Pediatric venous thromboembolism in relation to adults

ObjectiveThis review was performed to analyze the current knowledge and controversies in the pathophysiology, diagnosis, treatment, and outcomes of pediatric venous thromboembolism (VTE) compared with adults.MethodsSearches of the MEDLINE database and manual searches of the references of selected articles were performed to select reports for their relevance and quality of information on the similarities and differences in pathophysiology, diagnosis, and treatment of VTE in children and adults.ResultsSymptomatic VTE incidence is reported at a rate of 0.07 in every 10,000 children, which is significantly lower than the rate in adults. Pulmonary emboli in adolescents are rarely fatal, unlike in adults. VTE recurrence is also much lower in children. Young age has been shown to be protective of VTE, whereas central venous catheters are very important in pediatric venous thrombosis. The incidence of postthrombotic syndrome varies from 20% to 65%, with mild symptoms in most children. Cerebral and visceral vein thrombosis may lead to severe morbidity and death. Some factors of thrombophilia have a significant effect in the pediatric population; however, its overall significance is controversial. Most data on VTE treatment are extrapolated from studies in adults. Children with acute VTE should be treated with anticoagulation therapy. Treatment duration depends on the nature of the thrombosis and previous VTE events.ConclusionsThere is a paucity of prospective randomized studies with data determining not only the effect of VTE but also the treatment options in children. Thrombophilia is a risk factor for pediatric VTE, but its significance has not been thoroughly investigated. Guidelines specific to children for antithrombotic therapy, prophylaxis, and optimal duration need re-evaluation and support by strong evidence

Challenges for decision-makers when assessing within-class comparative effectiveness: the case of anticoagulation therapy for atrial fibrillation

In September 2020, the UK National Institute of HealthCare Excellence (NICE) published a draft report for consultation on anticoagulation therapy for stroke prevention in people with atrial fibrillation (AF) [1]. This intervention evidence review is part of the process of updating the NICE clinical guideline on management of AF [2] and addressed the question of which nonvitamin K oral anticoagulation (NOAC) therapy is most clinically and cost-effective for stroke prevention in people with AF. Four NOACs were included in the evidence review, each with a low and high dose formulation: apixaban, dabigatran, rivaroxaban and edoxaban, and all of which had been previously evaluated and recommended in NICE single technology appraisals [3–6]. On the basis of a systematic literature review to identify relevant evidence, network meta-analysis (NMA) to address comparative effectiveness, and subsequent cost–effectiveness analysis (CEA), the committee concluded that apixaban and dabigatran had the most favorable cost–effectiveness (CE) results of the four NOACs, at the NHS list prices and this led to a draft recommendation in the report that apixaban and dabigatran should be used as first-line options [1]. A further recommendation was made that patients who are stable on one of the other anticoagulants (rivaroxaban, edoxaban or warfarin) should discuss switching with their physician [1]. This draft decision by the committee, to recommend two NOACs within a class of four, represents an unusually strong recommendation to differentiate drugs within a particular class. This is especially so, given that the committee themselves state that the acquisition costs based on NHS list prices of the four NOACs are similar (page 74, line 28) [1]. This suggests that the opinion reached by the committee was grounded in the results of the NMA produced comparative effectiveness estimates that then formed the basis of the CEA. This manuscript reports on the process of examining the committee’s draft decision to differentiate drugs within the NOAC class on the basis of clinical and CE in light of the evidence considered by the committee. This manuscript was sponsored by the manufacturer of one of the NOACs that was not recommended as a first-line option by the committee (edoxaban, Daiichi Sankyo) in order to help them respond to the consultation process NICE initiated and which closed in November 2020. The aim of this manuscript is to elucidate the methodological challenges involved in any decision made by a reimbursement authority, such as NICE in the UK, and ask an open question regarding the strength of evidence of comparative effectiveness be required in order to differentiate similarly-priced drugs within a single drug class. The manuscript is structured around three further sections. The next section looks at the evidence on comparative effectiveness of seven key clinical outcomes, the need for NMA to generate those estimates of comparative effectiveness and the representation of uncertainty in the results of NMAs. The third section looks specifically at how the results of the NMA are then turned into a CEA that uses quality-adjusted life-years (QALYs) as the metric to synthesize the seven clinical outcomes into a QALY comparison, before considering the inclusion of costs and the representation of uncertainty in the CE results. A final section then discusses the challenges of making recommendations in the context of the uncertainty in clinical and CE both between the NOAC and vitamin-K antagonist (VKA) drug classes and within the NOAC class

Clinical significance of recurrent venous thromboembolism Significância clínica de tromboembolismo venoso recorrente

Recurrent venous thromboembolism is a significant problem leading to increased morbidity and mortality. It has a high impact on patients' quality of life and imposes a great financial burden on society. Cumulative recurrence has been reported as 40% at 10 years, while the chance of developing postthrombotic signs and symptoms in the lower extremities almost quadruples when ipsilateral. There is also a higher chance of developing pulmonary hypertension. Important factors for recurrence are unprovoked episodes of deep vein thrombosis, malignancy and older age. The evidence for other factors is controversial. Accurate diagnosis and treatment tailored to the patients' history, thrombotic events and risk factors are necessary to optimize management and prevent recurrence.<br>O tromboembolismo venoso recorrente é um problema importante que leva ao aumento da morbimortalidade. Impõe forte impacto à qualidade de vida dos pacientes e grande carga financeira para a sociedade. Acredita-se que a recorrência cumulativa atinja 40% em 10 anos, enquanto que a chance de desenvolver sinais e sintomas pós-trombóticos nas extremidades inferiores quase quadruplica no caso de trombose ipsilateral. Há também uma maior chance do desenvolvimento de hipertensão pulmonar. Fatores importantes para a recorrência são: episódios não provocados de trombose venosa profunda, malignidade e idade avançada. As evidências relacionadas a outros fatores são controversas. Diagnóstico preciso e tratamento adaptado ao histórico dos pacientes, aos eventos trombóticos e aos fatores de risco são necessários para otimizar o manejo e prevenir a recorrência

ILC Reference Design Report Volume 1 - Executive Summary

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization

International Linear Collider Reference Design Report Volume 2: PHYSICS AT THE ILC

This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described.This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described