Mechanical thrombectomy in patients with acute ischemic stroke: A cost-effectiveness and value of implementation analysis

BACKGROUND Recent clinical trials have demonstrated the efficacy of mechanical thrombectomy in acute ischemic stroke. AIMS To determine the cost-effectiveness, value of future research, and value of implementation of mechanical thrombectomy. METHODS Using UK clinical and cost data from the Pragmatic Ischemic Stroke Thrombectomy Evaluation (PISTE) trial, we estimated the cost-effectiveness of mechanical thrombectomy over time horizons of 90-days and lifetime, based on a decision-analytic model, using all existing evidence. We performed a meta-analysis of seven clinical trials to estimate treatment effects. We used sensitivity analysis to address uncertainty. Value of implementation analysis was used to estimate the potential value of additional implementation activities to support routine delivery of mechanical thrombectomy. RESULTS Over the trial period (90 days), compared with best medical care alone, mechanical thrombectomy incurred an incremental cost of £5207 and 0.025 gain in QALY (incremental cost-effectiveness ratio (ICER) £205,279), which would not be considered cost-effective. However, mechanical thrombectomy was shown to be cost-effective over a lifetime horizon, with an ICER of £3466 per QALY gained. The expected value of perfect information per patient eligible for mechanical thrombectomy in the UK is estimated at £3178. The expected value of full implementation of mechanical thrombectomy is estimated at £1.3 billion over five years. CONCLUSION Mechanical thrombectomy was cost-effective compared with best medical care alone over a patient’s lifetime. On the assumption of 30% implementation being achieved throughout the UK healthcare system, we estimate that the population health benefits obtained from this treatment are greater than the cost of implementation

An analysis of the temperature dependence of force, during steady shortening at different velocities, in (mammalian) fast muscle fibres

We examined, over a wide range of temperatures (10–35°C), the isometric tension and tension during ramp shortening at different velocities (0.2–4 L0/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L0) was 2.2 mm and sarcomere length ~2.5 μm. During a ramp shortening, the tension change showed an initial inflection of small amplitude (P1), followed by a larger exponential decline towards an approximate steady level; the tension continued to decline slowly afterwards and the approximate steady tension at a given velocity was estimated as the tension (P2) at the point of intersection between two linear slopes, as previously described (Roots et al. 2007). At a given temperature, the tension P2 declined to a lower level and at a faster rate (from an exponential curve fit) as the shortening velocity was increased; the temperature sensitivity of the rate of tension decline during ramp shortening at different velocities was low (Q10 0.9–1.5). The isometric tension and the P2 tension at a given shortening velocity increased with warming so that the relation between tension and (reciprocal) temperature was sigmoidal in both. In isometric muscle, the temperature T0.5 for half-maximal tension was ~10°C, activation enthalpy change (∆H) was ~100 kJ mol−1 and entropy change (∆S) ~350 J mol−1 K−1. In shortening, these were increased with increase of velocity so that at a shortening velocity (~4 L0/s) producing maximal power at 35°C, T0.5 was ~28°C, ∆H was ~200 kJ mol−1 and ∆S ~ 700 J mol−1 K−1; the same trends were seen in the tension data from isotonic release experiments on intact muscle and in ramp shortening experiments on maximally Ca-activated skinned fibres. In general, our findings show that the sigmoidal relation between force and temperature can be extended from isometric to shortening muscle; the implications of the findings are discussed in relation to the crossbridge cycle. The data indicate that the endothermic, entropy driven process that underlies crossbridge force generation in isometric muscle (Zhao and Kawai 1994; Davis, 1998) is even more pronounced in shortening muscle, i.e. when doing external work

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial.

