| 1. |
- Myte, Robin, et al.
(författare)
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Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:2, s. 327-337
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Tidskriftsartikel (refereegranskat)abstract
- Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.
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| 2. |
- Feldman, Inna, et al.
(författare)
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Effectiveness and cost-effectiveness of the Salut Programme : a universal health promotion intervention for parents and children-protocol of a register-based retrospective observational study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: There is inadequate evidence for the effectiveness and cost-effectiveness of health promotion interventions. The Salut Programme aims to reach all parents and children in the Vasterbotten County of Sweden with a combination of health promotion interventions initiated during pregnancy and continued over the childhood period. This study protocol describes an effectiveness study and an economic evaluation study, where the ongoing Salut Programme is compared to care-as-usual over the periods of pregnancy, delivery and the child's first 2 years of life. Methods: A register-based retrospective observational study design will be used with existing data sources with respect to exposures and outcomes. Outcomes of interest are clustered at 3 points: around the child's birth, 1 month after the child's birth and 2 years after the child's birth. We will simulate an experiment by retrospectively identifying and comparing children and their parents in the geographical areas where the Salut Programme was implemented since 2006 and onwards, and the areas where the Programme was not implemented before 2009. Outcomes will be analysed and compared for the premeasure period, and the postmeasure period for both groups. Our analysis combines difference-in-difference estimation with matching. A complementary analysis will be carried out on the longitudinal subsample of mothers who gave birth at least once during each of the time periods. The economic evaluation aims to capture the wider societal costs and benefits of the Salut Programme for the first 2 years of the children's lives. Incremental costs will be compared with incremental health gains and the results will be presented as a cost-consequence analysis. Ethics and dissemination: The Regional Ethical Review Board in Umea has given clearance for the Salut Programme research (2010-63-31M). No individual's identity will be revealed when presenting results. This study will provide information that can guide decision-makers to allocate resources optimally.
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| 3. |
- Gylling, Björn, 1978-, et al.
(författare)
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One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 947-956
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Tidskriftsartikel (refereegranskat)abstract
- Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.
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| 4. |
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| 5. |
- Myte, Robin, 1989-
(författare)
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Metabolic Risk Factors and Molecular Subtypes of Colorectal Cancer
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Colorectal cancer (CRC) is a heterogeneous disease developing from distinct pathways, resulting in tumor subtypes with large differences in clinical and molecular characteristics. Molecular characteristics are increasingly being used clinically to guide therapy. However, whether molecular subtypes of CRC differ in etiology or risk factors is not clear. Clarifying such potential differences may lead to an improved understanding of CRC etiology, with implications for CRC prevention and screening.Aim: The aim of this thesis was to investigate whether risk factors related to energy metabolism, such as body fatness, and one-carbon metabolism, such as circulating B-vitamin status, were associated with specific subtypes of CRC defined by molecular characteristics of the tumor. Methods: These prospective studies are based on data and blood samples from cohorts within the population-based Northern Sweden Health and Disease Study (NSHDS). Prospective CRC cases with available archived tumor tissue were analyzed for key molecular features (KRAS and BRAF mutation status, Microsatellite instability (MSI) status, and CpG Island Methylator Phenotype (CIMP) status). Paper I was a cohort study of metabolic factors related to the metabolic syndrome (117 687 participants). Paper II was a nested-case control study on circulating insulin resistance-markers and adipokines (1010 cases and 1010 matched controls). Papers III and IV were nested case-control studies of one-carbon metabolism biomarkers and genetic variants (613 cases and 1190 matched controls).Results: In paper I, we observed associations between metabolic factors, such as BMI, blood pressure, and blood lipids, and CRC risk consistent with previous studies. These associations were similar regardless of tumor KRAS and BRAF mutation status. In paper II, circulating biomarkers of insulin resistance and adipokines were not associated with the risk of CRC or specific molecular subtypes of CRC defined by KRAS and BRAF mutation or MSI status. In paper III, higher circulating levels of metabolites involved in the methionine cycle (namely, betaine and methionine) were associated with a lower CRC risk. In paper IV, we found no support for clear subtype-specific roles of any circulating one-carbon metabolism biomarker or genetic variants in CRC development.Conclusions: The result of these prospective studies suggests that metabolic factors related to energy metabolism and one-carbon metabolism are generally associated with the risk of CRC, regardless of major subtypes defined by key molecular tumor features. If causal, metabolic risk factors likely influence the risk of colorectal cancer through more than one carcinogenic pathway.
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| 6. |
- Pulkki-Brännström, Anni-Maria, et al.
(författare)
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The equity impact of a universal child health promotion programme
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 29:Suppl 4, s. 103-103
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to evaluate whether the Salut Programme, a universal child health promotion intervention, aimed to strengthen healthy lifestyles in northern Sweden, had any effect on income-related inequalities in positive birth outcomes for children and on healthcare use for children and their mothers.Methods: Mother’s residence and child’s date of birth determined whether the child and the mother belonged to the control group (areas that received care-as-usual) or the intervention group (areas with the intervention implemented from 2005), during the pre-measure period (children born 2002-2004) and the post-measure period (children born 2006-2008). The sum of parents’ taxable income was used for socioeconomic ranking. We computed the standard concentration index for six binary indicators of positive birth outcomes, and for inpatient and day patient care for children and mothers during the two years after delivery. Using a difference-in-difference approach, we assessed whether the extent of inequality changed over time between areas.Results: Income-related inequalities in child health status at birth and in child healthcare use were absent, except that full-term pregnancies were concentrated among the poor at pre-measure in the intervention group. However, mothers’ healthcare use was significantly pro-poor in the control group. The extent of inequality changed between pre- and post-measure periods for two outcomes: the pro-poor concentration of full-term pregnancies in the intervention group at pre-measure disappeared at post-measure; and an increase in pro-poor concentration of normal birth weight in the control group was not matched by a similar increase in the intervention group. Inequalities in healthcare use did not change significantly.Conclusions: Birth outcomes and child healthcare use seemed to be equitably distributed. However, the results raise concerns whether the intervention may have reduced the pro-poor concentration of positive birth outcomes.Key messagesThere are concerns that participation in universal health promotion programmes differs by socioeconomic status, although few public health interventions have been evaluated from an equity perspective.Birth outcomes and child healthcare use in Northern Sweden seemed to be equitably distributed across different socioeconomic groups.
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| 7. |
- Wallin, Gabriel, 1991-
(författare)
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Extensions of the kernel method of test score equating
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis makes contributions within the area of test score equating and specifically kernel equating. The first paper of this thesis studies the estimation of the test score distributions needed in kernel equating. There are currently two families of models implemented within kernel equating for this purpose, namely log-linear models and item response theory models. The impact of model selection criteria for these models on the equated scores are studied using both empirical and simulated data.The second paper focuses on the continuization of the estimated score distributions, where different bandwidth selection methods are studied. The study considers multiple data collection designs, sample sizes and score distributions and investigates how large impact the bandwidth selection has on the equated scores.When the test groups differ in their ability distributions it is necessary to adjust for such differences to make fair comparisons possible. The most common way of adjusting for ability imbalance is by using items that are common for both test forms, known as anchor items. If no such items are available, it has been suggested to use background information about the test-takers instead. However, when the covariate vector of background information increases, the combination of covariates with no observations tends to increase as well. The third paper of this thesis therefore suggests to transform the covariate vector into a scalar propensity score. Two equating estimators are suggested under this setting and the standard error of equating (SEE) for both estimators are given.The SEE for kernel equating has previously been derived using the delta method. The fourth paper revisits the Bahadur representation of sample quantiles to derive the SEE. Both methods of calculating the SEE are compared, and it is shown that they are equivalent for all common data collection designs when the terms of the Bahadur SEE are estimated using Taylor expansions. An implementation of an alternative estimator of the Bahadur SEE for which the equivalence result does not hold is also included to illustrate when the two methods differ.
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| 8. |
- Wallin, Gabriel, et al.
(författare)
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How to select the bandwidth in kernel equating : an evaluation of five different methods
- 2018
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Ingår i: Quantitative psychology. - Cham, Switzerland : Springer. - 9783319772486 - 9783319772493 ; , s. 91-100
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Bokkapitel (refereegranskat)abstract
- When using kernel equating to equate two test forms, a bandwidth needs to be selected. The bandwidth parameter determines the smoothness of the continuized score distributions and has been shown to have a large effect on the kernel density estimate. There are a number of suggested criteria for selecting the bandwidth, and currently four of them have been implemented in kernel equating. In this paper, all four of the existing bandwidth selectors suggested for kernel equating are evaluated and compared against each other using real test data together with a new criterion that implements leave-one-out cross-validation. Although the bandwidth methods generally were similar in terms of equated scores, there were potentially important differences in the upper part of the score scale where critical admission decisions are typically made.
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