Copenhagen University Hospital
CURIS (Copenhagen University Research Information System)Not a member yet
395145 research outputs found
Sort by
Long-term prognosis in early-onset atrial fibrillation without overt cardiovascular disease
No full textBACKGROUND: The prognostic implications of early-onset atrial fibrillation (AF) in patients without coexisting cardiovascular conditions are not clear.OBJECTIVE: To investigate the risk of long-term stroke, heart failure (HF), and mortality in patients with early-onset AF.METHODS: Using nationwide registers, we included adult patients with early-onset AF (18-45 years old) with a first-time AF diagnosis during 1999-2023 without co-existing cardiovascular conditions. All AF patients were matched with a control group from the background population without AF. The long-term absolute risks of stroke, HF, and death were estimated as well as standardized risk ratios (RR) comparing patients with and without AF.RESULTS: Among 7,632 patients with AF (median age: 39 years, 71% men, 1.9% cancer, 2.1% diabetes), clinically relevant crude risks of stroke (20-year risk: 6.89%, 95% CI 5.96%-7.82%), HF (20-year risk: 6.45%, 95% CI 5.60%-7.31%), and death (20-year risk: 7.10%, 95% CI 6.18%-8.02%) were observed. Comparing the AF cohort with a matched sample from the background population (median age: 38 years, 71% men, 1.1% cancer, 1.3% diabetes) revealed elevated standardized risks of stroke (RR: 2.00, 95% CI 1.67-2.33), HF (RR: 4.33, 95% CI 3.55-5.11), and death (RR: 1.37, 95% CI 1.17-1.57).CONCLUSIONS: Early-onset AF in patients without concomitant cardiovascular conditions was associated with increased long-term risk of cardiovascular complications, most notably a four- to five-fold increased risk of HF. Hence, AF in otherwise healthy young patients should be considered an important marker of increased risks of a future cardiomyopathy and HF events.</p
Deviation From Genetically Predicted BMI and All-Cause Mortality:A Cohort Study in the UK Biobank
No full textObjective: The relation between genetically predicted BMI (gBMI) and actual BMI may have health effects. This study examines the relationship between deviations from gBMI and all-cause mortality in 208,146 UK Biobank participants. Methods: We derived gBMI from polygenic risk scores, with deviations calculated as the difference between observed and predicted BMI. Cox proportional hazards models are adjusted for confounders and current BMI. Results: Downward deviations (> 2 SD below gBMI) were associated with significantly increased mortality (HR: 1.25, 95% CI: 1.01–1.55), whereas upward deviations (> 2 SD above) showed no significant effect (HR: 1.10, 95% CI: 0.93–1.29). The mortality exhibited the known nonlinear J-shaped association with observed BMI, here lowest at BMI ~22 kg/m2, but this nadir varied by genetic predisposition; thus, for individuals with high gBMI, lowest mortality occurred at higher observed BMI (24–26 kg/m2), while those with low or medium gBMI showed sharper increases in mortality at higher BMI. Conclusions: These findings highlight the possible importance of aligning current BMI to genetic predisposition, and future research should examine BMI deviations and their long-term health effects. This perspective may inform personalized obesity management strategies to optimize health outcomes.</p
Landscape-scale drivers of insect pest regulation in sugar beet
No full textRecent policy shifts sparked by environmental and health concerns, insecticide resistance development, and limited new registrations have caused a dwindling availability of chemical insecticides. Sugar beet, a major cash crop in temperate agricultural systems, relied on now banned neonicotinoid insecticide seed coatings for pest control, creating a need for sustainable alternatives. Using a monitoring dataset from 134 sugar beet fields in Denmark and Sweden collected over five years, we assessed landscape-scale drivers of the occurrence and damage of five dominant sugar beet pests in the region: black bean aphid, flea beetles, beet leafminers, pygmy mangold beetle and thrips. We found that insect pests generally cause limited damage to sugar beet in our study area, with damage thresholds for any of the five pests being exceeded in 20 % of the fields. Damage by thrips was more common in Denmark and damage by flea beetles and beet leafminer eggs were more common in Sweden. Pest occurrence or damage could only partly be explained by landscape-scale factors. Cropland cover was positively related to black bean aphid and thrips damage presence but negatively related to flea beetle and pygmy mangold beetle damage. Edge density was negatively related to black bean aphid occurrence but positively related to flea beetle damage. An inter-annual increase in host crop cover was positively related to flea beetle damage and crop diversity to beet leafminer infestation. We conclude that further research on the cause and countermeasures for insect pest outbreaks is needed to develop economically and environmentally sustainable insect pest regulation in sugar beet
