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Background: Anastomotic leakage is a serious complication following anterior resection for rectal cancer and may increase the risk of long-term bowel dysfunction. This study aimed to assess the long-term impact of anastomotic leakage on major low anterior resection syndrome (major LARS) at a uniform follow-up time.

Methods: We conducted a nationwide cohort study using the Swedish Colorectal Cancer Registry. Patients who underwent anterior resection for rectal cancer between 2015 and 2017 received the validated LARS questionnaire by mail 3 years after surgery. The primary outcome was major LARS among patients without a permanent stoma. Propensity score weighting was used to adjust for confounding, with covariates chosen using a directed acyclic graph. Sensitivity analyses included a dose–response analysis based on reoperation and an evaluation of a composite outcome of major LARS or permanent stoma.

Results: Of 1778 patients contacted, 1178 responded (66.2%). Among 1033 stoma-free patients, 52 (5.0%) had experienced a symptomatic anastomotic leak. Major LARS was reported in 69.2% and 52.9% of patients with and without leakage, respectively. Symptomatic anastomotic leakage increased the risk of major LARS (OR 2.09; 95% CI: 1.13–3.87) and this risk was higher in patients requiring reintervention (OR 2.78; 95% CI: 0.87–8.91) and when including permanent stoma in the outcome (OR 3.90; 95% CI: 2.20–6.91).

Conclusion: Anastomotic leakage significantly increased the risk of major LARS 3 years after anterior resection for rectal cancer. These findings underscore the importance of preventing anastomotic leakage to reduce long-term functional morbidity in patients who survive rectal cancer.

Background: Anastomotic leakage after anterior resection for rectal cancer is associated with long-term morbidity, such as bowel dysfunction, but its impact on health-related quality of life remains insufficiently studied. The aim of this study was to evaluate the association between anastomotic leakage and health-related quality of life 3 years after surgery.

Methods: In this population-based prospective cohort study, patients who underwent anterior resection for rectal cancer in Sweden between 2015 and 2017 were identified through the Swedish Colorectal Cancer Registry. Health-related quality of life was assessed 3 years after surgery using the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The primary outcome was the QLQ-C30 summary score. Targeted maximum likelihood estimation was applied to estimate the adjusted effect of anastomotic leakage on health-related quality of life.

Results: Of 1778 eligible patients, 1178 (66.3%) responded, including 104 (8.8%) with anastomotic leakage. Patients with anastomotic leakage reported a lower mean QLQ-C30 summary score compared to those without anastomotic leakage (80 vs 86, p < 0.001). After adjustment for confounders, anastomotic leakage was associated with a 4-point difference in summary score (p < 0.01). Patients with anastomotic leakage also reported worse body image. Compared with patients without anastomotic leakage, those with anastomotic leakage and no stoma reported more perianal skin irritation, while those with a stoma more frequently reported stool leakage from the stoma bag.

Conclusions: Anastomotic leakage after anterior resection is associated with a small negative effect on overall health-related quality of life 3 years after surgery. Nevertheless, specific functional impairments—particularly related to body image, and stoma- or perianal symptoms—persist and warrant attention. These findings highlight the importance of patient counseling and long-term follow-up after anastomotic leakage.

Aim: The selective use of defunctioning stomas in anterior resection for rectal cancer hinges on accurately predicting anastomotic leakage. The aim of this study was to develop a prediction model for use in a prospective randomized clinical trial.

Method: Colorectal Cancer Database (CRCBaSe) Sweden was used to identify patients who underwent low anterior resection for rectal cancer 2007–2021. Eligibility criteria mirrored the forthcoming SELective defunctioning Stoma Approach in low anterior resection for rectal cancer (SELSA) trial, including patients <80 years of age and with American Society of Anaesthesiologists' (ASA) physical status grade of <III; further, patients without a defunctioning stoma were excluded. The outcome comprised anastomotic leakage within 30 days or in-hospital. Candidate predictors included age, sex, ASA grade, cardiovascular disease, diabetes, body mass index (BMI), tumour stage, tumour height, and neoadjuvant therapy. Seven models were developed and internally validated using bootstrapping. A threshold of a predicted leakage risk of ≤10% was chosen for trial implementation. Validation was conducted using chart-reviewed data from a nested cohort.

