Long-Term Outcome of Graves' Disease: A Gender Perspective.

Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective. Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided. Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05). Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.

Fracture Incidence in Graves' Disease: A Population-Based Study.

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 21,261 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 10 years of 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 confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 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.

Long term outcome after toxic nodular goitre.

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.

Pharmacological differences between beta-blockers and postoperative mortality following colon cancer surgery.

ß-blocker therapy has been positively associated with improved survival in patients undergoing oncologic colorectal resection. This study investigates if the type of ß-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 ß-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 ß-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 ß-adrenergic blocking agents.

The association between the Revised Cardiac Risk Index and short-term mortality after hip fracture surgery.

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.

A nationwide observational cohort study of the relationship between beta-blockade and survival after hip fracture surgery.

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.

Statin therapy and its association with long-term survival after colon cancer surgery.

BACKGROUND: The current study aimed 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.

Statin Therapy Is Associated With Decreased 90-Day Postoperative Mortality After Colon Cancer Surgery.

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 through a nationwide register. PATIENTS: All adult patients undergoing elective surgery for colon cancer between 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 being 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, due to multiorgan failure, or resulting from a 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 whether this relationship is causal. See Video Abstract at http://links.lww.com/DCR/B738. LA TERAPIA CON ESTATINAS SE ASOCIA CON UNA DISMINUCIN DE LA MORTALIDAD POSOPERATORIA A LOS DAS DESPUS DE LA CIRUGA DE CNCER DE COLON: ANTECEDENTES:Ha habido informes contradictorios con respecto al efecto protector de la terapia con estatinas después de la cirugía de cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar la asociación entre la terapia con estatinas y la mortalidad postoperatoria después de la cirugía electiva por cáncer de colon.DISEÑO:Este estudio de cohorte poblacional es un análisis retrospectivo de datos recopilados prospectivamente del Registro Sueco de Cáncer Colorrectal.AJUSTES:La inclusión de pacientes se logró mediante la inclusión a través de un registro a nivel nacional.PACIENTES:Se incluyeron en el estudio todos los pacientes adultos sometidos a cirugía electiva por cáncer de colon en el período de enero de 2007 y septiembre de 2016. Los pacientes que habían recibido y recogido una receta de estatinas antes y después de la operación fueron asignados a la cohorte positiva de estatinas.PRINCIPALES MEDIDAS DE DESENLACES:Los desenlaces primarios y secundarios de interés fueron la mortalidad por cualquier causa a los 90 días y la mortalidad por causas específicas a los 90 días.RESULTADOS:Un total de 22.337 pacientes se sometieron a cirugía electiva por cáncer de colon durante el período de estudio, de los cuales 6.494 (29%) se clasificaron como usuarios de estatinas. Los usuarios de estatinas mostraron un beneficio significativo en la supervivencia a pesar de ser mayores, de tener una mayor carga de comorbilidad y de estar menos acondicionado para la cirugía. El análisis multivariado ilustró reducciones significativas en el riesgo de incidencia de mortalidad por cualquier causa a 90 días (índice de tasa de incidencia = 0,12, p < 0,001), así como muertes específicas ena 90 días debidas a sepsis, falla multiorgánica o dea enfermedades de origen cardiovascular y respiratorio.LIMITACIONES:Las limitaciones de este estudio incluyen su diseño observacional retrospectivo, que restringe la capacidad de realizar un seguimiento estandarizado de la terapia con estatinas. No se puede excluir confusión a partir de otras variables no controladas.CONCLUSIONES:Los usuarios de estatinas tuvieron un beneficio posoperatorio significativo con respecto a la mortalidad a corto plazo después de cirugía electiva por cáncer de colon en el estudio actual, sin embargo, se necesita más investigación para confirmar si eexiste una relación es causal. Consulte Video Resumen en http://links.lww.com/DCR/B738.

Beta-blockade is not associated with improved outcomes in isolated severe extracranial injury: an observational cohort study.

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.

Statin Use and Long-Term Mortality after Rectal Cancer Surgery.

