| 1. |
- Tragardh, Elin, et al.
(författare)
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Referring physicians underestimate the extent of abnormalities in final reports from myocardial perfusion imaging
- 2012
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Ingår i: EJNMMI Research. - 2191-219X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background It is important that referring physicians and other treating clinicians properly understand the final reports from diagnostic tests. The aim of the study was to investigate whether referring physicians interpret a final report for a myocardial perfusion scintigraphy (MPS) test in the same way that the reading nuclear medicine physician intended. Methods After viewing final reports containing only typical clinical verbiage and images, physicians in nuclear medicine and referring physicians (physicians in cardiology, internal medicine, and general practitioners) independently classified 60 MPS tests for the presence versus absence of ischemia/infarction according to objective grades of 1 to 5 (1 = no ischemia/infarction, 2 = probably no ischemia/infarction, 3 = equivocal, 4 = probable ischemia/infarction, and 5 = certain ischemia/infarction). When ischemia and/or infarction were thought to be present in the left ventricle, all physicians were also asked to mark the involved segments based on the 17-segment model. Results There was good diagnostic agreement between physicians in nuclear medicine and referring physicians when assessing the general presence versus absence of both ischemia and infarction (median squared kappa coefficient of 0.92 for both). However, when using the 17- segment model, compared to the physicians in nuclear medicine, 12 of 23 referring physicians underestimated the extent of ischemic area while 6 underestimated and 1 overestimated the extent of infarcted area. Conclusions Whereas referring physicians gain a good understanding of the general presence versus absence of ischemia and infarction from MPS test reports, they often underestimate the extent of any ischemic or infarcted areas. This may have adverse clinical consequences, and thus the language in final reports from MPS tests might be further improved and standardized.
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| 2. |
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| 3. |
- Blomström-Lundqvist, Carina, et al.
(författare)
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Effect of dronedarone vs. placebo on atrial fibrillation progression : a post hoc analysis from ATHENA trial
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:3, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo.Methods and results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as >= 6 months of AF/AFL until end of study) or permanent SR (defined as >= 6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21).Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.
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| 4. |
- Blomström-Lundqvist, Carina, et al.
(författare)
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Efficacy and safety of dronedarone by atrial fibrillation history duration : Insights from the ATHENA study.
- 2020
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 43:12, s. 1469-1477
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.HYPOTHESIS: Outcomes with dronedarone may also be impacted by duration of AF/AFL history.METHODS: In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long).RESULTS: Of 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo-treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65-0.96]) and intermediate (0.72 [0.56-0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66-1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug-related safety issues were identified.CONCLUSIONS: Patients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.
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| 5. |
- Fabritz, Larissa, et al.
(författare)
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Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
- 2021
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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| 6. |
- Gandhi, Sampada K., et al.
(författare)
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Risk of Major Bleeding in Patients With Atrial Fibrillation Taking Dronedarone in Combination With a Direct Acting Oral Anticoagulant (From a U.S. Claims Database)
- 2021
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 159, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- Dronedarone may increase exposure and the risk of major bleeding when prescribed with a direct oral anticoagulant (DOAC). This retrospective cohort study examined the risk of the first occurrence of major bleeding (hospitalization or emergency room visit for gastrointestinal [GI] bleeding, intracranial hemorrhage [ICH], or bleeding at other sites) among new users of apixaban, dabigatran, and rivaroxaban in patients with AF ≥18 years (January 1, 2007 to September 30, 2017) from the United States Truven Health MarketScan claims, comparing concomitant users of dronedarone to DOAC alone users in patients with atrial fibrillation (AF). No increased risk of major bleeding was associated with use of dronedarone and apixaban (adjusted Hazard Ratio [aHR]: 0.69 [95% confidence interval [CI]: 0.40, 1.17], p = 0.16), a modestly increased risk of GI bleeding but not overall bleeding was associated with use of dronedarone and dabigatran (aHR bleeding: 1.18 [95% CI: 0.89, 1.56], p = 0.26; aHR GI bleeding: 1.40 [95% CI: 1.01, 1.93]; p = 0.04) and an increased risk of overall bleeding, driven by GI bleeding, was associated with use of dronedarone and rivaroxaban (aHR bleeding: 1.31 [95% CI: 1.01, 1.69]; p = 0.04; aHR GI bleeding: 1.39 [95% CI: 0.98, 1.95]; p = 0.06), compared to each DOAC respectively. There was no increased risk of ICH associated with combined use of dronedarone and any DOAC. Prospective analyses, preferably randomized controlled studies, are needed to further explore the risk of major bleeding with concomitant use of DOACs and CYP3A4/P-gp inhibitors such as dronedarone.
