when diagnostic strategies are devised to improve their generalizability and acceptability.

Adult↗
PubMed2001

Diagnostic accuracy of triage tests to exclude pulmonary embolism.

We performed a study in 403 prospectively included patients with suspected pulmonary embolism to compare the accuracy of a combination of the SimpliRED D-dimer assay and an intuitive clinical probability estimate with either one alone. Based on a conjoint diagnostic refer, ence standard, including ventilation-perfusion lung scintigraphy and pulmonary angiography, the prevalence of pulmonary embolism was 31%. We demonstrated a high sensitivity (98%, 95% CI 95-100) and negative predictive value (94%, 95% CI 79-99) for the combination of the two tests. These figures were more favorable than for either test alone. The specificity of the combination was lower (11%, 95% CI 9-12) and consequently the proportion of patients in whom further diagnostic tests would have been avoided was only 8%. We conclude that the combined use of the SimpliRED test and the clinical probability estimate attains a higher sensitivity than either test alone. However, there remains a risk of false negatives and the exclusion efficiency is limited.

Adult↗
PubMed2001

Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism.

Right ventricular (RV) function is of major prognostic significance in patients with acute pulmonary embolism (PE). The aim of the present study was to evaluate the role of neurohormone plasma brain natriuretic peptide (BNP) in assessing RV function in patients with acute PE. BNP levels were measured in 16 consecutive patients with acute PE as diagnosed by high probability lung scintigraphy or pulmonary angiography. Twelve healthy age-matched volunteers served as controls. All 16 patients underwent standard echocardiography and blood tests during the first hour of presentation. In the patient group, survival was studied for a period of 30 days. Plasma BNP levels in patients with acute PE were higher than in controls (7.2 [95% CI 0.4 to 144.6] versus 1.4[95% CI 0.4 to 4.6] pmol/L, p = 0.0008). Plasma BNP was significantly higher in 5 patients with RV dysfunction compared to II patients with normal RV function (40.2 [95% CI 7.5 to 214.9] versus 3.3 [95% CI 0.4 to 24.9] pmol/L, p = 0.0003). RV systolic pressure was not significantly correlated with BNP (r = 0.42, p = ns). In conclusion, plasma BNP neurohormone levels might be of clinical importance as a supplementary tool for assessment of RV function in patients with acute PE.

Acute Disease↗
PubMed2000

Travel and risk of venous thrombosis.

In 1998 the term economy class syndrome was coined to describe the association between travel and thrombosis. A fair risk estimate, however, has not been done. We report the results of a prospective study, in which we kept the effect of bias to a minimum. We compared travel history in 788 patients with venous thrombosis with that of controls with similar symptoms but in whom the disease had been excluded. For air travel alone, the odds ratio was 1.0 (95% CI 0.3-3.0); also, no association was recorded for other methods of transportation. We have shown that, there is no increased risk of deep vein thrombosis among travellers.

Adolescent↗
PubMed2000

For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same?

Low-molecular-weight heparin compounds have been used in the treatment of patients with venous thromboembolism for approximately 15 years. Ever since their introduction, there has been discussion about whether low-molecular-weight heparin compounds differ in their efficacy and safety. The best answer would be provided by direct comparison of different low-molecular-weight heparin preparations; however, these trials have not been conducted. Classical meta-analysis has its limitations for such a comparison since only a very small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been the use of meta-regression to compare the efficacy and safety of different low-molecular-weight heparin compounds in the initial treatment of patients with venous thromboembolism. We used computerized literature searches to identify studies that compared dose-adjusted unfractionated heparin treatment with fixed dose subcutaneous low-molecular-weight heparin treatment in patients with established venous thromboembolism. The individual odds ratios of the studies were plotted against the absolute percentage of the major outcomes in the unfractionated heparin control group. Linear regression was used to find differences between different low-molecular-weight heparin compounds. There appears to be some variation in efficacy and safety among the currently available low-molecular-weight heparin preparations.

