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Aims: The present study investigates whether loneliness and social isolation are associated with poor physical and mental health among adolescents and young adults, and whether age and gender play a role in the associations of loneliness and social isolation with mental and physical health. Methods: This study used cross-sectional self-report data from the 2017 Danish Health and Morbidity Surveys titled 'How are you?' (N = 19,890, M = 22.6 years). Results: Logistic regression analyses showed that loneliness and social isolation were independently associated with poor physical and mental health. Loneliness was associated with increased odds of asthma, migraine, osteoarthritis, rheumatoid arthritis, hypertension, slipped disc/back pain, tinnitus, long-term mental illness, depressive symptomatology, anxiety symptomatology and alcohol problems. Social isolation was associated with decreased odds of having migraine, osteoarthritis and alcohol problems, and an increased risk of long-term mental illness and depressive symptomatology. Small age and gender differences were detected. Conclusions: In adolescents and young adults, loneliness and social isolation were associated with poor mental health and loneliness with poor physical health. These findings highlight the need for targeted prevention and intervention initiatives to alleviate loneliness and social isolation. [ABSTRACT FROM AUTHOR]

Objective: Heart failure (HF) is a leading cause of hospitalization. Clinical and socio-demographic factors have been associated with cardiac admissions, but little is known about the role of anxiety. We examined whether symptoms of anxiety were associated with cardiac hospitalizations at 12 months in HF patients.Methods: HF outpatients (N = 237) completed the Hospital Anxiety and Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff ≥8 was used to indicate probable clinical levels of anxiety and depression. At 12 months, a medical chart abstraction was performed to obtain information on cardiac hospitalizations.Results: The prevalence of symptoms of anxiety was 24.9% (59/237), and 27.0% (64/237) of patients were admitted for cardiac reasons at least once during the 12-month follow-up period. Symptoms of anxiety were neither significantly associated with cardiac hospitalizations in univariable logistic analysis [OR = 1.13, 95% CI (0.59-2.17), p = 0.72] nor in multivariable analysis [OR = 0.94, 95% CI (0.38-2.31), p = 0.89]. New York Heart Association (NYHA) functional class III [OR = 3.00, 95% CI (1.08-8.12), p = 0.04] and a history of HF-related hospitalizations [OR = 1.18, 95% CI (1.01-1.38), p = 0.03] were independently associated with 12-month cardiac admissions.Conclusions: The current study found no significant association between symptoms of anxiety and cardiac hospitalizations at 12 months in HF patients. In contrast, clinical indicators (i.e., NYHA class III and a history of HF-related hospitalizations) were significantly associated with admissions due to a cardiac cause. Future studies are warranted to investigate the importance of symptoms of anxiety in HF using a larger sample size and a longer follow-up duration. [ABSTRACT FROM AUTHOR]

Quality of life is an important patient-centered outcome and predictor of mortality in heart failure, but little is known about the role of personality as a determinant of quality of life in this patient group. We examined the influence of Type D personality (i.e., increased negative emotions paired with emotional non-expression) on quality of life in primary care heart failure patients, using a prospective study design. Heart failure patients ( n = 251) recruited from 44 primary care practices in Germany completed standardized questionnaires at baseline and 9 months. The prevalence of Type D was 31.9%. Type D patients experienced poorer emotional ( P < .001) and physical quality of life ( P = .01) at baseline and 9 months compared to non-Type D patients. There was no significant change in emotional ( P = .78) nor physical quality of life ( P = .74) over time; neither the interaction for time by Type D for emotional ( P = .31) nor physical quality of life ( P = .91) was significant, indicating that Type D exerted a stable effect on quality of life over time. Adjusting for demographics, New York Heart Association functional class, and depressive symptoms, Type D remained an independent determinant of emotional ( P = .03) but not physical quality of life ( P = .29). Primary care heart failure patients with a Type D personality experienced poorer emotional but not physical quality of life compared to non-Type D patients. Patients with this personality profile should be identified in primary care to see if their treatment is optimal, as both Type D and poor quality of life have been associated with increased morbidity and mortality. [ABSTRACT FROM AUTHOR]

