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- 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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- Kapun, Martin, et al.
(författare)
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Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
- 2021
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
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Tidskriftsartikel (refereegranskat)abstract
- Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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- Lappalainen, H. K., et al.
(författare)
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Overview: Recent advances in the understanding of the northern Eurasian environments and of the urban air quality in China - a Pan-Eurasian Experiment (PEEX) programme perspective
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:7, s. 4413-4469
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Tidskriftsartikel (refereegranskat)abstract
- The Pan-Eurasian Experiment (PEEX) Science Plan, released in 2015, addressed a need for a holistic system understanding and outlined the most urgent research needs for the rapidly changing Arctic-boreal region. Air quality in China, together with the long-range transport of atmospheric pollutants, was also indicated as one of the most crucial topics of the research agenda. These two geographical regions, the northern Eurasian Arctic-boreal region and China, especially the megacities in China, were identified as a "PEEX region". It is also important to recognize that the PEEX geographical region is an area where science-based policy actions would have significant impacts on the global climate. This paper summarizes results obtained during the last 5 years in the northern Eurasian region, together with recent observations of the air quality in the urban environments in China, in the context of the PEEX programme. The main regions of interest are the Russian Arctic, northern Eurasian boreal forests (Siberia) and peatlands, and the megacities in China. We frame our analysis against research themes introduced in the PEEX Science Plan in 2015. We summarize recent progress towards an enhanced holistic understanding of the land-atmosphere-ocean systems feedbacks. We conclude that although the scientific knowledge in these regions has increased, the new results are in many cases insufficient, and there are still gaps in our understanding of large-scale climate-Earth surface interactions and feedbacks. This arises from limitations in research infrastructures, especially the lack of coordinated, continuous and comprehensive in situ observations of the study region as well as integrative data analyses, hindering a comprehensive system analysis. The fast-changing environment and ecosystem changes driven by climate change, socio-economic activities like the China Silk Road Initiative, and the global trends like urbanization further complicate such analyses. We recognize new topics with an increasing importance in the near future, especially "the enhancing biological sequestration capacity of greenhouse gases into forests and soils to mitigate climate change" and the "socio-economic development to tackle air quality issues".
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- Waszczuk-Gajda, A, et al.
(författare)
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Complications of Autologous Stem Cell Transplantation in Multiple Myeloma: Results from the CALM Study
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies.
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