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OBJECTIVES: COVID-19 predisposes patients to thrombotic disease. The aim of this guidance document is to provide Belgian health-care workers with recommendations on anticoagulation management in COVID-19 positive patients. METHODS: These recommendations were based on current knowledge and a limited level of evidence. RESULTS: We formulated recommendations for the prophylaxis and treatment of COVID-related venous thromboembolism in ambulatory and hospitalised patients, as well as recommendations for the use of antithrombotic drugs in patients with prior indication for anticoagulation who develop COVID-19. CONCLUSIONS: These recommendations represent an easy-to-use practical guidance that can be implemented in every Belgian hospital and be used by primary care physicians and gynaecologists. Of note, they are likely to evolve with increased knowledge of the disease and availability of data from ongoing clinical trials. ispartof: ACTA CLINICA BELGICA vol:77 issue:2 pages:280-285 ispartof: location:England status: published

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

International audience

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery., SCOPUS: ar.j, info:eu-repo/semantics/published

The objective of this study was to estimate the total hospital cost per patient admitted through the emergency department with a primary diagnosis of pulmonary embolism (PE), and to identify the main components and predictors of costs.Actual costs of care of 652 consecutive patients hospitalised in 10 general hospitals in Belgium, including 31 outlier patients in terms of length of stay (4.8%), were obtained by aggregating all cost components contributing to care of each patient.In both inlier and outlier patients, the mean total cost per patient increased linearly with the degree of severity of illness classes related to the All Patient Refined Diagnosis Related Group (pAn increasing burden of comorbid illness was strongly associated with increasing actual cost for caring hospitalised patients for PE. Increasing age was associated with an increase in all main cost components.

Background: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients agedMethods: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (kappa = 0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively.Conclusion: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm. (C) 2015 Elsevier Ltd. All rights reserved.

To describe risk assessment models that have been developed to stratify patients into different risk levels of postoperative venous thromboembolism (VTE) and then to review the different methods of prophylaxis and to outline the evidence supporting their effectiveness and safety.Our review of the literature is focused on consensus documents, recent large randomized trials and meta-analyses.The risk of VTE is determined by the type of surgery and underlying patient factors. Risk assessment models are useful in stratifying patients into different VTE risk levels. However, multiple risk factors are often present in the same patient and in practice the evaluation of their relative contribution to the overall risk remains difficult. A variety of prophylactic strategies including physical and pharmacological methods have been shown to be effective in different patient groups. Patients with a moderate or high risk of VTE should receive prophylaxis consisting of an antithrombotic agent, unless contraindicated, used alone or in combination with a mechanical method. Recommendations concerning which prophylaxis to use and how intensive it should be are based mainly on data from trials using surrogate endpoints, and do not translate easily into practical decisions aiming to reduce the incidence of symptomatic events.Although risk assessment models and recommendations provided by consensus documents are of practical assistance, a decision concerning any patient is best made by combining recommendations of the literature with clinical judgment, including individual patient risk factors for thrombosis and bleeding.

Background Forty to 50 % of hospitalized patients with an acute medical illness have risk factors for venous thromboembolism (VTE) and it has been shown that VTE prophylaxis reduced the incidence of VTE events in these patients. However, a large multinational survey, the ENDORSE study, showed that only 37 % of medical patients with VTE risk factors actually received VTE prophylaxis. Objective To evaluate the impact over time of pharmacist-driven interventions aiming at increasing the appropriate use of VTE prophylaxis in acutely ill medical hospitalized patients. Setting A Belgian urban academic hospital. Method First, during 1 month, medical and nurse reports of all hospitalized medical patients were reviewed to evaluate the proportion of patients who were on prophylaxis according to clinical practice guidelines. Second, interventions were conducted and included unit-specific physician and nurse education, diffusion of educational tools summarizing VTE prophylaxis guidelines, and reminders. Third, the impact of the interventions on the proportion of patients receiving VTE prophylaxis according to clinical practice guidelines was evaluated after 3 months and 1 year. Main outcome measure Proportion of hospitalized medical patients receiving VTE prophylaxis according to clinical practice guidelines. Results The baseline evaluation showed that 36 % (26/72) of the patients at risk of VTE received VTE prophylaxis according to clinical practice guidelines. Three months and one year after the interventions, 68 % (55/81), and 72 % (58/81) of the patients at risk of VTE received VTE prophylaxis according to clinical practice guidelines. Among patients not at risk of VTE, 15 % (21/141), 8 % (24/290), and 8 % (27/330) respectively at baseline evaluation, 3 months and 1 year after the interventions, received VTE prophylaxis. Conclusion Pharmacist-driven interventions improved the proportion of acutely ill medical patients receiving VTE prophylaxis according to clinical practice guidelines and the benefit of the interventions was maintained after 1 year.

