| 1. |
- Bäck, Maria, et al.
(författare)
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The remote exercise SWEDEHEART study-Rationale and design of a multicenter registry-based cluster randomized crossover clinical trial (RRCT)
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 262, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs.Study design and objectives: The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self -preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular-and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control.Conclusions: The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if par-ticipation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care.Trial registration The study is registered atClinicalTrials.gov (Identifier: NCT04260958) (Am Heart J 2023;262:110-118.)
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| 2. |
- Cabrera, Carin C., et al.
(författare)
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Increased iron absorption in patients with chronic heart failure and iron deficiency
- 2020
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 26:5, s. 440-443
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iron deficiency (ID) is common in patients with chronic heart failure (CHF), but the underlying causes are not fully understood. We investigated whether ID is associated with decreased iron absorption in patients with CHF.Methods and Results: We performed an oral iron-absorption test in 30 patients and 12 controls. The patients had CHF with reduced (n = 15) or preserved (n = 15) ejection fraction and ID, defined as s- ferritin < 100 mu g/L, or s-ferritin 100-299 mu g/L and transferrin saturation < 20%. The controls had no HF or ID and were of similar age and gender. Blood samples were taken before and 2 hours after ingestion of 100 mg ferroglycin sulphate. The primary endpoint was the delta plasma iron at 2 hours. The delta plasma iron was higher in the group with HF than in the control group (median increase 83.8 [61.5;128.5] mu g/dL in HF vs 47.5 [ 30.7;61.5] mu g/dL in controls, P = 0.001), indicating increased iron absorption. There was no significant difference between the groups with preserved or reduced ejection fraction (P = 0.46).Conclusion: We found increased iron absorption in patients with CHF and ID compared to controls without ID and HF, indicating that reduced iron absorption is not a primary cause of the high prevalence of ID in patients with CHF.
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| 3. |
- Ekstrom, Mattias, et al.
(författare)
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Stimulated in vivo synthesis of plasminogen activator inhibitor 1 in human adipose tissue
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 108:3, s. 485-492
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Tidskriftsartikel (refereegranskat)abstract
- Plasminogen activator inhibitor type-1 (PAI-1) is one of the most important inhibitors of endogenous fibrinolysis. Adipose tissue is a suggested source of the elevated plasma levels o(-) PAI-1 in obesity. The relation between PAI-1 and inflammation is of particular interest, but current knowledge regarding regulation of PAI-1 in adipose tissue is mainly based on animal studies or ex vivo experiments on human cultured adipocytes. So far, no study has described stimulated gene expression and protein synthesis of PAI-1 in vivo in human adipose tissue. We used open heart surgery as a model of acute systemic inflammation. Twenty-two male patients underwent blood sampling and omental and subcutaneous adipose tissue biopsies for gene expression studies before and after surgery. Expression and localisation of PAI-1 antigen was evaluated by immunohistochemistry. After surgery gene expression of PAI-1 increased 27-fold in omental adipose tissue and three-fold in subcutaneous adipose tissue, but no differences were found in tissue-type plasminogen activator (t-PA) mRNA. PAI-1 antigen was localised within endothelial cells and in the adipose tissue interstitium close to vessels. The upregulated gene expression and protein synthesis in adipose tissue was followed by increased concentrations of PAI-1 antigen in plasma. In conclusion, we present for the first time that an acute systemic inflammation in humans increased gene expression and protein synthesis of PAI-1 in adipose tissue and that this increase was most prominent in omental adipose tissue. PAI-1 synthesis in adipose tissue due to acute systemic inflammation may be a link between inflammation and impaired endogenous fibrinolysis.
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| 4. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
- 2011
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
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Tidskriftsartikel (refereegranskat)abstract
- Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
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| 5. |
- Karlsson, Boris, 1987, et al.
