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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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- Wilkinson, John L., et al.
(författare)
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Pharmaceutical pollution of the world's rivers
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:8
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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- Guerriero, Giuseppe, et al.
(författare)
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Efficacy of transcutaneous vagus nerve stimulation as treatment for depression: A systematic review
- 2021
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Ingår i: Journal of Affective Disorders Reports. - : Elsevier BV. - 2666-9153. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcutaneous vagus nerve stimulation (tVNS) has been suggested as a treatment method for depression. Methods: A systematic review to systematically evaluate the efficacy of tVNS for the treatment of depression was conducted according to PRISMA guidelines. Primary outcomes were mortality, self-harm, depressive symptoms, and health-related quality of life (HRQoL). Secondary outcomes were anxiety symptoms, medication use, everyday functioning, complications, and patients’ experiences of treatment. Five databases were searched systematically. The included articles were critically appraised and certainty of evidence was assessed using GRADE. Results: Two studies evaluating efficacy and a case series collecting data on complications were included. One randomized trial (n = 37) and one cohort study (n = 160) comparing tVNS with sham-tVNS reported significant reduction in the tVNS group of self-rated (SMD = -0.82, 95%-CI = -1.50, -0.15) but not clinician-rated depressive symptoms, after two weeks, and of both self-rated (SMD = -0.99, 95%-CI = -1.32, -0.66) and clinician-rated (SMD = -0.89, 95%-CI = -1.22, -0.57) depressive symptoms, after four weeks, respectively. Furthermore, the cohort study found reduction of both self-rated (SMD = -0.66, 95%-CI = -0.98, -0.34) and clinician-rated (SMD = -0.14, 95%-CI = -0.46, 0.17) anxiety symptoms. One case series (n = 12), collecting data on complications, reported mild to moderate transient side effects. Limitations: Available studies are few and heterogeneous, have major study limitations, problems with directness and imprecision. Conclusions: It is uncertain whether tVNS reduces depressive symptoms and anxiety. Although existing studies show promising results, further studies are needed to increase the certainty of evidence. © 2021 The Authors
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- Ioannou, Leonidas G., et al.
(författare)
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Occupational heat stress : Multi-country observations and interventions
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Occupational heat exposure can provoke health problems that increase the risk of certain diseases and affect workers’ ability to maintain healthy and productive lives. This study investigates the effects of occupational heat stress on workers’ physiological strain and labor productivity, as well as examining multiple interventions to mitigate the problem. Methods: We monitored 518 full work-shifts obtained from 238 experienced and acclimatized individuals who work in key industrial sectors located in Cyprus, Greece, Qatar, and Spain. Continuous core body temperature, mean skin temperature, heart rate, and labor productivity were collected from the beginning to the end of all work-shifts. Results: In workplaces where self-pacing is not feasible or very limited, we found that occupational heat stress is associated with the heat strain experienced by workers. Strategies focusing on hydration, work-rest cycles, and ventilated clothing were able to mitigate the physiological heat strain experienced by workers. Increasing mechanization enhanced labor productivity without increasing workers’ physiological strain. Conclusions: Empowering la-borers to self-pace is the basis of heat mitigation, while tailored strategies focusing on hydration, work-rest cycles, ventilated garments, and mechanization can further reduce the physiological heat strain experienced by workers under certain conditions.
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- Ioannou, Michael, et al.
(författare)
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Sleep deprivation as treatment for depression: Systematic review and meta-analysis
- 2021
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 143:1, s. 22-35
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Forskningsöversikt (refereegranskat)abstract
- Objective To systematically review evidence on the efficacy and safety of sleep deprivation (SD) as a treatment option for patients with unipolar or bipolar depression. Methods A systematic review according to PRISMA guidelines was conducted. The certainty of evidence was assessed using the GRADE approach. Controlled trials were included in efficacy analysis, case series for evaluating complications and qualitative studies for patients' experiences. Results Eight controlled studies (368 patients), one qualitative study and seven case series (825 patients) were included. One week after treatment start, SD combined with standard treatment did not reduce depressive symptoms compared with standard treatment (standardized mean difference, SMD = -0.29, [95% confidence interval, CI: -0.84 to 0.25], p = 0.29). When excluding a study in elderly patients in a post hoc analysis, the difference was statistically significant (SMD = -0.54 ([95% CI: -0.86 to -0.22], p < 0.001)) but it diminished two weeks after treatment start. No superiority of SD was found compared with antidepressants, but SD may be superior to exercise in certain settings. It is uncertain whether SD affects quality of sleep, quality of life, everyday functioning or length of stay. Apart from switch to mania (ranging between 2.7% and 10.7%), no other serious complications were reported. Conclusion Sleep deprivation has been studied in a wide range of settings resulting in divergent results for the short-term efficacy on depressive symptoms. Post hoc analyses indicated that there may be a significant but transient effect in certain populations. Further studies should focus on identifying subgroups of responders as well as examining feasibility in routine clinical care.
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| 10. |
- Ioannou, Nikolaos, et al.
(författare)
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Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1 /PD-1 immunotherapy
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:2, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8(+) T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint illustrate the importance blockade-based combination therapy.
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