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| 4. |
- Verhoef, E, et al.
(författare)
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Disentangling polygenic associations between attention-deficit/hyperactivity disorder, educational attainment, literacy and language
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- Interpreting polygenic overlap between ADHD and both literacy-related and language-related impairments is challenging as genetic associations might be influenced by indirectly shared genetic factors. Here, we investigate genetic overlap between polygenic ADHD risk and multiple literacy-related and/or language-related abilities (LRAs), as assessed in UK children (N ≤ 5919), accounting for genetically predictable educational attainment (EA). Genome-wide summary statistics on clinical ADHD and years of schooling were obtained from large consortia (N ≤ 326,041). Our findings show that ADHD-polygenic scores (ADHD-PGS) were inversely associated with LRAs in ALSPAC, most consistently with reading-related abilities, and explained ≤1.6% phenotypic variation. These polygenic links were then dissected into both ADHD effects shared with and independent of EA, using multivariable regressions (MVR). Conditional on EA, polygenic ADHD risk remained associated with multiple reading and/or spelling abilities, phonemic awareness and verbal intelligence, but not listening comprehension and non-word repetition. Using conservative ADHD-instruments (P-threshold < 5 × 10−8), this corresponded, for example, to a 0.35 SD decrease in pooled reading performance per log-odds in ADHD-liability (P = 9.2 × 10−5). Using subthreshold ADHD-instruments (P-threshold < 0.0015), these effects became smaller, with a 0.03 SD decrease per log-odds in ADHD risk (P = 1.4 × 10−6), although the predictive accuracy increased. However, polygenic ADHD-effects shared with EA were of equal strength and at least equal magnitude compared to those independent of EA, for all LRAs studied, and detectable using subthreshold instruments. Thus, ADHD-related polygenic links with LRAs are to a large extent due to shared genetic effects with EA, although there is evidence for an ADHD-specific association profile, independent of EA, that primarily involves literacy-related impairments.
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| 5. |
- Acciarresi, M., et al.
(författare)
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Prestroke CHA(2)DS(2)-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study
- 2017
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 26:6, s. 1363-1368
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS < 3 or >= 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
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| 6. |
- Altavilla, R., et al.
(författare)
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Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin?
- 2019
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:8, s. 2093-2100
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
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| 8. |
- Paciaroni, M., et al.
(författare)
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Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema The ALESSA Score Study
- 2017
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 48:3, s. 726-732
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purposes-This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods-The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age 80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results-The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions-In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
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| 9. |
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| 10. |
- Nörholt, S.E, et al.
(författare)
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Analgesic efficacy with rapidly absorbed ibuprofen sodium dihydrate in postsurgical dental pain : results from the randomized QUIKK trial
- 2011
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Ingår i: International journal of clinical pharmacology and therapeutics. - : Dustri-Verlag Dr. Karl Feistle GmbH & Co. KG. - 0946-1965. ; 49:12, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid). MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, crossover trial, patients requiring surgical removal of two impacted or partially impacted mandibular third molars received: ibuprofen sodium dihydrate 400 mg plus conventional ibuprofen placebo (Group 1); or conventional ibuprofen 400 mg plus ibuprofen sodium dihydrate placebo (Group 2) following the first surgery. Patients were then crossed over to the alternative treatment. RESULTS: 72 patients were enrolled in Group 1 and 72 patients in Group 2. Ibuprofen sodium dihydrate produced faster initial pain relief than conventional ibuprofen as assessed by time to first pain relief (24.6 vs. 30.5 minutes; p = 0.004), and patient-assessed pain relief at 15 minutes ("some" to "complete" pain relief: 43% vs. 29%; p < 0.001) and 30 minutes (82% vs. 63%; p < 0.001) and pain intensity at 30 minutes (p < 0.001). Substantial pain relief with ibuprofen sodium dihydrate was twice that of conventional ibuprofen at 30 minutes (11% vs. 5%; not significant); 29% and 33% of patients did not reach substantial pain relief at 120 minutes. There were no adverse events leading to treatment discontinuation and only two serious adverse events (oral abscess and facial paresis with conventional ibuprofen) considered unrelated to treatment. CONCLUSIONS: Ibuprofen sodium dihydrate was as effective as conventional ibuprofen, but had a faster onset of initial pain relief and significantly reduced pain intensity within the first 30 minutes after administration, providing rapid clinically meaningful pain relief for patients.
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| 11. |
- Opdam, N J M, et al.
(författare)
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Longevity of posterior composite restorations : a systematic review and meta-analysis
- 2014
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Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 93:10, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this meta-analysis, based on individual participant data from several studies, was to investigate the influence of patient-, materials-, and tooth-related variables on the survival of posterior resin composite restorations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a search resulting in 12 longitudinal studies of direct posterior resin composite restorations with at least 5 years' follow-up. Original datasets were still available, including placement/failure/censoring of restorations, restored surfaces, materials used, reasons for clinical failure, and caries-risk status. A database including all restorations was constructed, and a multivariate Cox regression method was used to analyze variables of interest [patient (age; gender; caries-risk status), jaw (upper; lower), number of restored surfaces, resin composite and adhesive materials, and use of glass-ionomer cement as base/liner (present or absent)]. The hazard ratios with respective 95% confidence intervals were determined, and annual failure rates were calculated for subgroups. Of all restorations, 2,816 (2,585 Class II and 231 Class I) were included in the analysis, of which 569 failed during the observation period. Main reasons for failure were caries and fracture. The regression analyses showed a significantly higher risk of failure for restorations in high-caries-risk individuals and those with a higher number of restored surfaces.
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| 12. |
- Paciaroni, M., et al.
