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Ju, C., Wyss, R., Franklin, J. M., Schneeweiss, S., Häggström, J. & van der Laan, M. J. (2019). Collaborative-controlled LASSO for constructing propensity score-based estimators in high-dimensional data. Statistical Methods in Medical Research, 28(4), 1044-1063
Open this publication in new window or tab >>Collaborative-controlled LASSO for constructing propensity score-based estimators in high-dimensional data
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2019 (English)In: Statistical Methods in Medical Research, ISSN 0962-2802, E-ISSN 1477-0334, Vol. 28, no 4, p. 1044-1063Article in journal (Refereed) Published
Abstract [en]

Propensity score-based estimators are increasingly used for causal inference in observational studies. However, model selection for propensity score estimation in high-dimensional data has received little attention. In these settings, propensity score models have traditionally been selected based on the goodness-of-fit for the treatment mechanism itself, without consideration of the causal parameter of interest. Collaborative minimum loss-based estimation is a novel methodology for causal inference that takes into account information on the causal parameter of interest when selecting a propensity score model. This “collaborative learning” considers variable associations with both treatment and outcome when selecting a propensity score model in order to minimize a bias-variance tradeoff in the estimated treatment effect. In this study, we introduce a novel approach for collaborative model selection when using the LASSO estimator for propensity score estimation in high-dimensional covariate settings. To demonstrate the importance of selecting the propensity score model collaboratively, we designed quasi-experiments based on a real electronic healthcare database, where only the potential outcomes were manually generated, and the treatment and baseline covariates remained unchanged. Results showed that the collaborative minimum loss-based estimation algorithm outperformed other competing estimators for both point estimation and confidence interval coverage. In addition, the propensity score model selected by collaborative minimum loss-based estimation could be applied to other propensity score-based estimators, which also resulted in substantive improvement for both point estimation and confidence interval coverage. We illustrate the discussed concepts through an empirical example comparing the effects of non-selective nonsteroidal anti-inflammatory drugs with selective COX-2 inhibitors on gastrointestinal complications in a population of Medicare beneficiaries.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
Propensity score, average treatment effect, LASSO, model selection, electronic healthcare database, collaborative targeted minimum loss-based estimation
National Category
Probability Theory and Statistics
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-142764 (URN)10.1177/0962280217744588 (DOI)000463234000005 ()29226777 (PubMedID)
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2019-05-23Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Häggström, C., Zingmark, C., Löfgren Burström, A., . . . van Guelpen, B. (2019). Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status. International Journal of Cancer, 145(2), 327-337
Open this publication in new window or tab >>Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 2, p. 327-337Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
BRAF, KRAS, colorectal cancer, metabolic factors, microsatellite instability, risk factors
National Category
Cancer and Oncology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-158782 (URN)10.1002/ijc.32104 (DOI)30613980 (PubMedID)2-s2.0-85060622510 (Scopus ID)
Note

Originally included in thesis in manuscript form with title [Metabolic factors and colorectal cancer risk by KRAS and BRAF mutation status]

Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-06-11Bibliographically approved
Gylling, B., Myte, R., Ulvik, A., Ueland, P. M., Midttun, Ø., Schneede, J., . . . Palmqvist, R. (2019). One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. International Journal of Cancer, 144(5), 947-956
Open this publication in new window or tab >>One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. p. 68
Keywords
Biomarkers, colorectal cancer, metabolite ratios, B-vitamins, one-carbon metabolism
National Category
Clinical Laboratory Medicine
Research subject
Cancer Epidemiology
Identifiers
urn:nbn:se:umu:diva-142854 (URN)10.1002/ijc.31606 (DOI)000455041700003 ()29786139 (PubMedID)
Funder
Swedish Cancer Society, 12/501Swedish Cancer Society, 14/780
Note

Originally included in thesis in manuscript form

Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2019-02-14Bibliographically approved
Häggström, J. (2018). Data-driven Confounder Selection via Markov and Bayesian Networks. Biometrics, 74(2), 389-398
Open this publication in new window or tab >>Data-driven Confounder Selection via Markov and Bayesian Networks
2018 (English)In: Biometrics, ISSN 0006-341X, E-ISSN 1541-0420, Vol. 74, no 2, p. 389-398Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
National Category
Probability Theory and Statistics
Identifiers
urn:nbn:se:umu:diva-141453 (URN)10.1111/biom.12788 (DOI)000436403600001 ()
Funder
Swedish Research Council, 2013–672
Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2018-10-04Bibliographically approved
Wallin, G., Häggström, J. & Wiberg, M. (2018). How to select the bandwidth in kernel equating: an evaluation of five different methods. In: Marie Wiberg, Steven Culpepper, Rianne Janssen, Jorge González, Dylan Molenaar (Ed.), Quantitative psychology: the 82nd annual meeting of the Psychometric Society, Zurich, Switzerland, 2017 (pp. 91-100). Cham, Switzerland: Springer
Open this publication in new window or tab >>How to select the bandwidth in kernel equating: an evaluation of five different methods
2018 (English)In: Quantitative psychology: the 82nd annual meeting of the Psychometric Society, Zurich, Switzerland, 2017 / [ed] Marie Wiberg, Steven Culpepper, Rianne Janssen, Jorge González, Dylan Molenaar, Cham, Switzerland: Springer, 2018, p. 91-100Chapter in book (Refereed)
Abstract [en]

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.

