Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

BACKGROUND: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. OBJECTIVES: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. METHODS: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. RESULTS: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. CONCLUSION: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.

A Content Framework of a Novel Patient-Reported Outcome Measure for Detecting Early Adverse Events After Major Abdominal Surgery.

BACKGROUND: Systematic health monitoring with patient-reported outcome instruments may predict post-discharge complications after major surgery. The objective of this study was to conceptualize a novel patient-reported outcome instrument for detecting early adverse events within two weeks of discharge after major emergency abdominal surgery and colorectal cancer surgery. METHODS: This study was conducted in two phases. (1) An exhaustive health concept pool was generated using systematic content analysis of existing patient-reported outcome measures (N = 31) and semi-structured interviews of readmitted patients (N = 49) and health professionals (N = 10). Concepts were categorized into three major domains: 'Symptoms,' 'functional status,' and 'general health perception.' We calculated the frequency of each health concept as the proportion of patients, who experienced the respective concept prior to readmission. (2) Colorectal cancer surgeons (N = 13) and emergency general surgeons (N = 12) rated the relevance of each health concept (1 = irrelevant, 5 = very relevant) in the context of detecting post-discharge adverse events. We selected concepts with either a high mean relevance score (≥ 4) or a combination of moderate mean relevance score and high patient-reported frequency (≥ 3 and ≥ 20% or ≥ 2.5 and ≥ 50%, respectively). RESULTS: Content analysis of existing items with additions from patients and experts resulted in 58 health concepts, of which the majority were distinct symptoms (N = 40). The selection procedure resulted in 29 patient-reported health concepts relevant for detecting adverse events after discharge. CONCLUSION: The outlined framework provides content validity for future patient-reported outcome instruments detecting adverse events in the early post-discharge period after major emergency abdominal surgery and colorectal cancer surgery.

The impact of time to surgery on oncological outcomes in stage I-III dMMR colon cancer - A nationwide cohort study.

INTRODUCTION: One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer. MATERIALS AND METHODS: This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio. RESULTS: A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81-1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69-1.06; p = 0.14). CONCLUSION: No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery.

Randomized Trial of Surgical Left Atrial Appendage Closure: Protection Against Cerebrovascular Events.

Following open-heart surgery, atrial fibrillation and stroke occur frequently. Left atrial appendage closure added to elective open-heart surgery could reduce the risk of ischemic stroke. We aim to examine if routine closure of the left atrial appendage in patients undergoing open-heart surgery provides long-term protection against cerebrovascular events independently of atrial fibrillation history, stroke risk, and oral anticoagulation use. Long-term follow-up of patients enrolled in the prospective, randomized, open-label, blinded evaluation trial entitled left atrial appendage closure by surgery (NCT02378116). Patients were stratified by oral anticoagulation status and randomized (1:1) to left atrial appendage closure in addition to elective open-heart surgery vs standard care. The primary composite endpoint was ischemic stroke events, transient ischemic attacks, and imaging findings of silent cerebral ischemic lesions. Two neurologists blinded for treatment assignment adjudicated cerebrovascular events. In total, 186 patients (82% males) were reviewed. At baseline, mean (standard deviation (SD)) age was68 (9) years and 13.4% (n = 25/186) had been diagnosed with atrial fibrillation. Median [interquartile range (IQR)] CHA2DS2-VASc was 3 [2,4] and 25.9% (n = 48/186) were receiving oral anticoagulants. Mean follow-up was 6.2 (2.5) years. The left atrial appendage closure group experienced fewer cerebrovascular events; intention-to-treat 11 vs 19 (P = 0.033, n = 186) and per-protocol 9 vs 17 (P = 0.186, n = 141). Left atrial appendage closure as an add-on open-heart surgery, regardless of pre-surgery atrial fibrillation and oral anticoagulation status, seems safe and may reduce cerebrovascular events in long-term follow-up. More extensive randomized clinical trials investigating left atrial appendage closure in patients without atrial fibrillation and high stroke risk are warranted.

Glycemic profile and quality of recovery after emergency abdominal surgery-A prospective explorative cohort study.

