| 1. |
- de Heus, R. A. A., et al.
(författare)
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Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
- 2019
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Background-Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop >= 20/>= 10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 +/- 8.2 years and mean Mini-Mental State Examination score was 20.4 +/- 3.8. Baseline blood pressure was 137.8 +/- 14.0/77.0 +/- 8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo (P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI] 1.1 [0.8-1.5], P 0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7 +/- 13.8% versus 7.3 +/- 11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.
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| 2. |
- Dyer, A. H., et al.
(författare)
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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 3. |
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| 4. |
- Georgali, E., et al.
(författare)
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Experimental study of the 165Ho(n, 2n) reaction : Cross section measurements for the population of the 164Ho ground state and isomeric state from the threshold up to 20 MeV
- 2020
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 102:3
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Tidskriftsartikel (refereegranskat)abstract
- In the present work the 165Ho(n,2n) reaction was studied experimentally and theoretically for the population of the ground state (Jπ=1+) of the 164Ho product nucleus, as well as for the population of its isomeric state (Eex=139.8 keV, Jπ=6−). The cross sections of both the ground and isomeric state channels were measured at energies near the reaction threshold (Eth=8.04 MeV), at 10.1, 10.4, and 10.7 MeV, as well as at energies higher than 17 MeV, at 17.1, 18.1, 19.0, and 19.6 MeV. The adopted method was the activation technique relative to the 197Au(n,2n) 196Au and 27Al(n,α)24Na reference reactions. The quasi-monoenergetic neutron beams for the near threshold energies were produced via the 2H(d,n)3He reaction, while for the neutron beams above 17 MeV the 3H(d,n)4He reaction was utilized. In both cases the deuteron beams were delivered by the 5.5 MV Tandem Van de Graaff accelerator of the Institute of Nuclear and Particle Physics at N.C.S.R. “Demokritos”. Additional to the experimental study, calculations were performed using the talys code (v. 1.9). The experimental data of the present work along with the previous measurements were compared with the talys results so as to investigate the reproduction of the experimental data for the different level density models of the code.
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| 5. |
- Lawlor, B., et al.
(författare)
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Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated antiinflammatory and anti-tau activity in preclinical studies, properties that could have diseasemodifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged > 50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of >= 12 and < 27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease +/- specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADASCog 12 on placebo was 0.79 (95% CI, -0.07 +/- 1.64) at 13 weeks, 6.41 (5.33 +/- 7.49) at 52 weeks, and 9.63 (8.33 +/- 10.93) at 78 weeks and on nilvadipine was 0.88 (0.02 +/- 1.74) at 13 weeks, 5.75 (4.66 +/- 6.85) at 52 weeks, and 9.41 (8.09 +/- 10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
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| 6. |
- Leenhardt, R., et al.
(författare)
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Key research questions for implementation of artificial intelligence in capsule endoscopy
- 2022
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Ingår i: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. Objectives: In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Design: Modified three-round Delphi consensus online survey. Methods: The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Results: Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). Conclusion: In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.
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| 7. |
- Brouwer, PA, et al.
(författare)
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Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201 consecutive patients in a real-world setting
- 2018
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Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 10:10, s. 964-
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Tidskriftsartikel (refereegranskat)abstract
- We studied patients treated with the EmboTrap revascularization device in a prospective registry which is core laboratory evaluated by physicians from external centers. The goal was to determine how the EmboTrap would perform under the everyday conditions of a high-volume stroke center.MethodsWe examined all patients with acute stroke treated with the Embotrap device from October 2013 to March 2017 in our center. Imaging parameters and times were adjudicated by core laboratory personnel blinded to clinical information, treating physician, and clinical outcomes. Clinical evaluation was performed by independent neurologists and entered in a national registry. Evaluated endpoints were: successful revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b–3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0–2).Results201 consecutive patients with a median NIH Stroke Scale (NIHSS) score of 15 (range 2–30) were included. 170 patients (84.6%) achieved mTICI 2b–3 reperfusion. The median number of attempts was 2 (range 1–10) with 52.8% of the population achieving good functional outcomes (mRS 0–2) at 3 months. On univariate analysis, good functional outcome was associated with the number of attempts, puncture-to-reperfusion time, anterior circulation occlusion, and NIHSS score. On multivariate analysis, pre-treatment NIHSS (OR 0.845 per point, 95% CI 0.793 to 0.908, P<0.001) and puncture-to-reperfusion time (OR 0.9952 per min, 95% CI 0.9914 to 0.9975, P=0.023) were associated with good functional outcomes at 3 months.ConclusionThe Embotrap device has a high rate of successful reperfusion. Our core laboratory-audited single-center experience suggests the technical feasibility and safety of the Embotrap for first-line use in a real-world setting.
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| 8. |
- de Jong, Yde, et al.
(författare)
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PESI - a taxonomic backbone for Europe
- 2015
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Ingår i: Biodiversity Data Journal. - 1314-2836 .- 1314-2828. ; 3, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- Reliable taxonomy underpins communication in all of biology, not least nature conservation and sustainable use of ecosystem resources. The flexibility of taxonomic interpretations, however, presents a serious challenge for end-users of taxonomic concepts. Users need standardised and continuously harmonised taxonomic reference systems, as well as high-quality and complete taxonomic data sets, but these are generally lacking for non-specialists. The solution is in dynamic, expertly curated web-based taxonomic tools.The Pan-European Species-directories Infrastructure (PESI) worked to solve this key issue by providing a taxonomic e-infrastructure for Europe. It strengthened the relevant social (expertise) and information (standards, data and technical) capacities of five major community networks on taxonomic indexing in Europe, which is essential for proper biodiversity assessment and monitoring activities. The key objectives of PESI were: 1) standardisation in taxonomic reference systems, 2) enhancement of the quality and completeness of taxonomic data sets and 3) creation of integrated access to taxonomic information.This paper describes the results of PESI and its future prospects, including the involvement in major European biodiversity informatics initiatives and programs.
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| 9. |
- Georgali, E., et al.
(författare)
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Cross-section measurements of the Dy-156(n, 2n)Dy-155 reaction at neutron energies higher than 17 MeV
- 2021
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 104:6
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Tidskriftsartikel (refereegranskat)abstract
- In the present work the cross section of the 156Dy (n, 2n) 155Dy reaction (Eth = 9.51 MeV) was measured at neutron beam energies above 17 MeV: 17.1, 18.1, and 19.0 MeV. The irradiations were performed at the 5.5-MV tandem accelerator of the Institute of Nuclear and Particle Physics at N.C.S.R. "Demokritos", where quasimonoenergetic neutron beams were produced via the 3H (d, n) 4He reaction. The cross-section measurements were performed by means of the activation technique relative to the 27Al (n, alpha) 24Na reference reaction. Within the present work the experimental study is framed by theoretical calculations performed via the TALYS code (version 1.95).
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| 10. |
- Kasliwal, Mansi M., et al.
(författare)
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Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg(2), a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10(-25) yr(-1). The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (-16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than -16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day(-1) (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than -16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than <57% (<89%) of putative kilonovae could be brighter than -16.6 mag assuming flat evolution (fading by 1 mag day(-1)) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than <68% of putative kilonovae could be brighter than -16.6 mag. Comparing to model grids, we find that some kilonovae must have M-ej M, X-lan > 10(-4), or > 30 degrees to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of -16 mag would constrain the maximum fraction of bright kilonovae to <25%.
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