PubMed Health⌕ Search

Biomedical subjects

Harry R Büller

Publications and source records attributed to Harry R Büller.

At least 19 recordsLinked to original sources
PubMed2005

A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk.

BACKGROUND: A C1173T polymorphism in intron 1 of the VKORC1 gene has been claimed to determine the interindividual variability in the response to vitamin K antagonist therapy (VKA), but it is unknown whether it also influences bleeding risk. We aimed to confirm the relationship between C1173T status and phenprocoumon or acenocoumarol use, and to examine the risk of severe bleeding for the various genotypes. METHODS AND FINDINGS: We studied this in a case-control study of 110 patients who bled during VKA therapy and 220 control patients free of bleeding under the same therapy. To achieve the same target INR, CT genotype and TT genotype control patients required less phenprocoumon (CC genotype 2.9 mg/d [95% confidence interval (CI): 2.6-3.2], CT genotype 2.6 mg/d [95% CI: 2.1-3.1], TT genotype 1.4 mg/d [95 % CI: 1.1-1.7]) or acenocoumarol (CC genotype 3.2 mg/d [95% CI: 2.9-3.5], CT genotype 2.3 mg/d [95% CI: 2.1-2.5], TT genotype 1.7 mg/d [95% CI: 1.3-2.1]) than CC genotype control patients. Compared with CC genotype individuals, carriers of at least one T allele had an increased risk of bleeding in the phenprocoumon users (crude odds ratio = 2.6, 95% CI: 1.2-5.7), but not in acenocoumarol users (crude odds ratio = 1.2, 95% CI: 0.6-2.3). CONCLUSION: These findings encourage taking further steps towards the evaluation of the use of VKORC1 genetic testing for bleeding prevention in individuals who receive VKA therapy.

Acenocoumarol↗
PubMed2005

Risk of thromboembolism and bleeding after general surgery in patients with atrial fibrillation.

We provide insight into the risk of perioperative thromboembolism and bleeding in patients who have atrial fibrillation, use anticoagulants, and undergo a surgical procedure. Ninety-four patients underwent 121 noncardiac operations during a mean follow-up of 29 months. There was a 3.6-fold increased risk for all bleeding complications within 1 month after surgery compared with the control period (95% confidence interval 1.05 to 12.0). No thromboembolic event occurred in the first month after surgery compared with 11 events in the remaining period (0.4% per month).

Aged↗
PubMed2005

Cerebral white matter lesions predict both ischemic strokes and myocardial infarctions in patients with established atherosclerotic disease.

BACKGROUND: Cerebral white matter lesions (WML) are regarded as manifestations of small vessel disease, but have also been associated with large vessel atherosclerosis. We investigated whether WML have a predictive value for future ischemic events. METHODS AND RESULTS: Two-hundred-thirty patients with proven atherosclerotic disease, recent ischemic stroke (IS, n=70), recent myocardial infarction (MI, n=71), or peripheral arterial disease (PAD, n=89) were included. The presence of periventricular lesions (PVL) and deep white matter lesions (DWML) on MRI at entry and ischemic events during follow-up were registered. During follow-up with a mean duration of 3.5+/-1.4 years 22 patients had a MI, 21 patients suffered an IS and 2 patients died suddenly. The frequency of ischemic events during follow-up was higher among patients with PVL than in those without PVL (IS: 18% versus 5%, p=0.001; MI: 15% versus 7%, p=0.03; any ischemic event: 36% versus 11%, p<0.001). DWML was associated only with the combined outcome any ischemic event (p=0.04). In multivariate regression analysis the presence of PVL was independently associated with IS (HR 3.2 (95%CI 1.3-8.4) and MI (HR 3.4 (95%CI 1.4-8.0)). CONCLUSION: We observed an association between WML, especially PVL, and future ischemic strokes and myocardial infarctions in patients with established atherosclerotic disease.

Aged↗
PubMed2005

Combined training of GPs and practice-assistants on peripheral arterial disease: positive effects after six months.

OBJECTIVES: To improve the use of the ankle-brachial index (ABI) measurement, and management of patients with peripheral arterial disease (PAD) a combined training, targeting GPs and practice assistants (PAs) was developed. To measure the effect of the combined training on the management of patients with PAD, a cross-sectional study was performed. METHODS: Fifty consecutive patients referred by GPs to a vascular surgery out-patient clinic were analysed. Six months after the training an additional fifty patients were included. In all patients the ABI measurement, risk factor management, and treatment as performed by the GP, prior to referral, were analysed. RESULTS: The measurement of the ABI significantly increased from 10% before the training to 53% after the training (GPs with training: 83%, GPs without training: 35%; P: 0.001). The referral of patients with actual PAD significantly increased from 32% before the training to 70% after the training (GPs with training: 83%, GPs without training: 59%; P: 0.05). The presence and treatment of risk factors did not differ between the groups. CONCLUSIONS: Within the limitations of a before and after study the combined training of GPs and PAs appears to be an effective method to increase ABI measurements and significantly improve adequate diagnostics.

