| 1. |
- Afonso-Argilés, F. Javier, et al.
(författare)
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Emergency department and hospital admissions among people with dementia living at home or in nursing homes : results of the European RightTimePlaceCare project on their frequency, associated factors and costs
- 2020
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence is lacking on the differences between hospitalisation of people with dementia living in nursing homes and those living in the community. The objectives of this study were: 1) to describe the frequency of hospital admission among people with dementia in eight European countries living in nursing homes or in the community, 2) to examine the factors associated with hospitalisation in each setting, and 3) to evaluate the costs associated with it. Methods: The present study is a secondary data analysis of the RightTimePlaceCare European project. A cross-sectional survey was conducted with data collected from people with dementia living at home or who had been admitted to a nursing home in the last 3 months, as well as from their caregivers. Data on hospital admissions at 3 months, cognitive and functional status, neuropsychiatric symptoms, comorbidity, polypharmacy, caregiver burden, nutritional status, and falls were assessed using validated instruments. Multivariate regression models were used to investigate the factors associated with hospital admission for each setting. Costs were estimated by multiplying quantities of resources used with the unit cost of each resource and inflated to the year 2019. Results: The study sample comprised 1700 people with dementia living in the community and nursing homes. Within 3 months, 13.8 and 18.5% of people living in nursing homes and home care, respectively, experienced ≥1 hospital admission. In the nursing home setting, only polypharmacy was associated with a higher chance of hospital admission, while in the home care setting, unintentional weight loss, polypharmacy, falls, and more severe caregiver burden were associated with hospital admission. Overall, the estimated average costs per person with dementia/year among participants living in a nursing home were lower than those receiving home care. Conclusion: Admission to hospital is frequent among people with dementia, especially among those living in the community, and seems to impose a remarkable economic burden. The identification and establishment of an individualised care plan for those people with dementia with polypharmacy in nursing homes, and those with involuntary weight loss, accidental falls, polypharmacy and higher caregiver burden in the home care setting, might help preventing unnecessary hospital admissions.
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| 2. |
- Dharamshi, Jennah, et al.
(författare)
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Gene gain facilitated endosymbiotic evolution of Chlamydiae
- 2023
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Ingår i: Nature Microbiology. - : Springer Nature. - 2058-5276. ; 8, s. 40-54
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydiae is a bacterial phylum composed of obligate animal and protist endosymbionts. However, other members of the Planctomycetes-Verrucomicrobia-Chlamydiae superphylum are primarily free living. How Chlamydiae transitioned to an endosymbiotic lifestyle is still largely unresolved. Here we reconstructed Planctomycetes-Verrucomicrobia-Chlamydiae species relationships and modelled superphylum genome evolution. Gene content reconstruction from 11,996 gene families suggests a motile and facultatively anaerobic last common Chlamydiae ancestor that had already gained characteristic endosymbiont genes. Counter to expectations for genome streamlining in strict endosymbionts, we detected substantial gene gain within Chlamydiae. We found that divergence in energy metabolism and aerobiosis observed in extant lineages emerged later during chlamydial evolution. In particular, metabolic and aerobic genes characteristic of the more metabolically versatile protist-infecting chlamydiae were gained, such as respiratory chain complexes. Our results show that metabolic complexity can increase during endosymbiont evolution, adding an additional perspective for understanding symbiont evolutionary trajectories across the tree of life.
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| 3. |
- Haller, Paul M., et al.
(författare)
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Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus
- 2023
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Ingår i: European Journal of Preventive Cardiology. - 2047-4873 .- 2047-4881. ; 30:12, s. 1218-1226
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. 'METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81).CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.
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| 4. |
- Halter, Tamara, et al.