OBJECTIVE: The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). DESIGN: Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0-2 at day 90. RESULTS: Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13-21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0-1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0-2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). CONCLUSIONS: The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival. TRIAL REGISTRATION NUMBER: NCT01745692; Results

Prevalence and gender distribution of the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>The Metabolic syndrome (MetS) is a cardiovascular risk factor of public health significance and of recent has become a topical issue. The prevalence of diabetes mellitus (DM) is on the increase and with this scenario, a possible increase in burden of DM which may be largely attributed to cardiovascular complications is expected. The objective of this report is to determine the prevalence of the MetS and compare gender characteristics in subjects with type 2 DM.</p> <p>Methods</p> <p>Subjects with type 2 DM were recruited from an urban hospital for the study. Clinical data was obtained by interviewing the patients and referring to their Case folders. The anthropometric indices and blood pressure measurements were documented. Laboratory parameters analysed for included total cholesterol, high density and low density cholesterol, triglyceride and glycosylated haemoglobin. Statistical analysis included usage of Student's t test and chi square.</p> <p>Results</p> <p>963 patients with type 2 DM aged between 35-85 years were recruited for the study. The main outcome measures included the prevalence of the metabolic syndrome and the gender differences of its components. The prevalence of the metabolic syndrome was 86%. The frequency of occurrence of the MetS was similar for men (83%) and women (86%) and increased with age in both sexes. The prevalence of MetS increased from 11% among participants aged 20 through 29 years to 89% in participants aged 70 through 79. In our patients with DM, the commonest occurring and least detected MetS defining parameters are central obesity and elevated triglyceride levels respectively. The components of the MetS that differed significantly in both sexes was HDL-C. The combination of the components of the MetS were comparable in both genders and 5.8% of the subjects with the MetS had all components of the MetS.</p> <p>Conclusion</p> <p>The prevalence of the MetS in type 2DM is high in both genders and increases with age thus posing a potential high cardiovascular risk in this group of patients. The modifiable risk factors for the MetS should be a focus point in the management of subjects with type 2 DM,</p

Measurement of the hadronic photon structure function F_{2}^{γ} at LEP2

The hadronic structure function of the photon F_{2}^{γ} (x, Q²) is measured as a function of Bjorken x and of the photon virtuality Q² using deep-inelastic scattering data taken by the OPAL detector at LEP at e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. Previous OPAL measurements of the x dependence of F_{2}^{γ} are extended to an average Q² of 〈Q²〉=780 GeV² using data in the kinematic range 0.15<x<0.98. The Q² evolution of F_{2}^{γ} is studied for 12.1<〈Q²〉<780 GeV² using three ranges of x. As predicted by QCD, the data show positive scaling violations in F_{2}^{γ} with F_{2}^{γ} (Q²)/α = (0.08±0.02⁺⁰·⁰⁵_₀.₀₃) + (0.13±0.01⁺⁰·⁰¹_₀.₀₁) lnQ², where Q² is in GeV², for the central x region 0.10–0.60. Several parameterisations of F_{2}^{γ} are in qualitative agreement with the measurements whereas the quark-parton model prediction fails to describe the data

Measurement of the charm structure function F_{2,c)^{γ} of the photon at LEP

The production of charm quarks is studied in deep-inelastic electron–photon scattering using data recorded by the OPAL detector at LEP at nominal e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. The charm quarks have been identified by full reconstruction of charged D* mesons using their decays into D⁰π with the D⁰ observed in two decay modes with charged particle final states, Kπ and Kπππ. The cross-section σ^{D*} for production of charged D* in the reaction e⁺e⁻→e⁺e⁻D*Χ is measured in a restricted kinematical region using two bins in Bjorken x, 0.00140.1 the perturbative QCD calculation at next-to-leading order agrees perfectly with the measured cross-section. For x<0.1 the measured cross-section is 43.8±14.3±6.3±2.8 pb with a next-to-leading order prediction of 17.0⁺²·⁹_₂.₃ pb

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Measurement of triple gauge boson couplings from W⁺W⁻ production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb⁻¹. After combining with our previous measurements at centre-of-mass energies of 161–183 GeV we obtain κ = 0.97_{-0.16}^{+0.20}, g_{1}^{z} = 0.991_{-0.057}^{+0.060} and λ = -0.110_{-0.055}^{+0.058}, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their Standard Model values. These results are consistent with the Standard Model expectations

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol