| 1. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 2. |
- Underwood, J, et al.
(författare)
-
Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
-
Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
|
|
| 3. |
- Winston, A, et al.
(författare)
-
Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy
- 2016
-
Ingår i: HIV Medicine. - : Wiley. - 1468-1293 .- 1464-2662. ; 17:6, s. 471-478
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study.METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models.RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA.CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.
|
|
| 4. |
- Booiman, T., et al.
(författare)
-
High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid
- 2017
-
Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 4:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.
|
|
| 5. |
- Van Zoest, Rosan A, et al.
(författare)
-
Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers.
- 2018
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 217:1, s. 69-81
-
Tidskriftsartikel (refereegranskat)abstract
- Brain structural abnormalities have been reported in persons with HIV (PWH) on suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear.We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PWH on suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, using multimodal neuroimaging and cerebrospinal fluid (CSF) biomarkers.Compared to controls, PWH had lower grey matter volumes (-13.7 mL [95%-confidence interval -25.1, -2.2 mL]) and fractional anisotropy (-0.0073 [-0.012, -0.0024]), with the largest differences observed in those with prior clinical AIDS. Hypertension and CSF soluble CD14 concentration were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction=0.32 and Pinteraction=0.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV.The presence of lower grey matter volumes and more white matter microstructural abnormalities in well-treated PWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.
|
|
| 6. |
- Vakharia, V. N., et al.
(författare)
-
Computer-assisted planning for the insertion of stereoelectroencephalography electrodes for the investigation of drug-resistant focal epilepsy: an external validation study
- 2019
-
Ingår i: Journal of Neurosurgery. - 0022-3085. ; 130:2, s. 601-610
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE One-third of cases of focal epilepsy are drug refractory, and surgery might provide a cure. Seizure-free outcome after surgery depends on the correct identification and resection of the epileptogenic zone. In patients with no visible abnormality on MRI, or in cases in which presurgical evaluation yields discordant data, invasive stereoelectroencephalography (SEEG) recordings might be necessary. SEEG is a procedure in which multiple electrodes are placed stereotactically in key targets within the brain to record interictal and ictal electrophysiological activity. Correlating this activity with seizure semiology enables identification of the seizure-onset zone and key structures within the ictal network. The main risk related to electrode placement is hemorrhage, which occurs in 1% of patients who undergo the procedure. Planning safe electrode placement for SEEG requires meticulous adherence to the following: 1) maximize the distance from cerebral vasculature, 2) avoid crossing sulcal pial boundaries (sulci), 3) maximize gray matter sampling, 4) minimize electrode length, 5) drill at an angle orthogonal to the skull, and 6) avoid critical neurological structures. The authors provide a validation of surgical strategizing and planning with EpiNav, a multimodal platform that enables automated computer-assisted planning (CAP) for electrode placement with user-defined regions of interest. METHODS Thirteen consecutive patients who underwent implantation of a total 116 electrodes over a 15-month period were studied retrospectively. Models of the cortex, gray matter, and sulci were generated from patient-specific whole-brain parcellation, and vascular segmentation was performed on the basis of preoperative MR venography. Then, the multidisciplinary implantation strategy and precise trajectory planning were reconstructed using CAP and compared with the implemented manually determined plans. Paired results for safety metric comparisons were available for 104 electrodes. External validity of the suitability and safety of electrode entry points, trajectories, and target-point feasibility was sought from 5 independent, blinded experts from outside institutions. RESULTS CAP-generated electrode trajectories resulted in a statistically significant improvement in electrode length, drilling angle, gray matter-sampling ratio, minimum distance from segmented vasculature, and risk (p < 0.05). The blinded external raters had various opinions of trajectory feasibility that were not statistically significant, and they considered a mean of 69.4% of manually determined trajectories and 62.2% of CAP-generated trajectories feasible; 19.4% of the CAP-generated electrode-placement plans were deemed feasible when the manually determined plans were not, whereas 26.5% of the manually determined electrode-placement plans were rated feasible when CAP-determined plans were not (no significant difference). CONCLUSIONS CAP generates clinically feasible electrode-placement plans and results in statistically improved safety metrics. CAP is a useful tool for automating the placement of electrodes for SEEG; however, it requires the operating surgeon to review the results before implantation, because only 62% of electrode-placement plans were rated feasible, compared with 69% of the manually determined placement plans, mainly because of proximity of the electrodes to un-segmented vasculature. Improved vascular segmentation and sulcal modeling could lead to further improvements in the feasibility of CAP-generated trajectories.
|
|
| 7. |
- Gallenne, A., et al.
(författare)
-
A Geometrical 1% Distance to the Short-period Binary Cepheid V1334 Cygni
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 867:2
-
Tidskriftsartikel (refereegranskat)abstract
- Cepheid stars play a considerable role as extragalactic distances indicators, thanks to the simple empirical relation between their pulsation period and their luminosity. They overlap with that of secondary distance indicators, such as Type Ia supernovae, whose distance scale is tied to Cepheid luminosities. However, the period-luminosity (P-L) relation still lacks a calibration to better than 5%. Using an original combination of interferometric astrometry with optical and ultraviolet spectroscopy, we measured the geometrical distance d = 720.35 +/- 7.84 pc of the 3.33 day period Cepheid V1334 Cyg with an unprecedented accuracy of +/- 1%, providing the most accurate distance for a Cepheid. Placing this star in the P-L diagram provides an independent test of existing P-L relations. We show that the secondary star has a significant impact on the integrated magnitude, particularly at visible wavelengths. Binarity in future high-precision calibrations of the P-L relations is not negligible, at least in the short-period regime. Subtracting the companion flux leaves V1334 Cyg in marginal agreement with existing photometric-based P-L relations, indicating either an overall calibration bias or a significant intrinsic dispersion at a few percent level. Our work also enabled us to determine the dynamical masses of both components, M-1 = 4.288 +/- 0.133 M-circle dot (Cepheid) and M-2 = 4.040 +/- 0.048 M-circle dot (companion), providing the most accurate masses for a Galactic binary Cepheid system.
|
|
| 8. |
- Owusu, Richard A., et al.
(författare)
-
Which UGC features drive web purchase intent? : A spike-and-slab Bayesian Variable Selection Approach
- 2016
-
Ingår i: Internet Research. - 1066-2243. ; 26:1, s. 22-37
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to identify user-generated content (UGC) features that determine web purchase decision making. Design/methodology/approach - The authors embed a spike-and-slab Bayesian variable selection mechanism into a logistic regression model to identify the UGC features that are critical to web purchase intent. This enables us to make a highly reliable analysis of survey data. Findings -The results indicate that the web purchase decision is driven by the relevance, up-to-dateness and credibility of the UGC information content. Research limitations/implications - The results show that the characteristics of UGC are seen as positive and the medium enables consumers to sort information and concentrate on aspects of the message that are similar to traditional word-of-mouth (WOM). One important implication is the relative importance of credibility which has been previously hypothesized to be lower in the electronic word-of-mouth (e-WOM) context. The results show that consumers consider credibility important as the improved technology provides more possibilities to find out about that factor. A limitation is that the data are not fully representative of the general population but our Bayesian method gives us high analytical quality. Practical implications - The study shows that UGC impacts consumer online purchase intentions. Marketers should understand the wide range of media that provide UGC and they should concentrate on the relevance, up-to-dateness and credibility of product information that they provide. Originality/value - The analytical quality of the spike-and-slab Bayesian method suggests a new way of understanding the impact of aspects of UGC on consumers.
|
|
| 9. |
- Shete, PB, et al.
(författare)
-
Defining a migrant-inclusive tuberculosis research agenda to end TB
- 2018
-
Ingår i: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1815-7920. ; 22:8, s. 835-
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
|
|