BACKGROUND: The current study aimed to assess the association between regular statin therapy and postoperative long-term all-cause and cancer-specific mortality following curative surgery for rectal cancer. The hypothesis was that statin exposure would be associated with better survival. METHODS: Patients with stage I-III rectal cancer undergoing surgical resection with curative intent were extracted from the nationwide, prospectively collected, Swedish Colorectal Cancer Register (SCRCR) for the period from January 2007 and October 2016. Patients were defined as having ongoing statin therapy if they had filled a statin prescription within 12 months before and after surgery. Cox proportional hazards models were employed to investigate the association between statin use and postoperative five-year all-cause and cancer-specific mortality. RESULTS: The cohort consisted of 10,743 patients who underwent a surgical resection with curative intent for rectal cancer. Twenty-six percent (n = 2797) were classified as having ongoing statin therapy. Statin users had a considerably decreased risk of all-cause (adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI): 0.60-0.73, p < 0.001) and cancer-specific (adjusted HR 0.60, 95% CI: 0.47-0.75, p < 0.001) mortality up to five years following surgery. CONCLUSIONS: Statin use was associated with a lower risk of both all-cause and rectal cancer-specific mortality following curative surgical resections for rectal cancer. The findings should be confirmed in future prospective clinical trials.

Treatment of patients with Graves' disease in Sweden compared to international surveys of an 'index patient'.

INTRODUCTION: The treatment strategies for a 42-year-old female index patient with moderate Graves' disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. MATERIALS AND METHODS: From a Swedish cohort of 1186 GD patients (TT-12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This 'index patient cohort' was age 40-45, otherwise healthy female, with two children and uncomplicated GD. The applied first-line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT-12 cohort was also performed. RESULTS: In the 'Index cohort', 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (131I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where 131I was preferred. The distribution of treatment in the TT-12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19-22) patients, as was RAI in old (age 69-73) patients. The age-related, but not the gender-related, cases differed significantly from the entire TT-12 cohort. CONCLUSION: The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where 131I is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from 'real life' has been presented and compared to treatment preferences of international thyroid association surveys.

Hospital academic status is associated with failure-to-rescue after colorectal cancer surgery.

BACKGROUND: Failure-to-rescue is a quality indicator measuring the response to postoperative complications. The current study aims to compare failure-to-rescue in patients suffering severe complications after surgery for colorectal cancer between hospitals based on their university status. METHODS: Patients undergoing colorectal cancer surgery from January 2015 to January 2020 in Sweden were included through the Swedish Colorectal Cancer Registry in the current study. Severe postoperative complications were defined as Clavien-Dindo ≥3. Failure-to-rescue incidence rate ratios were calculated comparing university versus nonuniversity hospitals. RESULTS: A total of 23,351 patients were included in this study, of whom 2,964 suffered severe postoperative complication(s). University hospitals had lower failure-to-rescue rates with an incidence rate ratios of 0.62 (0.46-0.84, P = .002) compared with nonuniversity hospitals. There were significantly lower failure-to-rescue rates in almost all types of severe postoperative complications at university than nonuniversity hospitals. CONCLUSION: University hospitals have a lower risk for failure-to-rescue compared with nonuniversity hospitals. The exact mechanisms behind this finding are unknown and warrant further investigation to identify possible improvements that can be applied to all hospitals.

Statin therapy and postoperative short-term mortality after rectal cancer surgery.

AIM: This study aimed to assess the correlation between regular statin therapy and postoperative mortality following surgical resection for rectal cancer. METHOD: This retrospective cohort study included all adult patients undergoing abdominal rectal cancer surgery in Sweden between January 2007 and September 2016. Data were gathered from the Swedish Colorectal Cancer Registry, a large population-based prospectively collected registry. Statin users were defined as patients with one or more collected prescriptions of a statin within 12 months before the date of surgery. The statin-positive and statin-negative cohorts were matched by propensity scores based on baseline demographics. RESULTS: A total of 11 966 patients underwent surgical resection for rectal cancer, of whom 3019 (25%) were identified as statin users. After applying propensity score matching (1:1), 3017 pairs were available for comparison. In the matched groups, statin users demonstrated reduced 90-day all-cause mortality (0.7% vs. 5.5%, p < 0.001) and also showed significantly reduced cause-specific mortality due to cardiovascular and respiratory events, as well as sepsis and multiorgan failure. The significant postoperative survival benefit of statin users was seen despite a higher rate of cardiovascular comorbidity. CONCLUSION: Preoperative statin therapy displays a strong association with reduced postoperative mortality following surgical resection for rectal cancer. The results from the current study warrant further investigation to determine whether a causal relationship exists.

Pre-operative beta-blocker therapy does not affect short-term mortality after esophageal resection for cancer.