We examined the impact of co-occurring diabetes and hopelessness on 3-year prognosis in percutaneous coronary intervention patients. Consecutive patients (n = 534) treated with the paclitaxel-eluting stent completed a set of questionnaires at baseline and were followed up for 3-year adverse clinical events. The incidence of 3-year death/non-fatal myocardial infarction was 3.5% in patients with no risk factors (neither hopelessness nor diabetes), 8.2% in patients with diabetes, 11.2% in patients with high hopelessness, and 15.9% in patients with both factors (p = 0.001). Patients with hopelessness (HR: 3.28; 95% CI: 1.49-7.23) and co-occurring diabetes and hopelessness (HR: 4.89; 95% CI: 1.86-12.85) were at increased risk of 3-year adverse clinical events compared to patients with no risk factors, whereas patients with diabetes were at a clinically relevant but not statistically significant risk (HR: 2.40; 95% CI: 0.82-7.01). These results remained, adjusting for baseline characteristics and depressive symptoms. These findings testify to the importance of identifying patients with co-occurring risk factors, as they likely require special management in clinical practice in addition to standard medical treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although many studies have focused on post-myocardial infarction (MI) depression, there is limited information about the evolution and determinants of depressive symptoms in the first year post-MI. Therefore we examined (1) the course of depressive symptoms during the first year post-MI and (2) the predictors of these symptom trajectories. METHOD: To assess depressive symptoms, 287 patients completed the Beck Depression Inventory during hospitalization for MI, and 2, and 12 months post-MI. Personality was assessed with the Type-D scale during hospitalization. We used latent class analysis to examine the evolution of depressive symptoms over a 1-year period and multinomial logit regression analyses to examine predictors of these symptom trajectories. RESULTS: The course of depressive symptoms was stable during the first year post-MI. Four groups were identified and classified as non-depressed [40%, intercept (IC) 2.52], mildly depressed (42%, IC 6.91), moderately depressed (14%, IC 13.73) or severely depressed (4%, IC 24.54). In multivariate analysis, cardiac history (log OR(severe) 2.93, p=0.02; log OR(moderate) 1.81, p=0.02; log OR(mild) 1.46, p=0.01), history of depression (log OR(severe) 4.40, p<0.001; log OR(moderate) 1.97, p=0.03) and Type-D personality (log OR(severe) 4.22, p<0.001; log OR(moderate) = 4.17, p<0.001; log OR(mild) 1.66, p=0.02) were the most prominent risk factors for persistence of depressive symptoms during the first year post-MI. CONCLUSIONS: Symptoms of depression tend to persist during the first year post-MI. Cardiac history, prior depression and Type-D personality were identified as independent risk factors for persistence of depressive symptoms. The results of this study strongly argue for routine psychological screening during hospitalization for acute MI in order to identify patients who are at risk for chronicity of depressive symptoms and its deleterious effects on prognosis. [ABSTRACT FROM AUTHOR]

Background: This study examined the impact of clustering of device-related concerns and Type D personality on anxiety and depressive symptoms during a six-month period and the clinical relevance of shocks, implantable cardioverter defibrillator (ICD) concerns, and Type D. Methods: Consecutively implanted ICD patients (n = 176) completed questionnaires at baseline and six months and were divided into four risk groups: (1) No risk factors (neither ICD concerns nor Type D); (2) ICD concerns only; (3) Type D only; (4) Clustering (both ICD concerns and Type D). Results: The prevalence of Type D and concerns were 21.6% and 34.7%. Analysis of variance for repeated measures showed a reduction in anxiety over time (P < 0.001), with the risk groups exerting a stable (P = 0.14) but differential effect (P < 0.001); the highest level was seen in the clustering group. Similar results were found for depression, although depressive symptoms did not decrease (P = 0.08) and the impact of clustering was less clear. These results were confirmed in adjusted analysis, with shocks (P = 0.024) also being associated with anxiety but not depression. The impact of ICD concerns and Type D personality on anxiety and depression at baseline and six months was large (>/=0.8) compared to negligible to moderate for shocks (0.0-0.6). Conclusions: ICD patients with psychosocial risk factor clustering had the highest level of anxiety, whereas the pattern for depression was less consistent. Shocks influenced outcomes, but the impact was smaller compared to ICD concerns and Type D personality. It may be timely to expand the focus beyond shocks when seeking to identify ICD patients at risk for adverse clinical outcome due to their psychological profile. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) is a promising treatment in chronic heart failure (CHF). However, a subgroup of patients still report impaired health status, cardiac symptoms, and feelings of disability following CRT. The aims of this study were to examine (1) whether CHF patients treated with CRT improved in patient-centered outcomes and functional capacity, and (2) whether personality traits exert a stable effect on these outcomes over two months. Methods: Analyses are based on 31 patients (65% male; mean age 70 +/- 8) with CHF treated with CRT. Two weeks before and two months after CRT, patients completed the Type-D Scale (negative affectivity, i.e., tendency to experience negative emotions, and social inhibition, i.e., tendency to inhibit self-expression), the Minnesota Living with Heart Failure Questionnaire (disease-specific health status), and the Health Complaints Scale (cardiac symptoms and perceived disability), and performed the six-minute walking test (functional capacity). Results: There was an improvement in disease-specific health status (P< 0.001), cardiac symptoms (P = 0.001), perceived disability (P< 0.001), and functional capacity (P = 0.007) in all patients over two months. However, high negative affectivity patients reported significantly lower disease-specific health status (P = 0.046), and more cardiac symptoms (P = 0.035), and perceived disability (P = 0.015) as compared to low negative affectivity patients. There was no significant main effect for negative affectivity on functional capacity. High negative affectivity patients still reported lower disease-specific health status (P = 0.06) and significantly more perceived disability (P = 0.04) when adjusting for left ventricular ejection fraction, gender, and age. The effects of negative affectivity on patient-centered outcomes, as measured by Cohen's effect size index, were moderate to large. Conclusions: Patient-centered outcomes improved over a two-month period in patients treated with CRT, but negative affectivity exerted a stable, negative effect on health status, cardiac symptoms, and perceived disability. Personality traits should be taken into account when evaluating effects of CRT. [ABSTRACT FROM AUTHOR]

Background: The role of procalcitonin in diagnosing bacterial infection has mainly been studied in patients with severe infections. There is no study on the value of procalcitonin measurements in adults with lower respiratory tract infection (LRTI) treated in primary care.Aim: To evaluate the accuracy of plasma procalcitonin in predicting radiographic pneumonia, bacterial infection, and adverse outcome in a population of adults with LRTI treated in primary care.Design Of Study: Prospective, observational study.Setting: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark.Method: A total of 364 patients with LRTI were prospectively enrolled from 42 general practices. Patients were examined with chest radiography, microbiological analyses, and measurements of C-reactive protein (CRP) and procalcitonin. The outcome measure was hospitalisation within 4 weeks of enrollment.Results: Median procalcitonin was 0.05 ng/ml, which was below the functional sensitivity of the assay (0.06 ng/ml). In predicting radiographic pneumonia, bacterial infection, and hospitalisation, the sensitivities of procalcitonin >0.06 ng/ml were 0.70, 0.51, and 0.67, and of CRP were > or =20 mg/l, 0.73, 0.56, and 0.74 respectively. Corresponding positive predictive values were between 0.09 and 0.28.Conclusion: Both procalcitonin >0.06 ng/ml and CRP > or =20 mg/l were associated with radiographic pneumonia, bacterial infection, and subsequent hospitalisation, but positive predictive values were too low for any of the two inflammatory markers to be of use in clinical practice. To measure procalcitonin values accurately in the primary care setting, a more sensitive method is needed, but there was no indication that procalcitonin is superior to CRP in identifying patients with pneumonia, bacterial aetiology, or adverse outcome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Knowledge of predominant pathogens and their association with outcome are of importance for the management of lower respiratory tract infection (LRTI). As antibiotic therapy is indicated in pneumonia and not in acute bronchitis, a predictor of pneumonia is needed. AIM: To describe the aetiology and outcome of LRTI in adults with pneumonic and adults with non-pneumonic LRTI treated in general practice and to identify predictors of radiographic pneumonia. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 adults diagnosed with community-acquired LRTI by their GP were studied with chest radiography, vital signs, biochemical markers of inflammation (C-reactive protein [CRP] and leukocyte count), and microbiological examinations. Primary outcome measure was hospitalisation within 4 weeks. RESULTS: Pneumonia was radiographically verified in 48 of 364 patients (13%). Bacterial infection was seen more often in patients with pneumonia (33% versus 17%, P<0.001), and viral infection more often in non-pneumonic patients (26% versus 13%, P<0.05). Hospitalisation was more common in patients with pneumonia compared to non-pneumonic patients (19 versus 3%, P<0.001); and in patients with pneumococcal infection compared with patients without pneumococcal infection (26 versus 4%, P = 0.001). The positive predictive value of GPs' diagnosis of pneumonia was low (0.23), but the vital signs, CRP, and leukocyte count had comparably low positive predictive values (0.23-0.30). CONCLUSION: Streptococcus pneumoniae was the most common bacterial pathogen. The risk of hospitalisation was highest among patients with pneumonia or pneumococcal infection; this emphasises the importance of coverage of S. pneumoniae when treatment is indicated. CRP should not be introduced for diagnosis of radiographic pneumonia in general practice before its use has been investigated in prospective, controlled intervention trials using CRP-guided treatment algorithms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. METHODS: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. RESULTS: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (< or =60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). CONCLUSIONS: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice. [ABSTRACT FROM AUTHOR]

Aim: To investigate associations between Body Image concerns (BICs) measured by the ICD Body Image Concerns Questionnaire (ICD-BICQ) and other Patient-Reported-Outcomes (PROs), in a cohort of patients with an Implantable Cardioverter Defibrillator (ICD)., Methods and Results: In a cross-sectional survey, we included patients >18 years implanted with a first-time ICD (VVI, DDD and CRT-D) who had lived with their ICD from 3-24 months. They completed the 39-item ICD-BICQ together with the Generalized Anxiety Disorder-scale, Patient Health-Questionnaire, Type D-Scale, Health Status-Questionnaire and the Florida Patient Acceptance-Survey. Data were analyzed using linear regression to compare personality constructs between patients with and without BICs. Logistic repression and receiver operating characteristic curves were used to predict patients with BICs based on other PROs.A total of 330 patients completed the survey. Five patients were excluded due to re-operations leaving 325 patients in the analyses. A total of 20% reported BICs at the recommended cut-off at 36-points. Patients with BICs reported higher anxiety and depression levels, lower device acceptance and health status, had a Type D personality as compared to patients without BICs. FPAS was moderately able to predict BICs, while other PROs only had limited ability to predict BICs., Conclusion: Patients with BICs reported poorer PROs. The PRO instruments were not able to predict patients with BICs, indicating that the ICD-BICQ provides independent relevant clinical information. In clinical practice, healthcare professionals can use the ICD-BICQ to identify and obtain information on possible BICs. The ICD-BICQ can also be used to evaluate new operation techniques., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We report a minimalist gaseous sulfonyl-chloride-derived reagent for multicomponent bioconjugation with amine, phenol, or aniline reagents to afford urea or carbamate products. With the utilization of a gas-phase reagent for a reaction mediated by metal ions, a variety of biologically relevant molecules, such as saccharide, poly(ethylene glycol), fluorophore, and affinity tag, can be efficiently cross-linked to the N terminus or lysine side-chain amines on natural polypeptides or proteins.

