Carvedilol in the treatment of chronic heart failure: Lessons from The Carvedilol Or Metoprolol European Trial

Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both metoprolol and carvedilol have demonstrated beneficial effects in placebo-controlled trials. In The Carvedilol Or Metoprolol European Trial (COMET) two beta blockers were compared in a double-blind randomized matter. This is the first direct comparison between metoprolol and carvedilol of long-term effect on survival in patients with chronic heart failure. The all-cause mortality was signif icantly reduced in the favour of carvedilol. The dose and formulation of metoprolol used in this trial has caused debate, and it has been questioned whether a similar beta1-blockade is obtained in the two intervention groups. At this time there is an unresolved debate as to whether carvedilol is a superior beta-blocker or whether differences in beta1-blockade explained the results of COMET

Assisted ventilation in COPD:association between previous hospitalizations and mortality

BACKGROUND: In general, previous studies have shown an association between prior exacerbations and mortality in COPD, but this association has not been demonstrated in the subpopulation of patients in need of assisted ventilation. We examined whether previous hospitalizations were independently associated with mortality among patients with COPD ventilated for the first time. PATIENTS AND METHODS: In the Danish National Patient Registry, we established a cohort of patients with COPD ventilated for the first time from 2003 to 2011 and previously medicated for obstructive airway diseases. We assessed the number of hospitalizations for COPD in the preceding year, age, sex, comorbidity, mode of ventilation, survival to discharge, and days to death beyond discharge. RESULTS: The cohort consisted of 6,656 patients of whom 66% had not been hospitalized for COPD in the previous year, 18% once, 8% twice, and 9% thrice or more. In-hospital mortality was 45%, and of the patients alive at discharge, 11% died within a month and 39% within a year. In multivariate models, adjusted for age, sex, mode of ventilation, and comorbidity, odds ratios for in-hospital death were 1.26 (95% confidence interval [CI]: 1.11–1.44), 1.43 (95% CI: 1.19–1.72), and 1.56 (95% CI: 1.30–1.87) with one, two, and three or more hospitalizations, respectively. Hazard ratios for death after discharge from hospital were 1.32 (95% CI: 1.19–1.46), 1.76 (95% CI: 1.52–2.02), and 2.07 (95% CI: 1.80–2.38) with one, two, and three or more hospitalizations, respectively. CONCLUSION: Preceding hospitalizations for COPD are associated with in-hospital mortality and after discharge in the subpopulation of patients with COPD with acute exacerbation treated with assisted ventilation for the first time

Use of 18F-NaF PET in the staging of skeletal metastases of newly diagnosed, high-risk prostate cancer patients:a nationwide cohort study

OBJECTIVE: To determine whether preoperative staging of high-risk prostate cancer with (18)F-sodium-fluoride ((18)F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases. DESIGN: Nationwide, population-based cohort study using real-world data. SETTING: The study used national health registries, including all sites in Denmark from 2011 to 2018. PARTICIPANTS: Newly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either (18)F-NaF PET or bone scintigraphy. MAIN OUTCOME MEASURES: The risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival. RESULTS: Between 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent (18)F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the (18)F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving (18)F-NaF PET and bone scintigraphy, respectively. CONCLUSION: Patients with high-risk prostate cancer undergoing preoperative staging with (18)F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups

Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension

Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension. METHODS: 40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high in vitro antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before and after the study. Measurements were blinded to treatment allocation. RESULTS: In the interventional group overall FMD increased from 4% to 5.8% in the interventional group whereas in the control group FMD was stable (4% at baseline and 3.9% at the end of the study). The change in FMD in the interventional group was mainly due to a marked change in FMD in two participants while the other participants did not have marked changes in FMD. The observed differences were not statistically significant. Likewise significant changes in blood pressure or blood samples were not detected between or within groups. Diastolic blood pressure stayed essentially unchanged in both groups, while the systolic blood pressure showed a small non significant decrease (9 mm Hg) in the interventional group from a value of 153 mm Hg at start. CONCLUSION: Daily ingestion of 10 g dried broccoli sprouts does not improve endothelial function in the presence of hypertension in humans. TRIAL REGISTRATION: Clinicaltrials.gov NCT0025201

Applying the causal roadmap to longitudinal national Danish registry data: a case study of second-line diabetes medication and dementia

The causal roadmap is a formal framework for causal and statistical inference that supports clear specification of the causal question, interpretable and transparent statement of required causal assumptions, robust inference, and optimal precision. The roadmap is thus particularly well-suited to evaluating longitudinal causal effects using large scale registries; however, application of the roadmap to registry data also introduces particular challenges. In this paper we provide a detailed case study of the longitudinal causal roadmap applied to the Danish National Registry to evaluate the comparative effectiveness of second-line diabetes drugs on dementia risk. Specifically, we evaluate the difference in counterfactual five-year cumulative risk of dementia if a target population of adults with type 2 diabetes had initiated and remained on GLP-1 receptor agonists (a second-line diabetes drug) compared to a range of active comparator protocols. Time-dependent confounding is accounted for through use of the iterated conditional expectation representation of the longitudinal g-formula as a statistical estimand. Statistical estimation uses longitudinal targeted maximum likelihood, incorporating machine learning. We provide practical guidance on the implementation of the roadmap using registry data, and highlight how rare exposures and outcomes over long-term follow up can raise challenges for flexible and robust estimators, even in the context of the large sample sizes provided by the registry. We demonstrate how simulations can be used to help address these challenges by supporting careful estimator pre-specification. We find a protective effect of GLP-1RAs compared to some but not all other second-line treatments