Anticoagulants↗
PubMed2000

[CBO guideline 'Deep venous thrombosis and pulmonary embolism; revision of the earlier guidelines. Dutch Organization for Quality Assurance in Hospitals].

Diagnosis of clinically suspected deep venous thrombosis is based on a clinical score, serial compression ultrasonography and D-dimer assay. For the diagnosis of pulmonary embolism perfusion scintigraphy, ventilation scintigraphy, echography of the leg veins and pulmonary angiography in that order lead to the lowest mortality, morbidity and costs. Diagnostics with spiral CT followed by pulmonary angiography leads to equal mortality and fewer angiography procedures. Decision rules based on anamnesis, physical examination, blood gas analysis and chest radiograph have proved to be insufficiently reliable. The present D-dimer assays have too little sensitivity and too much variability. Thrombo-prophylaxis with low-molecular-weight heparin is indicated for general surgery, joint replacement of the knee or hip, cranial and spinal surgery, subarachnoid haemorrhage after surgical treatment of an aneurysm, acute myocardial infarction, ischaemic stroke or spinal cord lesion, intensive care patients, patients with acute paralysis due to a neuromuscular disorder, and bedridden patients with a risk factor. Prophylaxis has to be continued as long as the indication exists. In the acute phase of deep venous thrombosis or pulmonary embolism treatment with (low-molecular-weight) heparin in an adequate dose is necessary. When started at the same time as coumarin derivatives the treatment with heparin has to be continued for at least 5 days. The risk of postthrombotic syndrome after deep venous thrombosis will be lowered by carrying compression stockings for at least 2 years after the event.

Anticoagulants↗
PubMed2000

[Value of the 'non-diagnostic' lung scan--further classification as to the risk of pulmonary embolism not reliable].

OBJECTIVE: To determine to what extent the 'non-diagnostic' lung scans made because of a clinical suspicion of pulmonary embolism enable further determination of the risk of pulmonary embolism. DESIGN: Retrospective. METHOD: All non-diagnostic lung perfusion ventilation scans made in the Academic Medical Centre of Amsterdam in 1997 of 114 patients in succession (55 males and 59 females aged 27-85 years) were subjected to blind and independent re-evaluation by three observers (an experienced nuclear medicine expert, an experienced and an inexperienced intern) who, using a lung segment chart, estimated the risk of embolism as < 25%, 25-50%, 50-75% and > 75%. They did this first without and then with the chest X-ray. The findings were grouped on the basis of accordance or non-accordance with the pulmonary angiogram. The interobserver agreement was calculated by means of kappa statistics. RESULTS: Of 58 patients the lung scan could be compared with a chest X-ray and a pulmonary angiogram. In 43 patients with a normal angiogram the observers in an average of 50% of the scans estimated the risk of pulmonary embolism as < 25%, as against 25-50% in 27%, 50-75% in 9% and > 75% in 5%. In 15 patients with a deviant pulmonary angiogram, these figures were 22%, 38%, 20%, and 12%, respectively. The interobserver kappa for evaluation without chest X-ray was < or = 0.16, as against < or = 0.41% with the chest X-ray. CONCLUSIONS: A reliable classification of the risk of pulmonary embolism was not possible on the basis of non-diagnostic lung scans, regardless of whether the patient did or did not have pulmonary embolism. The interobserver variability was less when the lung scan was evaluated together with the chest X-ray, but even so it was unacceptably high.

Adult↗
PubMed2000

Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison.