(författare)
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Uncertainty Analysis and Order-by-Order Optimization of Chiral Nuclear Interactions
- 2016
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Ingår i: Physical Review X. - 2160-3308. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Chiral effective field theory (chi EFT) provides a systematic approach to describe low-energy nuclear forces. Moreover, chi EFT is able to provide well-founded estimates of statistical and systematic uncertainties-although this unique advantage has not yet been fully exploited. We fill this gap by performing an optimization and statistical analysis of all the low-energy constants (LECs) up to next-to-next-to-leading order. Our optimization protocol corresponds to a simultaneous fit to scattering and bound-state observables in the pion-nucleon, nucleon-nucleon, and few-nucleon sectors, thereby utilizing the full model capabilities of chi EFT. Finally, we study the effect on other observables by demonstrating forward-error-propagation methods that can easily be adopted by future works. We employ mathematical optimization and implement automatic differentiation to attain efficient and machine-precise first-and second-order derivatives of the objective function with respect to the LECs. This is also vital for the regression analysis. We use power-counting arguments to estimate the systematic uncertainty that is inherent to chi EFT, and we construct chiral interactions at different orders with quantified uncertainties. Statistical error propagation is compared with Monte Carlo sampling, showing that statistical errors are, in general, small compared to systematic ones. In conclusion, we find that a simultaneous fit to different sets of data is critical to (i) identify the optimal set of LECs, (ii) capture all relevant correlations, (iii) reduce the statistical uncertainty, and (iv) attain order-by-order convergence in chi EFT. Furthermore, certain systematic uncertainties in the few-nucleon sector are shown to get substantially magnified in the many-body sector, in particular when varying the cutoff in the chiral potentials. The methodology and results presented in this paper open a new frontier for uncertainty quantification in ab initio nuclear theory.
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| 6. |
- Leosdottir, Margret, et al.
(författare)
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Cohort profile: Data standards for cardiac rehabilitation structure and processes for the SWEDEHEART cardiac rehabilitation (SWEDEHEART-CR) registry
- 2023
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Data standards for quality registries should be evidence-based and follow guideline recommendations. To optimally monitor quality of care, not only patient-level variables, but also centre-level variables need to be included. Here we describe the development of variables to audit the structure and processes in cardiac rehabilitation for patients after myocardial infarction, and the resulting data standards to be implemented in the Swedish quality registry for cardiac disease, SWEDEHEART. The methodology used for the development of international clinical data standards for the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) was followed. Based on national guidelines for secondary prevention, candidate variables were prepared, after which a multiprofessional expert group on cardiac rehabilitation selected key variables and assured face validity. An external reference group had the role of peer reviewing, ascertaining content validity and test-retest reliability. The process has resulted in 30 data standards to be introduced into the SWEDEHEART cardiac rehabilitation registry and administered on centre-level biannually. The data standards include measures of human resources, centre requirements and process-based metrics. Including registry variables which audit centre-level structure and processes is essential to improve benchmarking and standardize monitoring of quality of care, covering both services provided and patient outcomes.
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| 7. |
- Linde, Cecilia, et al.
(författare)
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Baseline characteristics of 547 new onset heart failure patients in the PREFERS heart failure study
- 2022
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 9:4, s. 2125-2138
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Tidskriftsartikel (refereegranskat)abstract
- Aim We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology.Methods and results New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015-2018 and characterized by N-terminal pro brain natriuretic peptide (NT-proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) >= 50%) was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41-49%) and with HF with reduced LVEF (HFrEF; LVEF <= 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70-81 years; median; interquartile range) than HFrEF (67; 58-74; P < 0.001), more often women (49% vs. 30%; P < 0.001), and had significantly higher comorbidity burden. They more often had atrial fibrillation, hypertension, and renal dysfunction. NT-proBNP was lower in HFpEF (896; 462-1645 ng/L) than in HFrEF (1160; 563-2370; P = 0.005). In HFpEF, left ventricular (LV) diameters and volumes were smaller (P < 0.001) and septa! and posterior wall thickness and relative wall thickness higher (P < 0.001). E/e >= 14 was present in 26% of HFpEF vs. 32% of HFrEF (P = 0.017) and left atrial volume index > 34 mL/m(2) in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/e.Conclusions Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology.
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| 8. |
- Wiktelius, Daniel, et al.
(författare)
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In Situ Assembly of Choline Acetyltransferase Ligands by a Hydrothiolation Reaction Reveals Key Determinants for Inhibitor Design
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 60:2, s. 813-819
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Tidskriftsartikel (refereegranskat)abstract
- The potential drug target choline acetyltransferase (ChAT) catalyses the production of the neurotransmitter acetylcholine in cholinergic neurons, T-cells, and B-cells. Herein, we show that arylvinylpyridiniums (AVPs), the most widely studied class of ChAT inhibitors, act as substrate in an unusual coenzyme A-dependent hydrothiolation reaction. This in situ synthesis yields an adduct that is the actual enzyme inhibitor. The adduct is deeply buried in the active site tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the molecular recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target-catalysed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency and bioactivity.
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