Results: Of the 2727 eligible patients, 199 (7.3%) were registered with an anastomotic leakage. All models demonstrated similar performance, with prediction instability observed for risks exceeding 12.5%. The preferred model included three significant predictors: male sex (OR 2.00; 95% CI: 1.45–2.75), BMI >30 kg/m2 (OR 1.82; 95% CI: 1.21–2.74), and radiotherapy (OR 1.90; 95% CI: 1.35–2.69). The bootstrapped area under the curve (AUC) was 0.64 (95% CI: 0.62–0.65), with a negative predictive value of 94.6% (95% CI: 93.7%–95.6%). For the validation cohort, the corresponding estimates were 0.66 (95% CI: 0.59–0.74) and 89.5% (95% CI: 86.2%–92.5%).

Conclusion: Accuracy of anastomotic leakage prediction using registry-based data is moderate; however, the model's ability to rule out a >10% risk is considered appropriate for trial use.

Background: Anastomotic leakage after rectal cancer surgery is linked to reduced survival and higher recurrence rates. While an aggravated inflammatory response may worsen outcomes, few studies have explored the combined effects of leakage and inflammation.

Methods: This is a retrospective multicenter cohort study including patients operated with anterior resection for rectal cancer in Sweden during 2014–2018. Anastomotic leakage within 12 months was exposure and primary outcome was recurrence-free survival. Mediation analysis was performed to evaluate the potential effect of systemic inflammatory response, as measured by the highest postoperative C-reactive protein (CRP) level within 14 days of surgery. Confounders were chosen using a causal diagram.

Results: Some 1036 patients were eligible for analysis, of whom 218 (21%) experienced an anastomotic leakage. At the end of follow-up at a median of 61 months after surgery, recurrence-free survival amounted to 82.6% and 77.8% in the group with and without leakage, respectively. The median highest postoperative CRP value after surgery was higher in the leakage group (219 mg/l), compared with the group without leakage (108 mg/l). Leakage did not lead to worse recurrence-free survival (HR 0.66; 95% CI 0.43–0.94), and there was no apparent effect through postoperative highest CRP (HR 1.12; 95% CI 0.93–1.29).

Conclusions: In conclusion, anastomotic leakage, with its accompanying CRP increase, was not found to be associated with recurrence-free survival after anterior resection for rectal cancer in this patient cohort. Larger, even more detailed studies are needed to further investigate this topic.

Globally, stroke is the third-leading cause of mortality and disability combined, and one of the costliest diseases in society. More accurate predictions of stroke outcomes can guide healthcare organizations in allocating appropriate resources to improve care and reduce both the economic and social burden of the disease. We aim to develop and evaluate the performance and explainability of three supervised machine learning models and the traditional multinomial logistic regression (mLR) in predicting functional dependence and death three months after stroke, using routinely-collected data. This prognostic study included adult patients, registered in the Swedish Stroke Registry (Riksstroke) from 2015 to 2020. Riksstroke contains information on stroke care and outcomes among patients treated in hospitals in Sweden. Prognostic factors (features) included demographic characteristics, pre-stroke functional status, cardiovascular risk factors, medications, acute care, stroke type, and severity. The outcome was measured using the modified Rankin Scale at three months after stroke (a scale of 0-2 indicates independent, 3-5 dependent, and 6 dead). Outcome prediction models included support vector machines, artificial neural networks (ANN), eXtreme Gradient Boosting (XGBoost), and mLR. The models were trained and evaluated on 75% and 25% of the dataset, respectively. Model predictions were explained using SHAP values. The study included 102,135 patients (85.8% ischemic stroke, 53.3% male, mean age 75.8 years, and median NIHSS of 3). All models demonstrated similar overall accuracy (69%-70%). The ANN and XGBoost models performed significantly better than the mLR in classifying dependence with F1-scores of 0.603 (95% CI; 0.594-0.611) and 0.577 (95% CI; 0.568-0.586), versus 0.544 (95% CI; 0.545-0.563) for the mLR model. The factors that contributed most to the predictions were expectedly similar in the models, based on clinical knowledge. Our ANN and XGBoost models showed a modest improvement in prediction performance and explainability compared to mLR using routinely-collected data. Their improved ability to predict functional dependence may be of particular importance for the planning and organization of acute stroke care and rehabilitation.