Introduction: Remote patient monitoring (RPM) of heart failure patients has the potential to reduce healthcare resource use and costs, but current evidence has been inconclusive. This study aims assess the impact of RPM of heart failure patients with an implantable cardioverter defibrillator on medical resource use, direct medical costs, quality-adjusted life years (QALYs), and travel time of patients, and to estimate its commercial headroom in the Netherlands and Germany., Methods: Data from the REMOTE-CIED randomized controlled trial were used to calculate differences in length of hospital stay, outpatient clinic visits, telephone consults, emergency room visits, and travel time between patients on in-clinic follow-up and RPM in the Netherlands, Germany, and France. Incremental cardiac-related healthcare costs and QALYs were calculated and used to calculate the commercial headroom of RPM in the Netherlands and Germany. The impact of imputation, parameter, and case-mix uncertainty on these outcomes was explored using probabilistic analysis., Results: Length of hospitalization, number of unscheduled admissions, and number of outpatient visits were lower in the remote monitoring group in all three countries. Number of hospital admissions was higher, and number of calls was lower in the Netherlands and Germany but not in France. Costs were lower in both the Netherlands (-€1041, 95% confidence interval (CI): -€3308, €1005) and Germany (-€2865, 95% CI: -€7619, €1105), while incremental effectiveness differed: -0.003 (95% CI: -0.114, 0.107) QALY in the Netherlands and +0.086 (95% CI: -0.083, 0.256) in Germany. Commercial headroom was estimated at €881 (95% CI: -€5430, €7208) in the Netherlands and €5005 (95% CI: -€1339, €11,960) in Germany., Discussion: RPM was found to result in reduced medical resource use and travel time. Whether it is cost saving or cost effective strongly depends on the costs of remote monitoring., Trial Registration Number and Trial Register: ClinicalTrials.gov: NCT01691586., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Peptide cyclization has dramatic effects on a variety of important properties, enhancing metabolic stability, limiting conformational flexibility, and altering cellular entry and intracellular localization. The hydrophilic, polyfunctional nature of peptides creates chemoselectivity challenges in macrocyclization, especially for natural sequences without biorthogonal handles. Herein, we describe a gaseous sulfonyl chloride derived reagent that achieves amine-amine, amine-phenol, and amine-aniline crosslinking through a minimalist linchpin strategy that affords macrocyclic urea or carbamate products. The cyclization reaction is metal-mediated and involves a novel application of sulfine species that remains unexplored in aqueous or biological contexts. The aqueous method delivers unique cyclic or bicyclic topologies directly from a variety of natural bioactive peptides without the need for protecting-group strategies., (© 2024 Wiley-VCH GmbH.)

Background: Knowledge is limited on associations between social disconnectedness (i.e. loneliness and social isolation), health literacy and perceived treatment burden in individuals with cardiovascular disease (CVD). However, understanding these associations may be important for clinical practice., Methods: This study used cross-sectional self-reported data from the 2017 Danish health and morbidity survey entitled 'How are you?', investigating the associations of loneliness and social isolation with low health literacy and high treatment burden in individuals with CVD (n = 2521; mean age = 65.7 years)., Results: Logistic regression analysis showed that loneliness and social isolation were associated with low health literacy in terms of difficulties in 'understanding health information' (loneliness: adjusted odds ratio (AOR) = 1.32, 95% confidence intervals (CI) [1.16, 1.50]; social isolation: AOR = 1.47, 95% CI [1.24, 1.73]) and 'engaging with healthcare providers' (loneliness: AOR = 1.53, 95% CI [1.37, 1.70]; social isolation: AOR = 1.21, 95% CI [1.06, 1.40]) and associated with high treatment burden (loneliness: AOR = 1.49, 95% CI [1.35, 1.65]; social isolation: AOR = 1.20, 95% CI [1.06, 1.37])., Conclusions: Our findings show that loneliness and social isolation coexisted with low health literacy and high treatment burden in individuals with CVD. These findings are critical as socially disconnected individuals experience more health issues. Low health literacy and a high treatment burden may potentially exacerbate these issues., (© 2024. The Author(s).)

