| 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. |
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| 3. |
- Andersson, Jenny, 1976, et al.
(författare)
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The Volume Fraction of a Non-overlapping Germ-grain Model
- 2006
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Ingår i: Electronic Communications in Probability. - 1083-589X. ; 11, s. 78-88
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the volume fraction of a model of non--overlapping convex grains. It is obtained from thinning a Poisson process where each point has a weight and is the centre of a grain, by removing any grain that is overlapped by one of larger or equal weight. In the limit as the intensity of the Poisson process tends to infinity, the model can be identified with the intact grains in the dead leaves model if the weights are independent of the grain sizes. In this case we can show that the volume fraction is at most $1/2^d$ for $d=1$ or $2$ if the shape is fixed, but the size and the orientation are random. The upper bound is achieved for centrally symmetric sets of the same size and orientation. For general $d$ we can show the upper bound, $1/2^d$, for spherical grains with two--point radius distribution. If dependence between weight and size is allowed, it is possible to achieve a volume fraction arbitrarily close to one.
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| 4. |
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| 5. |
- Back, Erik, et al.
(författare)
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Permanent stoma rates after anterior resection for rectal cancer : risk prediction scoring using preoperative variables
- 2021
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 108:11, s. 1388-1395
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling.METHODS: Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk.RESULTS: Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive.CONCLUSION: Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.
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| 6. |
- Barros, Guilherme, et al.
(författare)
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Covariate selection for the estimation of marginal hazard ratios in high-dimensional data
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Hazard ratios are frequently reported in time-to-event and epidemiological studies to assess treatment effects. In observational studies, the combination of propensity score weights with the Cox proportional hazards model facilitates the estimation of the marginal hazard ratio (MHR). The methods for estimating MHR are analogous to those employed for estimating common causal parameters, such as the average treatment effect. However, MHR estimation in the context of high-dimensional data remain unexplored. This paper seeks to address this gap through a simulation study that consider variable selection methods from causal inference combined with a recently proposed multiply robust approach for MHR estimation. Additionally, a case study utilizing stroke register data is conducted to demonstrate the application of these methods. The results from the simulation study indicate that the double selection covariate selection method is preferable to several other strategies when estimating MHR. Nevertheless, the estimation can be further improved by employing the multiply robust approach to the set of propensity score models obtained during the double selection process.
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| 7. |
- Barros, Guilherme, 1992-
(författare)
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Estimation of hazard ratios from observational data with applications related to stroke
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this thesis is to examine some challenges that may emerge when conducting time-to-event studies based on observational data. Time-to-event (also called survival) is a setting that involves analyzing how different factors may influence the length of time until an individual experiences the event of interest. This type of analysis is commonly applied in fields such as medical research and epidemiology. In this thesis, which focuses on stroke, we are interested in the time to a recurrent stroke or the death of a patient who survived a first stroke.Hazard ratios are one of the main parameters estimated in time-to-event studies. Hazard ratios involve comparing the risk of experiencing the event between two groups, usually a treated group and an untreated group. They can also involve other factors, such as different age groups. Hazard ratios can be estimated from the data by using the Cox regression model.Observational data, in contrast to experimental data, involves data collected without any intervention or random assignment of treatment to the individuals. Confounders, that is, variables that distort or obscure the true relationship between treatment and outcome, are always present and need to be controlled for in observational studies.National registers are an important source of observational data. A national registry is a centralized database or system that collects, stores, and maintains information about a specific population or group of individuals within a country. Sweden is known for its detailed and complete national registers. In this thesis, data from the Swedish Stroke Register (Riksstroke) is used to study factors related to stroke.In time-to-event studies involving observational data, several challenges may arise for the researcher during data analysis. Some individuals may not experience the event during the observation period and thus the information about their time until the event is incomplete. These individuals are considered as censored. Some individuals may experience another event rather than the one of interest, a competing risk. Additionally, models must be properly constructed, with researchers selecting variables and determining the suitable functional form.Four papers are included in the thesis. Paper I demonstrates how to handle competing risks in survival analysis. The study involves comparing individuals with and without standard modifiable risk factors and their risks of a recurrent stroke or death using data from the Swedish Stroke Register.The estimation of marginal hazard ratios is a common theme in the other three papers. All involve simulation studies in order to extend methods and explore best practices when estimating marginal hazard ratios.Paper II explores non-parametric methods that can be used as alternatives to more traditional parametric methods when balancing datasets in order to estimate a marginal hazard ratio. A case study was also conducted using data from the Swedish Stroke Register involving the prescription of anticoagulants at hospital discharge after a stroke.Paper III is about how censoring affects marginal hazard ratio estimation, even with perfect balancing of the dataset. We study this issue, taking into consideration varying effect sizes and censoring rates. A procedure to attenuate the problem is also studied.Paper IV concerns covariate selection in the case of high-dimensional data. High-dimensional data involves cases in which the number of covariates in the study is comparable to the number of individuals, and therefore covariate selection methods are needed. In the paper, we explore some of these methods and suggest a best-performing procedure. As Paper II, Paper IV involves a case study of anticoagulant prescription using data from the Swedish Stroke Register.
