| 21. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 22. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 23. |
- Bajraktari, Gani, et al.
(författare)
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Comparison of drug-eluting balloon versus drug-eluting stent treatment of drug-eluting stent in-stent restenosis : A meta-analysis of available evidence
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 218, s. 126-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In-stent restenosis (ISR) remains an important concern despite the recent advances in the drug-eluting stent (DES) technology. The introduction of drug-eluting balloons (DEB) offers a good solution to such problem.OBJECTIVES: We performed a meta-analysis to assess the clinical efficiency and safety of DEB compared with DES in patients with DES-ISR.METHODS: A systematic search was conducted and all randomized and observational studies which compared DEB with DES in patients with DES-ISR were included. The primary outcome measure-major adverse cardiovascular events (MACE)-as well as individual events as target lesion revascularization (TLR), stent thrombosis (ST), myocardial infarction (MI), cardiac death (CD) and all-cause mortality, were analyzed.RESULTS: Three randomized and 4 observational studies were included with a total of 2052 patients. MACE (relative risk [RR]=1.00, 95% confidence interval (CI) 0.68 to 1.46, P=0.99), TLR (RR=1.15 [CI 0.79 to 1.68], P=0.44), ST (RR=0.37[0.10 to 1.34], P=0.13), MI (RR=0.97 [0.49 to 1.91], P=0.93) and CD (RR=0.73 [0.22 to 2.45], P=0.61) were not different between patients treated with DEB and with DES. However, all-cause mortality was lower in patients treated with DEB (RR=0.45 [0.23 to 0.87, P=0.019) and in particular when compared to only first generation DES (RR 0.33 [0.15-0.74], P=0.007). There was no statistical evidence for publication bias.CONCLUSIONS: The results of this meta-analysis showed that DEB and DES have similar efficacy and safety for the treatment of DES-ISR.
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| 24. |
- Bajraktari, Gani, et al.
(författare)
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Complete revascularization for patients with multivessel coronary artery disease and ST-segment elevation myocardial infarction after the COMPLETE trial : a meta-analysis of randomized controlled trials
- 2020
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Ingår i: IJC Heart & Vasculature. - : Elsevier. - 2352-9067. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recently published COMPLETE trial has demonstrated that patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), who underwent successful percutaneous coronary intervention (PCI) of both culprit and non-culprit (vs. culprit-only) lesions had a reduced risk of major adverse cardiac events (MACE), but not of cardiovascular or total mortality. The aim of this meta-analysis was to assess the efficacy of complete revascularization on cardiovascular or total mortality reduction using available randomized controlled trials (RCTs) including the COMPLETE trial, in hemodynamically stable STEMI patients with MVD. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 10 RCTs of 7033 patients with STEMI and MVD which compared complete (n = 3420) vs. only culprit lesion (n = 3613) PCI for a median 27.7 months follow-up. Random effect risk ratios were used to estimate for efficacy and safety outcomes. Results: Complete revascularization reduced the risk of MACE (10.4% vs.16.6%; RR = 0.59, 95% CI: 0.47 to 0.74, p < 0.0001), CV mortality (2.87% vs. 3.72%; RR = 0.73, 95% CI: 0.56 to 0.95, p = 0.02), reinfarction (5.1% vs. 7.1%; RR = 0.67, 95% CI: 0.52 to 0.86, p = 0.002), urgent revascularization (7.92% vs.17.4%; RR = 0.47, 95% CI: 0.30 to 0.73, p < 0.001), and CV hospitalization (8.68% vs.11.4%; RR = 0.65, 95% CI: 0.44to 0.96, p = 0.03) compared with culprit only revascularization. All-cause mortality, stroke, major bleeding events, or contrast induced nephropathy were not affected by the revascularization strategy. Conclusion: The findings of this meta-analysis suggest that in patients with STEMI and MVD, complete revascularization is superior to culprit-only PCI in reducing the risk of MACE outcomes, including cardiovascular mortality, without increasing the risk of adverse safety outcomes.
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| 25. |
- Bajraktari, Gani, et al.
(författare)
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Complete revascularization for patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease : a meta-analysis of randomized trials
- 2018
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 29:3, s. 204-215
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Despite the recent findings in randomized clinical trials (RCTs) with limited sample sizes and the updates in clinical guidelines, the current available data for the complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) at the time of primary percutaneous coronary intervention (PCI) are still contradictory.Aim: The aim of this meta-analysis of the existing RCTs was to assess the efficacy of the CR versus revascularization of infarct-related artery (IRA) only during primary PCI in patients with STEMI and multivessel disease (MVD).Patients and methods: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA-only. Random effect risk ratios (RRs) were calculated for efficacy and safety outcomes.Results: Ten RCTs with 3291 patients were included. The median follow-up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76; P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with IRA-only strategies. However, there was no significant difference in the risk of all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major bleeding events, and contrast-induced nephropathy.Conclusion: For patients with STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk of major adverse cardiac events, repeat revascularization, and cardiac death is reduced by CR. However, the risk for all-cause mortality and PCI-related complications is not different from the isolated culprit lesion-only treatment. Although these findings support the cardiac mortality and safety benefit of CR in stable STEMI, further large trials are required to provide better guidance for optimum management of such patients.