(författare)
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Ecology and evolution of chlamydial symbionts of arthropods
- 2022
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Ingår i: ISME Communications. - : Springer Nature. - 2730-6151. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- The phylum Chlamydiae consists of obligate intracellular bacteria including major human pathogens and diverse environmental representatives. Here we investigated the Rhabdochlamydiaceae, which is predicted to be the largest and most diverse chlamydial family, with the few described members known to infect arthropod hosts. Using published 16 S rRNA gene sequence data we identified at least 388 genus-level lineages containing about 14 051 putative species within this family. We show that rhabdochlamydiae are mainly found in freshwater and soil environments, suggesting the existence of diverse, yet unknown hosts. Next, we used a comprehensive genome dataset including metagenome assembled genomes classified as members of the family Rhabdochlamydiaceae, and we added novel complete genome sequences of Rhabdochlamydia porcellionis infecting the woodlouse Porcellio scaber, and of 'Candidatus R. oedothoracis' associated with the linyphiid dwarf spider Oedothorax gibbosus. Comparative analysis of basic genome features and gene content with reference genomes of well-studied chlamydial families with known host ranges, namely Parachlamydiaceae (protist hosts) and Chlamydiaceae (human and other vertebrate hosts) suggested distinct niches for members of the Rhabdochlamydiaceae. We propose that members of the family represent intermediate stages of adaptation of chlamydiae from protists to vertebrate hosts. Within the genus Rhabdochlamydia, pronounced genome size reduction could be observed (1.49-1.93 Mb). The abundance and genomic distribution of transposases suggests transposable element expansion and subsequent gene inactivation as a mechanism of genome streamlining during adaptation to new hosts. This type of genome reduction has never been described before for any member of the phylum Chlamydiae. This study provides new insights into the molecular ecology, genomic diversity, and evolution of representatives of one of the most divergent chlamydial families.
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| 5. |
- Jelley, Hannah, et al.
(författare)
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Carers' experiences of timely access to and use of dementia care services in eight European countries
- 2021
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Ingår i: Ageing & Society. - : Cambridge University Press. - 0144-686X .- 1469-1779. ; 41:2, s. 403-420
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Tidskriftsartikel (refereegranskat)abstract
- Timely access to care services is crucial to support people with dementia and their family carers to live well. Carers of people with dementia (N = 390), recruited from eight countries, completed semi-structured interviews about their experiences of either accessing or not using formal care services over a 12-month period in the Access to Timely Formal Care (Actifcare) study. Participant responses were summarised using content analysis, categorised into clusters and frequencies were calculated. Less than half of the participants (42.3%) reported service use. Of those using services, 72.8 per cent reported timely access and of those not using services 67.2 per cent were satisfied with this situation. However, substantial minorities either reported access at the wrong time (27.2%), or feeling dissatisfied or mixed feelings about not accessing services (32.8%). Reasons for not using services included use not necessary yet, the carer provided support or refusal. Reasons given for using services included changes in the condition of the person with dementia, the service's ability to meet individual needs, not coping or the opportunity to access services arose. Facilitators and barriers to service use included whether participants experienced supportive professionals, the speed of the process, whether the general practitioner was helpful, participant's own proactive attitude and the quality of information received. To achieve timely support, simplified pathways to use of formal care services are needed.
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| 6. |
- Lethin, Connie, et al.
(författare)
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Predicting caregiver burden in informal caregivers caring for persons with dementia living at home – A follow-up cohort study
- 2020
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Ingår i: Dementia. - London : Sage Publications. - 1471-3012 .- 1741-2684. ; 9:3, s. 640-660
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal studies of caregiver burden when caring for persons with dementia living at home are sparse. The aim of the study was to identify factors associated with caregiver burden and predicting increased burden related to caregivers, persons with dementia and formal care. Data were collected through interviews with 1223 caregivers in eight European countries. Bivariate and multivariate regression analyses were performed. Factors associated with caregiver burden included extensive informal care provision, decreased well-being and reduced quality of life for the caregiver and reduced cognition, decreased quality of life, severe neuropsychiatric symptoms and depression in the person with dementia and caregivers’ negative experience of quality of care. Factors predicting an increased burden were diminished caregiver well-being, severe neuropsychiatric symptoms of the person with dementia and caregivers’ negative perception of quality of care. The knowledge gained in this study may be useful in developing more adequate service systems and interventions to improve dementia care. © 2018, The Author(s) 2018.
