To Örebro University

Background: Guidelines in healthcare should be evidence-based, satisfy patient needs and improve patient outcome.

Methods: We performed a cost-utility analysis in Graves' disease (GD) and estimated incremental costs after the introduction of a national guideline adding the Graves' Recurrent Events After Therapy (GREAT) score with genetic determinants (GREAT+) to predict recurrence, a thyroid nurse, preoperative calcium/vitamin D treatment and thyroid-stimulating immunoglobulins.

Findings: Antithyroid drugs (ATDs) were less costly, achieved 0.88 quality-adjusted life years (QALYs) over 8 years and dominated over radioactive iodine (RAI) treatment. The relevant incremental cost-effectiveness ratio was ATD versus thyroid surgery (Tx). Tx was more costly than ATD but was also more effective. The incremental cost-effectiveness ratio was equal to 40,488 Euro per QALY gained. In recurrent GD, the QALY weight for surgery after ATD was 0.76 compared with 0.79 when surgery was the initial treatment. If individuals requiring surgery could be identified at start of first treatment, QALYs would be higher (6.32) and the cost lower (13,945 Euro). The net cost increase after the new guideline was 17.6%, which was partially an effect from more time being spent with the thyroid nurse. If the GREAT+ score was also applied, the total increased net cost was 14.8% if 24% of the tested patients changed treatment to Tx.

Interpretation: Tx was more cost-effective than RAI when ablative treatment is advocated. Prediction score for recurrence directing patients to earlier Tx is cost-effective and enables the introduction of a specialist thyroid nurse. Health economic evaluations should accompany future guidelines.

Introduction: Hyperthyroidism (HT) is treated with antithyroid drugs, radioactive iodine, or surgery. Previous studies have demonstrated that many patients undergo repeated treatment without remission and have impaired quality of life 6-10 years after diagnosis. This study aimed to evaluate different predictive machine learning models as a means of support in selecting treatment for HT.

Method: The study is based on a dataset of 2916 newly diagnosed HT patients between 2003-2005, who later were invited to participate in a 6-10 year follow-up study. This dataset underwent standard preprocessing for data representation and preparation for learning algorithms. Large Language Models were assessed as an alternative to encode medical records into sentence embeddings. Various regression models were trained and evaluated to predict the probability of a successful treatment based on nine features (Age, Sex, Diagnosis, thyroid-stimulating hormone receptor antibodies, T4-levels, TRAb (reference), TRAb (corrected), TRAb (positive), Thyroid-associated Ophthalmopathy.

Result: Two different multi-output regression models were trained and evaluated for each pre-processed dataset: Gradient-Boosting (GB) and Random Forest (RF). Root Mean Squared Error (RMSE) and the coefficient of determination, R2 score, were measured for evaluation metrics. RF trained on the traditionally pre-processed dataset showed best result, RMSE 0.1764 and R2 score 0.1460. However, the differences between both evaluated models and the approach in data preparation were negligible.

Discussion: This study show promising results in using prediction models for assessing the probability of successful treatment in individual patients. Further investigation is necessary regarding the choice of prediction models and how the data are prepared and represented.

Background Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods A total of 2134 patients with incident GD and 21261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to ten age, sex- and county-matched controls per patient were selected from databases from The National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and 95% confidence intervals. Results There were no significant differences in fracture rates between GD and controls but after adjustment for co-morbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 (1.05-7.64). The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

PURPOSE: Despite advances in the care of hip fractures, this area of surgery is associated with high postoperative mortality. Downregulating circulating catecholamines, released as a response to traumatic injury and surgical trauma, is believed to reduce the risk of death in noncardiac surgical patients. This effect has not been studied in hip fractures. This study aims to assess whether survival benefits are gained by reducing the effects of the hyper-adrenergic state with beta-blocker therapy in patients undergoing emergency hip fracture surgery.

METHODS: This is a retrospective nationwide observational cohort study. All adults [Formula: see text] 18 years were identified from the prospectively collected national quality register for hip fractures in Sweden during a 10-year period. Pathological fractures were excluded. The cohort was subdivided into beta-blocker users and non-users. Poisson regression with robust standard errors and adjustments for confounders was used to evaluate 30-day mortality.