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| 8. |
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| 9. |
- Barros, Guilherme W. F., et al.
(författare)
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Performance of modeling and balancing approach methods when using weights to estimate treatment effects in observational time-to-event settings
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- In observational studies weighting techniques are often used to overcome bias due to confounding. Modeling approaches, such as inverse propensity score weighting, are popular, but often rely on the correct specification of a parametric model wherein neither balance nor stability are targeted. More recently, balancing approach methods that directly target covariate imbalances have been proposed, and these allow the researcher to explicitly set the desired balance constraints. In this study, we evaluate the finite sample properties of different modeling and balancing approach methods, when estimating the marginal hazard ratio, through Monte Carlo simulations. The use of the different methods is also illustrated by analyzing data from the Swedish stroke register to estimate the effect of prescribing oral anticoagulants on time to recurrent stroke or death in stroke patients with atrial fibrillation. In simulated scenarios with good overlap and low or no model misspecification the balancing approach methods performed similarly to the modeling approach methods. In scenarios with bad overlap and model misspecification, the modeling approach method incorporating variable selection performed better than the other methods. The results indicate that it is valuable to use methods that target covariate balance when estimating marginal hazard ratios, but this does not in itself guarantee good performance in situations with, e.g., poor overlap, high censoring, or misspecified models/balance constraints.
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| 10. |
- Boström, Petrus, et al.
(författare)
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Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer : A Nationwide Cohort Study
- 2021
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:3, s. e236-e244
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to investigate the impact of tie level on oncological outcomes in rectal cancer surgery.Summary background data: Theoretically, a high tie of the inferior mesenteric artery could facilitate removal of apical node metastases and improve tumor staging accuracy. However, no appropriately sized randomized controlled trial exists and results from observational studies are not consistent.Methods: All stage I–III rectal cancer patients who underwent abdominal surgery with curative intention in 2007 to 2014 were identified and followed, using the Swedish Colorectal Cancer Registry. Primary outcome was cancer-specific survival, whereas overall and relative survival, locoregional and distant recurrence, and lymph node harvest were secondary outcomes, with high tie as exposure. We used propensity score matching to emulate a randomized controlled trial, and then performed Cox regression analyses to estimate hazard ratios (HRs) with confidence intervals (CIs).Results: Some 8287 patients remained for analysis, of which 37% had high tie surgery. After propensity score matching, the 5-year cancer-specific survival rate was overall 86% and we found no association between the level of tie and cancer-specific (HR 0.92, 95% CI 0.79–1.07) or overall (HR 0.98, 95% CI 0.89–1.08) survival, nor to locoregional (HR 0.85, 95% CI 0.59–1.23) or distant (HR 1.01, 95% CI 0.88–1.15) recurrence, nor to relative survival (HR 1.05, 95% CI 0.85–1.28). Stratification and sensitivity analyses were similarly insignificant, after adjustment for confounding. Total lymph node harvest was, however, increased after high tie surgery (P < 0.01), but no differences were seen regarding positive nodes (P = 0.72).Conclusion: In this nationwide cohort study, the level of tie did not influence any patient-oriented oncological outcome, neither overall nor in node-positive patients. This would allow the patient's anatomical configuration and the surgeon's preferences to determine the level of tie.
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