Plasma Measurement of D-Dimer as Diagnostic Aid in Suspected Venous Thromboembolism: An Overview

1994 ◽  
Vol 71 (01) ◽  
pp. 001-006 ◽  
Author(s):  
H Bounameaux ◽  
P de Moerloose ◽  
A Perrier ◽  
G Reber
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Elisa Test ◽  
Diagnostic Approach ◽  
Plasma Measurement ◽  
Patients At Risk ◽  
Elisa Technique ◽  
D Dimer

SummaryThis paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2–98.4) and specificity of 35.2% (95% Cl: 32.0–38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% Cl: 95.0–98.6) and specificity of 45.1% (95% Cl: 40.8–49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE.These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 μg/1) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result.The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

scholarly journals Real-time utilisation of administrative data in the ED to identify older patients at risk: development and validation of the Dynamic Silver Code

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e033374 ◽  
Author(s):  
Daniela Balzi ◽  
Giulia Carreras ◽  
Francesco Tonarelli ◽  
Luca Degli Esposti ◽  
Paola Michelozzi ◽  
...  
Keyword(s):  
At Risk ◽  
Cohort Study ◽  
Real Time ◽  
Administrative Data ◽  
Older Patients ◽  
Clinical Decision Making ◽  
External Validation ◽  
Clinical Decision ◽  
Patients At Risk ◽  
Ed Visits

ObjectiveIdentification of older patients at risk, among those accessing the emergency department (ED), may support clinical decision-making. To this purpose, we developed and validated the Dynamic Silver Code (DSC), a score based on real-time linkage of administrative data.Design and settingThe ‘Silver Code National Project (SCNP)’, a non-concurrent cohort study, was used for retrospective development and internal validation of the DSC. External validation was obtained in the ‘Anziani in DEA (AIDEA)’ concurrent cohort study, where the DSC was generated by the software routinely used in the ED.ParticipantsThe SCNP contained 281 321 records of 180 079 residents aged 75+ years from Tuscany and Lazio, Italy, admitted via the ED to Internal Medicine or Geriatrics units. The AIDEA study enrolled 4425 subjects aged 75+ years (5217 records) accessing two EDs in the area of Florence, Italy.InterventionsNone.Outcome measuresPrimary outcome: 1-year mortality. Secondary outcomes: 7 and 30-day mortality and 1-year recurrent ED visits.ResultsAdvancing age, male gender, previous hospital admission, discharge diagnosis, time from discharge and polypharmacy predicted 1-year mortality and contributed to the DSC in the development subsample of the SCNP cohort. Based on score quartiles, participants were classified into low, medium, high and very high-risk classes. In the SCNP validation sample, mortality increased progressively from 144 to 367 per 1000 person-years, across DSC classes, with HR (95% CI) of 1.92 (1.85 to 1.99), 2.71 (2.61 to 2.81) and 5.40 (5.21 to 5.59) in class II, III and IV, respectively versus class I (p<0.001). Findings were similar in AIDEA, where the DSC predicted also recurrent ED visits in 1 year. In both databases, the DSC predicted 7 and 30-day mortality.ConclusionsThe DSC, based on administrative data available in real time, predicts prognosis of older patients and might improve their management in the ED.

scholarly journals P114: Barriers and facilitators affecting implementation of a decision aid for the diagnosis of acute aortic syndrome: a qualitative study

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S106-S106
Author(s):  
C. Dmitriew ◽  
R. Ohle
Keyword(s):  
Decision Making ◽  
Clinical Practice ◽  
Practice Guidelines ◽  
Resource Use ◽  
Decision Aid ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Barriers And Facilitators ◽  
Acute Aortic Syndrome ◽  
D Dimer

Introduction: Acute aortic syndrome (AAS) is an uncommon, life-threatening emergency that is frequently misdiagnosed. The Canadian clinical practice guidelines for the diagnosis of AAS were developed in order to reduce the frequency of misdiagnoses and number of diagnostic tests. As part of the guidelines, a clinical decision aid was developed in order to facilitate clinician decision-making based on practice recommendations. The objective of this study was to identify barriers and facilitators among physicians to implementation of the decision aid. Methods: We conducted semi-structured interviews with emergency room physicians working at 5 sites distributed between urban academic and rural settings. We used purposive sampling, contacting ED physicians until data saturation was reached. Interview questions were designed to understand potential barriers and facilitators affecting the probability of decision aid uptake and accurate application of the tool. Two independent raters coded interview transcripts using an integrative approach to theme identification, combining an inductive approach to identification of themes within an organizing framework (Theoretical Domains Framework), discrepancies in coding were resolved through discussion until consensus was reached. Results: A majority of interviewees anticipated that the decision aid would support clinical decision making and risk stratification while reducing resource use and missed diagnoses. Facilitators identified included validation and publication of the guidelines as well as adoption by peers. Barriers to implementation and application of the tool included the fact that the use of D-dimer and knowledge of the rationale for its use in the investigation of AAS were not widespread. Furthermore, scoring components were, at times, out of alignment with clinician practices and understanding of risk factors. The complexity of the decision aid was also identified as a potential barrier to accurate use. Conclusion: Physicians were amenable to using the AAS decision aid to support clinical decision-making and to reduce resource use, particularly within rural contexts. Key barriers identified included the complexity of scoring and inclusion criteria, and the variable acceptance of D-dimer among clinicians. These barriers should be addressed prior to implementation of the decision aid during validation studies of the clinical practice guidelines.

