| 1. |
- Chastin, Sebastien, et al.
(författare)
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Joint association between accelerometry-measured daily combination of time spent in physical activity, sedentary behaviour and sleep and all-cause mortality : A pooled analysis of six prospective cohorts using compositional analysis
- 2021
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 55:22, s. 1277-1285
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality.METHODS: Federated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis.PARTICIPANTS: 130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden.MAIN OUTCOME: All-cause mortality (follow-up 4.3-14.5 years).RESULTS: Studies using wrist and hip accelerometer provided statistically different results (I2=92.2%, Q-test p<0.001). There was no association between duration of sleep and all-cause mortality, HR=0.96 (95% CI 0.67 to 1.12). The proportion of time spent in moderate to vigorous physical activity was significantly associated with lower risk of all-cause mortality (HR=0.63 (95% CI 0.55 to 0.71) wrist; HR=0.93 (95% CI 0.87 to 0.98) hip). A significant association for the ratio of time spent in light physical activity and sedentary time was only found in hip accelerometer-based studies (HR=0.5, 95% CI 0.42 to 0.62). In studies based on hip accelerometer, the association between moderate to vigorous physical activity and mortality was modified by the balance of time spent in light physical activity and sedentary time.CONCLUSION: This federated analysis shows a joint dose-response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour.
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| 2. |
- Ekelund, Ulf, et al.
(författare)
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Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality : systematic review and harmonised meta-analysis
- 2019
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Ingår i: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138. ; 366
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVETo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DESIGNSystematic review and harmonised meta-analysis.DATA SOURCESPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.ELIGIBILITY CRITERIAProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.DATA EXTRACTION AND ANALYSISGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.MAIN OUTCOME MEASUREAll cause mortality.RESULTS39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).CONCLUSIONHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.
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| 3. |
- Ernest, C. Steven, II, et al.
(författare)
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Methodological Comparison of In Vitro Binding Parameter Estimation : Sequential vs. Simultaneous Non-linear Regression
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:5, s. 866-877
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of simulated data was compared using sequential (NLR) and simultaneous non-linear regression (SNLR) to evaluate precision and accuracy of ligand binding parameter estimation. Commonly encountered experimental error, specifically residual error of binding measurements (RE), experiment-to-experiment variability (BEV) and non-specific binding (B-NS), were examined for impact of parameter estimation using both methods. Data from equilibrium, dissociation, association and non-specific binding experiments were fit simultaneously (SNLR) using NONMEM VI compared to the common practice of analyzing data from each experiment separately and assigning these as exact values (NLR) for estimation of the subsequent parameters. The greatest contributing factor to bias and variability in parameter estimation was RE of the measured concentrations of ligand bound; however, SNLR provided more accurate and less bias estimates. Subtraction of B-NS from total ligand binding data provided poor estimation of specific ligand binding parameters using both NLR and SNLR. Additional methods examined demonstrated that the use of SNLR provided better estimation of specific binding parameters, whereas there was considerable bias using NLR. NLR cannot account for BEV, whereas SNLR can provide approximate estimates of BEV. SNLR provided superior resolution of parameter estimation in both precision and accuracy compared to NLR.
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| 4. |
- Ernest II, Charles Steven, et al.
(författare)
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Simultaneous optimal experimental design for in vitro binding parameter estimation
- 2013
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science+Business Media B.V.. - 1567-567X .- 1573-8744. ; 40:5, s. 573-585
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous optimization of in vitro ligand binding studies using an optimal design software package that can incorporate multiple design variables through non-linear mixed effect models and provide a general optimized design regardless of the binding site capacity and relative binding rates for a two binding system. Experimental design optimization was employed with D- and ED-optimality using PopED 2.8 including commonly encountered factors during experimentation (residual error, between experiment variability and non-specific binding) for in vitro ligand binding experiments: association, dissociation, equilibrium and non-specific binding experiments. Moreover, a method for optimizing several design parameters (ligand concentrations, measurement times and total number of samples) was examined. With changes in relative binding site density and relative binding rates, different measurement times and ligand concentrations were needed to provide precise estimation of binding parameters. However, using optimized design variables, significant reductions in number of samples provided as good or better precision of the parameter estimates compared to the original extensive sampling design. Employing ED-optimality led to a general experimental design regardless of the relative binding site density and relative binding rates. Precision of the parameter estimates were as good as the extensive sampling design for most parameters and better for the poorly estimated parameters. Optimized designs for in vitro ligand binding studies provided robust parameter estimation while allowing more efficient and cost effective experimentation by reducing the measurement times and separate ligand concentrations required and in some cases, the total number of samples.
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| 5. |
- Mentre, France, et al.
(författare)
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Software for optimal design in population pharmacokinetics and pharmacodynamics : a comparison
- 2007
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Konferensbidrag (refereegranskat)abstract
- Introduction: Following the first theoretical work on optimal design for nonlinear mixed effect models, this research theme has rapidly grown both in methodological and application developments. There are now several different software tools that implement an evaluation of the Fisher information matrix for population PK and PD models and proposed optimization of the experimental designs. In 2006, the Population Optimal Design of Experiments workshop was created with a meeting every year in May (www.maths.qmul.ac.uk/~bb/PODE/PODE2007.html). This year at PODE07 a special session was organized to present different software tools for population PK/PD optimal design and to compare them with respect to their statistical methodology. Objectives: 1) To present the different software tools; 2) To compare the statistical methods implemented in these tools; 3) To report the conclusion of the PODE07 meeting with respect to future software development in population PK/PD design. Methods: The software tools will be compared with respect to: a) their availability, b) required language, c) library of PK or PD models, d) ability to deal with multiresponse models and/or with models defined by differential equations, e) approximations made to compute the Fisher information matrix, f) optimisation criteria, g)optimisation algorithms, h) ability to optimize design structure, i) ability to deal with constraints in sampling times, j) availability of optimisation trough sampling windows, k) assessment of user specified designs, l) ability to deal with unbalanced multiresponse designs, m) ability to deal with correlations between random effects, o) provided outputs ... Results: The five software tools discussed at PODE07 are (in alphabetical order): PFIM (S. Retout & F. Mentré), PkStaMP (S. Leonov), PopDes (K. Ogungbenro & I. Gueorguieva) PopED (A. Hooker), and WinPOPT (S. Duffull). Tables comparing the software with respect to the different aspects described in the method section will be reported. The conclusions of the PODE07 meeting regarding future software development for optimal design in population PK/PD will be presented.
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