Aged↗
PubMed2005

The effect of low molecular weight heparin on survival in patients with advanced malignancy.

PURPOSE: Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism. METHODS: Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding. RESULTS: In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25). CONCLUSION: A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation.

Adult↗
PubMed2005

Guidelines were developed for data collection from medical records for use in retrospective analyses.

OBJECTIVE: To construct a set of guidelines for data collection from medical records. STUDY DESIGN AND SETTING: Retrospective analysis of clinical data is often performed by physician-scientists. In such research, the source of clinical data is the patient's medical record; however, medical records are intended for patient care and the data are not systematically recorded for research purposes. We drew on recommendations in the literature and our own experience with a retrospective cohort study that uses a DNA bank to construct guidelines for data collection from medical records. RESULTS: The guidelines incorporate a number of strategies for accurate data collection, which are discussed and illustrated by application. CONCLUSION: With guidelines for data collection, the quality of research data is enhanced. A well-designed case record form and a handbook for standardized data collection are essential for training the data collectors and for ensuring fastidious searching of the record; however, certain kinds of information are not always well documented in patient records. Consequently, it is essential to perform a pilot study to assess the study design and to use additional questionnaires. Correct interpretation of clinical outcomes documented in the medical records often necessitates an independent adjudication committee to prevent bias in outcome definition.

Bias↗
PubMed2005

Smoking and the patency of lower extremity bypass grafts: a meta-analysis.

OBJECTIVE: Smoking is the major risk factor associated with the development and progression of peripheral arterial disease (PAD). To establish the best estimate of the effect of smoking, smoking cessation, and the dose-response relationship on the patency of lower extremity bypass grafts, we performed a systematic review. METHODS: A search of medical articles and reviews relating to the influence of smoking on the patency of arterial reconstructive grafts in patients with PAD was made. Studies considered for inclusion were those that evaluated the influence of smoking on the primary, secondary, or cumulative patency rates of arterial reconstructive surgery in the lower extremities in patients with PAD. Primary data were used to calculate summary estimates with standard meta-analysis techniques. RESULTS: The 29 eligible studies included 4 randomized clinical trials, 12 prospective studies, and 13 retrospective studies. The effect of smoking on graft patency in the randomized clinical trials and other prospective studies had a 3.09-fold (2.34 to 4.08; P < .00001) increase in graft failure. A comparison of patency rates among all studies that used autogenous or polyester grafts showed no difference. A clear dose-response relationship was present, with a decreased patency in heavy smokers compared with moderate smokers. Smoking cessation restores patency rates toward the never smokers group. CONCLUSION: Continued smoking after lower limb bypass surgery results in a threefold increased risk of graft failure. Smoking cessation, even if instigated after the operation, restored graft patency towards the patency of never smokers. These results indicate that adequate smoking cessation strategies in patients eligible for lower limb bypass surgery are of utmost importance.

Blood Vessel Prosthesis Implantation↗
PubMed2005

Compliance of Dutch orthopedic departments with national guidelines on thromboprophylaxis. A survey of Dutch orthopedic thromboprohylaxis.

All 110 Dutch orthopedic departments were sent a survey on perioperative thromboprophylaxis protocols, and 79% responded. After hip and knee replacements, all used pharmacological thromboprophylaxis: a low-molecular weight heparin (LMWH) in 87% of departments, which was most often combined with vitamin K antagonists (VKAs). LMWH was usually started preoperatively (91%). After discharge, VKAs were mostly prescribed (79%) for at least 6 weeks, and often for 3 months. 17% of departments used LMWH for 6 weeks, whereas in only 3% no post-discharge prophylaxis was given. In day-care surgery, including arthroscopies, 58% use LMWH and in short-stay surgery 80% administer LMWH during the hospital stay. Because of lack of conclusive evidence for day-care surgery, the national guidelines cannot support pharmacological prophylaxis in this setting. In general, Dutch orthopedic departments comply poorly with the national guidelines on extended thromboprophylaxis for hip and knee replacement surgery, which recommends postoperative LMWH for 6 weeks. They are divided in the use of pharmacological prophylaxis in day-care surgery.

Fibrinolytic Agents↗
PubMed2005

Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review.

