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Objectives: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. Methods: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. Results: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: −2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes. Conclusions: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.

Aims: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS). Methods and results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%). Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements.

Aims 3D echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use. Methods and results Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were as follows: LA reservoir strain (LASr) 30.8% (18.4–44.2%), LA conduit strain (LAScd) 19.1% (6.8–32.0%), LA contractile strain 11.7% (4.3–22.2%), total LA emptying fraction (LAEF) 61.4% (47.8–71.0%), passive LAEF 37.7% (17.4–53.9%), active LAEF 37.4% (22.2–52.5%), LA minimum volume index (LAVimin) 10.2 (5.9–18.5) mL/m2, and LA maximum volume index (LAVimax) 26.8 (16.5–40.1) mL/m2. All parameters changed significantly with increasing age (P value for all <0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (P for interaction < 0.001), LAScd (P for interaction < 0.001), LAVimin (P for interaction = 0.037), and total LAEF (P for interaction = 0.034) such that these parameters deteriorated faster with age in females than males. Conclusion We present age- and sex-specific reference material including limits of normality for LA strain, volume, and function by 3DE., BACKGROUND: Three-dimensional echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use.METHODS AND RESULTS: Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2,082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain (LASct) 11.7% (4.3-22.2%) total LA emptying fraction (LAEF) 61.4% (47.8-71.0%), passive LAEF 37.7% (17.4-53.9%), active LAEF 37.4% (22.2-52.5%), LA minimum volume index (LAVimin) 10.2 (5.9-18.5) ml/m2, LA maximum volume index (LAVimax) 26.8 (16.5-40.1) ml/m2. All parameters changed significantly with increasing age (p value for all <0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (p for interaction < 0.001), LAScd (p for interaction < 0.001), LAVimin (p for interaction = 0.037) and total LAEF (p for interaction = 0.034) such that these parameters deteriorated faster with age in females than males.CONCLUSION: We present age- and sex specific reference material including limits of normality for LA strain, volume, and function by 3DE.

Aims Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population. Methods and results The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4–6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00–1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio ‘was’ independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06–1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09–1.68), P = 0.005, per 5% increase]. Conclusion MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of age., Aims Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population. Methods and results The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4–6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00–1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio ‘was’ independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06–1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09–1.68), P = 0.005, per 5% increase]. Conclusion MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of ag

Aims Right ventricular free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) are associated with adverse events in various patient populations including patients with heart failure (HF). We sought to investigate the prognostic value of RVFWLS and RV4CLS for the development of incident HF in participants from the general population. Methods Participants from the 5th Copenhagen City Heart Study (2011–2015) without known chronic ischaemic heart disease or HF and results at baseline were included. RVFWLS and RV4CLS were obtained using two-dimensional speckle-tracking echocardiography from the right ventricular (RV)-focused apical four-chamber view. The primary endpoint was incident HF. Among 2740 participants (mean age 54 ± 17 years, 42% male), 43 (1.6%) developed HF during a median follow-up of 5.5 years (IQR 4.5–6.3). Both RVFWLS and RV4CLS were associated with an increased risk of incident HF during follow-up independent of age, sex, hypertension, diabetes, body mass index and tricuspid annular plane systolic excursion (TAPSE), (HR 1.06, 95%CI 1.00–1.11, P = 0.034, per 1% absolute decrease and HR 1.14, 95%CI 1.05–1.23, P = 0.001, per 1% absolute decrease, respectively). Left ventricular ejection fraction (LVEF) modified the association between RV4CLS and incident HF (P for interaction = 0.016) such that RV4CLS was only of prognostic importance among those with LVEF < 55% (HR 1.21, 95%CI 1.11–1.33, P < 0.001 vs. HR 0.94, 95%CI 0.80–1.10, P = 0.43 in patients with LVEF ≥ 55%). Conclusion In participants from the general population, both RVFWLS and RV4CLS were associated with a greater risk of incident HF independent of important baseline characteristics and TAPSE, and LVEF modified the relationship between RV4CLS and incident HF.

Aims Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population. Methods and results This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6–4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07–1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08–1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04–1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003). Conclusion Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction., AIMS: Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population.METHODS AND RESULTS: This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6-4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07-1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08-1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04-1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003).CONCLUSION: Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction.