RESULTS: 134,915 patients were included of whom 38.9% had ongoing beta-blocker therapy at the time of surgery. Beta-blocker users were significantly older and less fit for surgery. Crude 30-day all-cause mortality was significantly increased in non-users (10.0% versus 3.7%, p < 0.001). Beta-blocker therapy resulted in a 72% relative risk reduction in 30-day all-cause mortality (incidence rate ratio 0.28, 95% CI 0.26-0.29, p < 0.001) and was independently associated with a reduction in deaths of cardiovascular, respiratory, and cerebrovascular origin and deaths due to sepsis or multiorgan failure.

CONCLUSIONS: Beta-blockers are associated with significant survival benefits when undergoing emergency hip fracture surgery. Outlined results strongly encourage an interventional design to validate the observed relationship.

BACKGROUND: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort.

METHODS: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines.

RESULTS: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population.

CONCLUSION: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.

β-blocker therapy has been positively associated with improved survival in patients undergoing oncologic colorectal resection. This study investigates if the type of β-blocker used affects 90-day postoperative mortality following colon cancer surgery. The study was designed as a nationwide retrospective cohort study including all adult (≥ 18 years old) patients with ongoing β-blocker therapy who underwent elective and emergency colon cancer surgery in Sweden between January 1, 2007 and December 31, 2017. Patients were divided into four cohorts: metoprolol, atenolol, bisoprolol, and other beta-blockers. The primary outcome of interest was 90-day postoperative mortality. A Poisson regression model with robust standard errors was used, while adjusting for all clinically relevant variables, to determine the association between different β-blockers and 90-day postoperative mortality. A total of 9254 patients were included in the study. There was no clinically significant difference in crude 90-day postoperative mortality rate [n (%)] when comparing the four beta-blocker cohorts metoprolol, atenolol, bisoprolol and other beta-blockers. [97 (1.8%) vs. 28 (2.0%) vs. 29 (1.7%) vs. 11 (1.2%), p = 0.670]. This remained unchanged when adjusting for relevant covariates in the Poisson regression model. Compared to metoprolol, there was no statistically significant decrease in the risk of 90-day postoperative mortality with atenolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], bisoprolol [adj. IRR (95% CI): 1.45 (0.89-2.37), p = 0.132], or other beta-blockers [adj. IRR (95% CI): 0.92 (0.46-1.85), p = 0.825]. In patients undergoing colon cancer surgery, the risk of 90-day postoperative mortality does not differ between the investigated types of β-adrenergic blocking agents.

BACKGROUND: The current study aims to address the clinical equipoise regarding the association of ongoing statin therapy at time of surgery with long-term postoperative mortality rates after elective, curative, surgical resections of colon cancer by analyzing data from a large validated national register.

METHODS: All adults with stage I to III colon cancer who underwent elective surgery with curative intent between January 2007 and October 2016 were retrieved from the Swedish Colorectal Cancer Register, a prospectively collected national register. Patients were identified as having ongoing statin therapy if they filled a prescription within 12 months pre- and postoperatively. Study outcomes included 5-year all-cause and cancer-specific postoperative mortality. To reduce the impact of confounding from covariates owing to nonrandomization, the inverse probability of treatment weighting method was used. Subsequently, Cox proportional hazards models were fitted to the weighted cohorts.

RESULTS: In total, 19,118 patients underwent elective surgery for colon cancer in the specified period, of whom 31% (5,896) had ongoing statin therapy. Despite being older, having a higher preoperative risk, and having more comorbidities, patients with statin therapy had a higher postoperative survival. After inverse probability of treatment weighting, patients with statin therapy displayed a significantly lower mortality risk up to 5 years after surgery for both all-cause (hazard ratio 0.68, 95% confidence interval 0.63-0.74, P < .001) and cancer-specific mortality (hazard ratio 0.76, 95% confidence interval 0.66-0.89, P < .001).

CONCLUSION: The results of this study indicate that statin therapy is associated with a sustained reduction in all-cause and cancer-specific mortality up to 5 years after elective colon cancer surgery. The findings warrant validation in future prospective clinical trials.

BACKGROUND: There have been conflicting reports regarding a protective effect of statin therapy after colon cancer surgery.

OBJECTIVE: This study aimed to evaluate the association between statin therapy and the postoperative mortality following elective colon cancer surgery.

DESIGN: This population-based cohort study is a retrospective analysis of prospectively collected data from the Swedish Colorectal Cancer Register.

SETTINGS: Patient inclusion was achieved by inclusion through a nationwide register.

