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Biomedical subjects

Harry R Büller

Publications and source records attributed to Harry R Büller.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.

BACKGROUND: The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). OBJECTIVE: To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. DESIGN: Randomized, double-blind study. SETTING: 154 centers worldwide. PATIENTS: 2205 patients with acute symptomatic deep venous thrombosis. INTERVENTION: Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. MEASUREMENTS: The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. RESULTS: 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. LIMITATIONS: Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. CONCLUSIONS: Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

Aged↗

Estimates of risk of venous thrombosis during pregnancy and puerperium are not influenced by diagnostic suspicion and referral basis.

OBJECTIVES: The purpose of this study was to determine the relative risk of deep vein thrombosis (DVT) during pregnancy and puerperium in a setting that was not influenced by diagnostic suspicion and referral bias. STUDY DESIGN: Three hundred ninety-three consecutive females with suspicion of a first episode of venous thrombosis were referred in the same way to diagnostic centers. Medical history was obtained before objective testing for deep vein thrombosis. RESULTS: Seventy-six of the 393 females were diagnosed as having deep vein thrombosis; the others were used as control subjects. The odds ratios for pregnancy, cesarean section, and puerperium after adjustment for age, center, family history, and calendar time were, respectively, 5.7 (95% CI 2.5-12.9), 4.0 (95% CI 1.3-12.6), and 2.9 (95% CI 1.2-6.9). CONCLUSION: In this case-control study, in which patients and control patients were subject to the same referral and diagnostic procedures, we found similar risk estimates for pregnancy and puerperium as in previous studies. Our findings show that previous studies were less affected by diagnostic suspicion and referral bias than presumed.

Adolescent↗

Long-term follow-up of patients with suspected deep vein thrombosis of the upper extremity: survival, risk factors and post-thrombotic syndrome.

BACKGROUND: The outcome of upper extremity thrombosis in terms of morbidity, mortality and arm functionality is virtually unknown. We investigated mortality, risk factors, recurrent thrombosis and post-thrombotic syndrome (PTS) in patients with suspected upper extremity thrombosis. METHODS: Consecutive patients suspected of having deep vein thrombosis (DVT) of the upper extremity were followed for up to 53 months (mean 21 months). Venography and/or ultrasonography was used for diagnosis. Risk factors were identified from history and thrombophilia laboratory screening. PTS was assessed using a scoring system. Death, recurrent thrombosis and PTS were primary outcome measures. RESULTS: DVT of the upper extremity was diagnosed in 50 of 116 consecutive patients (43%). Malignancy and/or central venous lines were present in 37 of 50 (74%) patients with thrombosis. Inherited thrombophilia was diagnosed in 6 of 30 (20%) and 4 of 33 (12%) of the investigated patients with and without thrombosis, respectively (not significant). Twenty-five patients (50%) with thrombosis died during the follow-up period; this was associated with cancer in 84% of the deaths. Recurrent thrombosis was observed in four patients (8%) during follow-up. Symptoms of PTS were present in 4 of 22 patients (18%) with thrombosis and in 14 of 36 patients (39%) in whom thrombosis was excluded. CONCLUSIONS: Malignancy and central venous lines are major risk factors of upper extremity thrombosis. Thrombophilia seems to be unrelated to the presence or absence of upper extremity thrombosis. Thrombosis in combination with malignancy predicts poor survival. A scoring system can be used to assess the severity of PTS, but it does not discriminate PTS from other causes of arm complaints.

Journal Article↗

Influence of smoking on incidence and prevalence of peripheral arterial disease.