BACKGROUND: It has been postulated that the hyperadrenergic state caused by surgical trauma is associated with worse outcomes and that ß-blockade may improve overall outcome by downregulation of adrenergic activity. Esophageal resection is a surgical procedure with substantial risk for postoperative mortality. There is insufficient data to extrapolate the existing association between preoperative ß-blockade and postoperative mortality to esophageal cancer surgery. This study assessed whether preoperative ß-blocker therapy affects short-term postoperative mortality for patients undergoing esophageal cancer surgery. METHODS: All patients with an esophageal cancer diagnosis that underwent surgical resection with curative intent from 2007 to 2017 were retrospectively identified from the Swedish National Register for Esophagus and Gastric Cancers (NREV). Patients were subdivided into ß-blocker exposed and unexposed groups. Propensity score matching was carried out in a 1:1 ratio. The outcome of interest was 90-day postoperative mortality. RESULTS: A total of 1466 patients met inclusion criteria, of whom 35% (n = 513) were on regular preoperative ß-blocker therapy. Patients on ß-blockers were significantly older, more comorbid and less fit for surgery based on their ASA score. After propensity score matching, 513 matched pairs were available for analysis. No difference in 90-day mortality was detected between ß-blocker exposed and unexposed patients (6.0% vs. 6.6%, p = 0.798). CONCLUSION: Preoperative ß-blocker therapy is not associated with better short-term survival in patients subjected to curative esophageal tumor resection.

ß-adrenergic blockade is associated with a reduced risk of 90-day mortality after surgery for hip fractures.

BACKGROUND: There is a significant postoperative mortality risk in patients subjected to surgery for hip fractures. Adrenergic hyperactivity induced by trauma and subsequent surgery is thought to be an important contributor. By downregulating the effect of circulating catecholamines the increased risk of postoperative mortality may be reduced. The aim of the current study is to assess the association between regular ß-blocker therapy and postoperative mortality. METHODS: This cohort study used the prospectively collected Swedish National Quality Registry for hip fractures to identify all patients over 40 years of age subjected to surgery for hip fractures between 2013 and 2017 in Örebro County, Sweden. Patients with ongoing ß-blocker therapy at the time of surgery were allocated to the ß-blocker-positive cohort. The primary outcome of interest was 90-day postoperative mortality. Risk factors for 90-day mortality were evaluated using Poisson regression analysis. RESULTS: A total of 2443 patients were included in this cohort of whom 900 (36.8%) had ongoing ß-blocker therapy before surgery. The ß-blocker positive group was significantly older, less fit for surgery based on their American Society of Anesthesiologists classification and had a higher prevalence of comorbidities. A significant risk reduction in 90-day mortality was detected in patients receiving ß-blockers (adjusted incidence rate ratio=0.82, 95% CI 0.68 to 0.98, p=0.03). CONCLUSIONS: ß-blocker therapy is associated with a significant reduction in 90-day postoperative mortality after hip fracture surgery. Further investigation into this finding is warranted. LEVEL OF EVIDENCE: Therapeutic study, level III; prognostic study, level II.

Effects of beta-blocker therapy on mortality after elective colon cancer surgery: a Swedish nationwide cohort study.

OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression. PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality. RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001). CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.

Beta-Blocker Therapy in Severe Traumatic Brain Injury: A Prospective Randomized Controlled Trial.

BACKGROUND: Observational studies have demonstrated improved outcomes in TBI patients receiving in-hospital beta-blockers. The aim of this study is to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients. METHODS: Adult patients with severe TBI (intracranial AIS ≥ 3) were included in the study. Hemodynamically stable patients at 24 h after injury were randomized to receive either 20 mg propranolol orally every 12 h up to 10 days or until discharge (BB+) or no propranolol (BB-). Outcomes of interest were in-hospital mortality and Glasgow Outcome Scale-Extended (GOS-E) score on discharge and at 6-month follow-up. Subgroup analysis including only isolated severe TBI (intracranial AIS ≥ 3 with extracranial AIS ≤ 2) was carried out. Poisson regression models were used. RESULTS: Two hundred nineteen randomized patients of whom 45% received BB were analyzed. There were no significant demographic or clinical differences between BB+ and BB- cohorts. No significant difference in in-hospital mortality (adj. IRR 0.6 [95% CI 0.3-1.4], p = 0.2) or long-term functional outcome was measured between the cohorts (p = 0.3). One hundred fifty-four patients suffered isolated severe TBI of whom 44% received BB. The BB+ group had significantly lower mortality relative to the BB- group (18.6% vs. 4.4%, p = 0.012). On regression analysis, propranolol had a significant protective effect on in-hospital mortality (adj. IRR 0.32, p = 0.04) and functional outcome at 6-month follow-up (GOS-E ≥ 5 adj. IRR 1.2, p = 0.02). CONCLUSION: Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. LEVEL OF EVIDENCE: Level II; therapeutic. STUDY TYPE: Therapeutic study.

ß-Blockade in Rectal Cancer Surgery: A Simple Measure of Improving Outcomes.