Therapeutic Drug Monitoring of Imatinib and Impact on Clinical Decision Making.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4820-4820 ◽  
Author(s):  
Carolyn Blasdel ◽  
Yanfeng Wang ◽  
Theodore Lagattuta ◽  
Brian Druker ◽  
Laurie Letvak ◽  
...  
Keyword(s):  
Decision Making ◽  
Drug Monitoring ◽  
Dose Adjustment ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Therapeutic Drug ◽  
Dose Increase ◽  
Qrt Pcr ◽  
Drug Concentrations

Abstract OBJECTIVES: Imatinib (IM) has demonstrated durable clinical efficacy in the majority of chronic myeloid leukemia (CML) patients. Optimal response may be influenced by multiple innate and external factors, some of which may be controlled by monitoring plasma concentrations of the drug. This abstract reports 6 cases where analyzing plasma IM trough concentrations (Cmin) in patients treated with three commonly used IM doses (400, 600, and 800 mg daily) influenced clinical decision making. METHODS: IM trough blood samples were collected at a time before that day’s IM dosing. Plasma concentrations of IM were determined by a validated LC/MS/MS method. RESULTS: In large population studies of CML patients enrolled in Phase I, II, and III clinical trials, the mean Cmin levels of IM at 400 mg qd, 600 mg qd, and 400 mg bid doses were: 981 (±543, 55%, n=394), 1572 (±1032, 66%, n=14), and 3479 (±1264, 36%, n=14) ng/mL, respectively. Large inter-patient variability was shown at all three doses. Of the 6 cases detailed in the table below, 4 (ID 1, 3, 4, and 5) had dose reduction due to tolerability concerns with subsequent improvement of symptoms following dose adjustment. One patient (ID 2) had a dose increase because of a poor qRT-PCR response. Another (ID 6) had a dose increase due to low plasma IM exposure resulting from drug-drug interaction with phenytoin, a known inducer of CYP3A4 (the major metabolizing isozyme for IM). After dose adjustment, all six patients showed good clinical response to IM treatment. The new mean Cmin value in these patients was 2000 (±471) ng/mL, representing a 24% coefficient of variability. CONCLUSIONS: Although the data is limited, IM drug monitoring proved useful in managing tolerability, lack of efficacy, adherence or potential drug interactions that modulate imatinib drug concentrations. More prospective studies are needed to demonstrate the value of IM drug monitoring in routine clinical practice. Patient ID Age, Sex CML Stage IM Daily Dose 1st Cmin (ng/mL) Reason for Dose Change New Dosing Regimen New Cmin (ng/mL) CP, chronic phase1 1 54, f CP 200 mg bid, Jan 03 3048, Sep 05 transfusion-dependent, anemia, Sep 05 300 mg, Oct 05 2130, Jan 06 2 9, f CP 300 mg, Jan 05 not done qRT-PCR 0.016, Jan 06 400 mg, Jan 06 2341, Jul 06 3 13, f CP 300 mg bid, May 05; 700 mg, Aug 05; 600 mg, Sep 05 1966, Feb 06 nausea, fatigue, arthralgias, myalgia, ongoing 400 mg, Mar 06 1222, May 06 4 67, f CP 400 mg, Feb 05 not done myelosuppression, Mar 05 200 mg, Mar 05 1928, May 06 5 53, f CP 400 mg, Apr 03; 600 mg, May 03; 800 mg, Jul 04 not done inflammatory pulmonary reaction with shortness of breath; dose held, Mar 05 400 mg, Oct 05 2378, May 06 6 73, m CP 350 mg, on phenytoin, Apr 99 35, Jun 99 stopped phenytoin, Jul 99 500 mg, Jul 99 not done; qRT-PCR negative, Jul 06

scholarly journals Role of Physical Therapists in the Management of Individuals at Risk for or Diagnosed With Venous Thromboembolism: Evidence-Based Clinical Practice Guideline

2016 ◽  
Vol 96 (2) ◽  
pp. 143-166 ◽  
Author(s):  
Ellen Hillegass ◽  
Michael Puthoff ◽  
Ethel M. Frese ◽  
Mary Thigpen ◽  
Dennis C. Sobush ◽  
...  
Keyword(s):  
Decision Making ◽  
At Risk ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Clinical Decision Making ◽  
Physical Therapists ◽  
Physical Therapist ◽  
Patients At Risk

The American Physical Therapy Association (APTA), in conjunction with the Cardiovascular & Pulmonary and Acute Care sections of APTA, have developed this clinical practice guideline to assist physical therapists in their decision-making process when treating patients at risk for venous thromboembolism (VTE) or diagnosed with a lower extremity deep vein thrombosis (LE DVT). No matter the practice setting, physical therapists work with patients who are at risk for or have a history of VTE. This document will guide physical therapist practice in the prevention of, screening for, and treatment of patients at risk for or diagnosed with LE DVT. Through a systematic review of published studies and a structured appraisal process, key action statements were written to guide the physical therapist. The evidence supporting each action was rated, and the strength of statement was determined. Clinical practice algorithms, based on the key action statements, were developed that can assist with clinical decision making. Physical therapists, along with other members of the health care team, should work to implement these key action statements to decrease the incidence of VTE, improve the diagnosis and acute management of LE DVT, and reduce the long-term complications of LE DVT.