BACKGROUND: Previous studies on disparities in healthcare and outcome have shown conflicting results. The aim of this study was to assess differences in baseline characteristics, management, and outcome in myocardial infarction (MI) patients, by country of birth.

METHODS: In total, 194 259 MI patients (64% male, 15% foreign-born) from the nationwide SWEDEHEART registry were included and compared by geographic region of birth. The primary outcome was one-year major adverse cardiovascular events (MACE) including all-cause death, MI, and stroke. Secondary outcomes were long-term MACE (up to 12 years), the individual components of MACE, 30-day mortality, management, and risk factors. Logistic regression, Cox proportional hazard models and propensity score matching (PSM), accounting for baseline differences, were used.

RESULTS: Foreign-born patients were younger, often male, and had a higher cardiovascular (CV) risk factor burden, including smoking, diabetes, and hypertension. In PSM analyses, Asia-born patients had higher likelihood of revascularisation (OR 1.16, 95% CI 1.04-1.30), statins and betablocker prescription at discharge and a 34% lower risk of 30-day mortality. Furthermore, no statistically significant differences were found in the primary outcomes except for Asia-born patients having lower risk of one-year MACE (HR 0.85, 95% CI 0.73-0.98), driven by lower mortality (HR 0.72, 95% CI 0.57-0.91). The results persisted over long-term follow-up.

CONCLUSIONS: This study shows that in a system with universal healthcare coverage in which acute and secondary preventive treatments do not differ by country of birth, foreign-born patients, despite higher CV risk factor burden, will do at least as well as native-born patients.

Aim: Previous research has indicated that preoperative beta blocker therapy is associated with a decreased risk of complications after surgery for rectal cancer. This is thought to arise because of the anti-inflammatory activity of the drug. These results need to be reproduced and analyses extended to other drugs with such properties, as this information might be useful in clinical decision-making. The main aim of this work was to replicate previous findings of beta blocker use as a prognostic marker for postoperative leakage. We also investigated whether drug exposure might induce anastomotic leaks.

Method: This is a retrospective multicentre cohort study, comprising 1126 patients who underwent anterior resection for rectal cancer between 2014 and 2018. The use of any preoperative beta blocker was treated as the primary exposure, while anastomotic leakage within 12 months of surgery was the outcome. Secondary exposures comprised angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins and metformin. Using multivariable regression, we performed a replication analysis with a predictive aim for beta blockers only, while adjustment for confounding was done in more causally oriented analyses for all drugs. We estimated incidence rate ratio (IRR) and relative risk (RR) with 95% confidence intervals (CIs).

Results: Anastomotic leakage occurred in 20.6% of patients. Preoperative beta blockers were used by 22.7% of the cohort, while the leak distribution was almost identical between exposure groups. In the main replication analysis, no association could be detected (IRR 0.95, 95% CI 0.68–1.33). In the causally oriented analyses, only metformin affected the risk of leakage (RR 1.59, 95% Cl 1.31–1.92).

Conclusion: While previous research has suggested that preoperative beta blocker use could be prognostic of anastomotic leakage, this study could not detect any such association. On the contrary, our results indicate that preoperative beta blocker use neither predicts nor causes anastomotic leakage after anterior resection for rectal cancer.

Background: Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking.

Methods: This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported.

Results: A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes.

Conclusion: Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.

Background: The aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age.

Methods: This study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample.

Results: The longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3–9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time.

Conclusions: The Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences.

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.