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1.
  • Micah, Angela E., et al. (författare)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Forskningsöversikt (refereegranskat)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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2.
  • Ramírez-Tannus, M. C., et al. (författare)
  • The young stellar content of the giant H ii regions M8, G333.6 0.2, and NGC6357 with VLT/KMOS
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 633
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The identification and characterisation of populations of young massive stars in (giant) HII regions provides important constraints on (i) the formation process of massive stars and their early feedback on the environment, and (ii) the initial conditions for population synthesis models predicting the evolution of ensembles of stars. Aims. We identify and characterise the stellar populations of the following young giant HII regions: M 8, G333.6-0.2, and NGC 6357. Methods. We have acquired H- and K-band spectra of around 200 stars using the K-band Multi Object Spectrograph on the ESO Very Large Telescope. The targets for M 8 and NGC 6357 were selected from the Massive Young Star-Forming Complex Study in Infrared and X-ray (MYStIX), which combines X-ray observations with near-infrared (NIR) and mid-infrared data. For G333.6-0.2, the sample selection is based on the NIR colours combined with X-ray data. We introduce an automatic spectral classification method in order to obtain temperatures and luminosities for the observed stars. We analysed the stellar populations using their photometric, astrometric, and spectroscopic properties and compared the position of the stars in the Hertzprung-Russell diagram with stellar evolution models to constrain their ages and mass ranges. Results. We confirm the presence of candidate ionising sources in the three regions and report new ones, including the first spectroscopically identified O stars in G333.6-0.2. In M 8 and NGC 6357, two populations are identified: (i) OB main-sequence stars (M> 5 M-circle dot) and (ii) pre-main sequence stars (M approximate to 0.5 - 5M(circle dot)). The ages of the clusters are similar to 1-3 Myr, < 3 Myr, and similar to 0.5-3 Myr for M 8, G333.6-0.2, and NGC 6357, respectively. We show that MYStIX selected targets have > 90% probability of being members of the HII region, whereas a selection based on NIR colours leads to a membership probability of only similar to 70%.
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3.
  • Lopes, Renato D., et al. (författare)
  • Digoxin and Mortality in Patients With Atrial Fibrillation
  • 2018
  • Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:10, s. 1063-1074
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration $ 1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations $ 1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
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4.
  • Ramírez-Tannus, M. C., et al. (författare)
  • A relation between the radial velocity dispersion of young clusters and their age : Evidence for hardening as the formation scenario of massive close binaries
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of massive stars (> 8 M-circle dot) in OB associations are found in close binary systems. Nonetheless, the formation mechanism of these close massive binaries is not understood yet. Using literature data, we measured the radial-velocity dispersion (sigma (1D)) as a proxy for the close binary fraction in ten OB associations in the Galaxy and the Large Magellanic Cloud, spanning an age range from 1 to 6 Myr. We find a positive trend of this dispersion with the cluster's age, which is consistent with binary hardening. Assuming a universal binary fraction of f(bin) = 0.7, we converted the sigma (1D) behavior to an evolution of the minimum orbital period P-cutoff from similar to 9.5 years at 1 Myr to similar to 1.4 days for the oldest clusters in our sample at similar to 6 Myr. Our results suggest that binaries are formed at larger separations, and they harden in around 1 to 2 Myr to produce the period distribution observed in few million year-old OB binaries. Such an inward migration may either be driven by an interaction with a remnant accretion disk or with other young stellar objects present in the system. Our findings constitute the first empirical evidence in favor of migration as a scenario for the formation of massive close binaries.
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5.
  • Alexander, John H, et al. (författare)
  • Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine : A Secondary Analysis of a Randomized Clinical Trial
  • 2016
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 1:6, s. 673-681
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.OBJECTIVE: To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.DESIGN, SETTING, AND PARTICIPANTS: Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016.MAIN OUTCOMES AND MEASURES: Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat.RESULTS: Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance.CONCLUSIONS AND RELEVANCE: Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00412984.
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6.
  • Fanaroff, Alexander C., et al. (författare)
  • Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials : A Pooled Analysis of 9259 Deaths in 9 Trials
  • 2019
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 139:7, s. 863-873
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.
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7.
