| 1. |
- Connolly, Stuart J., et al.
(författare)
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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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| 2. |
- Melgarejo, Jesus D., et al.
(författare)
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Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 77:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R-2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and >= 96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R-2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R-2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.
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| 3. |
- Melgarejo, Jesus D., et al.
(författare)
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Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor
- 2021
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:9, s. 929-938
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan.METHODS In 4,663 young (18-49 years) and 7,185 older adults (>= 50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints.RESULTS In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were <= 2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P <= 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3.CONCLUSIONS From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.
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| 4. |
- Melinder, Jens, 1977-, et al.
(författare)
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The Lyα Reference Sample. XIV. Lyα Imaging of 45 Low-redshift Star-forming Galaxies and Inferences on Global Emission
- 2023
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Ingår i: Astrophysical Journal Supplement Series. - 0067-0049 .- 1538-4365. ; 266:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Lyα imaging of 45 low-redshift star-forming galaxies observed with the Hubble Space Telescope. The galaxies have been selected to have moderate to high star formation rates (SFRs) using far-ultraviolet (FUV) luminosity and Hα equivalent width criteria, but no constraints on Lyα luminosity. We employ a pixel stellar continuum fitting code to obtain accurate continuum-subtracted Lyα, Hα, and Hβ maps. We find that Lyα is less concentrated than FUV and optical line emission in almost all galaxies with significant Lyα emission. We present global measurements of Lyα and other quantities measured in apertures designed to capture all of the Lyα emission. We then show how the escape fraction of Lyα relates to a number of other measured quantities (mass, metallicity, star formation, ionization parameter, and extinction). We find that the escape fraction is strongly anticorrelated with nebular and stellar extinction, weakly anticorrelated with stellar mass, but no conclusive evidence for correlations with other quantities. We show that Lyα escape fractions are inconsistent with common dust extinction laws, and discuss how a combination of radiative transfer effects and clumpy dust models can help resolve the discrepancies. We present an SFR calibration based on Lyα luminosity, where the equivalent width of Lyα is used to correct for nonunity escape fraction, and show that this relation provides a reasonably accurate SFR estimate. We also show stacked growth curves of Lyα for the galaxies that can be used to find aperture loss fractions at a given physical radius.
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| 5. |
- Moreno-Martos, David, et al.
(författare)
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Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe
- 2023
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a ‘diagnosed’ and ‘hospitalized’ cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.
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| 6. |
- Na, Manli, et al.
(författare)
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The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of Staphylococcus aureus, a Core Mechanism of Septic Arthritis.
- 2020
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Ingår i: mBio. - 2150-7511. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus, including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δcoa, Δvwb, and Δcoa Δvwb) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δcoa Δvwb and Δvwb variants compared to WT or Δcoa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δvwb strain was used. Importantly, no difference in arthritis severity between the Δvwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis.IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.
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| 7. |
- Valerio, Luca, et al.
(författare)
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Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death : an analysis of 712 cases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 289:3, s. 325-339
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. Methods: In our individual-level analysis of 712 patients (2000–2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. Results: The median age was 21 (Q1–Q3: 17–33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8–7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4–14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36–0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45–3.80). Major bleeding occurred in 19 patients (2.9%; 1.9–4.5%), and 26 died (4.0%; 2.7–5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2–13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). Conclusions: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.
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