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| 7. |
- Handelsman, Yehuda, et al.
(författare)
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Impact of dronedarone on patients with atrial fibrillation and diabetes : A sub-analysis of the ATHENA and EURIDIS/ADONIS studies
- 2022
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1056-8727. ; 36:7
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This post hoc analysis evaluated efficacy and safety of dronedarone in atrial fibrillation (AF) and atrial flutter (AFL) patients with/without diabetes. Methods: Patients were categorized according to baseline diabetes status. Time-to-event analyses were performed using Kaplan-Meier method. Hazard-ratios were assessed using Cox models. Results: 945/4628 (dronedarone = 482; placebo = 463) patients in ATHENA and 215/1237 (dronedarone = 148; placebo = 67) patients in EURIDIS/ADONIS studies had diabetes. In ATHENA, there were higher rates of CV hospitalization/death in patients with diabetes (39.5%) than without diabetes (34.7%). Incidence of first CV hospitalization/death was lower in patients with diabetes treated with dronedarone (35.1%) than placebo (44.1%), and time to this event was longer in those treated with dronedarone than placebo (log-rank p = 0.005). Median AF/AFL recurrence time was longer in patients treated with dronedarone than placebo in patients with diabetes (ATHENA: 722 vs 527 days, log-rank p = 0.004; EURIDIS/ADONIS: 100 vs 23 days, log-rank p = 0.15) or without diabetes (ATHENA: 741 vs 492 days, log-rank p < 0.0001; EURIDIS/ADONIS: 120 vs 59 days, log-rank p = 0.0002). Occurrence of any treatment-related adverse events with dronedarone was similar for patients with/without diabetes and was comparable to placebo. Conclusions: Dronedarone reduced incidence of CV hospitalization/death, AF/AFL recurrence and increased time to these events in AF/AFL patients with/without diabetes. Trial registration: Not applicable, as it was a post hoc analysis. This article is based on previously conducted studies (ATHENA: NCT00174785, EURIDIS: NCT00259428, and ADONIS: NCT00259376).
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| 8. |
- Jönsson, Karl, et al.
(författare)
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Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: A subgroup analysis from the AURICULA registry in Sweden.
- 2011
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 128:4, s. 341-345
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal function is, however, unknown. MATERIALS AND METHODS: Using AURICULA, a Swedish registry for anticoagulation, estimated glomerular filtration rate (eGFR) was investigated in AF patients on warfarin treatment (n=2,603). The study group was compared with a healthy sample from the population (n=2,261). Two different creatinine prediction equations were used for calculating eGFR: the Lund-Malmö (LM) and MDRD Study equation. RESULTS: The fraction of AF patients with eGFR <30 and <45ml/min/1.73m(2) were 8.1% and 22.9% with the LM and 4.3% and 16.3% with the MDRD equation, respectively, and significantly higher than corresponding values in the reference population. GFR decreased with increasing age, where 11.4% and 5.6% of AF patients aged≥75years had eGFR <30ml/min/1.73m(2) according to the LM and MDRD equations, respectively. CONCLUSIONS: Severe renal impairment is common among AF patients on anticoagulant treatment with warfarin, especially at higher ages. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys.
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| 9. |
- Labaf, Ashkan, et al.
(författare)
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Thromboembolism, major bleeding and mortality in patients with mechanical heart valves : a population-based cohort study
- 2014
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 134:2, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Low incidences of thromboembolism (TE) and bleeding in patients with mechanical heart valves (MHV) have previously been reported. This study assesses the incidence of and clinical risk factors predicting TE, major bleeding and mortality in a clinical setting. Methods and results: All 546 patients undergoing anticoagulation treatment due to MHV replacement at hospitals in Malmo and Sundsvall in Sweden were monitored during 2008-2011 and the incidence of TE, major bleeding and mortality was prospectively followed. There were 398, 122 and 26 patients in the aortic group (AVR), mitral (MVR) group and the combined aortic/mitral valve group respectively. The incidence of TE was 1.8 and 2.2 per 100 patient-years in the AVR group MVR group respectively. The corresponding incidences of bleeding were 4.4 and 4.6, respectively. Independent predictor of thromboembolism was vascular disease (Odds ratio {OR}: 4.2; 95% CI: 1.0-17.4). Predictor of bleeding was previous bleeding (OR: 2.7; 95% CI: 1.4-5.3). Independent predictors of mortality was age (Hazard ratio {HR}: 1.03; 95% CI: 1.00-1.05), hypertension (HR: 2.4; 95% CI: 1.3-4.5), diabetes (HR: 2.4; 95% CI: 1.3-4.3) and alcohol overconsumption (HR: 5.2; 95% CI: 1.7-15.9). Standardized mortality/morbidity ratio for mortality and AMI was 0.99 (95% CI: 0.8-1.2) and 0.87 (95% CI: 0.5-1.2) respectively. Conclusion: The incidence of TE and major bleeding in this unselected clinical population exceeds that of previously reported retrospective and randomized trials. Despite this, mortality is equal to that of the general population.
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| 10. |
- Ma, Changsheng, et al.
(författare)
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Effect of Dronedarone in the Treatment of Atrial Fibrillation in the Asian Population : Post Hoc Analysis of the ATHENA Trial
- 2022
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 44:9, s. 1203-1213
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Limited data are available on the impact of dronedarone treatment in Asian patients with atrial fibrillation (AF) or atrial flutter (AFL). This post hoc analysis evaluated the efficacy and safety of dronedarone compared with placebo in populations from Asian and non-Asian regions randomized in the ATHENA trial (A Placebo-Controlled, Double-blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of CV Hospitalization or Death From Any Cause in Patients With AF/AFL). Methods: Time to first hospitalization for cardiovascular events or death from any cause (primary outcome) and time to first AF/AFL event recurrence (secondary outcome) were analyzed by Kaplan-Meier curves and Cox proportional hazards regression. Findings: The risk of experiencing the primary composite outcome was significantly lower in the dronedarone-treated patients in both the Asian (hazard ratio = 0.541; 95% CI, 0.320–0.914]) and non-Asian (hazard ratio = 0.768; 95% CI, 0.696–0.848) populations than in the placebo-treated patients. The median time to the first AF/AFL event recurrence was longer in the dronedarone-treated population than in the placebo-treated populations: 183 vs 92 days (P = 0.165) in the Asian population and 534 vs 196 days (P < 0.001) in the non-Asian population. Treatment-emergent adverse events in Asian (81.2% vs 78.4%) and non-Asian (71.4% vs 68.7%) populations and serious treatment-emergent adverse events in Asian (14.3% vs 15.7%) and non-Asian (20.3% vs 21.5%) patients were comparable in patients taking dronedarone compared with those taking placebo. Implication: Efficacy and tolerability of dronedarone were consistent in the Asian population compared with the non-Asian population in the ATHENA trial. These finding may aid Asian health care professionals to select the appropriate first-line treatment for Asian patients with AF/AFL.
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| 11. |
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| 12. |
- Mochalina, Natalia, et al.
(författare)
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Ischemic stroke rates decline in patients with atrial fibrillation as anticoagulants uptake improves : A Swedish cohort study
- 2017
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Ingår i: Thrombosis Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0049-3848 .- 1879-2472. ; 158, s. 44-48
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of the increased anticoagulants uptake on incidence rate of ischemic stroke is largely unknown. We assessed time trends in rates of ischemic stroke in patients with incident atrial fibrillation (AF) diagnosed between 2011 and 2013.Materials and methods: Population-based retrospective registry study of all 11,500 adults diagnosed with incident non-valvular atrial fibrillation in 2011-2013 in primary and secondary care and receiving oral anticoagulants (n = 4847), aspirin (n = 2850) or no treatment (n = 3766) in Skane County, Sweden. The primary outcome was the rate of ischemic stroke within 365 days after AF diagnosis.Results and conclusion: Cumulative incidence of ischemic stroke decreased from 2.87% (95% confidence interval (CI) 2.37-3.45%) to 1.93% (95% CI 1.54-2.41%) while the uptake of oral anticoagulants increased from 36.6% to 48.4% between 2011 and 2013 (regression coefficient - 0.08; 95% CI, - 0.09 to - 0.07, p < 0.001). The increased uptake of oral anticoagulants in the community is associated with decreased incidence of ischemic stroke in AF patients.
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| 13. |
- Navgren, Monica, et al.
