| 1. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 2. |
- Anderson, Christopher D., et al.
(författare)
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Genetic variants in CETP increase risk of intracerebral hemorrhage
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
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| 3. |
- Frykholm, Erik, 1985-, et al.
(författare)
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Effect and feasibility of non-linear periodized resistance training in people with COPD : study protocol for a randomized controlled trial
- 2019
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen.METHODS: This is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events.DISCUSSION: The proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD.TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03518723 . Registered on 13 April 2018.
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| 4. |
- Frykholm, Erik, 1985-, et al.
(författare)
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Inter-day test–retest reliability and feasibility of isokinetic, isometric, and isotonic measurements to assess quadriceps endurance in people with chronic obstructive pulmonary disease : A multicenter study
- 2018
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Ingår i: Chronic Respiratory Disease. - : Sage Publications. - 1479-9723 .- 1479-9731. ; 16, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The aims were to determine reliability and feasibility of measurements to assess quadriceps endurance in people with chronic obstructive pulmonary disease. Sixty participants (forced expiratory volume in one second (mean ± standard deviation) 55 ± 18% of predicted, age 67 ± 8 years) were tested in an inter-day, test–retest design. Isokinetic, isometric, and isotonic protocols were performed using a computerized dynamometer. Test–retest relative and absolute reliability was determined via intraclass correlation coefficient (ICC), coefficient of variation (CV%), and limits of agreement (LoA%). Isokinetic total work demonstrated very high relative reliability (ICC: [95% confidence interval] = 0.98 [0.94–0.99]) and the best absolute reliability (CV% (LoA%) = 6.5% (18.0%)). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64 [0.46–0.77], 0.88 [0.76–0.94], 0.91 [0.85–0.94]), and measures of absolute reliability (CV% (LoA%)) were 20.3% (56.4%), 14.9% (40.8%), and 15.8% (43.1%). For isokinetic total work and isometric measurements, participants performed better on retest (4.8% and 10.0%, respectively). The feasibility was similar across protocols with an average time consumption of less than 7.5 minutes. In conclusion, isokinetic, isometric, and isotonic measurements of quadriceps endurance were feasible to a similar extent and presented low-to-very high relative reliability. Absolute reliability seems to favor isokinetic total work measurements.
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| 5. |
- Frykholm, Erik, 1985-, et al.
(författare)
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Isotonic quadriceps endurance is better associated with daily physical activity than quadriceps strength and power in COPD : an international multicentre cross-sectional trial
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about modifiable determinants of daily physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is crucial to design effective PA interventions. The present study aimed to determine the contribution of quadriceps strength, power and endurance to daily PA in COPD. Additionally, for quadriceps endurance, we also aimed to determine to what extent the association varies according to the mode of movement (isotonic, isometric, or isokinetic). Using a multicentre cross-sectional trial design we determined the contribution of quadriceps function to daily PA (steps, sedentary time and time spent doing moderate-to-very-vigorous physical activity [MVPA]) using bivariate and partial Pearson correlation analysis (r) and multiple linear regression models (ΔR2). Pre-determined controlling factors were sex, age, body mass index (BMI), COPD-assessment test, forced expiratory volume in one second in percent of the predicted value (FEV1pred), and distance walked on the 6-minute walk test. Eighty-one patients with COPD (mean ± SD: age 67 ± 8 years, FEV1pred 57 ± 19%, daily steps 4968 ± 3319, daily sedentary time 1016 ± 305 min, and MVPA time 83 ± 45 min) were included. Small to moderate bivariate correlations (r =.225 to.452, p <.05) were found between quadriceps function and measures of PA. The best multiple linear regression models explained 38–49% of the variance in the data. Isotonic endurance was the only muscle contributor that improved all PA models; daily steps (ΔR2 =.04 [relative improvement 13%] p =.026), daily sedentary time (ΔR2 =.07 [23%], p =.005) and MVPA-minutes (ΔR2 =.08 [20%], p =.001). Isotonic endurance was also independently associated with most PA variables, even when controlling for strength, power or isometric-isokinetic endurance properties of the muscle (r =.246 to.384, p <.05). In contrast, neither strength, power, isometric-or isokinetic endurance properties of the muscle was independently associated with PA measures when controlling for isotonic endurance (r =.037 to.219, p >.05). To conclude, strength, power, and endurance properties of the quadriceps were low to moderately associated with PA in patients with COPD. Isotonic quadriceps endurance was the only quadriceps property that was independently associated with the different measures of PA after controlling for a basic set of known determinants of PA, quadriceps strength or power, or isometric or isokinetic quadriceps endurance. Future longitudinal studies should investigate its potential as a modifiable determinant of PA.
