Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae.

Comparison of the epidemiology, clinical characteristics, and mortality of patients with bloodstream infections (BSI) caused by extended-spectrum \u3b2-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) versus ESBL-producing Klebsiella pneumoniae (ESBL-KP

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Correlated long-range mixed-harmonic fluctuations measured in pp, p+Pb and low-multiplicity Pb+Pb collisions with the ATLAS detector

For abstract see published article

Performance of top-quark and W -boson tagging with ATLAS in Run 2 of the LHC

The performance of identification algorithms (“taggers”) for hadronically decaying top quarks and W bosons in pp collisions at √s=13 TeV recorded by the ATLAS experiment at the Large Hadron Collider is presented. A set of techniques based on jet shape observables are studied to determine a set of optimal cut-based taggers for use in physics analyses. The studies are extended to assess the utility of combinations of substructure observables as a multivariate tagger using boosted decision trees or deep neural networks in comparison with taggers based on two-variable combinations. In addition, for highly boosted top-quark tagging, a deep neural network based on jet constituent inputs as well as a re-optimisation of the shower deconstruction technique is presented. The performance of these taggers is studied in data collected during 2015 and 2016 corresponding to 36.1 fb −1 for the tt ¯ and γ+jet and 36.7 fb −1 −1 for the dijet event topologies

In situ calibration of large-radius jet energy and mass in 13 TeV proton–proton collisions with the ATLAS detector

The response of the ATLAS detector to largeradius jets is measured in situ using 36.2 fb−1 of √s = 13 TeV proton–proton collisions provided by the LHC and recorded by the ATLAS experiment during 2015 and 2016. The jet energy scale is measured in events where the jet recoils against a reference object, which can be either a calibrated photon, a reconstructed Z boson, or a system of well-measured small-radius jets. The jet energy resolution and a calibration of forward jets are derived using dijet balance measurements. The jet mass response is measured with two methods: using mass peaks formed by W bosons and top quarks with large transverse momenta and by comparing the jet mass measured using the energy deposited in the calorimeter with that using the momenta of charged-particle tracks. The transversemomentum and mass responses in simulations are found to be about 2–3% higher than in data. This difference is adjusted for with a correction factor. The results of the different methods are combined to yield a calibration over a large range of transverse momenta (pT). The precision of the relative jet energy scale is 1–2% for 200 GeV < pT < 2 TeV, while that of the mass scale is 2–10%. The ratio of the energy resolutions in data and simulation is measured to a precision of 10–15% over the same pT range

Measurement of the photon identification efficiencies with the ATLAS detector using LHC Run 2 data collected in 2015 and 2016

The efficiency of the photon identification criteria in the ATLAS detector is measured using 36.1 fb1 to 36.7 fb1 of pp collision data at s√=13 TeV collected in 2015 and 2016. The efficiencies are measured separately for converted and unconverted isolated photons, in four different pseudorapidity regions, for transverse momenta between 10 GeV and 1.5 TeV. The results from the combination of three data-driven techniques are compared with the predictions from simulation after correcting the variables describing the shape of electromagnetic showers in simulation for the average differences observed relative to data. Data-to-simulation efficiency ratios are determined to account for the small residual efficiency differences. These factors are measured with uncertainties between 0.5% and 5% depending on the photon transverse momentum and pseudorapidity. The impact of the isolation criteria on the photon identification efficiency, and that of additional soft pp interactions, are also discussed. The probability of reconstructing an electron as a photon candidate is measured in data, and compared with the predictions from simulation. The efficiency of the reconstruction of photon conversions is measured using a sample of photon candidates from Z→μμγ events, exploiting the properties of the ratio of the energies deposited in the first and second longitudinal layers of the ATLAS electromagnetic calorimeter

Clinical presentation and outcome of venous thromboembolism in COPD

Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known. The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2,984 COPD patients and 25,936 non-COPD patients included in the RIETE (Registro Informatizado de la Enfermedad TromboEmb\uf3lica) registry. This ongoing international, multi-centre registry includes patients with proven symptomatic PE or DVT. PE was the more frequent VTE presentation in COPD patients (n = 1,761, 59%). PE presentation was more significantly associated with COPD patients than non-COPD patients (OR 1.64, 95% CI 1.49-1.80). During the 3-month follow-up, mortality (10.8% versus 7.6%), minor bleeding (4.5% versus 2.3%) or first VTE recurrences as PE (1.5% versus 1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the most common cause of death. COPD patients presented more frequently with PE than DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed

Thrombolytic therapy and outcome of patients with an acute symptomatic pulmonary embolism

BACKGROUND: While the primary therapy for most patients with a pulmonary embolism (PE) consists of anticoagulation, the efficacy of thrombolysis relative to standard therapy remains unclear. METHODS: In this retrospective cohort study of 15,944 patients with an objectively confirmed symptomatic acute PE, identified from the multicenter, international, prospective, Registro Informatizado de la Enfermedad TromboEmb\uf3lica (RIETE registry), we aimed to assess the association between thrombolytic therapy and all-cause mortality during the first 3 months after the diagnosis of a PE. After creating two subgroups, stratified by systolic blood pressure (SBP) (< 100 mm Hg vs. other), we used propensity score-matching for a comparison of patients who received thrombolysis to those who did not in each subgroup. RESULTS: Patients who received thrombolysis were younger, had fewer comorbid diseases and more signs of clinical severity compared with those who did not receive it. In the subgroup with systolic hypotension, analysis of propensity score-matched pairs (n = 94 pairs) showed a non-statistically significant but clinically relevant lower risk of death for thrombolysis compared with no thrombolysis (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.36-1.46; P = 0.37). In the normotensive subgroup, analysis of propensity score-matched pairs (n = 217 pairs) showed a statistically significant and clinically meaningful increased risk of death for thrombolysis compared with no thrombolysis (OR 2.32; 95% CI, 1.15-4.68; P = 0.018). When we imputed data for missing values for echocardiography and troponin tests in the group of normotensive patients, we no longer detected the increased risk of death associated with thrombolytic therapy. CONCLUSIONS: In normotensive patients with acute symptomatic PE, thrombolytic therapy is associated with a higher risk of death than no thrombolytic therapy. In hemodynamically unstable patients, thrombolytic therapy is possibly associated with a lower risk of death than no thrombolytic therapy. However, study design limitations do not imply a causal relationship between thrombolytics and outcome

Suicidal ideation in a European Huntington's disease population

Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD. METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis. RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive. LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated. CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines