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Biomedical subjects

Evert de Jonge

Publications and source records attributed to Evert de Jonge.

At least 37 records · Page 2Linked to original sources

Investigating the effect of differences in entry criteria on trial populations: a method with an application in severe sepsis.

Multiple clinical trials that investigate the same intervention often use different entry criteria to enroll patients into the trials. This variation in entry criteria might lead to the selection of patients with different characteristics. If these characteristics are related to the effect measure (e.g. baseline mortality in a trial investigating mortality reduction) the results of the trials cannot be compared straightforwardly. Therefore it is important to investigate whether the use of different entry criteria leads to the selection of patients with different characteristics.To study differences in the characteristics of the study populations, one could use the data from the control groups of the trials. However, differences in characteristics of these study populations can be caused by differences in entry criteria as well as by clinical diversity. Based on the data from the trials these two causes cannot be distinguished. We propose a method to investigate the influence of differences in entry criteria on the characteristics of study populations. The method corrects for the effects of clinical diversity by simulating the patient selection process on an independent registry database. The method has been successfully applied in the area of severe sepsis.

Humans↗

Comparison of two temporal abstraction procedures: a case study in prediction from monitoring data.

This paper presents an empirical comparison of two temporal abstraction procedures, that were applied to derive predictive features for a prediction problem in intensive care medicine. The first procedure employs knowledge from practitioners to derive qualitative patterns of state changes; the second procedure searches through a large number of data summaries to discover those that have predictive value. The derived features were used to predict whether postsurgical patients would need mechanical ventilation longer then 24h. The data-driven temporal abstraction procedure was found to provide more informative predictors, resulting in better predictions.

Cardiac Surgical Procedures↗

New treatment strategies for disseminated intravascular coagulation based on current understanding of the pathophysiology.

A variety of clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. In addition, the massive and ongoing activation of coagulation, may result in depletion of platelets and coagulation factors, which may cause bleeding. Recent understanding of important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with sepsis and a derangement of coagulation. Thrombin generation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C system. Also, impaired fibrin degradation, due to high circulating levels of the fibrinolytic inhibitor plasminogen activator inhibitor, type 1 (PAI-1), contributes to enhanced intravascular fibrin deposition. Interestingly, an extensive cross-talk between activation of inflammation and coagulation exists, where inflammatory mediators (such as cytokines) not only activate the coagulation system, but vice versa activated coagulation proteases and protease inhibitors may modulate inflammation through specific cell receptors. Supportive strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways, for example by means of the administration of recombinant human activated protein C.

Anticoagulants↗

Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation.

OBJECTIVES: A diagnosis of disseminated intravascular coagulation (DIC) is hampered by the lack of an accurate diagnostic test. Based on the retrospective analysis of studies in patients with DIC, a scoring system (0-8 points) using simple and readily available routine laboratory tests has been proposed. The aim of this study was to prospectively validate this scoring system and assess its feasibility, sensitivity, and specificity in a consecutive series of intensive care patients. DESIGN: Prospective cohort of intensive care patients. SETTING: Adult intensive care unit in a tertiary academic center. PATIENTS: Consecutive patients with a clinical suspicion of disseminated intravascular coagulation. INTERVENTIONS: Patients were followed during their admission to the intensive care unit, and the DIC score was calculated every 48 hrs and compared with a "gold standard" based on expert opinion. In addition, an activated partial thromboplastin time (aPTT) waveform analysis, which has been reported to be a good predictor for the absence or presence of DIC, was performed. MEASUREMENTS AND MAIN RESULTS: We analyzed 660 samples from 217 consecutive patients. The prevalence of DIC was 34%. There was a strong correlation between an increasing DIC score and 28-day mortality (for each 1-point increment in the DIC score, the odds ratio for mortality was 1.25). The sensitivity of the DIC score was 91% and the specificity 97%. An abnormal aPTT waveform was seen in 32% of patients and correlated well with the presence of DIC (sensitivity 88%, specificity 97%). In 19% of patients, the aPTT waveform-based diagnosis of DIC preceded the diagnosis based on the scoring system. CONCLUSIONS: A diagnosis of DIC based on a simple scoring system, using widely available routine coagulation tests, is sufficiently accurate to make or reject a diagnosis of DIC in intensive care patients with a clinical suspicion of this condition. An aPTT waveform analysis is an interesting and promising tool to assist in the diagnostic management of DIC.