PATIENTS: All adult patients undergoing elective surgery for colon cancer between the period of January 2007 and September 2016 were included in the study. Patients who had received and collected a prescription for statins pre- and postoperatively were allocated to the statin positive cohort.

MAIN OUTCOME MEASURES: The primary and secondary outcomes of interest were 90-day all-cause mortality and 90-day cause-specific mortality.

RESULTS: A total of 22,337 patients underwent elective surgery for colon cancer during the study period, of whom 6,494 (29%) were classified as statin users. Statin users displayed a significant survival benefit despite being older, having a higher comorbidity burden, and less fit for surgery. Multivariate analysis illustrated significant reductions in the incidence risk for 90-day all-cause mortality (Incidence Rate Ratio = 0.12, p < 0.001) as well as 90-day cause-specific deaths due to sepsis, multiorgan failure, or of cardiovascular and respiratory origin.

LIMITATIONS: The limitations of this study include its observational retrospective design, restricting the ability to perform standardized follow-up of statin therapy. Confounding from other uncontrolled variables cannot be excluded.

CONCLUSIONS: Statin users had a significant postoperative benefit regarding short-term mortality following elective colon cancer surgery in the current study, however, further research is needed to ascertain if this relationship is causal. See Video Abstract at http://links.lww.com/DCR/B738.

PURPOSE: The post-operative mortality after hip fracture surgery is high and has remained largely unchanged during the last decades. The Revised Cardiac Risk Index (RCRI) is a tool used to evaluate the 30-day risk of, among other outcomes, post-operative mortality. The aim of this study is to determine the association between the RCRI score and post-operative mortality in patients undergoing hip fracture surgery.

METHODS: Data was obtained from the national hip fracture register which was cross-referenced with patients' electronic hospital records. All adults who underwent primary emergency hip fracture surgery in Orebro County, Sweden, between January 1, 2013 and December 31, 2017, were included. Patients were divided into two cohorts: low RCRI (score = 0-1) and high RCRI (score ≥ 2). A Poisson regression model was employed to investigate the association between a high RCRI score and 30- and 90-day post-operative mortality.

RESULTS: A total of 2443 patients, of whom 446 (18%) had a high RCRI score, were included in the current study. When adjusting for age, sex, comorbidities and type of surgery, the incidence of 30-day mortality increased by 46% in the high RCRI cohort (adj. IRR 1.46, 95% CI, 1.10-1.94, p = 0.010). Similar results were observed for 90-day mortality (adj. IRR 1.50, 95% CI, 1.21-1.84, p < 0.001).

CONCLUSION: The RCRI is applicable to patients that undergo surgery for traumatic hip fractures. A high RCRI score is associated with an increased incidence of both 30- and 90-day post-operative mortality. Future studies to evaluate these findings are needed.

BACKGROUND: There is evidence supporting the use of beta-blockade in patients with traumatic brain injury. The reduction in sympathetic drive is thought to underlie the relationship between beta-blockade and increased survival. There is little evidence for similar effects in extracranial injuries. This study aimed to assess the association between beta-blockade and survival in patients suffering isolated severe extracranial injuries.

METHODS: Patients treated at an academic urban trauma centre during a 5-year period were retrospectively identified. Adults suffering isolated severe extracranial injury [Injury Severity Score (ISS) ≥ 16 with Abbreviated Injury Score of ≤ 2 for any intracranial injury] were included. Patient characteristics and outcomes were collected from the trauma registry and hospital medical records. Patients were subdivided into beta-blocker exposed and unexposed groups. Patients were matched using propensity score matching. Differences were assessed using McNemar's or paired Student's t test. The primary outcome of interest was 90-day mortality and secondary outcome was in-hospital complications.

RESULTS: 698 patients were included of whom 10.5% were on a beta-blocker. Most patients suffered blunt force trauma (88.5%) with a mean [standard deviation] ISS of 24.6 [10.6]. Unadjusted mortality was higher in patients receiving beta-blockers (34.2% vs. 9.1%, p < 0.001) as were cardiac complications (8.2% vs. 1.4%, p = 0.002). Patients on beta-blockers were significantly older (69.5 [14.1] vs. 43.2 [18.0] years) and of higher comorbidity. After matching, no statistically significant differences were seen in 90-day mortality (34.2% vs. 30.1%, p = 0.690) or in-hospital complications.

CONCLUSIONS: Beta-blocker therapy does not appear to be associated with improved survival in patients with isolated severe extracranial injuries.