  • Hohnloser, Stefan H., et al. (författare)
  • Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight : Insights From the ARISTOTLE Trial
  • 2019
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 139:20, s. 2292-2300
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (> 120 kg) or low (= 60 kg) body weight because of a lack of data in these populations.METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n= 18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (= 60, > 60-120, > 120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding.RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (= 60 kg), 15 172 (83.6%) were in the midrange weight group (> 60-120 kg), and 982 (5.4%) were in the high-weight group (> 120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value> 0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (= 60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (> 60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value= 0.016).CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low-(= 60 kg) and highweight patients (> 120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low-and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight.
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8.
  • Lopes, Renato D., et al. (författare)
  • Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation : a secondary analysis of a randomised controlled trial
  • 2012
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9855, s. 1749-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. Methods ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2.0-3.0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. Findings Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or >= 3, p for interaction=0.4457; or CHA(2)DS(2)VASc 1, 2, or >= 3, p for interaction=0.1210) or bleeding (HAS-BLED 0-1, 2, or >= 3, p for interaction=0.9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0.4018; CHA(2)DS(2)VASc, p for interaction=0.2059; HAS-BLED, p for interaction=0.7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0.22, 95% CI 0.10-0.48) than in those with HAS-BLED scores of 0-1 (HR 0.66, 0.39-1.12; p for interaction=0.0604). Interpretation Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.
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9.
  • Patat, F., et al. (författare)
  • Optical atmospheric extinction over Cerro Paranal
  • 2011
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 527
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The present study was conducted to determine the optical extinction curve for Cerro Paranal under typical clear-sky observing conditions, with the purpose of providing the community with a function to be used to correct the observed spectra, with an accuracy of 0.01 mag airmass(-1). Additionally, this work was meant to analyze the variability of the various components, to derive the main atmospheric parameters, and to set a term of reference for future studies, especially in view of the construction of the Extremely Large Telescope on the nearby Cerro Armazones. Methods. The extinction curve of Paranal was obtained through low-resolution spectroscopy of 8 spectrophotometric standard stars observed with FORS1 mounted at the 8.2 m Very Large Telescope, covering a spectral range 3300-8000 angstrom. A total of 600 spectra were collected on more than 40 nights distributed over six months, from October 2008 to March 2009. The average extinction curve was derived using a global fit algorithm, which allowed us to simultaneously combine all the available data. The main atmospheric parameters were retrieved using the LBLRTM radiative transfer code, which was also utilised to study the impact of variability of the main molecular bands of O-2, O-3, and H2O, and to estimate their column densities. Results. In general, the extinction curve of Paranal appears to conform to those derived for other astronomical sites in the Atacama desert, like La Silla and Cerro Tololo. However, a systematic deficit with respect to the extinction curve derived for Cerro Tololo before the El Chichon eruption is detected below 4000 angstrom. We attribute this downturn to a non standard aerosol composition, probably revealing the presence of volcanic pollutants above the Atacama desert. An analysis of all spectroscopic extinction curves obtained since 1974 shows that the aerosol composition has been evolving during the last 35 years. The persistence of traces of non meteorologic haze suggests the effect of volcanic eruptions, like those of El Chichon and Pinatubo, lasts several decades. The usage of the standard CTIO and La Silla extinction curves implemented in IRAF and MIDAS produce systematic over/under-estimates of the absolute flux.
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10.
  • Ramirez-Tannus, M. C., et al. (författare)
  • Massive pre-main-sequence stars in M17
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 604
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation process of massive stars is still poorly understood. Massive young stellar objects (mYSOs) are deeply embedded in their parental clouds; these objects are rare, and thus typically distant, and their reddened spectra usually preclude the determination of their photospheric parameters. M17 is one of the best-studied H i i regions in the sky, is relatively nearby, and hosts a young stellar population. We have obtained optical to near-infrared spectra of previously identified candidate mYSOs and a few OB stars in this region with X-shooter on the ESO Very Large Telescope. The large wavelength coverage enables a detailed spectroscopic analysis of the photospheres and circumstellar disks of these candidate mYSOs. We confirm the pre-main-sequence (PMS) nature of six of the stars and characterise the O stars. The PMS stars have radii that are consistent with being contracting towards the main sequence and are surrounded by a remnant accretion disk. The observed infrared excess and the double-peaked emission lines provide an opportunity to measure structured velocity profiles in the disks. We compare the observed properties of this unique sample of young massive stars with evolutionary tracks of massive protostars and propose that these mYSOs near the western edge of the H i i region are on their way to become main-sequence stars (similar to 6-20 M-circle dot) after having undergone high mass accretion rates ((M) over dot(acc) similar to 10(-4)-10(3) M-circle dot yr(-1)). Their spin distribution upon arrival at the zero age main-sequence is consistent with that observed for young B stars, assuming conservation of angular momentum and homologous contraction.