Abstract 155: Prevalence of Self-Reported Risk Factors for Myocardial Infarction Among Patients With Venous Thromboembolism

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Julie Vanderpoel ◽  
Brahim Bookhart ◽  
Hillary J Gross ◽  
Marco DiBonaventura
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Venous Thromboembolism ◽  
Potential Risk ◽  
Clinical Decision Making ◽  
Smoking Status ◽  
Patient Characteristics ◽  
Clinical Decision ◽  
Family Medical History ◽  
The Mean

Objective: To identify the prevalence of risk factors that may be associated with a future myocardial infarction (MI) among patients with venous thromboembolism (VTE). Methods: This study was conducted using the 2010 wave of the National Health and Wellness Survey (NHWS). The NHWS is a self-administered, Internet-based questionnaire from a nationwide sample of adults (N=75,000). Only patients with a diagnosis of VTE, defined as a self-reported diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE), or both, were included in the analysis. Self-reported patient characteristics that may be potential risk factors for MI were collected, including sociodemographic characteristics, family medical history, and health behaviors (such as smoking status), as well as comorbidities. Included risk factors were based on a literature search. The risk factors were not weighted based on the strength of their potential association with a future MI. Thus, risk factors of varying significance were included and weighted equally. Findings: A total of 814 patients with VTE (519 with DVT, 196 with PE, and 99 with DVT and PE) were included in the analysis. Approximately 53% of the patients were female, and the mean age was 57 years. Among these patients, the mean number of reported risk factors that may be associated with a future MI was 5.6. Approximately 23% (n=189) of patients reported ≤3 risk factors, 55% (n=446) of patients had 4-7 risk factors, and 22% (n=179) of patients had ≥8 risk factors. Some of the more commonly reported risk factors included male gender (47%, n=381), obesity (53%, n=428), hypertension (53%, n=427), hyperlipidemia (49%, n=401), type 2 diabetes (21%, n=167), a family history of cardiovascular disease (81%, n=663), and currently smoking (22%, n=175). Conclusions: A high proportion of patients with VTE have risk factors for a future MI. Awareness of the prevalence of MI risk factors among patients with VTE may support optimal clinical decision-making for these patients. Providers should be cognizant of the potential risk for MI among patients with VTE when selecting treatment approaches. Additional research that considers the relative importance of each potential risk factor is needed to elucidate these findings.

Review: Laboratory markers quantifying prothrombin activation and actions of thrombin in venous and arterial thrombosis do not accurately assess disease severity or the effectiveness of treatment

2006 ◽  
Vol 96 (11) ◽  
pp. 568-577 ◽  
Author(s):  
Frederick Ofosu
Keyword(s):  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Cell Activation ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Thrombin Inhibitors ◽  
Treatment Modalities ◽  
Patients At Risk ◽  
Effective Drugs

SummaryThrombin is normally produced for hemostasis and physiological wound healing. Increased thrombin production in vivo, cell activation and inflammation mediated in part by thrombin are hallmarks of both arterial and venous thrombosis. Thrombin generates (pro) coagulant, mitogenic, inflammatory and anticoagulant responses by interacting witha variety of cells in vivo.Both direct and indirect thrombin inhibitors are effective drugs for preventing and treating the consequences of arterial and venous thrombosis. For these reasons, measurements of the production and activities of thrombin in vivo have the potential for gauging the extent of thromboembolism and the responses of patients to anticoagulant, antiplatelet and anti-inflammatory drugs. How-ever, a critical review of published information suggests that measurement of thrombin production and activity in patients at risk for and in patients with significant thrombosis generally does not provide information useful for clinical decision-making. This lack of clinical utility of levels of thrombin production in vivo may arise from two causes: the inability of the measurement to differentiate between physiological (hemostatic) and disease-related (pathological) sources and/or causes of thrombin production in vivo, and the inability of antithrombotic treatment modalities to permanently eliminate the stimuli that cause increased thrombin production evident in venous and arterial thrombosis.

Review of the Target-Specific Oral Anticoagulants in Development for the Treatment and Prevention of Venous Thromboembolism

2016 ◽  
Vol 29 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Sandeep Devabhakthuni ◽  
Connie H. Yoon ◽  
Kathleen J. Pincus
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Clinical Decision ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Treatment And Prevention

Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.

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