Aged↗

Comparison of methods for evaluation of a medical terminological system.

The importance of terminological systems (TS) to support standardized and structured documentation of medical data is commonly recognized. The usability of TS in real practice strongly depends on the completeness and the correctness of the content of the TS. We here present four different methods that can be applied to evaluate a TS' content. All four methods were applied in a case study. We make a comparison of 1) the results of two methods that focus on the completeness of the content and that differ in the application of the TS that they focus on and 2) the results of an automated and a manual evaluation of the correctness of the content. Finally we summarize the results of all four methods and analyze whether they overlap or complement each other.

Critical Care↗

Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.

BACKGROUND: Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care. METHODS: We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria. FINDINGS: In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus. INTERPRETATION: In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.

Adolescent↗

Training in data definitions improves quality of intensive care data.

BACKGROUND: Our aim was to assess the contribution of training in data definitions and data extraction guidelines to improving quality of data for use in intensive care scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II in the Dutch National Intensive Care Evaluation (NICE) registry. METHODS: Before and after attending a central training programme, a training group of 31 intensive care physicians from Dutch hospitals who were newly participating in the NICE registry extracted data from three sample patient records. The 5-hour training programme provided participants with guidelines for data extraction and strict data definitions. A control group of 10 intensive care physicians, who were trained according the to train-the-trainer principle at least 6 months before the study, extracted the data twice, without specific training in between. RESULTS: In the training group the mean percentage of accurate data increased significantly after training for all NICE variables (+7%, 95% confidence interval 5%-10%), for APACHE II variables (+6%, 95% confidence interval 4%-9%) and for SAPS II variables (+4%, 95% confidence interval 1%-6%). The percentage data error due to nonadherence to data definitions decreased by 3.5% after training. Deviations from 'gold standard' SAPS II scores and predicted mortalities decreased significantly after training. Data accuracy in the control group did not change between the two data extractions and was equal to post-training data accuracy in the training group. CONCLUSION: Training in data definitions and data extraction guidelines is an effective way to improve quality of intensive care scoring data.

APACHE↗

Prevention and treatment of bleeding by pro-hemostatic treatment strategies.

Pro-hemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. Pro-hemostatic interventions appear to be effective in reducing peri-operative blood loss and reducing transfusion requirements in specific situations and may be helpful adjuncts in the management of severe spontaneous and post-operative bleeding. The risk of a higher incidence of thrombotic complications associated with the use of pro-hemostatic therapy is unknown but seems not to be very high in clinical practice. There is a need for more systematic and adequately controlled clinical observations to better establish the efficacy and safety of pro-hemostatic interventions.

Antifibrinolytic Agents↗

Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects.

The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.

Blood Coagulation↗

Quality of data collected for severity of illness scores in the Dutch National Intensive Care Evaluation (NICE) registry.

OBJECTIVE: To analyse the quality of data used to measure severity of illness in the Dutch National Intensive Care Evaluation (NICE) registry, after implementation of quality improving procedures. DESIGN: Data were re-abstracted from the paper records of patients or the Patient Data Management System and compared to the data contained in the registry. The re-abstracted data were considered to be the gold standard. SETTING: ICUs of nine Dutch hospitals that had been collecting data for the NICE registry for at least 1 year. MEASUREMENT AND RESULTS: The mean percentages of inaccurate and incomplete data, per hospital, over all variables, were 6.1%+/-4.4 (SD) and 2.7%+/-4.4 (SD), respectively. The mean difference in severity of illness scores between registry data and re-abstracted data was 0.2 points for APACHE II and 0.4 points for SAPS II. The mean difference in predicted mortality according to APACHE II and SAPS II between registry data and re-abstracted data was 0.4% and 0.02%, respectively. CONCLUSIONS: The current data quality of the NICE registry is good and justifies evaluative research. These positive results might be explained by the implementation of several quality assurance procedures in the NICE registry, such as training and automatic data checks. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00134-002-1272-z

APACHE↗

Bioavailability of subcutaneous low-molecular-weight heparin to patients on vasopressors.