Place, publisher, year, edition, pages
Cham, Switzerland: Springer, 2018
Series
Springer Proceedings in Mathematics & Statistics, ISSN 2194-1009, E-ISSN 2194-1017 ; 233
Keywords
Kernel equating, Continuization, Bandwidth selection, Cross-validation
National Category
Probability Theory and Statistics
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-147091 (URN)10.1007/978-3-319-77249-3_8 (DOI)978-3-319-77248-6 (ISBN)978-3-319-77249-3 (ISBN)
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-12-14Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Schneede, J., Löfgren-Burström, A., Huyghe, J. R., . . . Van Guelpen, B. (2018). One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. PLoS ONE, 13(4), Article ID e0196233.
Open this publication in new window or tab >>One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed) Published
Abstract [en]

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147822 (URN)10.1371/journal.pone.0196233 (DOI)000430802400077 ()29694444 (PubMedID)
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2019-05-24Bibliographically approved
Häggström, J. (2018). Rejoinder to Discussions on: Data-driven confounder selection via Markov and Bayesian networks. Biometrics, 74(2), 407-410
Open this publication in new window or tab >>Rejoinder to Discussions on: Data-driven confounder selection via Markov and Bayesian networks
2018 (English)In: Biometrics, ISSN 0006-341X, E-ISSN 1541-0420, Vol. 74, no 2, p. 407-410Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
National Category
Probability Theory and Statistics
Identifiers
urn:nbn:se:umu:diva-152424 (URN)10.1111/biom.12783 (DOI)000436403600004 ()29096035 (PubMedID)
Available from: 2018-10-04 Created: 2018-10-04 Last updated: 2018-10-04Bibliographically approved
Chaparro, M. P., de Luna, X., Häggström, J., Ivarsson, A., Lindgren, U., Nilsson, K. & Koupil, I. (2017). Childhood family structure and women's adult overweight risk: A longitudinal study. Scandinavian Journal of Public Health, 45(5), 511-519
Open this publication in new window or tab >>Childhood family structure and women's adult overweight risk: A longitudinal study
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2017 (English)In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 45, no 5, p. 511-519Article in journal (Refereed) Published
Abstract [en]

AIM: The aim of this study was to investigate whether women's adult overweight and obesity risk was associated with their childhood family structure, measured as their mothers' marital status history, during the women's first 18 years of life.

METHODS: Using linked register data, we analyzed 30,584 primiparous women born in Sweden in 1975 who were between 19-35 years of age when their height and pre-pregnancy weight was recorded. The outcomes were women's overweight/obesity (body mass index (BMI) ≥ 25 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) and the predictor was mothers' marital status history, which was summarized using sequence analysis. We carried out nested logistic regression models adjusting for women's age and maternal sociodemographic characteristics.

RESULTS: Mothers' marital status history was summarized into six clusters: stable marriage, stable cohabitation, married then divorcing, cohabiting then separating, varied transitions, and not with father. In fully adjusted models and compared with women whose mothers belonged to the stable marriage cluster: (1) women whose mothers belonged to the other marital status clusters had higher odds of overweight/obesity (odds ratio (OR) ranging 1.15-1.19; p < 0.05); and (2) women whose mothers belonged to the stable cohabitation (OR = 1.31; 95% confidence interval (CI) = 1.14-1.52), cohabiting then separating (OR = 1.23; 95% CI = 1.01-1.49), varied transitions (OR = 1.24; 95% CI = 1.11-1.39), and not with father (OR = 1.24; 95% CI = 1.00-1.54) clusters had higher odds of obesity.

CONCLUSIONS: Women whose mothers were not in stable marriage relationships had higher odds of being overweight or obese in adulthood. The finding that even women raised in the context of stable cohabitation had higher odds of being overweight or obese is intriguing as these relationships are socially accepted in Sweden.