BACKGROUND: Recombinant activated factor VII (factor VIIa) is a prohemostatic agent that can be used for patients with complicated coagulation disorders. Recombinant factor VIIa is, however, increasingly used for several other indications, including patients with a preexistent normal coagulation system but who experience serious bleeding, for example, after major surgery or trauma. DATA SOURCE: We performed a systematic review of all published and unpublished clinical studies using MEDLINE (1966-2004) and all other sources available to assess the available evidence on the efficacy and safety of recombinant factor VIIa in patients with or without coagulation disorders. STUDY SELECTION: We found 483 articles related to the pharmacologic use of recombinant factor VIIa, including 28 clinical trials, 124 case series, and 176 case reports, which were all considered for this review. DATA SYNTHESIS: Recombinant factor VIIa is an effective and relatively potent prohemostatic agent in approximately 90% of patients with hemophilia and inhibiting antibodies and other types of complex coagulation disorders. The application of recombinant factor VIIa in other patients who experience severe bleeding is promising, and although sound evidence from controlled clinical trials is only scarcely available so far, forthcoming trials are likely to provide more substantiation for this use. Recombinant factor VIIa appears to be relatively safe with a 1-2% incidence of thrombotic complications based on published trials. CONCLUSIONS: More randomized controlled clinical trials are required to assess the efficacy and safety of recombinant factor VIIa for patients without a preexistent coagulation disorder and with severe bleeding. In the meantime, off-label use of recombinant factor VIIa may be considered in patients with life-threatening bleeding.

Acute Disease↗
PubMed2005

Protein S type III deficiency is no risk factor for venous and arterial thromboembolism in 168 thrombophilic families: a retrospective study.

Free protein S rather than total protein S levels are currently measured to detect inherited protein S deficiency. Because type III (free protein S) deficiency is still not established as risk factor for thrombosis, we assessed the absolute risk of venous and arterial thromboembolism in a family cohort study. Annual incidences in first-degree relatives with and without protein S deficiency type III were compared. Probands had experienced thrombosis and had either the prothrombin G20210A mutation, increased factor VIII:C levels or hyperhomocysteinemia. Relatives were tested for these thrombophilic disorders and factor V Leiden. Levels of antithrombin, protein C, total and free protein S, and factor XI:C were additionally measured. Of 500 relatives enrolled, 105 were excluded from analysis because they could not be classified, due to acquired conditions. Protein S deficiency type III was demonstrated in 60/395 remaining relatives (15%). Other thrombophilic defects were equally distributed among deficient and non-deficient relatives. Annual incidences of venous thromboembolism were 0.28 per 100 person-years [95% confidence interval (CI), 0.09-0.66] in deficient relatives versus 0.20 per 100 person-years (95% CI, 0.12-0.30) in non-deficient relatives [hazard ratio, 1.4 (95% CI, 0.4-4.0)]. For arterial thromboembolism these values were 0.16 per 100 person-years (95% CI, 0.03-0.46) versus 0.10 per 100 person-years (95% CI, 0.05-0.19) [hazard ratio, 1.5 (95% CI, 0.3-6.0)]. These results suggest that protein S deficiency type III is not associated with an increased risk of either venous or arterial thromboembolism.

Adolescent↗
PubMed2005

Effects of human cytomegalovirus infection on the coagulation system.

Pathophysiological mechanisms of acute vascular thrombosis are not fully understood. It has been suggested that different infectious pathogens are responsible agents of thrombotic disorders. The infection hypothesis is supported by an increasing number of reports on the interaction between acute infection and coagulation. Cytomegalovirus (CMV) is supposed to play an important role in apparently unprovoked thrombosis. We reviewed all human in vitro and in vivo studies on the influence of human CMV infection on the coagulation system, as well as all case reports of acute thrombosis during acute human CMV infection. In the published literature there is mounting evidence that human CMV may play a role in thrombotic disorders. Definitive conclusions, however, cannot be drawn, although the in vitro studies are convincing and offer insight in the pathogenesis.

Blood Coagulation↗
PubMed2005

Diagnostic strategy using a modified clinical decision rule and D-dimer test to rule out pulmonary embolism in elderly in- and outpatients.

