Recurrent events modelling of haemophilia bleeding events

2021 ◽  
Author(s):  
Andrew C. Titman ◽  
Martin J. Wolfsegger ◽  
Thomas F. Jaki
Keyword(s):  
Recurrent Events ◽  
Bleeding Events

Prospective, Open-label clinical Trial of Bivalirudin in Children with Venous Thromboembolism

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1165-1165
Author(s):  
Sarah H. O'Brien ◽  
Donald Yee ◽  
Jessica Lira ◽  
Neil A Goldenberg ◽  
Guy Young
Keyword(s):  
Venous Thromboembolism ◽  
Complete Resolution ◽  
High Performance ◽  
Recurrent Events ◽  
Bleeding Event ◽  
Thrombin Inhibitor ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Open Label ◽  
Partial Resolution

Abstract Abstract 1165 Background: Bivalirudin (BIV) is a direct thrombin inhibitor with a favorable pharmacologic profile in comparison to heparin. In a previous study in children <6 months of age with venous thromboembolism (VTE), bivalirudin was demonstrated to be a safe and potentially more effective anticoagulant. The present study's aims were to assess the safety, dosing, pharmacokinetics, pharmacodynamics, and efficacy of BIV in children >6 months of age. Methods: This prospective, open-label study evaluated the use of BIV for initial treatment of a new VTE in children between 6 months and 18 years of age. Eligible subjects received a BIV bolus of 0.125mg/kg followed by an initial continuous infusion of 0.125mg/kg/hour which was adjusted as needed to achieve a PTT of 1.5–2.5x their baseline PTT. BIV levels by high performance liquid chromatography and PTTs were tested simultaneously 5 times in the first 24 hours, daily thereafter and following all dose adjustments. Subjects remained on BIV until they were transitioned to long-term anticoagulant treatments. Imaging was required to confirm the presence of a VTE and follow-up imaging was obtained at 2–3 days and 30 days following initiation of anticoagulation. Subjects were closely monitored for bleeding and adverse events. Results: 18 subjects (11M:7F) ranging in age from 9 months-17 years completed the study. There were no major bleeding events and one minor bleeding event. Outcome of VTE: at 2–3 days, 2 subjects had complete resolution and 7 subjects had partial resolution while at 30 days, 7 subjects had complete resolution and 9 subjects had partial resolution. There were no symptomatic recurrent events or any asymptomatic local progressions by surveillance imaging. Seven subjects required no dose adjustments during their course of treatment ranging between 2–5 days. See figure for correlation of PTT with BIV levels [each circle represents one subject with their mean PTT and BIV level with the standard deviations (r2=0.64)]. Conclusions: BIV offers a potentially safer, more effective and pharmacologically more predictable alternative to heparin for initial anticoagulation of children with VTE. Pharmacokinetic-pharmacodynamic correlation was excellent suggesting PTT as an acceptable monitoring strategy for BIV in this population. Further studies comparing BIV to heparin should be conducted. Disclosures: Off Label Use: Bivalirudin is not approved for use in children. Goldenberg:Eisai Inc: Research Funding; Pfizer Inc: Membership on an entity's Board of Directors or advisory committees; CPC Clinical Research: Consultancy.

Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3256-3260 ◽  
Author(s):  
Fiona F. O'Connor ◽  
Denis C. Shields ◽  
Anthony Fitzgerald ◽  
Christopher P. Cannon ◽  
Eugene Braunwald ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Recurrent Events ◽  
High Dose ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
End Point ◽  
Dose Dependent Fashion ◽  
Glycoprotein Iiia ◽  
Coronary Syndromes

Abstract This study examined the influence of the PlApolymorphism of glycoprotein IIIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist, orbofiban, in patients with unstable coronary syndromes. Genotyping for the PlA polymorphism was performed in 1014 patients recruited into the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes–thrombolysis in myocardial infarction 16) trial, in which patients were randomized to low- or high-dose orbofiban or placebo for 1 year. The primary end point (n = 165) was a composite of death, myocardial infarction (MI), recurrent ischemia requiring rehospitalization, urgent revascularization, and stroke. Overall, orbofiban failed to reduce ischemic events when compared with placebo, but increased the rate of bleeding. In the whole population, PlA2 carriers had a significant increase in MI (n = 33) during follow up, with a relative risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P = .004). There was a significant interaction between treatment (placebo and orbofiban) and the PlA polymorphism for bleeding (n = 187; P = .05). Thus, while orbofiban increased bleeding in noncarriers (RR = 1.87, 1.29 to 2.71;P &lt; .001) in a dose-dependent fashion, it did not increase bleeding events in PlA2 carriers (RR = 0.87, 0.46 to 1.64). There was no interaction between treatment (placebo and orbofiban) and the PlA polymorphism for the primary end point (P = .10). However, in the patients receiving orbifiban there was a higher risk of a primary event (RR = 1.55, 1.03 to 2.34; P = .04) and MI (RR 4.27, 1.82 to 10.03;P &lt; .001) in PlA2 carriers compared with noncarriers. In contrast, there was no evidence that PlA2influenced the rate of recurrent events in placebo-treated patients. In patients presenting with an acute coronary syndrome, the PlA polymorphism of GPIIb/IIIa may explain some of the variance in the response to an oral GPIIb/IIIa antagonist.