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| 6. |
- Frykholm, Erik, 1985-, et al.
(författare)
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Test-retest reliability of three strategies to measure quadriceps muscle endurance in people with COPD
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Despite its clinical relevance, there is no consensus on how to measure quadriceps muscle endurance in people with COPD. Moreover, the reliability of available measurement strategies are only partly known.Aim: To determine test-retest reliability and feasibility of isokinetic, isometric and isotonic protocols to assess quadriceps muscle endurance in people with COPD.Method: Fifty nine participants (FEV1 of predicted 55±18%, age 67±8 years) were included and tested in an interday multicentre test-retest design with test occasions separated by 5-9 days. Quadriceps muscle endurance was assessed using isokinetic, isometric and isotonic knee extension protocols controlled by a computerized dynamometer. Relative reliability was determined by intra-class correlation coefficient (ICC)( two-way mixed effects, absolute agreement, single measurement) and absolute reliability by standard error of measurement (SEM).Result: Isokinetic measurements demonstrated very high relative reliability (ICC: [95% confidence interval] 0.97 [0.94-0.99]), and isometric and isotonic demonstrated high relative reliability (0.89 [0.79-0.94], and 0.89 [0.82-0.94], respectively). Mean values across test-retest occasions were 2122 joules, 49 seconds, and 29 repetitions, for isokinetic, isometric and isotonic measurements, respectively. Corresponding SEM values were 150 joules, 7 seconds, and 5 repetitions. All three measurement strategies were feasible with an average time consumption of less than 10 minutes and no major adverse events.Conclusion: The results indicate that isokinetic, isotonic and isometric measurements of quadriceps muscle endurance are reliable and feasible in people with COPD.
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| 7. |
- Gephine, Sarah, et al.
(författare)
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Specific contribution of quadriceps muscle strength, endurance, and power to functional exercise capacity in people with chronic obstructive pulmonary disease : a multicenter study
- 2021
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Ingår i: Physical Therapy. - : Oxford University Press. - 0031-9023 .- 1538-6724. ; 101:6, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Various functional muscle properties affect different aspects of functional exercise capacity in people with COPD. The purpose of this study was to investigate the contribution of quadriceps muscle strength, endurance, and power to the 6-minute walking distance (6MWD) and the 1-minute sit-to-stand test (1STS) performance in people with COPD.METHODS: The study was a prospective, multicenter cross-sectional study. Anthropometrics, Medical Research Council (MRC) dyspnea scale, lung function, 6MWD and the 1STS number of repetitions were assessed. Isometric quadriceps strength (Strength-ISOM) and endurance (Endurance-ISOM), isotonic quadriceps endurance (Endurance-ISOT), isokinetic quadriceps strength (Strength-ISOKIN), and power (Power-ISOKIN) were assessed on a computerized dynamometer while functional quadriceps power was determined during 5 sit-to-stand repetitions (Power-5STS). Univariate and multivariate analyses were performed to determine the contribution of functional muscle properties on the 6MWD and the 1STS number of repetitions.RESULTS: The study included 70 people with COPD (mean % predicted FEV1 = 58.9 [SD = 18.2]). The 6MWD correlated with each functional muscle property, except the Endurance-ISOM. The number of repetitions during the 1STS correlated with each functional muscle property except isometric measurements. Multivariate models explained respectively 60% and 39% of the variance in the 6MWD and 1STS number of repetitions, with Power-5STS being the muscle functional property with the strongest contribution to the models.CONCLUSION: Except for isometric endurance, quadriceps strength, endurance, and power were associated with functional exercise capacity in people with moderate COPD. Among these functional muscle properties, muscle power contributed the most to the 6MWD and 1STS number of repetitions, suggesting that muscle power is more relevant to functional exercise capacity than muscle strength or endurance in people with COPD.IMPACT: Understanding the individual contribution of muscle properties to functional status is important to designing interventions. This study provides the guidance that muscle power may be more important to functional exercise capacity than muscle strength or endurance in people with COPD.