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| 26. |
- Bajraktari, Gani, et al.
(författare)
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Long-Term Outcomes of Patients with Unprotected Left Main Coronary Artery Disease Treated with Percutaneous Angioplasty versus Bypass Grafting : A Meta-Analysis of Randomized Controlled Trials
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Treatment of patients with left main coronary artery disease (LMCA) with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The aim of this meta-analysis was to compare the long-term clinical outcomes of patients with unprotected LMCA treated randomly by PCI or CABG. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov database searches identified five randomized trials (RCTs) including 4499 patients with unprotected LMCA comparing PCI (n= 2249) vs. CABG (n= 2250), with a minimum clinical follow-up of five years. Random effect risk ratios were used for efficacy and safety outcomes. The study was registered in PROSPERO. The primary outcome was major adverse cardiac events (MACE), defined as a composite of death from any cause, myocardial infarction or stroke. Results: Compared to CABG, patients assigned to PCI had a similar rate of MACE (risk ratio (RR): 1.13; 95% CI: 0.94 to 1.36;p= 0.19), myocardial infarction (RR: 1.48; 95% CI: 0.97 to 2.25;p= 0.07) and stroke (RR: 0.87; 95% CI: 0.62 to 1.23;p= 0.42). Additionally, all-cause mortality (RR: 1.07; 95% CI: 0.89 to 1.28;p= 0.48) and cardiovascular (CV) mortality (RR: 1.13; 95% CI: 0.89 to 1.43;p= 0.31) were not different. However, the risk of any repeat revascularization (RR: 1.70; 95% CI: 1.34 to 2.15;p< 0.00001) was higher in patients assigned to PCI. Conclusions: The findings of this meta-analysis suggest that the long-term survival and MACE of patients who underwent PCI for unprotected LMCA stenosis were comparable to those receiving CABG, despite a higher rate of repeat revascularization.
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| 27. |
- Barazzoni, Rocco, et al.
(författare)
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Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:6, s. 1425-1433
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Tidskriftsartikel (refereegranskat)abstract
- The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic-and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition. (c) 2022 Elsevier Ltd. and European Society for Clinical Nutrition and Metabolism and American Society for Parenteral and Enteral Nutrition. All rights reserved.
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| 28. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 29. |
- Brugaletta, Salvatore, et al.
(författare)
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Morphology of coronary artery lesions assessed by virtual histology intravascular ultrasound tissue characterization and fractional flow reserve
- 2012
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Ingår i: The International Journal of Cardiovascular Imaging. - : Springer Science and Business Media LLC. - 1569-5794 .- 1875-8312 .- 1573-0743. ; 28:2, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- Fractional flow reserve (FFR) is an index of the physiological significance of a coronary stenosis. Patients who have lesions with a FFR of >0.80, even optimally treated with medication, have however a MACE rate ranging from 8 to 21%. Coronary plaques at high risk of rupture and clinical events can be also identified by virtual histology intravascular ultrasound (IVUS-VH) as plaques with high amount of necrotic core (NC) abutting the lumen. Aim of this exploratory study was to investigate whether the geometry and composition of lesions with FFR ≤ 0.80 were different from their counterparts. Fifty-five consecutive patients in whom FFR was clinically indicated on a moderate angiographic lesion, received also an imaging investigation on the same lesion with IVUS-VH. Data on plaque geometry and composition was analyzed. Patients were subdivided in two groups according to the value of FFR (> or ≤0.80). Lesions with a FFR ≤ 0.80 (n = 17) showed a slightly larger plaque burden than those with FFR > 0.80 (n = 38) (54.6 ± 0.7% vs. 51.7 ± 0.7% P = 0.1). In addition, they tend to have less content of necrotic core than their counterparts (14.2 ± 8% vs. 19.2 ± 10.2%, P = 0.08). No difference was found in the distribution of NC-rich plaques (fibroatheroma and thin-capped fibroatheroma) between groups (82% in FFR ≤ 0.80 vs. 79% in FFR > 0.80, P = 0.5). Although FFR ≤ 0.80 lesions have larger plaque size, they do not differ in composition from the ones with FFR > 0.80. Further exploration in a large prospective study is needed to study whether the lesions with FFR > 0.80 that are NC rich are the ones associated with the presence of clinical events at follow-up.
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| 30. |
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