Keywords
family structure, marital status, overweight, obesity, Sweden, sequence analysis
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-135030 (URN)10.1177/1403494817705997 (DOI)000404652000007 ()28482752 (PubMedID)881251 (Local ID)881251 (Archive number)881251 (OAI)
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2019-02-15Bibliographically approved
Persson, E., Häggström, J., Waernbaum, I. & de Luna, X. (2017). Data-driven algorithms for dimension reduction in causal inference. Computational Statistics & Data Analysis, 105, 280-292
Open this publication in new window or tab >>Data-driven algorithms for dimension reduction in causal inference
2017 (English)In: Computational Statistics & Data Analysis, ISSN 0167-9473, E-ISSN 1872-7352, Vol. 105, p. 280-292Article in journal (Refereed) Published
Abstract [en]

In observational studies, the causal effect of a treatment may be confounded with variables that are related to both the treatment and the outcome of interest. In order to identify a causal effect, such studies often rely on the unconfoundedness assumption, i.e., that all confounding variables are observed. The choice of covariates to control for, which is primarily based on subject matter knowledge, may result in a large covariate vector in the attempt to ensure that unconfoundedness holds. However, including redundant covariates can affect bias and efficiency of nonparametric causal effect estimators, e.g., due to the curse of dimensionality. In this paper, data-driven algo- rithms for the selection of sufficient covariate subsets are investigated. Under the assumption of unconfoundedness we search for minimal subsets of the covariate vector. Based on the framework of sufficient dimension reduction or kernel smoothing, the algorithms perform a backward elim- ination procedure testing the significance of each covariate. Their performance is evaluated in simulations and an application using data from the Swedish Childhood Diabetes Register is also presented.

Keywords
covariate selection, marginal co-ordinate hypothesis test, matching, kernel smoothing, type 1 diabetes mellitus
National Category
Probability Theory and Statistics
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-80696 (URN)10.1016/j.csda.2016.08.012 (DOI)000385604500019 ()
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC 2016/1-2Swedish Research Council, 2013-672Swedish Research Council, 07531Riksbankens Jubileumsfond, P11-0814:1
Available from: 2013-09-24 Created: 2013-09-24 Last updated: 2018-06-08Bibliographically approved
Häggström, J., Sampaio, F., Eurenius, E., Pulkki-Brännström, A.-M., Ivarsson, A., Lindkvist, M. & Feldman, I. (2017). Is the Salut Programme an effective and cost-effective universal health promotion intervention for parents and their children?: a register-based retrospective observational study. BMJ Open, 7(9), Article ID e016732.
Open this publication in new window or tab >>Is the Salut Programme an effective and cost-effective universal health promotion intervention for parents and their children?: a register-based retrospective observational study
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2017 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e016732Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: This study investigates the effectiveness and cost-effectiveness of the Salut Programme, a universal health promotion intervention, compared with care-as-usual, over the periods of pregnancy, delivery and the child's first 2 years of life.

METHOD: We adopted a register-based retrospective observational design using existing data sources with respect to both exposures and outcomes. Health outcomes and costs were compared between geographical areas that received care-as-usual (non-Salut area) and areas where the programme was implemented (Salut area). We included mothers and their children from both the Salut and non-Salut areas if: (1) the child was born 2002-2004 (premeasure period) or (2) the child was born 2006-2008 (postmeasure period). The effectiveness study adopted two strategies: (1) a matched difference-in-difference analysis using data from all participants and (2) a longitudinal analysis restricted to mothers who had given birth twice, that is, both in the premeasure and postmeasure periods. The economic evaluation was performed from a healthcare and a limited societal perspective. Outcomes were clustered during pregnancy, delivery and birth and the child's first 2 years.

RESULTS: Difference-in-difference analyses did not yield any significant effect on the outcomes. Longitudinal analyses resulted in significant positive improvement in Apgar scores, reflecting the newborn's physical condition, with more children having a normal Apgar score (1 min +3%, 5 min +1%). The cost of the programme was international dollar (INT$)308/child. From both costing perspectives, the programme yielded higher effects and lower costs than care-as-usual, being thus cost-saving (probability of around 50%).

CONCLUSIONS: Our findings suggest that the Salut Programme is an effective universal intervention to improve maternal and child health, and it may be good value for money; however, there is large uncertainty around the cost estimates.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
Keywords
Child Health, Cost-effectiveness, Health Promotion, Intervention Effectiveness, Maternal Health, Universal Intervention
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-139899 (URN)10.1136/bmjopen-2017-016732 (DOI)000412650700155 ()28939578 (PubMedID)
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2018-06-09Bibliographically approved
Projects
Methods for improving estimation of causal effects in observational studies [2013-00672_VR]; Umeå UniversityMethodological development for estimating marginal causal effects of non-randomized treatments on time-to-event outcomes [2018-01610_VR]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9086-7403

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