An evaluation of the effects of the European Commission's proposals for the Common Consolidated Corporate Tax Base

This paper evaluates the Common Consolidated Corporate Tax Base (CCCTB) recently proposed by the European Commission. We find that if the CCCTB is introduced as it is currently proposed (including loss consolidation), then it is likely to impose large tax revenue costs of about one fifth of the corporate tax base. Second, we show that an application of the CCCTB proposals at only the European Union (EU) level would overlook the extent of profit shifting out of the EU and could lock in further unnecessary revenue losses. Third, major EU profit-shifting countries such as Luxembourg, Ireland and the Netherlands may experience significant revenue losses. Based on our analysis, the main policy recommendation is to consider extending the approach to a worldwide system, which would simultaneously deal with profit shifting within and out of the EU, and appears to offer the best prospect for revenue-positive, welfare-enhancing reform. For this to be viable, an immediate priority is to collate cross-country-comparable data and provide precise assessments of the range of policy scenarios

Design and Baseline Characteristics of Participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) Trial of Dulaglutide's Cardiovascular Effects

DigitalThe aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.Ciencias Médicas y de la Salu

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Impact of gender on event rates at 1 year in patients with newly diagnosed non-valvular atrial fibrillation: contemporary perspective from the GARFIELD-AF registry.

OBJECTIVES: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) explored the impact of gender, risk factors and anticoagulant (AC) treatment on 1-year outcomes in patients with non-valvular atrial fibrillation (NVAF). DESIGN: GARFIELD-AF is a prospective non-interventional registry. SETTING: Investigator sites (n=1048) are representative of the care settings/locations in each of the 35 countries. PARTICIPANTS: Patients ≥18yrs with newly diagnosed (≤6 weeks' duration) NVAF and ≥1 investigator-determined stroke risk factors. MAIN OUTCOME MEASURES: Event rates per 100 person-years were estimated from the Poisson model and HRs and 95% CIs calculated. RESULTS: Of 28 624 patients (women 44.4%; men 55.6%) enrolled, there were more elderly (≥75 years) women (46.9%) than men (30.4%). All-cause mortality rates per 100 person-years (95% CI) for women and men were 4.48 (4.12 to 4.87) and 4.04 (3.74 to 4.38), respectively, stroke/systemic embolism (SE) (1.62 (1.41 to 1.87) and 1.17 (1.01 to 1.36)) and major bleeding (0.93 (0.78 to 1.13) and 0.79 (0.66 to 0.95)). After adjustment for baseline risk factors in treated and untreated patients, HRs (95% CI) for women (relative to men) for stroke/SE rates were 1.3-fold higher in women (HR 1.30 (1.04 to 1.63)), and similar for major bleeding (1.13 (0.85 to 1.50)) and all-cause mortality (1.05 (0.92 to 1.19)). Antithrombotic treatment patterns in men and women were almost identical. 63.8% women and 62.9% men received AC± antiplatelets. Relative to no AC treatment, the reduction in stroke/SE rates with AC treatment was greater (p=0.01) in men (HR 0.45 (0.33 to 0.61)) than women 0.77 (0.57 to 1.03). All-cause mortality reduction with AC treatment was similar (women: 0.65 (0.54 to 0.77); men: 0.57 (0.48 to 0.68)). The risk of major bleeding when treated with AC versus no AC was 2.33 (1.41 to 3.84) in men and 1.86 (1.16 to 2.99) in women (p value=0.53). CONCLUSIONS: Women have a higher risk of stroke/SE and the reduction in stroke/SE events rates with AC treatment is less in women than in men. TRIAL REGISTRATION NUMBER: NCT01090362

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data

OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up.Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION ClinicalTrials.gov NCT01090362