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| 2. |
- Boone, Sebastiaan C., et al.
(författare)
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Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue
- 2022
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 191:5, s. 886-899
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Tidskriftsartikel (refereegranskat)abstract
- Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R-2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm(2) and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R-2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R-2 = 0.63, RMSE = 42.4 cm(2), calibration slope = 0.94) but lower in MESA (R-2 = 0.44, RMSE = 60.7 cm(2), calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.
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| 3. |
- Eikenboom, Anna M, et al.
(författare)
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Quality of Conduct and Reporting of Propensity Score Methods in Studies Investigating the Effectiveness of Antimicrobial Therapy
- 2022
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Propensity score methods are becoming increasingly popular in infectious disease medicine to correct for confounding in observational studies. However, applying and reporting propensity score techniques correctly requires substantial knowledge of these methods. The quality of conduct and reporting of propensity score methods in studies investigating the effectiveness of antimicrobial therapy is yet undetermined.Methods: A systematic review was performed to provide an overview of studies (2005-2020) on the effectiveness of antimicrobial therapy that used propensity score methods. A quality assessment tool and a standardized quality score were developed to evaluate a subset of studies in which antibacterial therapy was investigated in detail. The scale of this standardized score ranges between 0 (lowest quality) and 100 (excellent).Results: A total of 437 studies were included. The absolute number of studies that investigated the effectiveness of antimicrobial therapy and that used propensity score methods increased 15-fold between the periods 2005-2009 and 2015-2019. Propensity score matching was the most frequently applied technique (65%), followed by propensity score-adjusted multivariable regression (25%). A subset of 108 studies was evaluated in detail. The median standardized quality score per year ranged between 53 and 61 (overall range: 33-88) and remained constant over the years.Conclusions: The quality of conduct and reporting of propensity score methods in research on the effectiveness of antimicrobial therapy needs substantial improvement. The quality assessment instrument that was developed in this study may serve to help investigators improve the conduct and reporting of propensity score methods.
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| 4. |
- Goetghebeur, Els, et al.
(författare)
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Formulating causal questions and principled statistical answers
- 2020
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Ingår i: Statistics in Medicine. - : WILEY. - 0277-6715 .- 1097-0258. ; 39:30, s. 4922-4948
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Tidskriftsartikel (refereegranskat)abstract
- Although review papers on causal inference methods are now available, there is a lack of introductory overviews onwhatthey can render and on the guiding criteria for choosing one particular method. This tutorial gives an overview in situations where an exposure of interest is set at a chosen baseline ("point exposure") and the target outcome arises at a later time point. We first phrase relevant causal questions and make a case for being specific about the possible exposure levels involved and the populations for which the question is relevant. Using the potential outcomes framework, we describe principled definitions of causal effects and of estimation approaches classified according to whether they invoke the no unmeasured confounding assumption (including outcome regression and propensity score-based methods) or an instrumental variable with added assumptions. We mainly focus on continuous outcomes and causal average treatment effects. We discuss interpretation, challenges, and potential pitfalls and illustrate application using a "simulation learner," that mimics the effect of various breastfeeding interventions on a child's later development. This involves a typical simulation component with generated exposure, covariate, and outcome data inspired by a randomized intervention study. The simulation learner further generates various (linked) exposure types with a set of possible values per observation unit, from which observed as well as potential outcome data are generated. It thus provides true values of several causal effects. R code for data generation and analysis is available on , where SAS and Stata code for analysis is also provided.
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| 5. |
- Gouw, Samantha C., et al.
(författare)
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F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 119:12, s. 2922-2934
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Forskningsöversikt (refereegranskat)abstract
- This systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. Asystematic literature search was performed to include cohort studies published in peer-reviewed journals with data on inhibitor incidences in the various F8 gene mutation types and a mutation detection rate of at least 80%. Pooled odds ratios (ORs) of inhibitor development for different types of F8 gene mutations were calculated with intron 22 inversion as the reference. Data were included from 30 studies on 5383 patients, including 1029 inhibitor patients. The inhibitor risk in large deletions and nonsense mutations was higher than in intron 22 inversions (pooled OR = 3.6, 95% confidence interval [95% CI], 2.3-5.7 and OR = 1.4, 95% CI, 1.1-1.8, respectively), the risk in intron 1 inversions and splice-site mutations was equal (pooled OR = 0.9; 95% CI, 0.6-1.5 and OR = 1.0; 95% CI, 0.6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar. (Blood. 2012;119(12):2922-2934)
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| 6. |
- Lindmark, Anita, 1986-
(författare)
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Statistical methods for register based studies with applications to stroke
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis adds to the area of register based research, with a particular focus on health care quality and (in)equality. Contributions are made to the areas of hospital performance benchmarking, mediation analysis, and regression when the outcome variable is limited, with applications related to Riksstroke (the Swedish stroke register).An important part of quality assurance is to identify, follow up, and understand the mechanisms of inequalities in outcome and/or care between different population groups. The first paper of the thesis uses Riksstroke data to investigate socioeconomic differences in survival during different time periods after stroke. The second paper focuses on differences in performance between hospitals, illustrating the diagnostic properties of a method for benchmarking hospital performance and highlighting the importance of balancing clinical relevance and the statistical evidence level used.Understanding the mechanisms behind observed differences is a complicated but important issue. In mediation analysis the goal is to investigate the causal mechanisms behind an effect by decomposing it into direct and indirect components. Estimation of direct and indirect effects relies on untestable assumptions and a mediation analysis should be accompanied by an analysis of how sensitive the results are to violations of these assumptions. The third paper proposes a sensitivity analysis method for mediation analysis based on binary probit regression. This is then applied to a mediation study based on Riksstroke data.Data registration is not always complete and sometimes data on a variable are unavailable above or below some value. This is referred to as censoring or truncation, depending on the extent to which data are missing. The final two papers of the thesis are concerned with the estimation of linear regression models for limited outcome variables. The fourth paper presents a software implementation of three semi-parametric estimators of truncated linear regression models. The fifth paper extends the sensitivity analysis method proposed in the third paper to continuous outcomes and mediators, and situations where the outcome is truncated or censored.
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| 7. |
- van Schie, Rianne M F, et al.
(författare)
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Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data
- 2011
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:15, s. 1909-1917
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Polymorphisms in CYP2C9 and VKORC1 influence patients' phenprocoumon (PHE) and acenocoumarol (ACE) dose requirements. To provide physicians with tools to estimate the patient's individual dose, we aimed to develop algorithms for PHE and ACE. METHODS AND RESULTS: In two Dutch anticoagulation clinics, data on age, sex, height, weight, co-medication, coumarin derivative doses, and international normalized ratio values were obtained from 624 patients taking PHE and 471 taking ACE. Single nucleotide polymorphisms relevant to coumarin derivative dosing on the CYP2C9 and VKORC1 genes were determined. Using multiple linear regression, we developed genotype-guided and non-genotype-guided algorithms to predict the maintenance dose with patient characteristics and genetic information. In addition, loading doses were derived from the calculated maintenance doses. We performed external validation in an independent data set with 229 PHE and 168 ACE users. CYP2C9 and VKORC1 genotype, weight, height, sex, age, and amiodarone use contributed to the maintenance dose of PHE and ACE. The genotype-guided algorithms explained 55.9% (PHE) and 52.6% (ACE) of the variance of the maintenance dose, the non-genetic algorithms 17.3% (PHE) and 23.7% (ACE). Validation in an independent data set resulted in an explained variation of 59.4% (PHE) and 49.0% (ACE) for the genotype-guided algorithms and for 23.5% (PHE) and 17.8% (ACE) for the non-genotype-guided algorithms, without height and weight as parameters. CONCLUSION: To our knowledge, these are the first genotype-guided loading and maintenance dose algorithms for PHE and ACE using large cohorts. The utility of these algorithms will be tested in randomized controlled trials.
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| 8. |
- van Velzen, Alice S., et al.
(författare)
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Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients : Results of the INSIGHT case-control study
- 2017
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 15:7, s. 1422-1429
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Tidskriftsartikel (refereegranskat)abstract
- Essentials: Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Summary: Background: Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives: We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods: We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results: Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1/ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions: Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.
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| 9. |
- Verhoef, Talitha I., et al.
(författare)
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A Randomized Trial of Genotype-Guided Dosing of Acenocoumarol and Phenprocoumon
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:24, s. 2304-2312
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy.Methods: We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks.Results: A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events.Conclusions: Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy.
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