(författare)
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Bleeding complications related to warfarin treatment: a descriptive register study from the anticoagulation clinic at Helsingborg Hospital
- 2014
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 38:1, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- The most common indication for treatment with warfarin is the prevention of ischemic stroke in patients with atrial fibrillation. Time in therapeutic range (TTR) is an important tool to evaluate the quality of anticoagulation treatment. The aim of this study was to investigate the quality of treatment and the incidence of bleeding complications in patients on warfarin treatment treated by the anticoagulation clinic in Helsingborg. This is the first study that has specifically focused on the spontaneous reporting of bleeding complications in a real-world population. A total of 4,400 patients with a total of 8,394 patient years were registered, in the database Journalia AVK, during the time period November 1, 2007 to November 1, 2010. The mean age was 72 years. TTR was 73.3 % for the whole population. 421 patients suffered from haemorrhagic events. The frequency of major and fatal bleedings and intracranial haemorrhage (ICH) were 1.6, 0.2 and 0.5 % per patient-year, respectively. A correlation between age and severe bleeding (major, fatal and ICH) (p = 0.003) was seen, but no correlation between gender and severe bleeding (p = 0.27). In 60 out of 455 bleeding events the complication had been reported to the anticoagulation clinic. At the anticoagulation clinic in Helsingborg the quality of warfarin treatment is good compared to previous results described in the literature, with regards to bleeding complications and efficacy. However, in our study, we confirm that the spontaneous reporting of bleeding complications related to warfarin is inadequate, and that review of patient records is needed to assure proper follow-up.
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| 14. |
- Pundi, Krishna, et al.
(författare)
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Dronedarone Versus Sotalol in Antiarrhythmic Drug-Naive Veterans With Atrial Fibrillation
- 2023
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Ingår i: Circulation: Arrhythmia and Electrophysiology. - 1941-3149. ; 16:8, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system. METHODS: Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug-naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes. RESULTS: The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHA2DS2-VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88-1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68-1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38-0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37-0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant. CONCLUSIONS: Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials.
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| 15. |
- Reynolds, Matthew R., et al.
(författare)
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Novel methodology for the evaluation of symptoms reported by patients with newly diagnosed atrial fibrillation : Application of natural language processing to electronic medical records data
- 2023
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 34:4, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Understanding symptom patterns in atrial fibrillation (AF) can help in disease management. We report on the application of natural language processing (NLP) to electronic medical records (EMRs) to capture symptom reports in patients with newly diagnosed (incident) AF. Methods and Results: This observational retrospective study included adult patients with an index diagnosis of incident AF during January 1, 2016 through June 30, 2018, in the Optum datasets. The baseline and follow-up periods were 1 year before/after the index date, respectively. The primary objective was identification of the following predefined symptom reports: dyspnea or shortness of breath; syncope, presyncope, lightheadedness, or dizziness; chest pain; fatigue; and palpitations. In an exploratory analysis, the incidence rates of symptom reports and cardiovascular hospitalization were assessed in propensity-matched patient cohorts with incident AF receiving first-line dronedarone or sotalol. Among 30 447 patients with an index AF diagnosis, the NLP algorithm identified at least 1 predefined symptom in 9734 (31.9%) patients. The incidence rate of symptom reports was highest at 0–3 months post-diagnosis and lower at >3–6 and >6–12 months (pre-defined timepoints). Across all time periods, the most common symptoms were dyspnea or shortness of breath, followed by syncope, presyncope, lightheadedness, or dizziness. Similar temporal patterns of symptom reports were observed among patients with prescriptions for dronedarone or sotalol as first-line treatment. Conclusion: This study illustrates that NLP can be applied to EMR data to characterize symptom reports in patients with incident AF, and the potential for these methods to inform comparative effectiveness.
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| 16. |
- Rickhag, Mattias, et al.
(författare)
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Apolipoprotein D is elevated in oligodendrocytes in the peri-infarct region after experimental stroke: influence of enriched environment.
