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| 2. |
- Klasson, Caritha, et al.
(författare)
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Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care : A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.
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| 3. |
- Klasson, Caritha, et al.
(författare)
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Vitamin D and Fatigue in Palliative Cancer : A Cross-Sectional Study of Sex Difference in Baseline Data from the Palliative D Cohort
- 2021
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Ingår i: Journal of Palliative Medicine. - : Mary Ann Liebert Inc. - 1096-6218 .- 1557-7740. ; 24:3, s. 433-437
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatigue is one of the most distressing symptoms in patients with advanced cancer. Previous studies have shown an association between low vitamin D levels and fatigue. Objectives: The aim of this study was to investigate the association between vitamin D levels and self-assessed fatigue in cancer patients admitted to palliative care, with focus on possible sex differences. Design: This is a cross-sectional study. Subjects: Baseline data from 530 screened patients, 265 women and 265 men, from the randomized placebo-controlled trial "Palliative-D" were analyzed. Measurements: Vitamin D status was measured as 25-hydroxyvitamin D (25-OHD) and fatigue was assessed with EORTC-QLQ-PAL15 and with Edmonton Symptom Assessment System (ESAS). Results: In men, there was a significant correlation between 25-OHD and fatigue measured with the "Tiredness question" (Q11) in EORTC-QLQ-PAL15 (p < 0.05), where higher 25-OHD levels were associated with less fatigue. No correlation between 25-OHD and fatigue was seen for women. Fatigue measured with ESAS did not show any significant association with 25-OHD levels neither in men nor in women. Conclusion: Low vitamin D levels were associated with more fatigue in men but not in women. The study underscores the importance of subgroup analysis of men and women when evaluating the effect of vitamin D in clinical trials since the effect may differ between the sexes. The ongoing "Palliative-D study" will reveal whether vitamin D supplementation may counteract fatigue in both men and women.ClinicalTrial.gov: NCT03038516.
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| 5. |
- Xu, Hong, et al.
(författare)
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Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care : Data From the Stockholm GeroCovid Study.
- 2021
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 22:8, s. 1565-1573
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic.DESIGN: Observational study.SETTING AND PARTICIPANTS: Altogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non-COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included.METHODS: Across admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented.RESULTS: In patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non-COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non-COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19.CONCLUSIONS AND IMPLICATIONS: Mortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.
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| 6. |
- Ahlström, Christer, et al.
(författare)
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Fit-for-duty test for estimation of drivers sleepiness level: Eye movements improve the sleep/wake predictor
- 2013
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Ingår i: Transportation Research Part C. - : Elsevier. - 0968-090X .- 1879-2359. ; 26, s. 20-32
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Tidskriftsartikel (refereegranskat)abstract
- Driver sleepiness contributes to a considerable proportion of road accidents, and a fit-for-duty test able to measure a drivers sleepiness level might improve traffic safety. The aim of this study was to develop a fit-for-duty test based on eye movement measurements and on the sleep/wake predictor model (SWP, which predicts the sleepiness level) and evaluate the ability to predict severe sleepiness during real road driving. Twenty-four drivers participated in an experimental study which took place partly in the laboratory, where the fit-for-duty data were acquired, and partly on the road, where the drivers sleepiness was assessed. A series of four measurements were conducted over a 24-h period during different stages of sleepiness. Two separate analyses were performed; a variance analysis and a feature selection followed by classification analysis. In the first analysis it was found that the SWP and several eye movement features involving anti-saccades, pro-saccades, smooth pursuit, pupillometry and fixation stability varied significantly with different stages of sleep deprivation. In the second analysis, a feature set was determined based on floating forward selection. The correlation coefficient between a linear combination of the acquired features and subjective sleepiness (Karolinska sleepiness scale, KSS) was found to be R = 0.73 and the correct classification rate of drivers who reached high levels of sleepiness (KSS andgt;= 8) in the subsequent driving session was 82.4% (sensitivity = 80.0%, specificity = 84.2% and AUC = 0.86). Future improvements of a fit-for-duty test should focus on how to account for individual differences and situational/contextual factors in the test, and whether it is possible to maintain high sensitive/specificity with a shorter test that can be used in a real-life environment, e.g. on professional drivers.
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| 9. |
- Correa, Fernando, et al.
(författare)
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Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: Restoring effects of inhibitors of HDACs, p38 MAPK and GSK3β.
- 2011
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Ingår i: Neurobiology of disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 44:1, s. 142-51
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Tidskriftsartikel (refereegranskat)abstract
- Histone deacetylase (HDAC) inhibitors have promising neuroprotective and anti-inflammatory properties although the exact mechanisms are unclear. We have earlier showed that factors from lipopolysaccharide (LPS)-activated microglia can down-regulate the astroglial nuclear factor-erythroid 2-related factor 2 (Nrf2)-inducible anti-oxidant defence. Here we have evaluated whether histone modification and activation of GSK3β are involved in these negative effects of microglia. Microglia were cultured for 24h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0)) or activated with 10ng/mL of LPS to produce MCM(10). Astrocyte-rich cultures treated with MCM(10) showed a time-dependent (0-72h) increase in astroglial HDAC activity that correlated with lower levels of acetylation of histones H3 and H4 and decreased levels of the transcription factor Nrf2 and γ-glutamyl cysteine ligase modulatory subunit (γGCL-M) protein levels. The HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) elevated the histone acetylation levels, restored the Nrf2-inducible anti-oxidant defence and conferred protection from oxidative stress-induced (H(2)O(2)) death in astrocyte-rich cultures exposed to MCM(10). Inhibitors of GSK3β (lithium) and p38 MAPK (SB203580) signaling pathways restored the depressed histone acetylation and Nrf2-related transcription whereas an inhibitor of Akt (Ly294002) caused a further decrease in Nrf2-related transcription. In conclusion, the study shows that well tolerated drugs such as VPA and lithium can restore an inflammatory induced depression in the Nrf2-inducible antioxidant defence, possibly via normalised histone acetylation levels.
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| 10. |
- Correa, Fernando, et al.
(författare)
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Dual TNF alpha-Induced Effects on NRF2 Mediated Antioxidant Defence in Astrocyte-Rich Cultures: Role of Protein Kinase Activation
- 2012
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Ingår i: Neurochemical Research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 37:12, s. 2842-2855
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNF alpha on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, gamma glutamylcysteine ligase (gamma GCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of gamma GCL (gamma GCL-C and gamma GCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNF alpha. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNF alpha increased GSH, gamma GCL activity, the protein levels of gamma GCL-M, gamma GCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3 beta further enhanced transcription. In contrast treatment with TNF alpha for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNF alpha. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3 beta, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNF alpha (24 h treatment) protected the cells from oxidative stress through elevated gamma GCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNF alpha is detrimental.
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