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11.
  • van Gelder, M. L., et al. (författare)
  • VLT/X-shooter spectroscopy of massive young stellar objects in the 30 Doradus region of the Large Magellanic Cloud
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
  • Tidskriftsartikel (refereegranskat)abstract
    • The process of massive star (M >= 8 M-circle dot) formation is still poorly understood. Observations of massive young stellar objects (MYSOs) are challenging due to their rarity, short formation timescale, large distances, and high circumstellar extinction. Here, we present the results of a spectroscopic analysis of a population of MYSOs in the Large Magellanic Cloud. We took advantage of the spectral resolution and wavelength coverage of X-shooter (300-2500 nm), which is mounted on the European Southern Observatory Very Large Telescope, to detect characteristic spectral features in a dozen MYSO candidates near 30 Doradus, the largest starburst region in the Local Group hosting the most massive stars known. The X-shooter spectra are strongly contaminated by nebular emission. We used a scaling method to subtract the nebular contamination from our objects. We detect H alpha, beta, [OI] 630.0 nm, CaII, infrared triplet [FeII] 1643.5 nm, fluorescent FeII 1687.8 nm, H-2 2121.8 nm, Br gamma, and CO bandhead emission in the spectra of multiple candidates. This leads to the spectroscopic confirmation of ten candidates as bona fide MYSOs. We compared our observations with photometric observations from the literature and find all MYSOs to have a strong near-infrared excess. We computed lower limits to the brightness and luminosity of the MYSO candidates, confirming the near-infrared excess and the massive nature of the objects. No clear correlation is seen between the Br gamma luminosity and metallicity. Combining our sample with other LMC samples results in a combined detection rate of disk features, such as fluorescent FeII and CO bandheads, which is consistent with the Galactic rate (40%). Most of our MYSOs show outflow features.
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12.
  • Vinereanu, Dragos, et al. (författare)
  • Heart rate and death and hospitalization for heart failure in patients with persistent or permanent atrial fibrillation : Insights from the ARISTOTLE trial
  • 2023
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 265, s. 132-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations.
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15.
  • Al-Khatib, Sana M., et al. (författare)
  • Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation : results from the ARISTOTLE trial
  • 2013
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:31, s. 2464-2471
  • Tidskriftsartikel (refereegranskat)abstract
    • It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF). A total of 18 201 patients with AF [2786 (15.3) with paroxysmal and 15 412 (84.7) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction 0.71), all-cause mortality (P for interaction 0.75), and major bleeding (P for interaction 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions 0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98; P 0.003, adjusted P 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81; P 0.0002, adjusted P 0.066). The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.
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16.
  • Alexander, Karen P, et al. (författare)
  • Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity : Insights from the ARISTOTLE trial
  • 2019
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 208, s. 123-131
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.
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17.
  • Almasri, Nihad A., et al. (författare)
  • Functional profiles of children with cerebral palsy in Jordan based on the association between gross motor function and manual ability
  • 2018
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood. A major challenge for delivering effective services for children with CP is the heterogeneity of the medical condition. Categorizing children into homogeneous groups based on functional profiles is expected to improve service planning. The aims of this study were to (1) to describe functional profiles of children with CP based on the Gross Motor Function Classification System-Expanded & Revised (GMFCS-E & R) and the Manual Ability Classification System (MACS); and (2) to examine associations and agreements between the GMFCS-E & R and the MACS for all participants then for subgroups based on subtypes of CP and chronological age of children. Methods: A convenience sample of 124 children with CP (mean age 4.5, SD 2.9years, 56% male) participated in the study. Children were classified into the GMFCS-E & R and the MACS levels by research assistants based on parents input. Research assistants determined the subtypes of CP. Results: Thirty six percent of the participants were able to ambulate independently (GMFCS-E & R levels I-II) and 64% were able to handle objects independently (MACS levels I-II). The most common functional profile of children with CP in our study is the "manual abilities better than gross motor function". An overall strong correlation was found between the GMFCS-E & R and the MACS (r s =.73, p<.001), the correlations vary significantly based on subtypes of CP and chronological age of children. A very strong correlation was found in children with spastic quadriplegia (r s =.81, p<.001), moderate with spastic diplegia (r s =.64, p<.001), and weak with spastic hemiplegia (r s =.37, p<.001). Conclusions: The GMFCS- E & R and the MACS provide complementary but distinctive information related to mobility and manual abilities of children with CP. Subtypes of CP and chronological age differentiated functional profiles. Functional abilities of children with CP in Jordan have similar patterns to children with CP in other countries. Functional profiles can inform clinicians, researchers, and policy makers.