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| 7. |
- Michelet, Mona, et al.
(författare)
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Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia : a longitudinal study
- 2021
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Ingår i: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 26:4, s. 725-734
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia.METHODS We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates.RESULTS Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up.CONCLUSION Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.
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| 8. |
- Parrotta, Ilaria, et al.
(författare)
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Depression in People With Dementia and Caregiver Outcomes : Results From the European Right Time Place Care Study
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:6, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the cross-sectional associations between depression in people with dementia and both caregiver burden and quality of life in 8 European countries, and to test these associations compared with the presence of other neuropsychiatric symptoms. Design: Cross-sectional study. Setting and Participants: In total, 1223 dyads comprised of informal caregivers and people with dementia living in a community-dwelling setting, recruited from the Right Time Place Care study, a cohort survey from 8 European countries. Measures: To test the associations between depression (according to the Cornell Scale for Depression in Dementia) and informal caregiver burden (defined by the Zarit scale and hours of supervision in terms of Resource Utilization in Dementia), distress (defined by the Neuropsychiatric Inventory Questionnaire distress score), and quality of life (according to the visual analogue scale and 12-item General Health Questionnaire). Results: Linear regressions showed an association between depression and main outcomes (Zarit scale: β 3.7; P = .001; hours of supervision: β 1.7; P = .004; Neuropsychiatric Inventory Questionnaire distress score: β 1.2; P = .002). A similar association was found concerning psychological and overall well-being (12-item General Health Questionnaire: β 1.8; P < .001; Euroqol Visual Analogue Scale: β −4.1; P = .003). Both associations remained significant despite the presence of other NPS and after adjusting for confounders. Conclusions and Implications: Further studies are needed to assess whether providing tailored strategies for optimizing diagnosis and managing of depression in people with dementia might improve caregiver quality of life and reduce their burden in the community-dwelling setting.
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| 9. |
- Redmer, Torben, et al.
(författare)
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JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression
- 2024
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Ingår i: Molecular Cancer. - : BioMed Central (BMC). - 1476-4598. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.Methods: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.Results: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.Conclusions: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes. Graphical Abstract: (Figure presented.).
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| 10. |
- Sarris, Theodoros, et al.
(författare)
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Plasma-neutral interactions in the lower thermosphere-ionosphere : The need for in situ measurements to address focused questions
- 2023
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Ingår i: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 9
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Forskningsöversikt (refereegranskat)abstract
- The lower thermosphere-ionosphere (LTI) is a key transition region between Earth's atmosphere and space. Interactions between ions and neutrals maximize within the LTI and in particular at altitudes from 100 to 200 km, which is the least visited region of the near-Earth environment. The lack of in situ co-temporal and co-spatial measurements of all relevant parameters and their elusiveness to most remote-sensing methods means that the complex interactions between its neutral and charged constituents remain poorly characterized to this date. This lack of measurements, together with the ambiguity in the quantification of key processes in the 100-200 km altitude range affect current modeling efforts to expand atmospheric models upward to include the LTI and limit current space weather prediction capabilities. We present focused questions in the LTI that are related to the complex interactions between its neutral and charged constituents. These questions concern core physical processes that govern the energetics, dynamics, and chemistry of the LTI and need to be addressed as fundamental and long-standing questions in this critically unexplored boundary region. We also outline the range of in situ measurements that are needed to unambiguously quantify key LTI processes within this region, and present elements of an in situ concept based on past proposed mission concepts.
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| 11. |
- Tobiasson, Magnus, et al.
(författare)
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Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
- 2024
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:12, s. 1378-1390
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODS: Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTS: Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).CONCLUSION: Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662).
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