Pharmacokinetics and Tolerability of Factor XIII Concentrates Prepared from Human Placenta or Plasma: a Crossover Randomised Study

1995 ◽  
Vol 74 (02) ◽  
pp. 622-625 ◽  
Author(s):  
H H Brackmann ◽  
R Egbring ◽  
A Ferster ◽  
P Fondu ◽  
J M Girardel ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomised Study ◽  
The Mean ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study ◽  
Fxiii Activity ◽  
Observation Period

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

Stroke Prevention in Non-Valvular Atrial Fibrillation

1997 ◽  
Vol 17 (03) ◽  
pp. 166-169
Author(s):  
Judith O’Brien ◽  
Wendy Klittich ◽  
J. Jaime Caro
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Care Home ◽  
Relevant Literature ◽  
Clinical Trial Data ◽  
Outcome Data ◽  
Sensitivity Analyses ◽  
Bleeding Events ◽  
Discharge Data ◽  
The Cost

SummaryDespite evidence from 6 major clinical trials that warfarin effectively prevents strokes in atrial fibrillation, clinicians and health care managers may remain reluctant to support anticoagulant prophylaxis because of its perceived costs. Yet, doing nothing also has a price. To assess this, we carried out a pharmacoe-conomic analysis of warfarin use in atrial fibrillation. The course of the disease, including the occurrence of cerebral and systemic emboli, intracranial and other major bleeding events, was modeled and a meta-analysis of the clinical trials and other relevant literature was carried out to estimate the required probabilities with and without warfarin use. The cost of managing each event, including acute and subsequent care, home care equipment and MD costs, was derived by estimating the cost per resource unit, the proportion consuming each resource and the volume of use. Unit costs and volumes of use were determined from established US government databases, all charges were adjusted using cost-to-charge ratios, and a 3% discount rate was applied to costs incurred beyond the first year. The proportions of patients consuming each resource were estimated by fitting a joint distribution to the clinical trial data, stroke outcome data from a recent Swedish study and aggregate ICD-9 specific, Massachusetts discharge data. If nothing is done, 3.2% more patients will suffer serious emboli annually and the expected annual cost of managing a patient will increase by DM 2,544 (1996 German Marks), from DM 4,366 to DM 6,910. Extensive multiway sensitivity analyses revealed that the higher price of doing nothing persists except for very extreme combinations of inputs unsupported by literature or clinical standards. The price of doing nothing is thus so high, both in health and economic terms, that cost-consciousness as well as clinical considerations mandate warfarin prophylaxis in atrial fibrillation.

Recurrent Stroke Risk in Pilots with Atrial Fibrillation

2020 ◽  
Vol 91 (4) ◽  
pp. 352-357
Author(s):  
Jessica Tedford ◽  
Valerie Skaggs ◽  
Ann Norris ◽  
Farhad Sahiar ◽  
Charles Mathers
Keyword(s):  
Atrial Fibrillation ◽  
General Population ◽  
Recurrent Events ◽  
Stroke Risk ◽  
Event Rate ◽  
Recurrent Stroke ◽  
Previous History ◽  
Recurrent Event ◽  
Recurrence Rates ◽  
Medical Certification

INTRODUCTION: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in the general population and is considered disqualifying aeromedically. This study is a unique examination of significant outcomes in aviators with previous history of both AF and stroke.METHODS: Pilots examined by the FAA between 2002 and 2012 who had had AF at some point during his or her medical history were reviewed, and those with an initial stroke or transient ischemic attack (TIA) during that time period were included in this study. All records were individually reviewed to determine stroke and AF history, medical certification history, and recurrent events. Variables collected included medical and behavior history, stroke type, gender, BMI, medication use, and any cardiovascular or neurological outcomes of interest. Major recurrent events included stroke, TIA, cerebrovascular accident, death, or other major events. These factors were used to calculate CHA2DS2-VASc scores.RESULTS: Of the 141 pilots selected for the study, 17.7% experienced a recurrent event. At 6 mo, the recurrent event rate was 5.0%; at 1 yr, 5.8%; at 3 yr 6.9%; and at 5 yr the recurrent event rate was 17.3%. No statistical difference between CHA2DS2-VASc scores was found as it pertained to number of recurrent events.DISCUSSION: We found no significant factors predicting risk of recurrent event and lower recurrence rates in pilots than the general population. This suggests CHA2DS2-VASc scores are not appropriate risk stratification tools in an aviation population and more research is necessary to determine risk of recurrent events in aviators with atrial fibrillation.Tedford J, Skaggs V, Norris A, Sahiar F, Mathers C. Recurrent stroke risk in pilots with atrial fibrillation. Aerosp Med Hum Perform. 2020; 91(4):352–357.

