Cost-effectiveness analysis of atezolizumab in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen: a United Kingdom health care perspective

BackgroundCost-effectiveness of atezolizumab, as a treatment for advanced non-small-cell lung cancer (NSCLC) patients who cannot receive a platinum-containing regimen,was still unknown. Our objective was to evaluate the cost-effectiveness of atezolizumab vs. chemotherapy in this indication from the perspective of UK healthcare system.MethodsFrom the global, randomised, open-label, phase III IPSOS trial, clinical inputs and patient characteristics were obtained. A partitioned survival model with three health states was built: Progression-free survival, progressed disease and death. A lifetime time horizon was applied, with an annual discount rate of 3.5%. Additionally, the willingness-to-pay threshold of £50,000/QALY was utilized. Primary outcomes were quality-adjusted life-year (QALY), costs, and incremental cost-effectiveness ratio (ICER). Sensitivity, scenario, and subgroup analyses were used to assess the reliability of base-case results. Price simulations were carried out in order to provide information for the pricing strategy at specific willingness-to-pay threshold.ResultsIn the base-case analysis, atezolizumab resulted in a gain of 0.28 QALYs and an ICER of £94,873/QALY compared to chemotherapy, demonstrating no cost-effectiveness. Price simulation results revealed that atezolizumab would be preferred at a price lower than £2,215 (a reduction of 41.8%) at the willingness-to-pay threshold of £50,000. Sensitivity, scenario and subgroup analyses revealed these conclusions were generally robust, the model was most sensitive to the price of atezolizumab and subsequent medication. Furthermore, atezolizumab was found to be more cost-effective for patients displaying a positive PD-L1 expression, with an ICER of £72,098/QALY as compared to chemotherapy.ConclusionAtezolizumab is not cost-effective for patients with advanced NSCLC ineligible for platinum-containing regimen, potential price reduction is necessary

Physiological dynamics as indicators of plant response to manganese binary effect

IntroductionHeavy metals negatively affect plant physiology. However, plants can reduce their toxicity through physiological responses. Broussonetia papyrifera is a suitable candidate tree for carrying out the phytoremediation of manganese (Mn)-contaminated soil.MethodsConsidering that Mn stress typically exerts a binary effect on plants, to reveal the dynamic characteristics of the physiological indexes of B. papyrifera to Mn stress, we conducted pot experiments with six different Mn concentrations (0, 0.25, 0.5, 1, 2, and 5 mmol/L) for 60 days. In addition to the chlorophyll content, malondialdehyde (MDA), proline (PRO), soluble sugar, superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the absorption and transfer characteristics of Mn, and root structure were also measured.ResultsPhytoremedial potential parameters such as the bioconcentration factor (BCF) and translocation factor (TF) displayed an increasing trend with the increase of Mn concentration. At lower Mn concentrations (<0.5 mmol/L), the TF value was <1 but crossed 1 when the Mn concentration exceeded 100 mmol/L. The Mn distribution in various tissues was in the following order: leaf > stem > root. The root structure analysis revealed that low-level concentrations of Mn (1 mmol/L) promoted root development. Mn concentration and stress duration had significant effects on all measured physiological indexes, and except soluble sugar, Mn concentration and stress time displayed a significant interaction on the physiological indexes.DiscussionOur study demonstrates that the physiological indexes of B. papyrifera display dynamic characteristics under Mn stress. Thus, during the monitoring process of Mn stress, it appears to be necessary to appropriately select sampling parts according to Mn concentration

Native defect association in beta-Ga2O3 enables room-temperature p-type conductivity

The room temperature hole conductivity of the ultra wide bandgap semiconductor beta Ga2O3 is a pre-requisite for developing the next-generation electronic and optoelectronic devices based on this oxide. In this work, high-quality p-type beta-Ga2O3 thin films grown on r-plane sapphire substrate by metalorganic chemical vapor deposition (MOCVD) exhibit Rho = 50000Ohm.cm resistivity at room temperature. A low activation energy of conductivity as Ea2=170 meV was determined, associated to the oxygen - gallium native acceptor defect complex. Further, taking advantage of cation (Zn) doping, the conductivity of Ga2O3:Zn film was remarkably increased by three orders of magnitude, showing a long-time stable room-temperature hole conductivity with the conductivity activation energy of around 86 meV.Comment: 21pages; 9figure

Ultrafast Structural Dynamics along the β − γ Phase Transition Path in MnAs

International audienceWe investigate the orthorhombic distortion and the structural dynamics of epitaxial MnAs layers on GaAs(001) using static and time-resolved x-ray diffraction. Laser-induced intensity oscillations of Bragg reflections allow us to identify the optical phonon associated with orthorhombic distortion and to follow its softening along the path towards an undistorted phase of hexagonal symmetry. The frequency of this mode falls in the THz range, in agreement with recent calculations. Incomplete softening suggests that the $\beta-\gamma$ transformation deviates from a purely second-order displacive transition

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

Search for charged Higgs bosons in decays of top quarks in p-pbar collisions at sqrt(s) = 1.96 TeV

7 pages, 2 figuresWe report the recent charged Higgs search in top quark decays in 2.2/fb CDF data. This is the first attempt to search for charged Higgs using fully reconstructed mass assuming H->c-sbar in small tan beta region. No evidence of a charged Higgs is observed in the CDF data, hence 95% upper limits are placed at B(t->H+b)We report on the first direct search for charged Higgs bosons decaying into cs̅ in tt̅ events produced by pp̅ collisions at √s=1.96  TeV. The search uses a data sample corresponding to an integrated luminosity of 2.2  fb-1 collected by the CDF II detector at Fermilab and looks for a resonance in the invariant mass distribution of two jets in the lepton+jets sample of tt̅ candidates. We observe no evidence of charged Higgs bosons in top quark decays. Hence, 95% upper limits on the top quark decay branching ratio are placed at B(t→H+b)< 0.1 to 0.3 for charged Higgs boson masses of 60 to 150  GeV/c2 assuming B(H+→cs̅ )=1.0. The upper limits on B(t→H+b) are also used as model-independent limits on the decay branching ratio of top quarks to generic scalar charged bosons beyond the standard model.Peer reviewe

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Transverse-momentum and pseudorapidity distributions of charged hadrons in pp collisions at √s=0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at root s = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(ch)/d eta vertical bar(vertical bar eta vertical bar and pp collisions. The results at 2.36 TeV represent the highest-energy measurements at a particle collider to date