Results of a questionnaire on the treatment of patients with Behçet's syndrome: a trend for more intensive treatment.

OBJECTIVES: To determine the preferred treatment for patients with Behçet's syndrome. METHODS: A questionnaire was given to all participants of the 2010 meeting of the International Society for Behçet's Disease. RESULTS: Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. CONCLUSIONS: Although consensus about how to treat patients with Behçet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behçet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present.

Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study.

OBJECTIVE: We observed 3 patients who developed severe venous and arterial thromboembolic events during treatment with adalimumab, 2 of whom had rheumatoid arthritis (RA) and 1 of whom had psoriatic arthritis. Antiadalimumab antibodies were detected in all 3 patients. We undertook this study to determine whether the development of antiadalimumab antibodies was associated with thromboembolic events during adalimumab treatment. METHODS: A retrospective search (with blinding with regard to antiadalimumab antibody status) for thromboembolic events was performed in a prospective cohort of 272 consecutively included adalimumab-treated RA patients. Incidence rates were calculated and hazard ratios (HRs) were estimated using Cox regression. None of the index patients were part of the cohort. RESULTS: Antiadalimumab antibodies were detected in 76 of 272 patients (28%). Eight thromboembolic events were found, 4 of which had occurred in patients with antiadalimumab antibodies. The incidence rate was 26.9/1,000 person-years for patients with antiadalimumab antibodies and 8.4/1,000 person-years for patients without those antibodies (HR 3.8 [95% confidence interval 0.9-15.3], P = 0.064). After adjustment for duration of followup, age, body mass index, erythrocyte sedimentation rate, and prior thromboembolic events, the HR was 7.6 (95% confidence interval 1.3-45.1) (P = 0.025). CONCLUSION: These findings suggest that the occurrence of venous and arterial thromboembolic events during adalimumab treatment is higher in patients with antiadalimumab antibodies than in those without antiadalimumab antibodies. Patient numbers were relatively small; therefore, validation in other cohorts is mandatory.

Prevalence of and risk factors for the metabolic syndrome in women with systemic lupus erythematosus.

OBJECTIVE: To examine the prevalence of the metabolic syndrome and the relationship between metabolic syndrome score (MetS score) and disease characteristics and cardiovascular events (CVEs) in women with SLE. METHODS: Demographic and clinical data were collected in 141 female SLE patients. The prevalence of the metabolic syndrome was defined by a modified National Cholesterol Education Program (NCEP/ATP III) definition. Metabolic syndrome was defined as MetS score >or= 3. RESULTS: Twenty-three (16%) of the 141 SLE patients (mean age 39+/-12 years, mean disease duration 6.2+/-6.6 years) fulfilled the criteria of the metabolic syndrome. The mean MetS score was significantly higher in patients with SLE and a history of cardiovascular events (CVEs) than in those without a previous CVE. In linear multiple regression analysis, a high MetS score was significantly associated with previous intravenous methylprednisolone use, older age, higher ESR, higher C3 levels and higher serum creatinine levels. CONCLUSIONS: In our female SLE patients, a high prevalence of the metabolic syndrome was found as compared to healthy women in the Amsterdam Growth and Health Longitudinal Study. Independent risk factors for high MetS score in patients with SLE are previous treatment with intravenous methylprednisolone, renal insufficiency, older age, higher ESR and higher C3 levels. These results suggest that assessment of the metabolic syndrome in patients with SLE might be important to identify subgroups of patients that are at disproportional high risk of developing cardiovascular disease and diabetes mellitus.

Survey of the management of deep vein thrombosis in general practice in the Netherlands.