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18.
  • Bensby, Thomas, et al. (författare)
  • Chemical evolution of the galactic bulge as traced by microlensed dwarf and subgiant stars. II. Ages, metallicities, detailed elemental abundances, and connections to the Galactic thick disc
  • 2010
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 512
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Bulge is the least understood major stellar population of the Milky Way. Most of what we know about the formation and evolution of the Bulge comes from bright giant stars. The underlying assumption that giants represent all the stars, and accurately trace the chemical evolution of a stellar population, is under debate. In particular, recent observations of a few microlensed dwarf stars give a very different picture of the evolution of the Bulge from that given by the giant stars. Aims. We aim to resolve the apparent discrepancy between Bulge metallicity distributions derived from microlensed dwarf stars and giant stars. Additionally, we aim to put observational constraints on the elemental abundance trends and chemical evolution of the Bulge. Methods. We perform a detailed elemental abundance analysis of dwarf stars in the Galactic bulge, based on high-resolution spectra that were obtained while the stars were optically magnified during gravitational microlensing events. The analysis method is the same as for a large sample of F and G dwarf stars in the Solar neighbourhood, enabling a fully differential comparison between the Bulge and the local stellar populations in the Galactic disc. Results. We present detailed elemental abundances and stellar ages for six new dwarf stars in the Galactic bulge. Combining these with previous events, here re-analysed with the same methods, we study a homogeneous sample of 15 stars, which constitute the largest sample to date of microlensed dwarf stars in the Galactic bulge. We find that the stars span the full range of metallicities from [Fe/H] = -0.72 to + 0.54, and an average metallicity of <[Fe/H]> = -0.08 +/- 0.47, close to the average metallicity based on giant stars in the Bulge. Furthermore, the stars follow well-defined abundance trends, that for [Fe/H]<0 are very similar to those of the local Galactic thick disc. This suggests that the Bulge and the thick disc have had, at least partially, comparable chemical histories. At sub-solar metallicities we find the Bulge dwarf stars to have consistently old ages, while at super-solar metallicities we find a wide range of ages. Using the new age and abundance results from the microlensed dwarf stars we investigate possible formation scenarios for the Bulge.
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19.
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20.
  • Binnewies, Julia, et al. (författare)
  • Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium
  • 2022
  • Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 36
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes.Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts.Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed.Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.
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21.
  • Brandhorst, Heide, 1962-, et al. (författare)
  • A new oxygen carrier for improved long-term storage of human pancreata before islet isolation
  • 2010
  • Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 89:2, s. 155-60
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata.METHODS: After 24-hr storage in preoxygenated PFD or F6H8S5, pancreata were processed using Liberase HI for pancreas dissociation and a Ficoll gradient for islet purification. Islet quality assessment was performed measuring glucose-stimulated insulin release, viability, islet ATP content, and posttransplant function in diabetic nude mice.RESULTS: Compared with PFD, F6H8S5 significantly increased the intrapancreatic partial oxygen pressure and islet ATP content. This corresponded to an increase of islet yield, recovery after culture, glucose stimulation index, viability, and improved graft function in diabetic nude mice.CONCLUSIONS: The present findings indicate clearly that F6H8S5 improves isolation outcome after prolonged ischemia compared with PFD. This observation seems to be related to the significant lipophilicity and almost pancreas-specific density of F6H8S5. Moreover, these characteristics facilitate pancreas shipment without using custom-made transport vessels as required for PFD.