OBJECTIVE: Many studies have been published regarding the influence of smoking on the incidence and prevalence of peripheral arterial disease (PAD). A systematic review was performed to establish the magnitude of the effect of smoking on the development of PAD, and a possible dose-response relationship. METHODS: English-language articles were reviewed by 2 observers using a standardized form, and were summarized in tabular form. Data were extracted by 2 independent observers. Where possible, outcome data, expressed in terms of prevalence or incidence, were recalculated as odds ratio or relative risk, with never-smokers as the reference group, or if this was not available the nonsmoker group. Most studies did not provide primary data. Therefore the weighted means were reported as a summary estimate, provided that a funnel plot between sample size and observed effect size made publication bias unlikely. RESULTS: Sixteen articles describing 17 studies were included in the analysis. Four of the studies were prospective, and 13 were cross-sectional. The prevalence of symptomatic PAD was increased 2.3-fold in current smokers. Even in former smokers the prevalence was substantially increased by a factor of 2.6. A clear dose-response relationship, with a strong increase in risk for PAD in heavy smokers was observed. In countries where approximately 30% of the population are smokers, 50% of PAD can be attributed to smoking. CONCLUSIONS: Smoking is a potent risk factor for symptomatic PAD, with an important and consistent dose-response relationship. With the persistence of high risk for PAD in former smokers, tobacco control programs should continue to advocate smoking cessation, but focus even more on preventing future generations from ever starting to smoke.

Adult↗

Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice.

To explore social aspects of asymptomatic carriership of factor V Leiden mutation (FVL) and how carriers have experienced procedure of screening for FVL, we have performed a qualitative study using semi-structured interviews. Seventeen carriers of FVL without history of venous thromboembolism (VTE) were interviewed. Carriership of FVL has the potential to influence daily life by inducing concerns, stigmatisation and problems with insurances. Furthermore, proper procedure of screening is important because carriers have many questions concerning progeny, risk factors for VTE and preventive measures. Both health worker and the individual to be screened for FVL need to be fully aware of the possible consequences of screening and the fact that proper screening comprises more than only the collection of a blood sample or explaining the amount of risk for VTE induced by a genetic defect. Any guideline to be developed for the screening for FVL should take this into account too.

Adult↗

Biomarkers in pulmonary embolism.

PURPOSE OF REVIEW: Controversy exists about the precise role of thrombolytic therapy in normotensive patients with pulmonary embolism. To resolve this controversy two major questions must be addressed. First, can a subgroup of normotensive pulmonary embolism patients with a high risk for adverse outcomes, such as in-hospital mortality or early recurrent venous thromboembolism, be identified? Second, is there convincing evidence that the benefits of more aggressive therapy counterbalance its risks?Troponin I and T as well as brain natriuretic peptide (BNP) have recently been introduced as promising tools in the risk assessment of patients with pulmonary embolism. RECENT FINDINGS: The studies in series of patients with pulmonary embolism showed prevalences of elevated cardiac biomarkers of 16 to 84%. Positive predictive values for in-hospital mortality varied from 6 to 44%, whereas negative predictive values for uneventful outcome were above 93% in all studies. SUMMARY: Although a correlation between elevated biomarkers and in-hospital mortality in pulmonary embolism patients is present in most of the studies, the positive predictive value appears to be insufficient to extend the indication for thrombolytic therapy to all patients with elevated biomarkers. Future research is necessary to show whether combining different biomarkers with echocardiography is more useful.

Biomarkers↗

Antithrombotic therapy and cancer.

PURPOSE OF THE REVIEW: To assess the current evidence from recent clinical trials investigating antithrombotic agents for the prophylaxis and treatment of venous thromboembolism in cancer patients and for the effects of these agents on cancer progression. RECENT FINDINGS: A growing body of evidence supports the preventive use of antithrombotic strategies in subgroups of cancer patients. Moreover, in the long-term management of deep venous thrombosis in cancer patients, low-molecular-weight heparin seems to represent a valid alternative to vitamin K antagonists. Finally, several studies have claimed a direct anticancer activity and a positive impact on prognosis of some antithrombotic agents, eg, aspirin and low-molecular-weight heparin. SUMMARY: Although recent evidence suggests low-molecular-weight heparin as a possible option in the management and prevention of venous thromboembolism in cancer patients, more evidence from large randomized, prospective, controlled trials is needed to determine the exact the magnitude of the risk-benefit ratio associated with its use. The promising results on the effects of antithrombotic agents in the prognosis of cancer patients deserve further evaluation to estimate the potential and the feasibility of this approach.

Anticoagulants↗