Purpose: To describe an exclusion endoluminal technique for management of abdominal aortic aneurysms among high-risk patients with complex anatomic features. Methods: From January 1995 to December 1996, among 143 patients with infrarenal abdominal aortic aneurysm treated by means of endograft placement, 9 (6.3%) had complex aortic or aortoiliac morphologic features. For these patients, the endograft was delivered through a femoral cutdown in an occluding aortoiliac configuration. The contralateral iliac artery was occluded with an iliac endograft. Axillofemoral bypass grafting was performed. Computed tomographic scans were obtained regularly. Results: There was 1 postoperative death of severe arrhythmia. All aneurysms were found to be affected by thrombosis on immediately postoperative computed tomographic scans, except in 1 patient with a proximal leak, which was managed successfully with angiographic embolization. The mean follow-up time was 12 months. Aortic aneurysm diameter decreased from 2 mm at 6 months (2 patients) to 6 mm at 12 months (6 patients). All axillofemoral bypass grafts are patent. Conclusions: Placement of an occluding endograft associated with axillofemoral bypass grafting is a good alternative for patients at high risk with complex anatomic features. Longer-term follow-up study is needed to evaluate this endoluminal technique. (J Vasc Surg 1998;28:651-6.)

We report two cases of septic arthritis of the knee caused by Aspergillus: one by Aspergillus terreus in a cirrhotic patient and the other by Aspergillus fumigatus after vascular graft infection. The recovery of these organisms in synovial fluid should be considered as pathogenic, particularly in immunocompromised hosts. The pathogenic mechanism is discussed and the literature is reviewed.

The number of hospitalizations for atrial fibrillation has increased dramatically. This increase, in the number of hospital stays will continue, given the growth projections based on epidemiological data, and will contribute to significantly increase expenses for the social security system.The objective of this study was to evaluate the length of hospital stay, the average cost borne by social security, and the types of hospital stay expenditures for patients admitted through the emergency department for atrial fibrillation.Patients were identified by using the minimal clinical summaries of seven general hospitals in Belgium in 2008. Only hospitalized patients having as primary diagnosis code ICD-9-CM 42731 'atrial fibrillation'were selected for this study. Hospital billing files were analysed in order to isolate the costs borne by social security. Outliers were isolated in order not to have results influenced by patients having an atypical length of stay.Results show that the mean length of stay was 8.6 days and the mean cost charged to social security was euro 3,066.02 per hospital stay.The mean cost of care was strongly associated with the degree of severity index related to the APR-DRG. Approximately 85% of the total cost was related to the cost of hospital days and medical procedures with medical imaging and laboratory tests being the two main cost inductors. 18% of patients had cardioversion during their hospital stay, including 4% who had only that treatment. 19% of patients used amiodarone. Flecainide and propafenone were also used, but less frequently.The mean cost of care for AF patients admitted via the emergency department is strongly associated with the degree of severity. Approximately 85% of the total cost is related to the cost of hospital days and medical procedures. Hypertension is the most common secondary diagnosis. An optimal treatment of this risk factor could help to reduce the risk of atrial fibrillation, and thereby reduce the morbidity and costs associated with this disease.

