| 1. |
- de Heus, R. A. A., et al.
(author)
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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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In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 8:10
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Journal article (peer-reviewed)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. |
- Lawlor, B., et al.
(author)
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Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
- 2018
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In: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
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Journal article (peer-reviewed)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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| 4. |
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| 5. |
- Hamilton, B. R., et al.
(author)
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Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement
- 2021
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In: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 51:7, s. 1401-1415
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Journal article (peer-reviewed)abstract
- Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.
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| 6. |
- Båth, Magnus, 1974, et al.
(author)
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Investigation of image components affecting the detection of lung nodules in digital chest radiography
- 2005
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In: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422. ; 5749, s. 231-242
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Journal article (other academic/artistic)abstract
- The aim of this work was to investigate and quantify the effects of system noise, nodule location, anatomical noise and anatomical background on the detection of lung nodules in different regions of the chest x-ray. Simulated lung nodules of diameter 10 mm but with varying detail contrast were randomly positioned in four different kinds of images: 1) clinical images collected with a 200 speed CR system, 2) images containing only system noise (including quantum noise) at the same level as the clinical images, 3) clinical images with removed anatomical noise, 4) artificial images with similar power spectrum as the clinical images but random phase spectrum. An ROC study was conducted with 5 observers. The detail contrast needed to obtain an Az of 0.80, C0.8, was used as measure of detectability. Five different regions of the chest x-ray were investigated separately. The C0.8 of the system noise images ranged from only 2% (the hilar regions) to 20% (the lateral pulmonary regions) of those of the clinical images. Compared with the original clinical images, the C0.8 was 16% lower for the de-noised clinical images and 71% higher for the random phase images, respectively, averaged over all five regions. In conclusion, regarding the detection of lung nodules with a diameter of 10 mm, the system noise is of minor importance at clinically relevant dose levels. The removal of anatomical noise and other noise sources uncorrelated from image to image leads to somewhat better detection, but the major component disturbing the detection is the overlapping of recognizable structures, which are, however, the main aspect of an x-ray image.
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| 7. |
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| 8. |
- Bolton, Kim, et al.
(author)
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Carbon Nanotube Growth Mechanisms
- 2007
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In: Proceedings of Diamond 2007, the 18th European Conference on Diamond, Diamond-Like Materials, Carbon Nanotubes, Nitrides and Silicon Carbide.
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Conference paper (peer-reviewed)abstract
- We have used a variety of computational methods to study key aspects of single-walled carbon nanotube (SWNT) growth. Molecular dynamics (MD) studies based on an empirical force field showed; for example; why SWNT growth occurs in a temperature window and why; for 1-2 nm catalyst particles; the SWNT diameter varies linearly with the size of the particle. In addition; the liquid or solid phase of the catalyst particle is strongly dependent on particle size; and smaller particles (< 1.5 nm) are liquid at typical chemical vapor deposition temperatures whereas larger particles (> 5 nm) are solid. The phase of particles of intermediate sizes depends on the exact temperature and on their carbon content. The effect of substrates on metal-carbide properties and SWNT growth has been studied by combing density functional (DFT) and MD methods. A major effect of flat; inert substrates is to flatten the catalyst particles thereby increasing their melting points. DFT has also been used to study the catalyst-SWNT interaction which is critical for the growth of long SWNTs; and is also being used to study the importance of the SWNT cap structure on its chirality. This knowledge is important; for example; when using SWNTs as seeds for the growth of longer nanotubes.
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