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22.
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23.
  • Carnicelli, Anthony P., et al. (författare)
  • Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation
  • 2021
  • Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 107:9, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug.Methods/Results We performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by <= 30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events <= 30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation.Conclusion Premature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.
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24.
  • Cowper, Patricia A., et al. (författare)
  • Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective : Results From the ARISTOTLE Randomized Clinical Trial
  • 2017
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 2:5, s. 525-534
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.OBJECTIVE To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.DESIGN, SETTING, AND PARTICIPANTS This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.INTERVENTIONS Apixaban therapy vs warfarin therapy.MAIN OUTCOMES AND MEASURES Within-trial resource use and costwere compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.RESULTS Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$ 60; 95% CI, -$ 2728 to $ 2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($ 53 925 per quality-adjusted life year, with 98% likelihood of meeting a $ 100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.CONCLUSIONS AND RELEVANCE Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.
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25.
  • Dalgaard, Frederik, et al. (författare)
  • Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial
  • 2020
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 141:1, s. 10-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.Methods:The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.Results:Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11–2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16–2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.Conclusions:A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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26.
  • De Caterina, Raffaele, et al. (författare)
  • History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial
  • 2016
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 175, s. 175-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.
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27.
  • Decin, L., et al. (författare)
  • (Sub)stellar companions shape the winds of evolved stars
  • 2020
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 369:6509, s. 1497-1500
  • Tidskriftsartikel (refereegranskat)abstract
    • Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe.
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28.
  • Flaker, Greg, et al. (författare)
  • Amiodarone, Anticoagulation, and Clinical Events in Patients With Atrial Fibrillation Insights From the ARISTOTLE Trial
  • 2014
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 64:15, s. 1541-1550
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. OBJECTIVES This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. METHODS Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. RESULTS In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. CONCLUSIONS Amiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone.
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29.
  • Friedman, Barbara Bodorkos, et al. (författare)
  • Are People Ready for Personalized Brain Health? Perspectives of Research Participants in the Lifebrain Consortium
  • 2020
  • Ingår i: The Gerontologist. - : Oxford University Press. - 0016-9013 .- 1758-5341. ; 60:6, s. E374-E383
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain.DESIGN AND METHODS: We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis.RESULTS: Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries.DISCUSSION AND IMPLICATIONS: Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.
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30.
  • Garcia, David, et al. (författare)
  • Management and clinical outcomes in patients treated with apixaban versus warfarin undergoing procedures
  • 2014
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 124:25, s. 3692-3698
  • Tidskriftsartikel (refereegranskat)abstract
    • Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted pre-procedure; whether bridging therapy was used; and the proportion of patients who experienced important clinical outcomes during the 30 days post-procedure. Of 10,674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted pre-procedure 37.5% of the time. During the 30 days post-procedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/4530 (0.57%) procedures among warfarin-treated patients (OR 0.601; 95% CI 0.322–1.120). Major bleeding occurred in 74/4560 (1.62%) procedures in the apixaban arm and 86/4454 (1.93%) in the warfarin arm (OR 0.846; 95% CI 0.614–1.166). The risk of death was similar with apixaban (54/4624 [1.17%]) and warfarin (49/4530 [1.08%]) (OR 1.082; 95% CI 0.733–1.598). Among patients in ARISTOTLE, the 30-day post-procedure stroke, death, and major bleeding rates were low and similar in apixaban- and warfarin-treated patients, regardless of whether anticoagulation was stopped beforehand. Our findings suggest that many patients on chronic anticoagulation can safely undergo procedures; some will not require a pre-procedure interruption of anticoagulation. ARISTOTLE ClinicalTrials.gov number (NCT00412984).
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31.