BACKGROUND: To investigate the management of (suspected) deep vein thrombosis in general practice. METHODS: Self completing postal questionnaire among a random sample of 692 general practitioners in the Netherlands. RESULTS: The overall response rate was 58%. Eighty-nine percent of the respondents initiated objective evaluation. Less than 3% usually make the diagnosis on clinical grounds only. Ninety-two percent initiated adequate treatment for the last patient with deep vein thrombosis. No more than 4% usually treat patients with acenocoumarol alone. Respondents frequently referred a patient to a specialist, 41% to confirm the diagnosis and 85% for treatment. Already 44% feel that management of deep vein thrombosis is a mandate of the general practitioner. For those who do not, the availability of diagnostic and therapeutic facilities are the main obstacles. CONCLUSION: In general practice objective diagnostic methods to evaluate suspected deep vein thrombosis are routinely used and patients receive adequate treatment. Although patients are frequently referred to the hospital many general practitioners feel that they should be able to take care of these patients themselves. (See Editorial p. 133)

Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.

BACKGROUND: The main purpose of ventilation scanning, as adjunct to perfusion lung scintigraphy, in acute pulmonary embolism is to allow for the classification of segmental perfusion defects as mismatched, which is generally accepted as proof for the presence of pulmonary embolism. We examined whether this function of the ventilation scan could be replaced by the chest X-ray. METHODS: In 389 consecutive patients with suspected pulmonary embolism and at least one segmental perfusion defect we classified the ventilation/perfusion (V/Q) scan and chest X-ray/perfusion (X/Q) scan as either mismatched or matched. Furthermore we analyzed whether this comparison was different in subgroups of patients with concomitant congestive heart failure or chronic obstructive pulmonary disease. RESULTS: Overall agreement between the X/Q and V/Q scan diagnostic category was found in 341 of 389 patients (88%; 95% CI 84-92%). The positive predictive value for obtaining a mismatched V/Q scan result in case of a mismatched X/Q scan result was 86% (95% CI 81-90%). If the X/Q scan yielded only matched defects the V/Q scan resulted in the same classification in 90% (95% CI 85-95%). Analysis of the small subgroup of patients with chronic obstructive pulmonary disease showed that a mismatched X/Q scan was confirmed by V/Q scanning in 21 of 34 cases (62%; 95% CI 45-78%). CONCLUSION: This study shows that in the great majority of patients with clinically suspected acute pulmonary embolism combination of chest X-ray with perfusion scintigraphy reliably replaced ventilation/perfusion scintigraphy in defining (mis)-matching of segmental perfusion defects. These results need confirmation before the chest X-ray can fully obviate the use of ventilation scintigraphy.

Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study.

BACKGROUND: Although the incidence of the postthrombotic syndrome (PTS) has been addressed in patients with symptomatic deep vein thrombosis (DVT), less information is available on the incidence in patients who develop asymptomatic DVT after major hip or knee arthroplasty. OBJECTIVES: To determine whether symptomatic PTS occurs more frequently in patients who develop DVT after hip or knee arthroplasty than those who are free of DVT and to provide an estimate of the incidence of PTS in patients who had undergone major hip or knee arthroplasty and had proximal DVT, distal (calf) DVT, or no DVT. DESIGN AND SETTING: A cross-sectional study conducted at the Hamilton Health Sciences Corporation, Hamilton, Ontario, and the Academic Medical Centre, Amsterdam, the Netherlands. SUBJECTS AND METHODS: Two hundred fifty-five subjects who had undergone major hip or knee arthroplasty 2 to 7 years previously and had routine predischarge venography showing proximal DVT (n = 25), distal DVT (n = 66), or no DVT (n = 164) were enrolled from March 1993 through December 1998. The presence of symptomatic PTS confirmed by the presence of objectively confirmed venous valvular incompetence was ascertained. RESULTS: The rates of PTS were low and not significantly different among the 3 subgroups: 1 (4.0%, 95% confidence interval [CI] = 0.1%-20.4%) of 25 patients with proximal DVT, 4 (6.1%, 95% CI = 1.7%-14.8%) of 66 patients with distal DVT, and 7 (4.3%, 95% CI = 1.7%-8.6%) of 164 patients with no DVT. CONCLUSIONS: Symptomatic PTS is an uncommon complaint after major hip or knee arthroplasty. Patients who develop postoperative proximal or distal DVT and who receive 6 to 12 weeks of anticoagulant therapy are not predisposed to PTS.

Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.

Recent studies have suggested that both the subjective judgement of a physician and standardized clinical models can be helpful in the estimation of the probability of the disease in patients with suspected pulmonary embolism (PE). We performed a multi-center study in consecutive in- and outpatients with suspected PE to compare the potential diagnostic utility of these methods. Of the 517 study patients, 160 (31%) were classified as having PE. Of these patients, 14% had a low probability as estimated by the treating physician, while 25 to 36% were categorized as having a low clinical probability with the use of two previously described clinical models. The objectively confirmed prevalence of PE in these three low probability categories was 19%, 28% and 28%, respectively. The three methods yielded comparable predictive values for PE in the other probability categories. We conclude that a physician's clinical judgement alone and two standardized clinical models, although comparable, perform disappointingly in categorizing the pre-test probability in patients with suspected PE.

Is the prevalence of the factor V Leiden mutation in patients with pulmonary embolism and deep vein thrombosis really different?

INTRODUCTION: Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. METHODS: We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultrasonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. RESULTS: In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. CONCLUSION: In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.

[Recombinant factor VIIa (eptacog alfa): a new therapeutic option for patients with severe bleeding disorder due to inhibitory antibodies against a coagulation factor]. / Recombinantfactor VIIa (eptacog alfa): nieuwe therapeutische optie bij patiënten met een ernstige bloeding door antistoffen tegen een stollingsfactor.

In 2 patients with severe haemorrhage (a 63-year-old man with haemophilia A (the factor VIII level was 29%) and a 44-year-old woman), of an inhibitory antibody against factor VIII was diagnosed. The development of recombinant factor VIIa (eptacog alpha) has made available a new therapeutic option for patients with an inhibitory antibody against a coagulation factor. Both patients were treated successfully with the new factor after other forms of treatment had failed. The new concept of the coagulation cascade on which the treatment with eptacog alpha is based assumes that the lack of an amplifying loop in the coagulation which takes place via factor IX (in combination with factor VIII) can be compensated by extra stimulation of the principal route (tissue factor-factor VIIa --> factor X) by pharmacological amounts of factor VIIa.

Observer and biological variation of a rapid whole blood D-dimer test.

In consecutive patients with suspected venous thromboembolism the interobserver variability of the SimpliRED D-dimer test was evaluated by two observers who independently scored one plate, the between assay variation was performed simultaneously by a third independent observer, who assessed a second plate. The biological variation was studied, 1-4 hours later by an independent evaluation. A total of 155 patients entered the study, venous thromboembolism was present in 42 patients (28%). The interobserver variability was 2/83 samples, with a kappa of 0.95 (95% confidence interval 0.88-1.0). The between assay variation was 2/98, with a kappa value of 0.96 (95% confidence interval 0.90-1.0). When testing the biological variation the observers disagreed in 2 of 69 patients (3%). The SimpliRED D-dimer assay has a good to excellent interobserver variability, between assay variation and reproducibility.

The treatment of deep vein thrombosis and pulmonary embolism.

Deep vein thrombosis and pulmonary embolism can be considered as one clinical entity, termed venous thromboembolism, because of their comparable pathogenesis, treatment and prognosis. In this clinical spectrum of venous thromboembolism a gradient in severity of the disease can be recognized. Therapeutic strategies should be adapted to the extent of the thrombotic disease, varying from surgical or thrombolytic therapy in life-threatening disease to a watchful waiting diagnostic follow-up approach in minimal disease. In patients with established venous thromboembolism (low molecular weight) (LMWH), heparin should be initiated. An overview will be given of the safety and efficacy of the different therapeutic modalities such as thrombectomy, thrombolytic therapy, a watchful waiting diagnostic approach and unfractionated heparin. Furthermore, clinical studies comparing LMWH with unfractionated heparin in the initial treatment of venous thromboembolism will be reviewed.