Venous thromboembolism is a frequent complication in patients admitted to intensive care units (ICU), despite prophylactic treatment with subcutaneous low-molecular-weight (LMW) heparin. We postulated that poor efficacy of subcutaneous heparin might be due to administration of vasopressors, which could cause impaired peripheral circulation and inadequate systemic bioavailability of the anticoagulant. We compared concentrations of factor Xa activity in three groups of 15 patients: individuals in ICU who had and had not received vasopressors, and general surgery patients. Those who received vasopressors had lower plasma concentrations of factor-Xa activity than patients in ICU not on vasopressors and postoperative controls. Patients in ICU who take vasopressors could need higher doses of LMW heparin, or a different mode of administration of the drug, to attain adequate thrombosis prophylaxis.

Anticoagulants↗

Management of bleeding disorders by prohemostatic therapy.

Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. These treatment strategies may be applied to specifically correct a defect in one of the pathways of coagulation, but have in some situations also been shown to be effective in reducing bleeding in patients without a primary defect in coagulation. Besides the transfusion of platelets in case of thrombocytopenia or severe platelet disorders, a pharmacological improvement of primary hemostasis may be achieved by the administration of desmopressin. The administration of DDAVP results in a marked increase in the plasma concentration of Von Willebrand factor (and associated coagulation factor VIII) and (also by yet unexplained additional mechanisms) a remarkable potentiation of primary hemostasis as a consequence. DDAVP is used for the prevention and treatment of bleeding in patients with von Willebrand disease or mild hemophilia A, and further in patients with an impaired function of primary hemostasis, such as in patients with uremia, liver cirrhosis or in patients with aspirin-associated bleeding. Based on the current insight that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII(a) pathway, recombinant factor VIIa has been developed as a prohemostatic agent and has recently become available for clinical use. Indeed, in uncontrolled clinical studies this compound has been shown to exert a potent procoagulant activity and appeared to be highly effective in the prevention and treatment of bleeding, although most experience so far has been obtained in patients with severe and complicated coagulation defects. At present, a more general use of this agent for bleeding patients without an apparent coagulation defect is the subject of a number of ongoing clinical trials. Agents that exert anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The pro-hemostatic effect of these agents proceeds not only by the inhibition of fibrinolysis (thereby shifting the procoagulant/anticoagulant balance towards a more procoagulant state), but also due to a protective effect on platelets, as has been demonstrated at least for aprotinin. The mechanism of this platelet-protective effect has, besides a potential prevention of plasmin-mediated loss of platelet receptors not been elucidated. Whether the pro-hemostatic effect of the anti-fibrinolytic agents will eventually result in a higher incidence of thromboembolic complications is still a matter of debate (see further), however, this has so far not been shown in straightforward clinical trials.

Coagulants↗

The diagnosis of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. In recent years, the pathogenetic pathways leading to DIC have been largely identified, which could result in more precise diagnostic tests for this disorder. However, the clinical and laboratory diagnosis of DIC may remain difficult, since routinely available tests do not specifically assess ongoing thrombin generation. Molecular markers for activation of coagulation and fibrinogen to fibrin conversion are highly sensitive but also disappointedly aspecific for the diagnosis of DIC. Moreover, these tests are often not available in most settings for daily clinical care. A combination of widely available tests, however, may be helpful in making the diagnosis of DIC, according to a recently developed algorithm.

Algorithms↗

Therapeutic intervention in disseminated intravascular coagulation: have we made any progress in the last millennium?

Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Thrombin generation proceeds via the (extrinsic) tissue factor/activated factor VII route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin and the protein C and protein S system. Also, impaired fibrin degradation, due to high circulating levels of plasminogen activator inhibitor type-I, contributes to enhanced intravascular fibrin deposition. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways, by means of the administration of antithrombin concentrate or (activated) protein C.

Anticoagulants↗