98 research outputs found

    Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: Two randomised, double-blind, phase 3, non-inferiority trials

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    none27siBackground Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. Methods In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov, numbers NCT01780506 and NCT01797445. Findings We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI -0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change -3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change -1·30 vs -2·86; p<0·0001) and hip (-0·66 vs -2·95; p<0·0001) at 48 weeks. Interpretation Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Funding Gilead Sciences.openSax, Paul E; Wohl, David; Yin, Michael T.; Post, Frank; Dejesus, Edwin; Saag, Michael; Pozniak, Anton; Thompson, Melanie; Podzamczer, Daniel; Molina, Jean Michel; Oka, Shinichi; Koenig, Ellen; Trottier, Benoit; Andrade-Villanueva, Jaime; Crofoot, Gordon; Custodio, Joseph M.; Plummer, Andrew; Zhong, Lijie; Cao, Huyen; Martin, Hal; Callebaut, Christian; Cheng, Andrew K.; Fordyce, Marshall W.; Mccallister, Scott; for the GS-US-292-0104/0111 Study Team [...; Pierluigi Viale; ...]Sax, Paul E; Wohl, David; Yin, Michael T.; Post, Frank; Dejesus, Edwin; Saag, Michael; Pozniak, Anton; Thompson, Melanie; Podzamczer, Daniel; Molina, Jean Michel; Oka, Shinichi; Koenig, Ellen; Trottier, Benoit; Andrade-Villanueva, Jaime; Crofoot, Gordon; Custodio, Joseph M.; Plummer, Andrew; Zhong, Lijie; Cao, Huyen; Martin, Hal; Callebaut, Christian; Cheng, Andrew K.; Fordyce, Marshall W.; Mccallister, Scott; for the GS-US-292-0104/0111 Study Team [..; Pierluigi Viale; ..

    The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

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    The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

    Mechanical stability of the CMS strip tracker measured with a laser alignment system

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    Observation of top quark pairs produced in association with a vector boson in pp collisions at s=8 √s=8TeV

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    Measurements of the cross sections for top quark pairs produced in association with a W or Z boson are presented, using 8 TeV pp collision data corresponding to an integrated luminosity of 19.5 fb −1 , collected by the CMS experiment at the LHC. Final states are selected in which the associated W boson decays to a charged lepton and a neutrino or the Z boson decays to two charged leptons. Signal events are identified by matching reconstructed objects in the detector to specific final state particles from t t ¯ W tt¯W or t t ¯ Z tt¯Z decays. The t t ¯ W tt¯W cross section is measured to be 382 − 102 + 117 fb with a significance of 4.8 standard deviations from the background-only hypothesis. The t t ¯ Z tt¯Z cross section is measured to be 242 − 55 + 65 fb with a significance of 6.4 standard deviations from the background-only hypothesis. These measurements are used to set bounds on five anomalous dimension-six operators that would affect the t t ¯ W tt¯W and t t ¯ Z tt¯Z cross sections

    Search for Resonant Production of High-Mass Photon Pairs in Proton-Proton Collisions at root s=8 and 13 TeV

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    Angular analysis of the decay B-0 -> K*(0)mu(+)mu(-) from pp collisions at root s=8 TeV

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    Search for supersymmetry in events with a photon, a lepton, and missing transverse momentum in pp collisions at root s=8 TeV

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    Search for a charged Higgs boson in pp collisions at root s=8 TeV

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    Transverse momentum spectra of inclusive b jets in pPb collisions atv root s(NN)=5.02 TeV

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    Reconstruction and identification of τ lepton decays to hadrons and ντ at CMS

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    This paper describes the algorithms used by the CMS experiment to reconstruct and identify tau -> hadrons + nu(tau) decays during Run 1 of the LHC. The performance of the algorithms is studied in proton-proton collisions recorded at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The algorithms achieve an identification efficiency of 50-60%, with misidentification rates for quark and gluon jets, electrons, and muons between per mille and per cent levels
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