OBJECTIVE: To ascertain whether regular ß-blocker exposure can improve short- and long-term outcomes after rectal cancer surgery. BACKGROUND: Surgery for rectal cancer is associated with substantial morbidity and mortality. There is increasing evidence to suggest that there is a survival benefit in patients exposed to ß-blockers undergoing non-cardiac surgery. Studies investigating the effects on outcomes in patients subjected to surgery for rectal cancer are lacking. METHODS: All adult patients undergoing elective abdominal resection for rectal cancer over a 10-year period were recruited from the prospectively collected Swedish Colorectal Cancer Registry. Patients were subdivided according to preoperative ß-blocker exposure status. Outcomes of interest were 30-day complications, 30-day cause-specific mortality, and 1-year all-cause mortality. The association between ß-blocker use and outcomes were analyzed using Poisson regression model with robust standard errors for 30-day complications and cause-specific mortality. One-year survival was assessed using Cox proportional hazards regression model. RESULTS: A total of 11,966 patients were included in the current study, of whom 3513 (29.36%) were exposed to regular preoperative ß-blockers. A significant decrease in 30-day mortality was detected (incidence rate ratio = 0.06, 95% confidence interval: 0.03-0.13, P < 0.001). Deaths of cardiovascular nature, respiratory origin, sepsis, and multiorgan failure were significantly lower in ß-blocker users, as were the incidences in postoperative infection and anastomotic failure. The ß-blocker positive group had significantly better survival up to 1 year postoperatively with a risk reduction of 57% (hazard ratio = 0.43, 95% confidence interval: 0.37-0.52, P < 0.001). CONCLUSIONS: Preoperative ß-blocker use is strongly associated with improved survival and morbidity after abdominal resection for rectal cancer.

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism.

Background: The treatment efficacy of antithyroid drug (ATD) therapy, radioactive iodine (131I), or surgery for Graves' hyperthyroidism is well described. However, there are a few reports on the long-term total outcome of each treatment modality regarding how many require levothyroxine supplementation, the need of thyroid ablation, or the individual patient's estimation of their recovery. Methods: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003 and 2005 (n = 2430). The patients were invited to participate in a longitudinal study spanning 8 ± 0.9 years (mean ± standard deviation) after diagnosis. We were able to follow 1186 (60%) patients who had been treated with ATD, 131I, or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities, and lifestyle factors through questionnaires and a review of the individual's medical history records. Results: At follow-up, the remission rate after first-line treatment choice with ATD was 45.3% (351/774), with 131I therapy 81.5% (324/264), and with surgery 96.3% (52/54). Among those patients who had a second course of ATD, 29.4% achieved remission (vs. the 45.3% after the first course of ATD). The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of whom 23% (278/1186) had received surgery, 43% (505/1186) had received 131I therapy, including 2% (20/1186) who had received both surgery and 131I. Patients who received ATD as first-line treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the 131I treated, and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%. Conclusion: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus, has unexpected long-term consequences for many patients.

The Relationship Between Severe Complications, Beta-Blocker Therapy and Long-Term Survival Following Emergency Surgery for Colon Cancer.

BACKGROUND: Emergency surgery for colon cancer carries significant morbidity, and studies show more than doubled mortality when comparing elective to emergency surgery. The relationship between postoperative complications and survival has been outlined. Beta-blocker therapy has been linked to improved postoperative outcomes. This study aims to assess the impact of postoperative complications on long-term survival following emergency surgery for colon cancer and to determine whether beta-blockade can reduce complications. STUDY DESIGN: This cohort study utilized the prospective Swedish Colorectal Cancer Registry to identify adults undergoing emergency colon cancer surgery between 2011 and 2016. Prescription data for preoperative beta-blocker therapy were collected from the national drug registry. Cox regression was used to evaluate the effect of beta-blocker exposure and complications on 1-year mortality, and Poisson regression was used to evaluate beta-blocker exposure in patients with major complications. RESULTS: A total of 3139 patients were included with a mean age of 73.1 [12.4] of which 671 (21.4%) were prescribed beta-blockers prior to surgery. Major complications occurred in 375 (11.9%) patients. Those suffering major complications showed a threefold increase in 1-year mortality (adjusted HR = 3.29; 95% CI 2.75-3.94; p < 0.001). Beta-blocker use was linked to a 60% risk reduction in 1-year mortality (adjusted HR = 0.40; 95% CI 0.26-0.62; p < 0.001) but did not show a statistically significant association with reductions in major complications (adjusted IRR = 0.77; 95% CI 0.59-1.00; p = 0.055). CONCLUSION: The development of major complications after emergency colon cancer surgery is associated with increased mortality during one year after surgery. Beta-blocker therapy may protect against postoperative complications.