- 2008
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 28:3, s. 551-562
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Tidskriftsartikel (refereegranskat)abstract
- Injury to the brain (e.g., stroke) results in a disruption of neuronal connectivity and loss of fundamental sensori-motor functions. The subsequent recovery of certain functions involves structural rearrangements in areas adjacent to the infarct. This remodeling of the injured brain requires trafficking of macromolecular components including cholesterol and phospholipids, a transport carried out by apolipoproteins including apolipoprotein D (apoD). We investigated the changes in the levels of apoD mRNA and protein, and its cellular localization during a recovery period up to 30 days after experimental stroke in the rat brain. In the core of the brain infarct, apoD immunoreactivity but not mRNA increased in dying pyramidal neurons, indicative of cellular redistribution of lipids. During 2 to 7 days of recovery after stroke, the apoD levels increased in the peri-infarct and white matter areas in cells identified as mature oligodendrocytes. The apoD expressing cells were conspicuously located along the rim of the infarct, suggesting a role for apoD in tissue repair. Furthermore, housing animals in an enriched environment improved sensori-motor function and increased the apoD levels. Our data strongly suggest that apoD is involved in regenerative processes and scar formation in the peri-infarct area presumably by enhancing lipid trafficking.
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| 17. |
- Rickhag, Mattias, et al.
(författare)
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Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue
- 2006
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 96:1, s. 14-29
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify biological processes relevant for cell death and survival in the brain following stroke, the postischemic brain transcriptome was studied by a large-scale cDNA array analysis of three peri-infarct brain regions at eight time points during the first 24 h of reperfusion following middle cerebral artery occlusion in the rat. K-means cluster analysis revealed two distinct biphasic gene expression patterns that contained 44 genes (including 18 immediate early genes), involved in cell signaling and plasticity (i.e. MAP2K7, Sprouty2, Irs-2, Homer1, GPRC5B, Grasp). The first gene induction phase occurred at 0-3 h of reperfusion, and the second at 9-15 h, and was validated by in situ hybridization. Four gene clusters displayed a progressive increase in expression over time and included 50 genes linked to cell motility, lipid synthesis and trafficking (i.e. ApoD, NPC1, G3P-dehydrogenase1, and Choline kinase) or cell death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G-protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling pathways occurs in surviving tissue, concomitant with a progressive and persistent activation of cell proliferation signifying tissue regeneration, which provide the means for cell survival and postischemic brain plasticity.
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| 18. |
- Rickhag, Mattias, et al.
(författare)
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Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain.
- 2007
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1151, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated the spatial and temporal activation pattern for these genes during the first 24 h of reperfusion following 2-h occlusion of the middle cerebral artery. Neuritin showed a persistent activation in frontal-cingulate cortex while Arc displayed a biphasic response. Also, in dentate gyrus, activation was observed at 0–6 h of reperfusion for Neuritin and 0–12 h of reperfusion for Arc while BDNF was induced 0–9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part of long-term synaptic responses of ischemic brain tissue.
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| 19. |
- Ruscher, Karsten, et al.
(författare)
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Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke.
- 2009
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 29, s. 1796-1805
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions that differentially improve recovery after occlusion of the middle cerebral artery occlusion (MCAO). We found that after MCAO the ApoE levels increased in the injured hemisphere over a 30 days recovery period. The exception was a proximal narrow peri-infarct rim, in which ApoE was solely localized in S100beta(+)/glial fibrillary acidic protein (GFAP) negative reactive astrocytes at 4 to 7 days of recovery. Enriched housing after MCAO caused a marked decrease in ApoE levels compared with standard housing conditions, particularly in the ApoE/S100beta(+) reactive astrocytes. In addition, the levels of interleukin 1beta were lower in animals housed in an enriched environment. We propose that during the subacute phase after experimental stroke a zone for tissue reorganization with low cellular ApoE levels is formed. We conclude that the strong sensori-motor stimulation provided by enriched housing conditions mitigates the inflammatory response after stroke decreasing the level of ApoE that may contribute to the observed improvement of functional recovery.Journal of Cerebral Blood Flow & Metabolism advance online publication 22 July 2009; doi:10.1038/jcbfm.2009.96.
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| 20. |
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| 21. |
- Ruscher, Karsten, et al.
(författare)
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The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke.
- 2011
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 134:3, s. 732-746
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Tidskriftsartikel (refereegranskat)abstract
- Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride, an agonist of the sigma-1 receptor, starting two days after injury, enhanced the recovery of lost sensorimotor function without decreasing infarct size. The sigma-1 receptor was found in the galactocerebroside enriched membrane microdomains of reactive astrocytes and in neurons. Sigma-1 receptor activation increased the levels of the synaptic protein neurabin and neurexin in membrane rafts in the peri-infarct area, while sigma-1 receptor silencing prevented sigma-1 receptor-mediated neurite outgrowth in primary cortical neuronal cultures. In astrocytic cultures, oxygen and glucose deprivation induced sigma-1 receptor expression and actin dependent membrane raft formation, the latter blocked by sigma-1 receptor small interfering RNA silencing and pharmacological inhibition. We conclude that sigma-1 receptor activation stimulates recovery after stroke by enhancing cellular transport of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection.