  • Goldstein, Sarah A., et al. (författare)
  • Characteristics and Outcomes of Atrial Fibrillation in Patients With Thyroid Disease (from the ARISTOTLE Trial)
  • 2019
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 124:9, s. 1406-1412
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether patients with atrial fibrillation (AF) and thyroid disease are clinically distinct from those with AF and no thyroid disease is unknown. Furthermore, the effectiveness of anticoagulation for prevention of AF-related thromboembolic events in patients with thyroid disease has not been adequately studied. Patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, which compared apixaban with warfarin in patients with AF (n = 18,201), were categorized by thyroid disease history at randomization (hypothyroidism, hyperthyroidism, and no thyroid disease). Adjusted hazard ratios derived from Cox models were used to compare outcomes by thyroid disease history. Associations between randomized treatment and outcomes by thyroid disease history were examined using Cox models with interaction terms. A total of 18,021/18,201 (99%) patients had available thyroid disease history at randomization: 1,656 (9%) had hypothyroidism, 321 (2%) had hyperthyroidism, and 16,044 (89%) had no thyroid disease. When compared with those without a history of thyroid disease, patients with hypo- or hyperthyroidism were more likely to be female (60.4% vs 32.1%; 52.0% vs 32.1%; both p < 0.0001). Patients with hypothyroidism were older (73 vs 70 years, p < 0.0001) and more likely to have had previous falls (8.7% vs 4.3%, p < 0.0001). There was no difference in clinical outcomes by thyroid disease history. The benefit of apixaban compared with warfarin was similar regardless of thyroid disease history (interaction p > 0.10). In conclusion, despite differences in baseline characteristics of patients with and without thyroid disease, their clinical outcomes were similar. The benefit of apixban compared with warfarin was preserved regardless of thyroid disease history.
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32.
  • Guimaraes, Patricia O., et al. (författare)
  • Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation : Insights from the ARISTOTLE trial
  • 2017
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 227, s. 443-449
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Methods: Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30 days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. Results: In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed Al' had a similar risk of stroke/systemic embolism (HR = 1.07, 95% CI = 0.80-1.42; p 0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR = 1.21, 95% Cl 1.02-1.43; p 0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AI' diagnosis (all interaction p-values >0.12). Conclusion: Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis.
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33.
  • Hess, Paul L., et al. (författare)
  • Sudden Cardiac Death After Non-ST-Segment Elevation Acute Coronary Syndrome
  • 2016
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 1:1, s. 73-79
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE In the current therapeutic era, the risk for sudden cardiac death (SCD) after non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely. OBJECTIVE To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD. DESIGN, SETTING, AND PARTICIPANTS This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015. MAIN OUTCOMES AND MEASURES Sudden cardiac death. RESULTS Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to calculate the risk for SCD in trials with systematic collection of left ventricular ejection fraction had a C index of 0.77. An integer-based score was developed from this model and yielded a calculated SCD probability ranging from 0.1% to 56.7%(C statistic, 0.75). In a multivariable model that included time-dependent clinical events occurring after the index hospitalization for ACS, SCD was associated with recurrentmyocardial infarction (hazard ratio [HR], 2.95; 95% CI, 2.29-3.80; P <.001) and any hospitalization (HR, 2.45; 95% CI, 1.98-3.03; P <.001), whereas coronary revascularization had a negative relationship with SCD (HR, 0.75; 95% CI, 0.58-0.98; P =.03). CONCLUSIONS AND RELEVANCE In the current therapeutic era, SCD accounts for about one-third of cardiovascular deaths after NSTE ACS. Risk stratification can be performed with good accuracy using commonly collected clinical variables. Clinical events occurring after the index hospitalization are underappreciated but important risk factors.
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34.
  • Kahrs, Birgitte H., et al. (författare)
  • Fetal rotation during vacuum extractions for prolonged labor : a prospective cohort study
  • 2018
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:8, s. 998-1005
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim of the study was to investigate fetal head rotation during vacuum extraction. Material and methods: We conducted a prospective cohort study from November 2013 to July 2016 in seven European hospitals. Fetal head position was determined with transabdominal or transperineal ultrasound and categorized as occiput anterior (OA), occiput transverse (OT) or occiput posterior (OP) position. Main outcome was the proportion of fetuses rotating during vacuum extraction. Secondary outcomes were conversion of delivery method, duration of vacuum extraction, umbilical artery pH <7.10 and agreement between clinical and ultrasound assessments. Results: The study population comprised 165 women. During vacuum extraction 117/119 (98%) remained in OA and two fetuses rotated to OP position. Rotation from OT to OA position occurred in 14/19 (74%) and to OP position in 5/19 (26%). Rotation from OP to OA position occurred in 15/25 (60%), and 10/25 (40%) fetuses remained in OP position. Delivery information was missing in two cases. The conversion rate from vacuum extraction to cesarean section or forceps was 10% in the OA group vs. 23% in the non-OA group; p < 0.05. The estimated duration of vacuum extraction was significantly shorter in OA fetuses, 7 min vs. 10 min (log rank test p < 0.01). There was no significant difference in umbilical artery pH < 7.10 between OA and non-OA position. Cohens Kappa of agreement between clinical and ultrasound assessments was 0.42 (95% CI 0.26–0.57). Conclusion: Most fetuses in OP or OT positions rotated to OA position during vacuum extraction, but the proportion of failed vacuum extractions remained high.