Associations between degrees of postoperative hyperglycemia and morbidity has previously been established. There may be an association between the glycemic profile and patient-reported recovery, and this may be a target for perioperative quality improvements. We aimed to investigate the association between metrics of the 30-day glycemic profile and patient-reported recovery in nondiabetic patients after major abdominal surgery. In a prospective, explorative cohort study, nondiabetic adult patients undergoing acute, major abdominal surgery were included within 24 h after surgery. Interstitial fluid glucose concentration was measured for 30 consecutive days with a continuous glucose measurement device. The validated questionnaire 'Quality of Recovery-15' was used to assess patient-reported quality of recovery on postoperative days 10, 20, and 30. Follow-up time was divided into five-day postoperative intervals using days 26-30 as a reference. Linear mixed models were applied to investigate temporal changes in mean p-glucose, coefficient of variation, time within 70-140 mg/dl, and time above 200 mg/dl in relation to patient-reported recovery. Twenty-seven patients completed the study per protocol. A hyperglycemic event (>200 mg/dl) occurred in 18 of 27 patients (67%) within the first three postoperative days. Compared to the reference period, the coefficient of variation was significantly increased during all time intervals, indicating prolonged postoperative insulin resistance. During 30 days of follow-up, patient-reported recovery was associated with the coefficient of variation measured for 3 and 5 days before the corresponding recovery score assessment (recovery score estimate -1.52 [p < .001] and -0.92 [p = .006], respectively). We did not find an association between the remaining metrics and patient-reported recovery. Alterations in the glycemic profile are frequent and prolonged during the first postoperative month after major surgery probably due to peripheral insulin resistance. Our findings indicate that high-glycemic variation is associated with poorer patient-reported recovery and might represent a proxy for care improvements in the postoperative period.

Incidence and clinical predictors of 30-day emergency readmission after colorectal cancer surgery - A nationwide cohort study.

AIM: The aim of this study was to investigate the risk and predictors of 30-day emergency readmission and surgical reintervention after discharge from colorectal cancer surgery with curative intent in Denmark. METHOD: This is a retrospective cohort study using Danish nationwide registry data. We included all patients who underwent colorectal tumour resection with curative intent between 1 January 2005 and 1 December 2018. The primary outcome was 30-day emergency readmission, defined as any emergency hospital visit within 30 days of discharge. Secondary outcomes were 30-day emergency readmission with a minimum duration of 2 days and 30-day emergency readmission including any abdominal procedure. Twenty-three candidate predictors including patient comorbidities, tumour characteristics, surgical treatment and length of stay were evaluated using multivariate logistic regression models. Length of stay was categorized into percentiles and standardized according to year of surgery. RESULTS: Of the 40 782 patients included in the study, 8360 (20.5%) were readmitted within 30 days of discharge. Median time to readmission was 6 days (interquartile range 2-15 days). A total of 4968 patients (12.2%) were readmitted for at least 2 days, and 793 patients (1.9%) underwent an abdominal procedure during their readmission. The strongest predictors of 30-day readmission were length of stay below the fifth percentile (OR 2.36; P < 0.001) and American Society of Anesthesiologists score IV (OR 2.21; P < 0.001). CONCLUSION: Emergency readmission is frequent after colorectal cancer surgery with curative intent, and almost 10% of readmitted patients require surgical reintervention. An increased focus on predicting preventable readmissions might facilitate interventions to reduce morbidity and hospital expenses.

Developing prediction models for short-term mortality after surgery for colorectal cancer using a Danish national quality assurance database.

PURPOSE: The majority of colorectal cancer surgeries are performed electively, and treatment is often decided at the multidisciplinary team conference. Although the average 30-day mortality rate is low, there is substantial population heterogeneity from young, healthy patients to frail, elderly patients. The individual risk of surgery can vary widely, and tailoring treatment for colorectal cancer may lead to better outcomes. This requires prediction of risk that is accurate and available prior to surgery. METHODS: Data from the Danish Colorectal Cancer Group database was transformed into the Observational Medical Outcomes Partnership Common Data Model. Models were developed to predict the risk of mortality within 30, 90, and 180 days after colorectal cancer surgery using only covariates decided at the multidisciplinary team conference. Several machine-learning models were trained, but due to superior performance, a Least Absolute Shrinkage and Selection Operator logistic regression was used for the final model. Performance was assessed with discrimination (area under the receiver operating characteristic and precision recall curve) and calibration measures (calibration in large, intercept, slope, and Brier score). RESULTS: The cohort contained 65,612 patients operated for colorectal cancer in the period from 2001 to 2019 in Denmark. The Least Absolute Shrinkage and Selection Operator model showed an area under the receiver operating characteristic for 30-, 90-, and 180-day mortality after colorectal cancer surgery of 0.871 (95% CI: 0.86-0.882), 0.874 (95% CI: 0.864-0.882), and 0.876 (95% CI: 0.867-0.883) and calibration in large of 1.01, 0.98, and 1.01, respectively. CONCLUSION: The postoperative short-term mortality prediction model showed excellent discrimination and calibration using only preoperatively known predictors.

New-onset of postoperative atrial fibrillation is likely to recur in the absence of other triggers.