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| 22. |
- Schnabel, Renate B, et al.
(författare)
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Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation : the 8th AFNET/EHRA consensus conference
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 6-27
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Tidskriftsartikel (refereegranskat)abstract
- Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
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| 23. |
- Shamloo, Mehrdad, et al.
(författare)
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Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia
- 2006
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 24:10, s. 2705-2720
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Tidskriftsartikel (refereegranskat)abstract
- Basic helix-loop-helix PAS domain proteins form a growing family of transcription factors. These proteins are involved in the process of adaptation to cellular stresses and environmental factors such as a change in oxygen concentration. We describe the identification and characterization of a recently cloned PAS domain protein termed Npas4 in ischemic rat brain. Using gene expression profiling following middle cerebral artery occlusion, we showed that the Npas4 mRNA is differentially expressed in ischemic tissue. The full-length gene was cloned from rat brain and its spatial and temporal expression characterized with in situ hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in the brain and is highly up-regulated in ischemic tissues following both focal and global cerebral ischemic insults. Immunohistochemistry revealed a strong expression in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a protein of similar to 100 kDa. In brain samples, however, in addition to the 100 kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the 100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for activation and/or deactivation of this protein in response to ischemic brain injury.
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| 24. |
- Singh, Jagmeet P., et al.
(författare)
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Phased target trial design and meta-analysis in a head-to-head treatment comparison
- 2023
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:Suppl. 1, s. 444-444
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: For conditions with rare clinical outcomes, real-world treatment comparisons are challenging to design and prone to confounding.Objectives: To present a robust methodologic approach for rigorous and transparent assessment of rare outcomes using real-world data.Methods: We emulated a target trial using an active comparator, new-user design to compare dronedarone to sotalol for rhythm control in atrial fibrillation (AF) as both are recommended for similar patient phenotypes. Using one protocol, a pre-specified stepwise approach was implemented across 4 datasets (Optum CDM; IBM MarketScan; Veterans Affairs Electronic Health Records; Swedish National Patient Register). Meta-analysis was used to ensure sufficient capture of specific, rare primary outcomes (cardiovascular (CV) hospitalization and ventricular proarrhythmia) and to evaluate consistency of findings across patient populations. Steps 1–3 focused on cohort selection, propensity score matching (PSM), baseline equipoise and residual confounding assessment via negative control outcome analyses. In steps 4–6, outcomes in the individual cohorts were analyzed using an as-treated approach and Cox proportional hazards models. Step 7 included a heterogeneity assessment, meta-analysis using fixed effects models, and hypothesis testing using a hierarchical approach. In step 8, sensitivity analyses, including E-values and Inverse Probability of Censoring Weighting, were conducted to verify the robustness of findings.Results: In step 1, 35,467 sotalol and 27,955 dronedarone patients with AF who were antiarrhythmic drug-naive were identified across databases. In steps 2–3, 23,275 dronedarone patients were PS-matched to 23,275 sotalol patients. Baseline covariates were well-balanced and little-to-no residual confounding was observed via the negative control analyses. Individual HRs were estimated in steps 4–6, and, when no significant heterogeneity between databases was observed, hazard ratios (HRs) were pooled across datasets in step 7. For example, for CV hospitalization, dronedarone was superior to sotalol with no heterogeneity (HR: 0.91; 95% CI: 0.85, 0.97; Cochran Q p-value: 0.32). Eleven sensitivity analyses were conducted in step 8 and confirmed that findings were generally robust.Conclusions: An active comparator, new-user design using the target trial approach coupled with meta-analysis generated consistent findings across databases and countries using one protocol. Similar methods, including a pre-specified stepwise approach, negative control outcome, and tests for robustness should be considered for real-world studies where specific, rare outcomes need to be examined in a rigorous and transparent way.
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| 25. |
- Smith, Gustav, et al.
(författare)
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Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score.
- 2012
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Ingår i: EuroIntervention. - 1969-6213. ; 8:6, s. 672-678
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. Methods and results: We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048). Conclusions: TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.
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