The P2Y4 receptor is a new member of the P2Y family which functionally behaves as a pyrimidinergic receptor. The pharmacological properties of the human P2Y4 receptor have been characterized following its stable expression in 1321N1 astrocytoma cells. UTP induced a biphasic accumulation of inositol trisphosphates, with an early peak at 30 s followed by a smaller but more sustained accumulation. ATP was a pure antagonist at early times and later behaved as a partial agonist. At 20 min, the rank order of potency of various nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP. Diadenosine polyphosphates also stimulated the production of inositol trisphosphates (after 20 min), more potently than ATP, but their maximal effect represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited strongly the UTP response, whereas suramin was inactive and reactive blue 2 had an intermediate effect. Pertussis toxin inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4 receptor can exist in two distinct activation states differing in terms of time-course, specificity for uridine nucleotides and G-protein coupling.

1. Adenine nucleotides stimulate the synthesis and release of prostacyclin and nitric oxide (two potent platelet aggregation inhibitors) by endothelial cells from different origins. These responses are mediated by P2 purinergic receptors, coupled to the production of inositol (1,4,5)trisphosphate (InsP3) and to the increase of intracytoplasmic calcium concentration. 2. In bovine aortic endothelial cells (BAEC), both 2-MeSATP and UTP stimulate the production of InsP3. By experiments of additivity and cross desensitization, we have confirmed the expression of both P2Y/P2Y1 and P2U/P2Y2 receptors on these cells. Moreover, these receptors are not segregated on different subpopulations but are co-localized on the same cells. 3. The action of UTP on InsP3 production was inhibited by pertussis toxin and was unaffected by a pretreatment with phorbol 12-myristate, 13-acetate (PMA). On the other hand, the response induced by 2-MeSATP was inhibited by PMA but insensitive to pertussis toxin. These results suggest that P2Y/P2Y1 and P2U/P2Y2 receptors are respectively coupled to Gq/G11 and G1 proteins. 4. Northern blotting experiments revealed the expression of the P2Y1 (doublet of 2 and 2.2 kb) and of the P2Y2 (2.4 kb) receptor messengers in BAEC. A signal corresponding to the P2Y2 mRNA was also detectable in human umbilical vein endothelial cells. 5. These various results thus demonstrate the expression of the P2Y1 and P2Y2 receptors in vascular endothelial cells.

We used polymerase chain reaction (PCR) to detect cytomegalovirus (CMV) deoxyribonucleic acid (DNA) in the bronchoalveolar lavages (BAL) of 16 CMV-infected patients with active disease. We also tested PCR on a control group of 20 patients including latently infected patients without evidence of active CMV infection. Results were compared with those of CMV culture and of a rapid method of diagnosis which detects CMV in BAL cells by nucleic acid hybridization. PCR allowed the diagnosis in 93% of the actively infected patients compared to 73% for the CMV culture. Among the 20 control patients without evidence of active CMV infection, PCR was negative in all the 24 BAL tested. Hybridization on BAL cells with the CMV probe detected nine out of 10 actively infected patients, but the specificity of the test was only 68.5%. In our experience, PCR appears to be at least as sensitive as CMV culture, it provides results faster and it performs better than the detection of the virus by hybridization on BAL cells. Only active CMV infection was detected with the PCR conditions used in our study. This suggests that the PCR can be applied to bronchoalveolar lavage fluids as a rapid method to detect CMV lung infection.

We report an unusual case of vascular graft infection caused by Aspergillus fumigatus that began with a false aneurysm, major arterial emboli, and septic arthritis. Successful treatment included resection of the infected graft, restoration of circulation by extraanatomic bypass, and administration of amphotericin B and itraconazole, a new antifungal agent. Graft infection in the case reported herein most likely occurred during surgery and took place during an insidious outbreak of postoperative infection.