Contextual Equality Saturation
No full textEquality saturation is a semantics-based technique for automatically and efficiently proving that two programs are equivalent modulo a fixed set of equality axioms. In this paper, we extend the equality saturation technique with contextual reasoning in order to perform rewriting under assumptions that are locally valid inside a conditional branch. This is based on a new notion of cyclic e-graphs with contextual annotations. We experimentally validate the efficiency and scalability of this new technique by proving equivalence of several families of programs where contextual reasoning is required.</p
Initiation of SGLT2 inhibitors versus mineralocorticoid receptor antagonists as third-line therapy in heart failure with reduced ejection fraction:a nationwide cohort study
No full textBackground: Heart failure with reduced ejection fraction (HFrEF) guidelines recommend early initiation of four foundational therapies—renin-angiotensin system inhibitors (RASI), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In clinical practice, these drugs are usually introduced sequentially, and optimal sequencing remains uncertain. This study investigated the effectiveness of initiating SGLT2 inhibitors versus MRAs as the third foundational therapy following RASI and beta-blockers. Methods: This was a nationwide non-interventional study in Denmark, July 2020–2023. Patients with HFrEF (left ventricular ejection fraction ≤40%) aged ≥45 years on background RASI and beta-blockers were included. An active-comparator new-user design was used to emulate a trial-like comparison. Baseline characteristics were balanced using inverse-probability of treatment weighting based on propensity scores. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular death, heart failure hospitalization, and their composite. Weighted hazard ratios (wHRs) were estimated using proportional hazards regression. Findings: The study included 4185 new MRA users (63% spironolactone, 37% eplerenone) and 2565 new SGLT2 inhibitor users (74% dapagliflozin, 26% empagliflozin). All-cause mortality occurred in 423 MRA users (unweighted rate 6.3 per 100 person-years) and 155 SGLT2 inhibitor users (5.8 per 100 person-years). In weighted analysis comparing SGLT2 inhibitors to MRAs, the wHR was 0.70 (95% CI 0.57–0.86; absolute risk difference −2.1 per 100 person-years, 95% CI –0.9 to −3.2). For the composite secondary outcome, the wHR was 0.83 (95% CI 0.71–0.97); for cardiovascular death, 0.65 (95% CI 0.49–0.87); and for heart failure hospitalization, 0.89 (95% CI 0.74–1.07). Interpretation: Initiating SGLT2 inhibitors as the third foundational therapy after RASI and beta-blockers was associated with significantly lower risk of all-cause mortality compared to MRAs. These findings support the prioritization of SGLT2 inhibitors in treatment sequencing for HFrEF. Funding: This study was supported by the Novo Nordisk Foundation and Karolinska Institutet.</p
Psychedelics produce enduring behavioral effects and functional plasticity through mechanisms independent of structural plasticity
No full textActivation of serotonin 2A (5-HT2A) receptors is thought to underly the long-lasting antidepressant effects of psychedelics such as psilocybin, but beyond that, the molecular and cellular mechanisms involved are not well understood. Recent preclinical studies using mice have primarily examined relatively short time points after psychedelic administration, which does not address the long-lasting effects of psilocybin in humans (i.e., several months or more). We utilized a rat experimental system to demonstrate that both psilocybin and the selective 5-HT2A receptor agonist 25CN-NBOH reduce immobility in the forced swim test without a decrease in effect size for at least three months after a single administration of the psychedelic. There were no overt behavioral differences between psilocybin and 25CN-NBOH treated animals, suggesting 5-HT2A receptor activation is sufficient to produce long-lasting behavioral changes. Functional cellular plasticity in neurons from the medial prefrontal cortex (mPFC) of these animals was assessed using brain