BACKGROUND: Incident atrial fibrillation (AF) is reported in 10%-65% of patients without previous AF diagnosis after open heart surgery. The risk of late AF recurrence after a postoperative AF onset is unclear, and it is controversial whether AF limited to the postoperative period should elicit oral anticoagulation (OAC) therapy. The primary objective of this study was to evaluate the long-term recurrence of AF in patients developing new-onset peri-procedural AF. PATIENTS AND METHODS: Patients (n=189) with available baseline and follow-up data included in Left Atrial Appendage Closure with Surgery trial were coded for known AF at baseline and for postoperative first-time AF diagnosis. AF occurrence was classified as follows: peri-procedural ≤7 days postoperatively, early >7 days but ≤3 months and late >3 months. Patients with no AF recurrence registered during follow-up were invited to undergo Holter monitoring. RESULTS: A total of 163 (86.2%) patients had no history of AF. Among these, 80 (49.1%) developed new-onset peri-procedural AF. After a mean follow-up of 3.7±1.6 years, late AF occurred in 35 of the 80 (43.8%) patients who developed peri-procedural AF and in 6 additional patients (7.2%) who remained in sinus rhythm until discharge (hazard ratio [HR] 9.3, 95% CI 3.8-22.4, p<0.001). Patients with peri-procedural AF and early AF had 12.24 times higher risk of late AF (95% CI 4.76-31.45, p<0.001) as compared to the group with no postoperative AF. CONCLUSION: New-onset of AF after open heart surgery has a high rate of recurrence and should not be regarded as a self-limiting phenomenon secondary to surgery.

Main and interactive effects of physical activity, fitness and body mass in the prevention of cancer from the Copenhagen Male Study.

Little knowledge exists about the role of cardiorespiratory fitness (CRF) or its interaction with excess adiposity determined by body mass index (BMI) in cancer prevention. A total of 5,128 middle-aged men, without a history of cancer at baseline in 1970-71, were examined for subsequent incidence and mortality of several cancer types. Participants' data were linked with cancer registration and mortality data to March 2017. During 47 years of follow-up, a total of 1,920 incident cases and 1,638 cancer-related deaths were ascertained. BMI, particularly obesity, was associated with (i) incidence and (ii) mortality from respiratory/thoracic cancers; and (iii) all cancer-cause mortality. The respective adjusted hazard ratios (HRs) were: (i) 0.51 (95%CI:0.32-0.79), (ii) 0.48 (95%CI:0.30-0.75) and (iii) 0.73 (95%CI:0.59-0.89) when compared obese men (BMI ≥30 kg/m2) to men with healthy-BMI (<25 kg/m2). Increasing CRF was inversely associated with incidence and mortality of respiratory/thoracic cancers, HRs 0.78 (95%CI:0.67-0.90) and 0.73 (95%CI:0.63-0.84) respectively; and all cancer-cause incidence 0.92 (95%CI:0.86-0.98) and mortality 0.85 (95%CI:0.79-0.91). Physical activity (PA) was not associated with most outcomes. We found no evidence of interactions between CRF or PA and BMI on cancer risk. This evidence suggests that midlife CRF is associated with lowered risk of cancer incidence and mortality with no evidence of cancer risk modification by BMI.

Midlife Cardiorespiratory Fitness and the Long-Term Risk of Mortality: 46 Years of Follow-Up.

BACKGROUND: A high cardiorespiratory fitness (CRF) level is recommended to promote healthy aging. However, the association between CRF and very-long-term prognosis is unclear, and reverse causation may bias results in studies with shorter follow-up. OBJECTIVES: This study investigated the association between CRF and mortality in middle-aged, employed men free of cardiovascular disease (CVD). METHODS: Participants from the Copenhagen Male Study, established in 1970 to 1971, were included and stratified into 4 age-adjusted maximal oxygen consumption (Vo2max) categories: below the lower limit of normal (lowest 5%); low normal (45%); high normal (45%); and above the upper limit of normal (top 5%). Vo2max was estimated by using a bicycle ergometer. Multivariable restricted mean survival time models were performed for all-cause and cardiovascular mortality using Danish national registers. RESULTS: A total of 5,107 men with a mean age of 48.8 ± 5.4 years were included in the study. During the 46 years of follow-up, 4,700 (92%) men died; 2,149 (42.1%) of the men died of CVD. Compared with below the lower limit of normal CRF, low normal CRF was associated with 2.1 years (95% confidence interval [CI]: 0.7 to 3.4; p = 0.002), high normal with 2.9 years (95% CI: 1.5 to 4.2; p < 0.001), and above upper limit of normal with 4.9 years (95% CI: 3.1 to 6.7; p < 0.001) longer mean life expectancy. Each unit increase in Vo2max was associated with a 45-day (95% CI: 30 to 61; p < 0.001) increase in longevity. Estimates for cardiovascular mortality were similar to all-cause mortality. Results were essentially unchanged when excluding individuals who died within the first 10 years of follow-up, suggesting a minimal role of reverse causation. CONCLUSIONS: CRF was significantly related to longevity over the course of 4 decades in middle-aged, employed men free of CVD. The benefits of higher midlife CRF extend well into the later part of life.

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

BACKGROUND: Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. METHODS: One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. RESULTS: During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). CONCLUSIONS: In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. TRIAL REGISTRATION: LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.