BACKGROUND: Vitamin K antagonist treatment is effective for prevention and treatment of thromboembolic events but frequent laboratory control and dose-adjustment are essential. Small portable devices have enabled patient self-monitoring of anticoagulation and self-adjustment of the dose. We compared this self-management of oral anticoagulant therapy with conventional management by a specialist anticoagulation clinic in a randomised cross-over study. METHODS: 50 patients on long-term oral anticoagulant treatment were included in a randomised controlled crossover study. Patients were self-managed or were managed by the anticoagulation clinic for a period of 3 months. After this period the alternative strategy was followed for each patient. Prothrombin time (expressed as international normalised ratio [INR]) were measured at intervals of 1-2 weeks in both periods without knowledge of type of management. The primary endpoint was the number of measurements within the therapeutic range (therapeutic target value +/-50.5 INR units). FINDINGS: There was no significant difference in the overall quality of control of anticoagulation between the two study periods. Patients were for 55% and for 49% of the treatment period within a range of +/-0.5 from the therapeutic target INR during self-management and anticoagulation clinic management, respectively (p=0.06). The proportion of patients who spent most time in the therapeutic target range was larger during self-management than during anticoagulation clinic-guided management. The odds ratio for a better control of anticoagulation (defined as the period of time in the therapeutic target range) during self-management compared with anticoagulation clinic-guided management was 4.6 (95% CI 2.1-10.2). A patient-satisfaction assessment showed superiority of self-management over conventional care. INTERPRETATION: Self-management of INR in the population in this study is feasible and appears to result in control of anticoagulation that is at least equivalent to management by a specialist anticoagulation clinic. It is also better appreciated by patients. Larger studies are required to assess the effect of this novel management strategy on the incidence of thromboembolic or bleeding complications.

Administration, Oral↗
PubMed2000

Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.

BACKGROUND: Patients who have had an episode of symptomatic venous thromboembolism are usually treated for at least five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin. Thereafter, they received a three month course of a vitamin K antagonist, with a dose adjusted to achieve an International Normalized Ratio between 2.0 and 3.0. Some patients have contraindications to vitamin K antagonists. In addition, treatment with vitamin K antagonists has the disadvantage of regular laboratory measurements. OBJECTIVES: The objective of this review was to evaluate the efficacy and safety of long-term treatment of symptomatic venous thromboembolism with low-molecular-weight heparins compared with vitamin K antagonists. SEARCH STRATEGY: Computerized searches of MEDLINE, EMBASE and Current Contents were made and relevant journals were hand-searched using the search strategy described by the Cochrane Peripheral Vascular Disease Group. In addition, randomized clinical trials were located through personal communication with colleagues. Where necessary, the reviewers contacted pharmaceutical companies for further information. SELECTION CRITERIA: Two reviewers evaluated studies independently for methodological quality. DATA COLLECTION AND ANALYSIS: Two reviewers reviewed and extracted data independently using a standard form. Primary analysis concerned all patients in the studies during the period of randomized treatment. Additional separate analyses were performed for category I and category II studies; studies that used similar initial treatments in both study arms and those that used different treatment regimes during the initial treatment; and the total period of follow-up in the different studies. MAIN RESULTS: Five studies were identified that fulfilled our predefined criteria (three category I and two category II studies). When all five studies were combined, a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.72; 95% CI [0.42, 1.23]) was found. In category I studies, analysis of the pooled data showed a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). This OR was mainly due to one possibly confounded study, and after omitting this study from the analysis a statistically non-significant reduction of the risk of recurrent symptomatic venous thromboembolism in favor of vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). No differences in the risk of bleeding (OR 0.63; 95% CI [0.21, 1.88]) and mortality (OR 1.13; 95% CI [0.47, 2.69] were observed. REVIEWER'S CONCLUSIONS: Low-molecular-weight heparins are possibly as effective and safe as vitamin K antagonists in the prevention of recurrent symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but have the disadvantage of much higher medicinal costs. Treatment with low-molecular-weight heparin is possibly a safe alternative in some patients; for example patients who live in geographically inaccessible places; patients who are reluctant to go to the thrombosis service on a regular basis; and patients with contraindications to vitamin K antagonists (e.g. pregnant women). Therefore, in the absence of definitive evidence on the safety and efficacy of low-molecular-weight heparins compared with vitamin K antagonists, we believe that treatment with vitamin K antagonists is still the treatment of choice in the prevention of recurrent symptomatic venous thromboembolism after an episode of deep venous thrombosis, in the majority of patients.

Anticoagulants↗