INTRODUCTION: The Wells score is widely used in the assessment of pretest probability of pulmonary embolism (PE). The revised Geneva score is a fully standardized clinical decision rule that was recently validated and further simplified. We compared the predictive accuracy of these two scores. METHODS: Data from 339 patients clinically suspected of PE from two prospective management studies were used and combined. Pretest probability of PE was assessed prospectively by the Wells score. The simplified revised (SR) Geneva score was calculated retrospectively. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The overall prevalence of PE was 19%. Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4% (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81). The Wells score performed better than the simplified revised Geneva score in patients with a high suspicion of PE (p

To describe the drugs used to treat venous thromboembolism (VTE) and to review particular aspects of the management (elastic stockings, thrombolysis, thrombectomy, vena cava filter).Our review of the literature is focused on consensus documents and recent large randomized trials.Subcutaneous low molecular weight heparins (LMWH) have been shown to be both safe and effective for the initial treatment of VTE and have largely replaced unfractionated heparin, unless there is a contraindication to LMWH such as severe renal insufficiency. Low molecular weight heparins or unfractionated heparin are usually administered for five to seven days. Treatment is gradually switched from heparin to oral vitamin K antagonists (VKA) which are usually started the same day as heparin. The duration of oral anticoagulation must be tailored to the individual patient according to the presence of reversible or continuing risk factors. In patients with active cancer, long-term treatment of VTE with LMWH has been shown to be more effective than oral anticoagulation and is recommended for the first three to six months of long-term anticoagulant therapy as an alternative approach to VKA. Elastic stockings are recommended because they have been shown to prevent postthrombotic syndrome. Thrombolysis is, usually, not justified for the treatment of deep venous thrombosis, but is used in cases of massive pulmonary embolism with arterial hypotension and/or shock. Vena cava filter placement is mainly indicated in patients with a proximal deep venous thrombosis and an absolute contraindication to anticoagulation.The initial management of patients with acute VTE has largely been simplified due to the use of LMWH. Early conversion to VKA is recommended for the great majority of patients. New agents, such as anti-Xa or oral thrombin inhibitors, are promising alternatives to heparins or VKA.

The role of ATP and ADP as intercellular mediators is now well established. The presence of the nucleotides in extracellular fluids can result from several mechanisms: cell lysis, selective permeabilization of the plasma membrane and exocytosis of secretory vesicles, such as platelet dense bodies. Extracellular adenine nucleotides are rapidly degraded by ectonucleotidases expressed inter alia on the surface of endothelial cells. They act on cells via the family of P2 receptors which encompasses more than 5 subtypes, some of which have been cloned recently. The P2T, P2U and P2Y receptors belong to the superfamily of receptors coupled to G proteins, whereas the P2X receptor is a cation channel and the P2Z receptor a non-selective pore. ATP and ADP stimulate the endothelial production of prostacyclin (PGI2) and nitric oxide (NO), two vasodilators and inhibitors of platelet aggregation, via an increase in cytosolic Ca2+. This action of adenine nucleotides is believed to limit the extent of intravascular platelet aggregation and to help localize thrombus formation to areas of endothelial damage. The endothelial response to nucleotides is mediated by at least two distinct subtypes of P2 receptors, P2Y and P2U, both coupled to phospholipase C.

The purpose of this study was to identify patients who were more likely to experience septicemia after endoscopic biliary drainage. In an attempt to determine the relative importance of each risk factor and their possible interdependancy to more precisely identify high-risk patients and to deduce some guidelines for prevention, a discriminant regression analysis of risk factors for septicemia was used. Clinical, biological, and radiological data of 34 consecutive patients who experienced septicemia within 3 days after endoscopic biliary stenting were reviewed retrospectively and compared with data of a group of 71 patients without any septic complication. If only data available before the procedure were used in the discriminant analysis, prior cholangitis and leucocytosis appeared as significant risk factors, but the linear combination of these data could not predict septicemia in 50% of cases. When information concerning the quality of drainage after the procedure was introduced into the analysis, 91% of the septicemic patients were identified, and other expected risk factors such as the nature of the stricture, the type of drainage, or prior cholangitis and leukocytosis had no or marginal predictive values. Patients referred from centers where duodenoscopes might have been poorly disinfected appeared to be at higher risk for Pseudomonas aeruginosa septicemia. These results emphasize the crucial role of the quality of drainage as a risk for septicemia. Regarding the prevention of infection, it is concluded from this study that (a) pure diagnostic endoscopic retrograde cholangiopancreatography should be avoided in obstructed patients if drainage cannot be performed during the same procedure; (b) drainage should be as complete as possible; (c) antibiotics should be administered before ERCP to every patient with suspected obstructive jaundice and should cover P. aeruginosa if local epidemiological data suggest that there is a problem with disinfection of the endoscopes; and (d) the quality of drainage should guide the duration of antibiotic prophylaxis.

