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- Grahn, Oskar, et al.
(författare)
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Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer
- 2021
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Ingår i: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes. Methods: A cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation. Results: The cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99). Conclusion: Conventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.
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- Grahn, Oskar, et al.
(författare)
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Postoperative non-steroidal anti-inflammatory drugs in relation to recurrence, survival and anastomotic leakage after surgery for colorectal cancer
- 2022
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Ingår i: Colorectal Disease. - : Blackwell Publishing. - 1462-8910 .- 1463-1318. ; 24:8, s. 933-942
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate whether non-steroidal anti-inflammatory drugs (NSAIDs) could be beneficial or harmful when used perioperatively for colorectal cancer patients, as inflammation may affect occult disease and anastomotic healing.METHODS: This is a protocol-based retrospective cohort study on colorectal cancer patients operated between 2007 and 2012 at 21 hospitals in Sweden. The NSAID exposure was retrieved from postoperative analgesia protocols, while outcomes and patient data were retrieved from the Swedish Colorectal Cancer Registry. Older or severely comorbid patients, as well as those with disseminated or non-radically operated tumours were excluded. Multivariable regression with adjustment for confounders was performed, estimating hazard ratios (HRs) for long-term and odds ratios (ORs) for short-term outcomes, including 95% confidence intervals (CIs).RESULTS: Some 6945 patients remained after exclusion, of which 3996 were treated at hospitals where an NSAID protocol was in place. No association was seen between NSAIDs and recurrence-free survival (HR 0.97; 95% CI 0.87-1.09). However, a reduction in cancer recurrence was detected (HR 0.83; 95% 0.72-0.95), which remained significant when stratifying into locoregional (HR 0.68; 95% CI 0.48-0.97) and distant recurrences (HR 0.85; 95% CI 0.74-0.98). Anastomotic leakage was less frequent (HR 0.69%; 95% CI 0.51-0.94) in the NSAID-exposed, mainly due to a risk reduction in colo- and ileo-rectal anastomoses (HR 0.47; 95% CI 0.33-0.68).CONCLUSION: There was no association between NSAID exposure and recurrence-free survival, but an association with improved cancer recurrence and the rate of anastomotic leakage was detected, which may depend on tumour site and anastomotic location.
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- Lundin, Mathias, 1971-, et al.
(författare)
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Estimation of causal effects in observational studies with interference between units
- 2014
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Ingår i: Statistical Methods & Applications. - : Springer Science and Business Media LLC. - 1618-2510 .- 1613-981X. ; 23:3, s. 417-433
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Tidskriftsartikel (refereegranskat)abstract
- Causal effects are usually estimated under the assumption of no interference between individuals. This assumption means that the potential outcomes for one individual are unaffected by the treatments received by other individuals. In many situations, this is not reasonable to assume. Moreover, not taking interference into account could result in misleading conclusions about the effect of a treatment. For two-stage observational studies, where treatment assigment is randomized in the first stage but not in the second stage, we propose IPW estimators of direct and indirect causal effects as defined by Hudgens and Halloran (J Am Stat Assoc 103(482):832-842, 2008) for two-stage randomized studies. We illustrate the use of these estimators in an evaluation study of an implementation of Triple P (a parenting support program) within preschools in Uppsala, Sweden.
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- Lundin, Mathias, 1971-
(författare)
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Sensitivity Analysis of Untestable Assumptions in Causal Inference
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis contributes to the research field of causal inference, where the effect of a treatment on an outcome is of interest is concerned. Many such effects cannot be estimated through randomised experiments. For example, the effect of higher education on future income needs to be estimated using observational data. In the estimation, assumptions are made to make individuals that get higher education comparable with those not getting higher education, to make the effect estimable. Another assumption often made in causal inference (both in randomised an nonrandomised studies) is that the treatment received by one individual has no effect on the outcome of others. If this assumption is not met, the meaning of the causal effect of the treatment may be unclear. In the first paper the effect of college choice on income is investigated using Swedish register data, by comparing graduates from old and new Swedish universities. A semiparametric method of estimation is used, thereby relaxing functional assumptions for the data. One assumption often made in causal inference in observational studies is that individuals in different treatment groups are comparable, given that a set of pretreatment variables have been adjusted for in the analysis. This so called unconfoundedness assumption is in principle not possible to test and, therefore, in the second paper we propose a Bayesian sensitivity analysis of the unconfoundedness assumption. This analysis is then performed on the results from the first paper. In the third paper of the thesis, we study profile likelihood as a tool for semiparametric estimation of a causal effect of a treatment. A semiparametric version of the Bayesian sensitivity analysis of the unconfoundedness assumption proposed in Paper II is also performed using profile likelihood. The last paper of the thesis is concerned with the estimation of direct and indirect causal effects of a treatment where interference between units is present, i.e., where the treatment of one individual affects the outcome of other individuals. We give unbiased estimators of these direct and indirect effects for situations where treatment probabilities vary between individuals. We also illustrate in a simulation study how direct and indirect causal effects can be estimated when treatment probabilities need to be estimated using background information on individuals.
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