The Time of Drama in Nietzsche and Deleuze: A Life as Performative Interaction

2010 ◽  
Vol 4 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Arno Böhler
Keyword(s):  
Recurrent Events ◽  
Active Participation ◽  
Eternal Return ◽  
The Third ◽  
Close Study

Nietzsche's model of eternal return triggers a drama of affirmation, the overcoming of a simple miming of our ancestors in favour of an active participation in the counter-actualisation of hidden potentials in recurrent events. Based on a close study of Zarathustra's struggle to free himself from a suffocating nihilism, the paper focuses on the revelatory caesura that ushers in what Deleuze calls the third synthesis of time, a time of ‘doing’ rather than reflection.

New Drugs for Thromboembolic Prevention in Atrial Fibrillation

2010 ◽  
Vol 6 (4) ◽  
pp. 64
Author(s):  
Jose L Merino ◽  
Jose López-Sendón ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Negative Impact ◽  
Vitamin K Antagonists ◽  
Coagulation Factor ◽  
Developed Countries ◽  
New Drugs ◽  
Risk Scores ◽  
Bleeding Events ◽  
Risk Patients

Atrial fibrillation (AF) is the most frequent sustained arrhythmia and its prevalence is increasing in developed countries. This progressive increase and the negative impact of this arrhythmia on the patient’s prognosis make AF one of the main healthcare problems faced today. This has led to intense research into the main aspects of AF, one of them being thromboembolism prevention. AF patients have a four to five times higher risk of stroke than the general population. Several factors increase thromboembolic risk in patients with AF and the use of risk scores, such as the Congestive Heart Failure, Hypertension, Age Greater than 75, Diabetes, and Prior Stroke or Transient Ischemic Attack (CHADS2), have been used to identify the best candidates for anticoagulation. Antithrombotic drugs are the mainstay of therapy for embolic prevention. The clinical use of these drugs is based on the risk–benefit ratio, where benefit is the reduction of stroke and systemic embolic events and risk is mostly driven by the increase in bleeding events. Generally, antiplatelets are indicated for low-risk patients in light of the fact anticoagulants are the drug of choice for moderate- or high-risk patients. Vitamin K antagonists have been the only option for oral anticoagulation for the last 50 years. However, these drugs have many pharmacodynamic and pharmacokinetic problems. The problems of anticoagulation with vitamin K antagonists have led to the investigation of new drugs that can be administered orally and have a better dose–response relationship, a shorter half-life and, in particular, higher efficacy and safety without the need for frequent anticoagulation controls. The drugs that have been studied most thoroughly in patients with AF are inhibitors of the activated coagulation factor X and inhibitors of coagulation factor II (thrombin), including ximelagatran and dabigatran. In addition, non-pharmacological therapies have been developed to prevent recurrent embolism in certain patient populations.

TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

2020 ◽  
Vol 14 ◽  
Author(s):  
Johny Nicolas ◽  
Usman Baber ◽  
Roxana Mehran
Keyword(s):  
Percutaneous Coronary Intervention ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
High Risk Patients ◽  
Risk Of Death ◽  
Percutaneous Coronary ◽  
Risk Patients

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p<0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.

Postscript

2015 ◽  
Vol 1 (1) ◽  
pp. 127-132
Author(s):  
Stephen Hugh-Jones
Keyword(s):  
New York ◽  
Recurrent Events ◽  
Historical Documents ◽  
York Academy ◽  
American Museum ◽  
International Conference ◽  
Interdisciplinary Field ◽  
American Tropics ◽  
Academy Of Sciences

The previous paper was first published in 1982, when ethnoastronomy was still in its infancy. It appeared in Ethnoastronomy and Archaeoastronomy in the American Tropics, Tony Aveni and Gary Urton’s edited proceedings of an international conference held at the American Museum of Natural History’s Hayden Planetarium in New York under the auspices of the New York Academy of Sciences. Aveni and Urton were true pioneers who opened up a new interdisciplinary field of research that brought together astronomers, anthropologists, archaeologists, historians and others, all interested in astronomical knowledge amongst contemporary indigenous societies, in how buildings, settlements and archaeological monuments were aligned with recurrent events in the sky, and in how such alignments matched up with astronomical information contained in ancient codices and other historical documents and in contemporary ethnographic accounts.

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