slice electrophysiology. Functional plasticity was evident for both psychedelics several months after treatment, and Layer 5 excitatory pyramidal neurons demonstrated significant changes in resting membrane potential, firing rates, and synaptic excitation. Recorded neurons were examined by microscopy for synaptic density and spine classification, which found no differences between control and psychedelic-treated. Gene expression studies for several presynaptic and postsynaptic markers in the mPFC indicated no differences in expression between groups. Together, our results indicate a single treatment with a psychedelic is sufficient to elicit very long-lasting behavioral and cellular changes through enduring function plasticity rather than structural plasticity.</p
Changes in maintenance immunosuppression after pediatric kidney transplantation - a report from the Nordic pediatric kidney transplantation registry
No full textBACKGROUND: Few studies are available on changes in maintenance immunosuppression after pediatric kidney transplantation (KT). This is a retrospective registry analysis of the long-term medication modifications in the Nordic countries.METHODS: All pediatric KT recipients transplanted between the years 2005 and 2016 were identified from the Scandiatransplant registry. Of the 482 patients, 345 met the inclusion criteria: age below 16 years at KT and at least 2 years post-transplant follow-up.RESULTS: A change in maintenance immunosuppression occurred in 160 patients (46.4%) at 2.0 (interquartile range 1.0-3.0) years median time from KT. The most common change (35.8%) was switching cyclosporine A (CsA) to tacrolimus (Tac). Initial CsA treatment was modified significantly more often compared to Tac (72.0% vs. 6.0%; p < 0.001). Modifications of mycophenolate mofetil (MMF) were observed more often in recipients aged < 2 (75.0%) and 2-5 (55.6%) years compared with 5-16 years (13.2%; p < 0.001); particularly, MMF discontinuation was common (< 2 years 45.8% and 2-5 years 38.9%). Otherwise, initial immunosuppression remained mainly unchanged. The main reasons for changing CsA to Tac were cosmetic side effects (26.2%), rejections (26.2%), and declining graft function (23.0%). In case of rejection or declining graft function, CsA-to-Tac conversion slowed the decrease in measured glomerular filtration rate. MMF modifications did not affect graft survival from 2 to 7.5 years post-transplant.CONCLUSIONS: Maintenance immunosuppression is modified in almost half of pediatric KT recipients. Particularly, CsA conversion to Tac and young recipients' MMF modifications are common.</p
Decision Support Tools for Adjusting Perioperative Opioid Dosing as Individualised Postoperative Pain Management:A Systematic Review
No full textINTRODUCTION: Despite decades of efforts to optimize procedure-specific pain management, up to 60% of surgical patients still experience moderate to severe pain and opioid-related adverse effects. Current guidelines primarily rely on standardised dosing protocols rather than individual patient characteristics, offering limited support for tailoring opioid therapy to patient-specific needs. This systematic review aimed to identify studies on decision support tools for adjusting perioperative systemic opioid dosing as individualised postoperative pain management and evaluate their effects on postoperative outcomes.METHODS: We searched EMBASE, MEDLINE and Cochrane Library up to August 2025 for studies including adult surgical patients developing, validating or testing decision support tools (prediction models or nociception monitoring systems). Prediction model studies had to include at least two predictors and target the first 24 postoperative hours. Intervention studies had to report pain, opioid use, or opioid-related adverse events within 24 h. Studies on chronic pain, intraoperative-only agents (e.g., remifentanil), or unpublished literature were excluded. Risk of bias was assessed using the Prediction model Risk of Bias Assessment Tool in prediction model studies and Cochrane Risk of Bias and ROBINS-I tool in intervention studies. We conducted meta-analyses for intervention studies (RCTs only) when outcomes were comparable.RESULTS: We included 19 studies on decision support tools for perioperative opioid management: seven development and one impact study on personalised prediction models and 11 intervention studies on nociception monitoring systems. All prediction model studies predicted postoperative opioid requirements, had a high risk of bias, limited external validation and poor overall performance (R2 range: 0.100-0.313). None were clinically