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35.
  • Khan, Farooq-Ahmad, et al. (författare)
  • Ruthenium Nanoparticles Intercalated in Montmorillonite (nano-Ru@MMT) Is Highly Efficient Catalyst for the Selective Hydrogenation of 2-Furaldehyde in Benign Aqueous Medium
  • 2021
  • Ingår i: Catalysts. - : MDPI AG. - 2073-4344. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemoselective hydrogenation of 2-furaldehyde to furfuryl alcohol using green solvents is an important research area to get eco-friendly fuels and fine chemicals. Herein, we report ruthenium nanoparticles (similar to 1.8 nm) intercalated in montmorillonite as an efficient catalytic system, which can selectively hydrogenate 2-furaldehyde in a benign aqueous medium. The complete conversion was observed at 40 degrees C with 1 MPa H-2, the selectivity of furfuryl alcohol being >99%, and turnover number 1165. After a catalytic run, the montmorillonite-supported ruthenium nanoparticles can be recycled and reused without losing their activity and selectivity.
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36.
  • Kirchhof, Paulus, et al. (författare)
  • Personalized management of atrial fibrillation : Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference
  • 2013
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:11, s. 1540-1556
  • Tidskriftsartikel (refereegranskat)abstract
    • The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.
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37.
  • Lopes, Renato D., et al. (författare)
  • Apixaban for Reduction In Stroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial : Design and rationale
  • 2010
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:3, s. 331-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of complications when patients' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naive population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding.
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38.
  • Lopes, Renato D., et al. (författare)
  • Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy
  • 2017
  • Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:22, s. 2980-2987
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received >= 1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was >= 4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-termmorbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.
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39.
  • Lopes, Renato D., et al. (författare)
  • Warfarin Use and Outcomes in Patients with Atrial Fibrillation Complicating Acute Coronary Syndromes
  • 2010
  • Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 123:2, s. 134-140
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation. METHODS: Of the 23,208 patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A, and Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trials, 4.0% (917 patients) had atrial fibrillation as an in-hospital complication and were discharged alive. Cox proportional hazards models were performed to assess 6-month outcomes after discharge. RESULTS: Overall, 13.5% of patients with an acute coronary syndrome complicated by atrial fibrillation received warfarin at discharge. Warfarin use among patients with atrial fibrillation had no relation with estimated stroke risk; similar rates were observed across Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack (CHADS(2)) scores (0, 13%; 1, 14%: >= 2, 13%) and across different bleeding risk categories (low risk, 11.9%: intermediate risk, 13.3%; high risk, 11.1%). Among patients with in-hospital atrial fibrillation, warfarin use at discharge was independently associated with a lower risk of death or myocardial infarction within 6 months of discharge (hazard ratio 0.39; 95% confidence interval, 0.15-0.98). CONCLUSION: Warfarin is associated with better 6-month outcomes among patients with atrial fibrillation complicating an acute coronary syndrome, but its use is not related to CHADS(2) score or bleeding risk.
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40.
  • McMurray, John J. V., et al. (författare)
  • Left Ventricular Systolic Dysfunction, Heart Failure, and the Risk of Stroke and Systemic Embolism in Patients With Atrial Fibrillation Insights From the ARISTOTLE Trial
  • 2013
  • Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:3, s. 451-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. Methods and Results-The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Conclusions-Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.
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41.
  • Sana, H., et al. (författare)
  • A dearth of short-period massive binaries in the young massive star forming region M17 Evidence for a large orbital separation at birth?