Ethnic disparities in out-of-hospital cardiac arrest:A population-based cohort study among adult Danish immigrants

BACKGROUND: Ethnicity might impact out-of-hospital cardiac arrest (OHCA) risk, but it has scarcely been studied in Europe. We aimed to assess whether ethnicity influenced the risk of OHCA of cardiac cause in Danish immigrants and its interplay with risk factors for OHCA and socioeconomic status. METHODS: This nationwide study included all immigrants between 18 and 80 years present in Denmark at some point between 2001 and 2020. Regions of origin were defined as Africa, Arabic countries, Asia, Eastern Europe, Latin America, and Western countries. OHCAs with presumed cardiac cause were identified from the Danish Cardiac Arrest Registry. FINDINGS: Overall, among 1,011,565 immigrants, a total of 1,801 (0.2%) OHCAs (median age 64 (Q1-Q3 53–72) years, 72% males) occurred. The age- and sex- standardized (reference: Western countries) incidence of OHCA (/1,00,000 person-years) was 34.6 (27.8–43.4) in African, 34.1 (30.4–38.4) in Arabic, 33.5 (29.3–38.2) in Asian, 35.6 (31.9–39.6) in Eastern European, and 16.2 (9.0–27.2) in Latin American immigrants. When selecting Western origin as a reference, and after adjusting on OHCA risk factors, Arabic (HR 1.18, 95%CI 1.04–1.35; P=0.01), Eastern European (HR 1.28, 95%CI 1.13–1.46; P<0.001), and African origin (HR 1.34, 95%CI 1.10–1.63; P<0.01) were associated with higher risk of OHCA, whereas Latin American origin (HR 0.58, 95%CI 0.35–0.0.96; P=0.03) was associated with lower risk of OHCA. Comparable results were observed when adjusting on education level and economic status. INTERPRETATION: This study emphasizes that ethnicity is associated with OHCA risk, even when considering traditional cardiac arrest risk factors. FUNDING: R Garcia received a grant from the Fédération Française de Cardiologie for his post-doctoral fellowship and this work was supported by the Novo Nordisk Foundation Tandem Programme 2022 (grant# 31364)

Surgical treatment of patients with infective endocarditis:changes in temporal use, patient characteristics, and mortality—a nationwide study

BACKGROUND: Valve surgery guidelines for infective endocarditis (IE) are unchanged over decades and nationwide data about the use of valve surgery do not exist. METHODS: We included patients with first-time IE (1999–2018) using Danish nationwide registries. Proportions of valve surgery were reported for calendar periods (1999–2003, 2004–2008, 2009–2013, 2014–2018). Comparing calendar periods in multivariable analyses, we computed likelihoods of valve surgery with logistic regression and rates of 30 day postoperative mortality with Cox regression. RESULTS: We included 8804 patients with first-time IE; 1981 (22.5%) underwent surgery during admission, decreasing by calendar periods (N = 360 [24.4%], N = 483 [24.0%], N = 553 [23.5%], N = 585 [19.7%], P = < 0.001 for trend). For patients undergoing valve surgery, median age increased from 59.7 to 66.9 years (P ≤ 0.001) and the proportion of males increased from 67.8% to 72.6% (P = 0.008) from 1999–2003 to 2014–2018. Compared with 1999–2003, associated likelihoods of valve surgery were: Odds ratio (OR) = 1.14 (95% CI: 0.96–1.35), OR = 1.20 (95% CI: 1.02–1.42), and OR = 1.10 (95% CI: 0.93–1.29) in 2004–2008, 2009–2013, and 2014–2018, respectively. 30 day postoperative mortalities were: 12.7%, 12.8%, 6.9%, and 9.7% by calendar periods. Compared with 1999–2003, associated mortality rates were: Hazard ratio (HR) = 0.96 (95% CI: 0.65–1.41), HR = 0.43 (95% CI: 0.28–0.67), and HR = 0.55 (95% CI 0.37–0.83) in 2004–2008, 2009–2013, and 2014–2018, respectively. CONCLUSIONS: On a nationwide scale, 22.5% of patients with IE underwent valve surgery. Patient characteristics changed considerably and use of valve surgery decreased over time. The adjusted likelihood of valve surgery was similar between calendar periods with a trend towards an increase while rates of 30 day postoperative mortality decreased. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02761-z