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| 8. |
- Jakobsson, Johan, et al.
(författare)
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Quality of aerobic training description and its relation to intervention efficacy in chronic obstructive pulmonary disease trials : study protocol for a systematic review, meta-analysis and meta-regression
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Chronic obstructive pulmonary disease (COPD) is a major global health concern, characterised by ventilatory constraints, decreased cardiovascular fitness and reduced limb muscle function, profoundly affecting patients’ quality of life. Aerobic training plays a crucial role in the treatment of COPD, but the variability in methodologies and incomplete reporting of key components in aerobic training trials limits the assessment of their effectiveness. This systematic review aims to critically evaluate the application of training principles and reporting of key components in aerobic training trials in randomised controlled trials (RCTs) in the COPD literature.Methods and analysisThe protocol adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol guidelines. The review will include RCTs utilising aerobic training in individuals with COPD. A comprehensive search, following a predefined search strategy will identify studies published from 2007 to 2024 in English from MEDLINE, Embase, CINAHL, CENTRAL and PEDro. Studies including people with COPD and any aerobic training intervention will be included. Two reviewers will independently screen abstracts and titles for inclusion. Two reviewers will independently conduct the screening of full-text documents and data extraction. Study quality will be assessed using the Tool for the assESsment of sTudy quality and bias in Exercise, specifically developed for exercise training studies. The certainty of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. A systematic synthesis will be provided, with meta-analyses and meta-regression when appropriate.Ethics and disseminationAs this review will involve the analysis of published data, ethical approval is not required. The findings of this review will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration number CRD42021247343.
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| 9. |
- Lewczuk, Piotr, et al.
(författare)
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
- 2018
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Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
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Tidskriftsartikel (refereegranskat)abstract
- In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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| 10. |
- Westra, Bennie, et al.
(författare)
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Quality of resistance training description in COPD trials: study protocol for a systematic review
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Limb muscle dysfunction is a common manifestation in patients with chronic obstructive pulmonary disease (COPD). Optimising of limb muscle function is therefore an important goal during pulmonary rehabilitation of patients with COPD. Resistance training (RT) is the best available intervention to achieve this goal. Previous systematic reviews on RT primarily focused on methodological quality. However, the intervention holds the essence of each experimental study. Replication of RT interventions requires clear, complete and accessible reporting of the essential components. The American College of Sports Medicine (ACSM) provides evidencebased guidelines for RT prescription and recommends RT models specific to desired outcomes, that is, improvements in strength, muscular hypertrophy, power or local muscle endurance. The aim of this review is to investigate if the application of the RT principles and key training variables is described sufficiently in current evidence on the effects of RT interventions in patients with COPD.Methods and analysis: Any research study (randomised, non-randomised controlled, controlled pre–post studies and observational studies) with an RT intervention in patients with COPD will be considered for this systematic review. Potentially relevant studies published in English from inception to 1 October 2017 will be identified from Embase, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Physiotherapy Evidence Database (PEDro). Studies exploring the effects of RT following a single session and RT interventions limited to other respiratory chronic diseases will not be included. Additionally, studies including non-COPD participants will be excluded, if the COPD data are not separated. Pairs of reviewers will independently extract data using data collecting sheets. Quality appraisal of RT description will be performed in timeframes according to the latest published ACSM position statement on exercise or RT.Ethics and dissemination: This protocol is a systematic review and therefore ethical approval is not required. The results of this review will be disseminated through peer-reviewed publication and presented at scientific conferences.
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