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 599
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The formation of massive stars remains poorly understood and little is known about their birth multiplicity properties. Here, we aim to quantitatively investigate the strikingly low radial-velocity dispersion measured for a sample of 11 massive pre- and near main-sequence stars (sigma(1D) = 5.6 +/- 0.2 km s(-1)) in the very young massive star forming region M 17, in order to obtain first constraints on the multiplicity properties of young massive stellar objects.Methods. We compute the radial-velocity dispersion of synthetic populations of massive stars for various multiplicity properties and we compare the obtained sigma(1D) distributions to the observed value. We specifically investigate two scenarios: a low binary fraction and a dearth of short-period binary systems.Results. Simulated populations with low binary fractions (f(bin) = 0.12(-0.09)(+0.16)) or with truncated period distributions (P-cutoff > 9 months) are able to reproduce the low sigma(1D) observed within their 68%-confidence intervals. Furthermore, parent populations with f(bin) > 0.42 or P-cutoff < 47 d can be rejected at the 5%-significance level. Both constraints are in stark contrast with the high binary fraction and plethora of short-period systems in few Myr-old, well characterized OB-type populations. To explain the difference in the context of the first scenario would require a variation of the outcome of the massive star formation process. In the context of the second scenario, compact binaries must form later on, and the cut-off period may be related to physical length-scales representative of the bloated pre-main-sequence stellar radii or of their accretion disks.Conclusions. If the obtained constraints for the M 17's massive-star population are representative of the multiplicity properties of massive young stellar objects, our results may provide support to a massive star formation process in which binaries are initially formed at larger separations, then harden or migrate to produce the typical (untruncated) power-law period distribution observed in few Myr-old OB binaries.
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42.
  • Saracino, S., et al. (författare)
  • Updated radial velocities and new constraints on the nature of the unseen source in NGC1850 BH1
  • 2023
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:2, s. 3162-3171
  • Tidskriftsartikel (refereegranskat)abstract
    • A black hole candidate orbiting a luminous star in the Large Magellanic Cloud young cluster NGC 1850 (∼100 Myr) has recently been reported based on radial velocity and light-curve modelling. Subsequently, an alternative explanation has been suggested for the system: a bloated post-mass transfer secondary star (Minitial ∼ 4–5 M⊙ and Mcurrent ∼ 1–2 M⊙) with a more massive, yet luminous companion (the primary). Upon reanalysis of the MUSE spectra, we found that the radial velocity variations originally reported were underestimated (K2, revised = 176 ± 3 km s−1 versus K2, original = 140 ± 3 km s−1) because of the weighting scheme adopted in the full-spectrum fitting analysis. The increased radial velocity semi-amplitude translates into a system mass function larger than previously deduced (frevised = 2.83 M⊙versus foriginal = 1.42 M⊙). By exploiting the spectral disentangling technique, we place an upper limit of 10 per cent of a luminous primary source to the observed optical light in NGC1850 BH1, assuming that the primary and secondary are the only components contributing to the system. Furthermore, by analysing archival near-infrared data, we find clues to the presence of an accretion disc in the system. These constraints support a low-mass post-mass transfer star but do not provide a definitive answer whether the unseen component in NGC1850 BH1 is indeed a black hole. These results predict a scenario where, if a primary luminous source of mass M ≥ 4.7 M⊙ is present in the system (given the inclination and secondary mass constraints), it must be hidden in a optically thick disc to be undetected in the MUSE spectra
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43.
  • Sharma, Abhinav, et al. (författare)
  • Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation : Insights From the ARISTOTLE Trial
  • 2018
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:16, s. 1666-1676
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. Methods: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. Results: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death. Conclusions: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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44.
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45.
  • Vinereanu, Dragos, et al. (författare)
  • Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin : a secondary analysis of a randomized controlled trial
  • 2015
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:46, s. 3268-
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation.METHODS AND RESULTS: Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex.CONCLUSION: In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women.TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984.
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46.
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47.
  • Wallentin, Lars, et al. (författare)
  • Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation
  • 2013
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:22, s. 2166-2176
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR).Methods and ResultsThe trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53–1.00) and 0.88 (95% CI, 0.57–1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74–1.13) and 0.91 (95% CI, 0.71–1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36–0.70) and 0.75 (95% CI, 0.58–0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR.ConclusionsThe benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers’ and patients’ predicted quality of international normalized ratio control.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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48.
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