tested or provided advice on optimal opioid dosing. For intervention trials evaluating nociception monitoring systems, meta-analyses showed no significant effect on pain, opioid use, or opioid-related adverse events within 24 h after surgery. No studies tested risk stratified/individualised opioid treatment.CONCLUSION: No prediction model study provided concrete guidance for individualising systemic opioid treatment. Nociception monitor-guided opioid doses did not improve acute postoperative pain, opioid use or opioid-related adverse events.EDITORIAL COMMENT: This systematic review assessed if available tested prediction models for individual guiding of opioid analgesic dosing, including monitors designed to assess nociceptive signal influence on clinical status, were of benefit in clinical practice. Findings, for outcomes analgesic effect, opioid dosing, or adverse events related to opioids, none of the models or systems have been demonstrated to have cliear clinical utility for optimizing opioid dosing.</p
Restrictive Versus Standard Intravenous Fluid Therapy and Endothelial Glycocalyx Shedding in ICU Patients With Septic Shock—A Preplanned Sub-Study of the Randomized CLASSIC Trial
No full textShedding of the endothelial glycocalyx may be a pathophysiological mechanism in septic shock, to which intravenous (IV) fluid therapy may contribute. We aimed to investigate the effects of restrictive versus standard IV fluid therapy on glycocalyx shedding in adult intensive care unit (ICU) patients with septic shock. In this preplanned sub-study of the CLASSIC trial, ICU patients with septic shock were randomized to restrictive or standard IV fluid therapy at one Danish and one Swedish ICU between February 2020 and October 2021. Plasma markers of glycocalyx shedding were measured at four timepoints: within the first hour after randomization (T0), the following morning (T1), the morning after (T2), at ICU discharge or up to 90 days after randomization (T3). The primary outcome was the change in plasma hyaluronan levels from T0 to T1. A total of 54 patients were included, below the planned sample size of 200, leading to important differences between groups. Mean hyaluronan levels decreased by 11 ng/mL (95% CI 35–41) more in the restrictive group compared to the standard group from T0 to T1. The interaction effect between group and time was non-significant (p value: 0.872). In this underpowered sub-study we found no statistically significant difference in endothelial glycocalyx shedding between adult ICU patients with septic shock randomized to restrictive versus standard IV fluid therapy. We consider these findings hypothesis-generating; further research is needed to confirm these results.Shedding of the endothelial glycocalyx may be a pathophysiological mechanism in septic shock, to which intravenous (IV) fluid therapy may contribute. We aimed to investigate the effects of restrictive versus standard IV fluid therapy on glycocalyx shedding in adult intensive care unit (ICU) patients with septic shock. In this preplanned sub-study of the CLASSIC trial, ICU patients with septic shock were randomized to restrictive or standard IV fluid therapy at one Danish and one Swedish ICU between February 2020 and October 2021. Plasma markers of glycocalyx shedding were measured at four timepoints: within the first hour after randomization (T0), the following morning (T1), the morning after (T2), at ICU discharge or up to 90 days after randomization (T3). The primary outcome was the change in plasma hyaluronan levels from T0 to T1. A total of 54 patients were included, below the planned sample size of 200, leading to important differences between groups. Mean hyaluronan levels decreased by 11 ng/mL (95% CI 35–41) more in the restrictive group compared to the standard group from T0 to T1. The interaction effect between group and time was non-significant (p value: 0.872). In this underpowered sub-study we found no statistically significant difference in endothelial glycocalyx shedding between adult ICU patients with septic shock randomized to restrictive versus standard IV fluid therapy. We consider these findings hypothesis-generating; further research is needed to confirm these results. Editorial Comment: In this substudy of the CLASSIC trial, glycocalyx degredation products and related substances were measured serially in sepsic study participants randomized to restrictive or usual fluid treatment protocols. No differences between treatment glycocalyx degredation product and related substance levels were observed. Trial Registration: ClinicalTrials.gov identifier: NCT04282252.</p