(författare)
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Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
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Tidskriftsartikel (refereegranskat)abstract
- Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.
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| 14. |
- Sirivåg, K, et al.
(författare)
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Physical EXercise Augmented COGnitive Behaviour Therapy for Older Adults with Generalised Anxiety Disorder (PEXACOG)
- 2016
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Konferensbidrag (refereegranskat)abstract
- Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exercise in combination with CBT, and our understanding of clinical characteristics of GAD and mechanisms involved in treatment effect. Treatment rationale, procedures and protocols will be presented in detail together with preliminary results from the initial feasibility study comprises eight participants.
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| 16. |
- Krishna Vadivel, Chella, et al.
(författare)
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Staphylococcus aureus induce drug resistance in cancer T cells in Sézary Syndrome
- 2024
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 143:15, s. 1496-1512
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Tidskriftsartikel (refereegranskat)abstract
- Key Points Enterotoxins from Staphylococcus aureus bacteria induce drug resistance in primary malignant T cells in Sézary syndrome. Targeting bacteria, their toxins, and downstream signaling pathways in malignant T cells abrogate the induction of drug resistance. Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T cell lymphoma (CTCL), are prone to Staphylococcus aureus (S. aureus) infections and have a poor prognosis due to treatment-resistance. Here, we report that S. aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T-cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S. aureus and recombinant SE significantly inhibit cell death induced by HDAC inhibitor romidepsin in primary malignant T-cells from SS patients. Bacterial killing by engineered, bacteriophage-derived, S. aureus-specific endolysin (XZ.700) abrogates the effect of S. aureus supernatant. Likewise, mutations in MHC Class II binding sites of SE type-A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates TCR, NFB, and JAK/STAT signaling pathways (previously associated with drug-resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein Kinase C (upstream of NFB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by proteasome/NFB inhibitor bortezomib. Inhibition of JAK/STAT only blocks SE-induced rescue of malignant T-cells in some but not all patients, suggesting two distinct ways SE can induce drug resistance. In conclusion, we show that S. aureus enterotoxins induce drug-resistance in primary malignant T-cells. These findings suggest that S. aureus enterotoxins cause clinical treatment-resistance in SS patients and that anti-bacterial measures may improve the outcome of cancer-directed therapy in patients harboring S. aureus
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| 17. |
- Langeland, E, et al.
(författare)
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One size does not fit all. Should gambling loss limits be based on income?
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13, s. 1005172-
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has suggested empirically based gambling loss limits, with the goal of preventing gambling related harm in the population. However, there is a lack of studies relating gambling loss limits to individual factors such as income. The current study examines whether gambling loss limits should be income-specific.Materials and methodsThe dataset was derived from three representative cross-sectional surveys of the Norwegian population and consisted of 14,630 gamblers. Four income groups, based on a quartile approximation, were formed. Gambling related harm was measured with the Problem Gambling Severity Index (PGSI), and precision-recall (PR) analyses were used to identify loss limits for the different income groups at two levels of gambling severity: moderate-risk gambling and problem gambling.ResultsFor both levels of gambling severity, we found the lowest income group to have the lowest gambling loss limits, and the highest income group to have the highest loss limits, which compared to the loss limits for the total sample, were lower and higher, respectively. Calculating the cut-offs for moderate-risk gamblers, we found a consistently ascending pattern from the lowest to the highest income group. Calculating the cut-offs for problem gamblers, we found a similar pattern except for the two middle income groups.ConclusionThe results suggest that income moderates empirically derived gambling loss limits. Although replication is required, income-based gambling loss limits may have higher applied value for preventing gambling related harm, compared to general loss limits aimed at the entire population.
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| 18. |
- Sirevåg, K, et al.
(författare)
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Physical EXercise Augmented COGnitive Behaviour Therapy for Older Adults with Generalised Anxiety Disorder (PEXACOG)
- 2018
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Konferensbidrag (refereegranskat)abstract
- Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exercise in combination with CBT, and our understanding of clinical characteristics of GAD and mechanisms involved in treatment effect. Treatment rationale, procedures and protocols will be presented in detail together with preliminary results from the initial feasibility study comprises eight participants
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| 19. |
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| 20. |
- Sirivåg, K, et al.
(författare)
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Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG) : Study protocol and feasibility results from a randomised controlled trial
- 2018
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Konferensbidrag (refereegranskat)abstract
- Background. Generalised anxiety disorder (GAD) is prevalent among older adults. These patients exhibit impaired response to cognitive behaviour therapy (CBT), and physical exercise has been recommended as a potential add-on intervention to improve efficacy. The current study is a randomised clinical trial that will compare CBT augmented with physical exercise, or CBT combined with attention placebo, and the current study assessing the feasibility of testing procedures and the experimental combined treatment measures.Methods. 4 participants were included in the feasibility study, and feasibility was assessed trough completion and attendance rates of testing and treatment sessions. Primary outcome measures were remission as assessed by an independent clinical rater using the Anxiety Disorders Interview Schedule for DSM-IV, and by symptom reduction on Penn State Worry Questionnaire. Manipulation check was assessed by physical tests of change in aerobic capacity and strength. Participants were measured on clinical, biological, physiological and neuropsychological tests at pre-, interim and post-treatment.Results. Completed treatment protocol for the RCT will be presented. 3 of 4 participants completed the full protocol including testing and the experimental augmented treatment. Participants completed 100% and 80% of CBT and physical exercise content, respectively. The three completers had large improvements on primary outcome and on manipulation checks.Conclusion. The testing procedures and experimental augmented treatment appear to be feasible. The preliminary findings indicate that this combined intervention can be efficacious.
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