Excluding or confirming pulmonary embolism remains a diagnostic challenge. In elderly patients pulmonary embolism is associated with substantial co-morbidity and mortality, and many elderly patients with suspected pulmonary embolism are inpatients. The safety and efficacy of the combination of a clinical probability (CDR) and d-dimer test in excluding pulmonary embolism in this group is unclear. We retrospectively analysed data of two prospective studies of consecutive in-and outpatients with suspected pulmonary embolism. The patients were categorized into three age groups: <65 years, 65-75 years and >75 years. The sensitivity, negative predictive value and the proportion of patients with the combination of a non-high CDR score according to Wells (< or = 4) and a normal d-dimer result were calculated for each group. In 747 consecutive patients with suspected pulmonary embolism, sensitivity and negative predictive value of a non-high CDR and a normal d-dimer result in outpatients (n=538) of all age categories (<65 years, 65-75 years and >75 years) were both 100%. These tests were, however, less reliable for inpatients(n=209), irrespective of their age (sensitivity 91% [ CI: 79-98%], negative predictive value 88 % [CI: 74-96%]. The proportion of both in-and outpatients >75 years with a non-high CDR and a normal d-dimer concentration was only 14%, whereas this was 22% in patients 65-75 years and 41% among in-and outpatients <65 years, respectively. In elderly outpatients the combination of a non-high CDR and a normal d-dimer result is a safe strategy to rule out pulmonary embolism. However, in inpatients this algorithm is not reliable to safely exclude pulmonary embolism. In addition, the proportion of patients >65 years in which this strategy excludes pulmonary embolism is markedly lower compared to younger patients.

Adolescent↗
PubMed2005

Treatment of superficial vein thrombosis to prevent deep vein thrombosis and pulmonary embolism: a systematic review.

BACKGROUND AND OBJECTIVES: The aim of this systematic review was to summarize the evidence from randomized controlled trials (RCT) concerning the efficacy and safety of medical or surgical treatments of superficial vein thrombosis (SVT) for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE). DESIGN AND METHODS: A systematic search was performed in MEDLINE, EMBASE and the Cochrane (CENTRAL) database to identify all randomized trials that evaluated the effect of surgical or medical treatment in the prevention of venous thromboembolism (VTE) in patients with SVT of the legs. RESULTS: Five studies were included. Pooling of the data was not possible due to the heterogeneity among the studies. Moreover, three studies had major methodological drawbacks limiting the clinical applicability of the results. One of the remaining (pilot) studies showed a non-significant trend in favor of high- compared to low-dose unfractionated heparin for the prevention of VTE. The last remaining study showed a non-significant trend in favor of short-term treatment with low-molecular-weight heparin (LMWH) or a non-steroidal anti-inflammatory drug (NSAID) as compared to placebo shortly after treatment with respect to VTE, but the apparent benefit disappeared after three months of follow-up. Active treatment of SVT reduced the incidences of SVT extension or recurrence. INTERPRETATION AND CONCLUSIONS: Treatment with a therapeutic or prophylactic dose of LMWH or a NSAID reduces the incidence of SVT extension or recurrence, but not VTE. More RCT are needed before any evidence-based recommendations on the treatment of SVT for the prevention of VTE can be given. With the present lack of solid evidence we would suggest treating patients with at least intermediate doses of LMWH.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study.

BACKGROUND: The prothrombin 20210A mutation has been associated with an increased risk of venous thromboembolism (VTE). Its relationship with arterial disease and pregnancy-related complications is, however, still uncertain. The aim of this study was to estimate the incidences of first venous and arterial thrombotic events and pregnancy-related complications in relatives of patients with the mutation. METHODS: After clinical classification, the presence of the mutation was determined in first-degree relatives of consecutive patients with the mutation and a history of VTE or premature atherosclerosis. Relatives with and without the mutation were compared. RESULTS: Of all relatives, 204 (50%) were heterozygous, 5 were homozygous, and 198 had a normal genotype. The annual incidence of a first episode of VTE was 0.35% and 0.18% in carriers and noncarriers, respectively (odds ratio [OR], 1.9; 95% confidence interval [CI], 0.9-4.1); the annual incidence of a first arterial thrombosis was 0.22% and 0.15% in carriers and noncarriers, respectively (OR, 2.3; 95% CI, 0.8-6.3). The annual incidence of a first myocardial infarction was 0.14% (95% CI, 0.05%-0.23%) and 0.05% (0.01%-0.14%) in carriers and noncarriers, respectively (OR, 4.7; 95% CI, 1.0-22.5; P =.06). In particular, homozygous carriers were at increased risk of VTE (OR, 6.0; 95% CI, 1.3-27.2), whereas a history of VTE in the proband influenced the risk of VTE in the relatives. Women with the mutation did not experience significantly more pregnancy-related complications than their relatives with a normal genotype. CONCLUSIONS: The prothrombin mutation is a mild risk factor for VTE within families of carriers but does not seem to play an important role in arterial thrombotic disease, with the exception of myocardial infarction, or in pregnancy-related complications.

Adolescent↗
PubMed2004

Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial.

CONTEXT: Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. OBJECTIVE: To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. DESIGN: Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. SETTING AND PARTICIPANTS: Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. INTERVENTION: After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). MAIN OUTCOME MEASURES: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. RESULTS: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (-24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. CONCLUSION: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

Adolescent↗