A survey of the diagnostic and therapeutic management of patients with suspected pulmonary embolism in the Netherlands.

BACKGROUND: Pulmonary embolism (PE) remains a complex diagnostic problem. Many diagnostic modalities are available. Several published guidelines have failed to yield a uniform approach. We have assessed the current diagnostic and therapeutic management of patients with clinically suspected PE in the Netherlands. METHODS: A questionnaire was sent to internists and pulmonologists, who were then asked to detail their diagnostic and therapeutic management in their last patient seen with suspected PE. RESULTS: 1571 questionnaires were sent out (response rate 64%). 95% of the patients with suspected PE underwent a perfusion scan (in 91% within 24 h). 1.6% of the respondents had no available perfusion scan facility. Of those who underwent a perfusion scan, 62% had ventilation scan (66% with segmental defects, 80% with subsegmental defects, 27% with a normal perfusion scan). Tests for deep vein thrombosis were performed in 58% of the patients and pulmonary angiography was carried out in 6.1%. Anticoagulant treatment was instituted in 73.2% of all patients. CONCLUSIONS: The perfusion lung scan is appropriately used as the initial step in the diagnostic workup of patients with suspected PE. Ventilation scanning is overused in patients with subsegmental perfusion defects and normal scan results, whereas it is underused in patients with segmental defects. Additional ventilation scan results had a limited influence on treatment decisions. There is still considerable overtreatment of patients with suspected PE.

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

BACKGROUND: The standard diagnostic approach in patients suspected of having pulmonary embolism starts with perfusion-ventilation lung scanning. If the resulting scan is not diagnostic, pulmonary angiography should be done. The use of tests for deep venous thrombosis has been advocated as an adjunct to establishing the diagnosis of pulmonary embolism, but no prospective studies have provided adequate information about the value of these tests. OBJECTIVE: To determine the accuracy and potential clinical utility of compression ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective cohort study with blinded assessment of ultrasonographic results. SETTING: Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and specificity of compression ultrasonography. Perfusion-ventilation scanning and angiography were the conjoint gold standard for determining the presence or absence of pulmonary embolism. Also calculated were the number of angiograms and lung scans avoided and the number of patients unnecessarily treated when compression ultrasonography was included in the diagnostic strategy. RESULTS: The overall sensitivity of compression ultrasonography for deep venous thrombosis in patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was 97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before lung scanning would avoid approximately 14% of lung scans and 9% of angiograms but would lead to unnecessary treatment of 13% of patients who have an abnormal ultrasonographic result (2% to 4% of all those receiving anticoagulation). When compression ultrasonography is done only in patients with a nondiagnostic lung scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26% of patients who have an abnormal ultrasonographic result (2% of all patients receiving anticoagulation). CONCLUSION: The diagnostic value of compression ultrasonography for the detection of deep venous thrombosis in patients suspected of having pulmonary embolism is limited; the gain in diagnostic efficiency obtained through the use of ultrasonography may be offset by a loss in diagnostic accuracy.

Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients.

UNLABELLED: In this study we assessed the reliability of a rapid bed-side whole blood D-dimer assay prospectively in patients with clinically suspected venous thromboembolism, referred to the Academic Medical Centre, Amsterdam. In consecutive outpatients with clinically suspected deep vein thrombosis or pulmonary embolism we measured the sensitivity, specificity and negative predictive value of the assay compared to the outcome of standard diagnostic tests and 3-month follow-up. A total of 234 patients were included; the prevalence of venous thromboembolism was 29%. A sensitivity, specificity and negative predictive value of 100% (95% CI: 95% - 100%), 58% (95% CI: 50%-65%) and 100% (95% CI:96% - 100%), respectively, were obtained. The exclusion rate was 41% of all referred patients. CONCLUSION: The SimpliRED whole blood D-dimer assay appears to be a simple and reliable method for the exclusion of venous thromboembolism in symptomatic outpatients.