Because of their antimicrobial activity and pharmacologic properties, fluoroquinolones should be particularly suitable for the treatment of lower respiratory tract infections, although they might be less efficient in pneumococcal diseases. In fact, the overall clinical success rate of enoxacin, ofloxacin, pefloxacin, and ciprofloxacin is greater than 85%, and their efficacy compares favorably with that of other antibiotics. For acute exacerbation of chronic bronchitis, however, beta-lactam or macrolide agents probably remain a first choice unless sputum reveals gram-negative pathogens; in the same way, drugs other than quinolones seem better indicated in community-acquired pneumonia because of the prevalence of Streptococcus pneumoniae in these infections. In contrast, nosocomial pulmonary infections due to gram-negative pathogens should be excellent candidates for therapy with new quinolones. These drugs, used with or without erythromycin and rifampin, might be useful in the treatment of legionnaires' disease.

After massive alcohol intake, a patient under disulfiram therapy developed a severe cardiovascular collapse unresponsive to dopamine but successfully reversed with norepinephrine. Resistance to dopamine could be related to norepinephrine depletion caused by disulfiram. Norepinephrine could, therefore, represent the treatment of choice of these life-threatening conditions.

Glomerular filtration rate (GFR) may be computed using the kinetics of the renal distribution volume curve Vt = Rt/Pt and a power fit of the plasma curve Pt = Pot-B. It can be demonstrated that GFR = d(Vt)/d(t)(1-B). The method is largely independent of background subtraction, allowing nonequivocal renal function determination in all cases. In a preliminary series of 20 patients, the linear regression coefficient of computed GFR with true clearance measurement by multiple blood samples method was 0.97 with a standard error on the estimate of the clearance of 5.5 ml.

The authors report a case of vertebral arteriovenous fistula that has been disclosed three years after central venous cannulation (CVC). The real inci dence of this complication is discussed and various clinical presentations are enumerated. From a review of the literature, some recommendations are made to prevent the diagnosis from being missed and chiefly to reduce the risk of arterial puncture that results in fistula formation.

Clinical and bacteriological data from 55 patients who developed septicemia within 3 days after ERCP were collected. Forty-four patients presented with septicemia after therapeutic endoscopy, with incomplete drainage in forty, eight after diagnostic ERCP performed in obstructed bile ducts in another center and not followed by endoscopic therapy, and three with a normal common bile duct after diagnostic ERCP. The incidence of septicemia is significantly higher in cases of malignant obstruction than in benign obstruction (21% vs 3%; p less than 0.01), due mainly to the problems of drainage associated with tumoral infiltration. Forty-eight patients (87%) had incomplete bile duct drainage when they developed septicemia, and among the seven remaining cases, 3 had cholecystitis and 3 abscesses in the biliopancreatic area. Previous diagnostic ERCP without drainage was also clearly associated with septicemia after therapeutic ERCP. The most commonly isolated bacteria from blood and bile cultures were Pseudomonas aeruginosa and Escherichia coli. P. aeruginosa was observed mainly in patients referred from other centers after previous diagnostic ERCP, and was unusual in patients without previous ERCP. It is associated with problems in the disinfection of the scopes. Six deaths were attributed to sepsis, always in patients with incomplete biliary drainage which could not be improved. In most of the cases, septicemia after ERCP is related to incomplete bile duct drainage, and in some cases, to biliopancreatic infected collections. Careful disinfection of the endoscopes and other endoscopic devices is mandatory to avoid an unacceptably high rate of P. aeruginosa infection.