A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs.Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens.Results For 63-year-old CTEPH patients with a 14-month diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at EUR 117100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life-years and 2.04 QALYs. The associated cost increase was EUR 44654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of EUR 21900/QALY.Conclusion Our constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health economic standards, additional costs remain below the deemed acceptable limit of EUR 50000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay.Analysis and support of clinical decision makin

Thrombosis: A major contributor to global disease burden

AbstractThrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low, middle and high income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 individuals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70years of age or more. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted-life-years (DALYs) lost in low and middle income countries, and second in high income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low, middle, and high income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilization of preventive measures will reduce the burden

Incomplete echocardiographic recovery at 6\ua0months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial

Introduction: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. Methods: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) \u2018post-PE impairment\u2019 (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II\u2013IV. Results: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. Conclusions: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19: JACC State-of-the-Art Review

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs. © 2021 American College of Cardiology Foundatio

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

Search for long-lived neutral particles in pp collisions at s√=13 TeV that decay into displaced hadronic jets in the ATLAS calorimeter

This paper describes a search for pairs of neutral, long-lived particles decaying in the ATLAS calorimeter. Long-lived particles occur in many extensions to the Standard Model and may elude searches for new promptly decaying particles. The analysis considers neutral, long-lived scalars with masses between 5 and 400 GeV, produced from decays of heavy bosons with masses between 125 and 1000 GeV, where the long-lived scalars decay into Standard Model fermions. The analysis uses either 10.8 fb−1 or 33.0 fb−1 of data (depending on the trigger) recorded in 2016 at the LHC with the ATLAS detector in proton–proton collisions at a centre-of-mass energy of 13 TeV. No significant excess is observed, and limits are reported on the production cross section times branching ratio as a function of the proper decay length of the long-lived particles

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV

Differential cross-sections for events with missing transverse momentum and jets measured with the ATLAS detector in 13 TeV proton-proton collisions

Measurements of inclusive, diferential cross-sections for the production of events with missing transverse momentum in association with jets in proton-proton collisions at √s = 13 TeV are presented. The measurements are made with the ATLAS detector using an integrated luminosity of 140 fb−1 and include measurements of dijet distributions in a region in which vector-boson fusion processes are enhanced. They are unfolded to correct for detector resolution and efficiency within the fiducial acceptance, and are designed to allow robust comparisons with a wide range of theoretical predictions. A measurement of differential cross sections for the Z → νν process is made. The measurements are generally well-described by Standard Model predictions except for the dijet invariant mass distribution. Auxiliary measurements of the hadronic system recoiling against isolated leptons, and photons, are also made in the same phase space. Ratios between the measured distributions are then derived, to take advantage of cancellations in modelling effects and some of the major systematic uncertainties. These measurements are sensitive to new phenomena, and provide a mechanism to easily set constraints on phenomenological models. To illustrate the robustness of the approach, these ratios are compared with two common Dark Matter models, where the constraints derived from the measurement are comparable to those set by dedicated detector-level searches