Background Colorectal cancer screening programmes (CRCSPs) are implemented worldwide despite recent evidence indicating more physical harm occurring during CRCSPs than previously thought. Therefore, we aimed to review the evidence on physical harms associated with endoscopic diagnostic procedures during CRCSPs and, when possible, to quantify the risk of the most serious types of physical harm during CRCSPs, i.e. deaths and cardiopulmonary events (CPEs). Methods Systematic review with descriptive statistics and random-effects meta-analyses of studies investigating physical harms following CRCSPs. We conducted a systematic search in the literature and assessed the risk of bias and the certainty of the evidence. Results We included 134 studies for review, reporting findings from 151 unique populations when accounting for multiple screening interventions per study. Physical harm can be categorized into 17 types of harm. The evidence was very heterogeneous with inadequate measurement and reporting of harms. The risk of bias was serious or critical in 95% of assessments of deaths and CPEs, and the certainty of the evidence was very low in all analyses. The risk of death was assessed for 57 populations with large variation across studies. Meta-analyses indicated that 3 to 23 deaths occur during CRCSPs per 100,000 people screened. Cardiopulmonary events were assessed for 55 populations. Despite our efforts to subcategorize CPEs into 17 distinct subtypes, 41% of CPE assessments were too poorly measured or reported to allow quantification. We found a tendency towards lower estimates of deaths and CPEs in studies with a critical risk of bias. Discussion Deaths and CPEs during CRCSPs are rare, yet they do occur during CRCSPs. We believe that our findings are conservative due to the heterogeneity and low quality of the evidence. A standardized system for the measurement and reporting of the harms of screening is warranted., Background Colorectal cancer screening programmes (CRCSPs) are implemented worldwide despite recent evidence indicating more physical harm occurring during CRCSPs than previously thought. Therefore, we aimed to review the evidence on physical harms associated with endoscopic diagnostic procedures during CRCSPs and, when possible, to quantify the risk of the most serious types of physical harm during CRCSPs, i.e. deaths and cardiopulmonary events (CPEs). Methods Systematic review with descriptive statistics and random-effects meta-analyses of studies investigating physical harms following CRCSPs. We conducted a systematic search in the literature and assessed the risk of bias and the certainty of the evidence. Results We included 134 studies for review, reporting findings from 151 unique populations when accounting for multiple screening interventions per study. Physical harm can be categorized into 17 types of harm. The evidence was very heterogeneous with inadequate measurement and reporting of harms. The risk of bias was serious or critical in 95% of assessments of deaths and CPEs, and the certainty of the evidence was very low in all analyses. The risk of death was assessed for 57 populations with large variation across studies. Meta-analyses indicated that 3 to 23 deaths occur during CRCSPs per 100,000 people screened. Cardiopulmonary events were assessed for 55 populations. Despite our efforts to subcategorize CPEs into 17 distinct subtypes, 41% of CPE assessments were too poorly measured or reported to allow quantification. We found a tendency towards lower estimates of deaths and CPEs in studies with a critical risk of bias. Discussion Deaths and CPEs during CRCSPs are rare, yet they do occur during CRCSPs. We believe that our findings are conservative due to the heterogeneity and low quality of the evidence. A standardized system for the measurement and reporting of the harms of screening is warranted.

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.

Purpose: Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. Methods: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. Results: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: −20.5 vs. −22.7%, whole-layer GLS: −17.7 vs. −19.4%, epicardial GLS: −15.3 vs. −16.9%, p <.001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03–1.20); whole-layer GLS: OR = 1.14 (1.04–1.24); epicardial GLS: OR = 1.16 (1.05–1.29), per 1% absolute decrease). Conclusion: In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS.

Danmark anses for at være en af de mest digitaliserede velfærdsstater i verden (OECD 2023) med en omfattende offentlig digital infrastruktur, der ideelt set sikrer borgerne gnidningsløs interaktion med de offentlige myndigheder. Talrige statslige og fællesoffentlige digitaliseringsstrategier har flyttet mødet mellem borgere og myndigheder til digitale kontaktflader, der skal gøre kommunikationen lettere og mere tilgængelig og brugervenlig (f.eks. Regeringen, KL, Danske Regioner 2022, 2016). I takt med at det fysiske møde mellem borger og stat er blevet erstattet af digital kontakt, forventes borgerne at anskaffe den teknologi, som kan understøtte kontakten. Der ligger heri en implicit magtanvendelse fra myndighedernes side, da borgerne forventes at sørge for, at det tekniske udstyr, der muliggør digital selvbetjening, findes i hjemmet.

Dette speciale sætter fokus på læreres samarbejde om kompetenceorienteret STEM-undervisning. Specialet undersøger gennem aktionsforskning, hvilke muligheder og udfordringer lærere oplever ved arbejdet med at planlægge, gennemføre og evaluere STEM-undervisning i udskolingen. Der er lagt særlig vægt på lærernes arbejde med at operationalisere og evaluere kompetencer, herunder peerfeedback og lærer-elev-dialoger. Interventionerne fra aktionsforskningen består af tre sparringssessioner, suppleret af to mellemliggende observationer. Data fra sparringssessionerne er analyseret ved hjælp af både tematisk analyse og netværksanalyse. Konklusionen fremhæver muligheder og udfordringer forbundet til STEM-undervisningens åbne natur, koblingen af matematik til STEM-undervisning, samarbejdet mellem lærere på tværs af forskellige teams, operationalisering og evaluering af kompetencer, peerfeedbacks rolle i STEM-undervisning, samt læreres professionelle udvikling med fokus på øvelse og ekstern sparring., This thesis focuses on teachers work and cooperation in STEM-education. Through action research it examines the challenges and opportunities linked to planning, implementing, and evaluating teaching in lower secondary school from a teacher perspective. The thesis puts special attention to operationalization and evaluation of competencies through evaluation methods. These methods include peer feedback and teacher-student-dialogues. The interventions from the action research consist of three sessions with external sparring supplied by two observations in class between the sessions. Research data from the sessions is analyzed through both thematic analysis and network analysis. The conclusion pinpoints challenges and opportunities linked to the ill-defined open-ended nature of STEM-education, the incorporation of mathematics in STEM-education, cooperation between teachers across different teams, operationalization and evaluation of competencies, the role of peer feedback in STEM-education, and teachers’ professional development with focus on practice and external sparring.