Background: Integrated care, in particular the 'Blended Collaborative Care (BCC)' strategy, may have the potential to improve health-related quality of life (HRQoL) in multimorbid patients with heart failure (HF) and psychosocial burden at no or low additional cost. The ESCAPE trial is a randomised controlled trial for the evaluation of a BCC approach in five European countries. For the economic evaluation of alongside this trial, the four main objectives were: (i) to document the costs of delivering the intervention, (ii) to assess the running costs across study sites, (iii) to evaluate short-term cost-effectiveness and cost-utility compared to providers' usual care, and (iv) to examine the budgetary implications., Methods: The trial-based economic analyses will include cross-country cost-effectiveness and cost-utility assessments from a payer perspective. The cost-utility analysis will calculate quality-adjusted life years (QALYs) using the EQ-5D-5L and national value sets. Cost-effectiveness will include the cost per hospital admission avoided and the cost per depression-free days (DFD). Resource use will be measured from different sources, including electronic medical health records, standardised questionnaires, patient receipts and a care manager survey. Uncertainty will be addressed using bootstrapping., Discussion: The various methods and approaches used for data acquisition should provide insights into the potential benefits and cost-effectiveness of a BCC intervention. Providing the economic evaluation of ESCAPE will contribute to a country-based structural and organisational planning of BCC (e.g., the number of patients that may benefit, how many care managers are needed). Improved care is expected to enhance health-related quality of life at little or no extra cost., Trial Registration: The study follows CHEERS2022 and is registered at the German Clinical Trials Register (DRKS00025120)., (© 2024. The Author(s).)

Contemporary management of atrial fibrillation (AF) has become increasingly complex. Therefore, strong efforts have been made during the past decade to develop models for structured, integrated care for patients with AF. These have also been incorporated in international guidelines for the management of patients with AF. However, implementation of integrated care approaches in daily clinical practice is scarce and far from optimal, and it may require a re-thinking of the structure of the healthcare system. The reasons for the poor implementation are many, from limited time and economic resources to deficits in postgraduate education of healthcare professionals, lack of involvement of patients in how integrated care should be designed, and fragmentation of the healthcare system. Moreover, patients' psychological challenges, which not only impact patients' adherence to treatment but, if untreated, increase their risk of morbidity, mortality, and poor quality of life, are not given sufficient attention. It is time to start a necessary discussion of what integrated care should be, what it should contain, and what is necessary to implement it in daily clinical practice., Competing Interests: Conflict of interest: A.B. has received research grants from Theravance, the Zealand Region, the Canadian Institutes of Health Research, the European Union Interreg 5A Programme, the Danish Heart Foundation, and the Independent Research Fund Denmark and a lecture honorarium from Bristol Myers Squibb outside the submitted work. S.S.P. and J.M.H. have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The reliability of near-infrared spectroscopy (NIRS) for measuring cerebral oxygenation (ScO 2 ) is controversial due to the possible contamination from extracranial tissues. We compared ScO 2 measured with the NIRS optode on the forehead, the skull and the dura mater in anaesthetised patients undergoing craniotomy. We hypothesised that ScO 2 measured directly on the skull and the dura mater would differ from ScO 2 measured on the skin., Methods: This prospective observational study included 17 adult patients scheduled for elective craniotomy. After induction of general anaesthesia, ScO 2 was measured on the forehead skin, as well as on the skull and on the dura mater in the surgical field. The primary comparison was the difference in ScO 2 measured on the dura mater and on ScO 2 measured on the skin; secondary comparisons were the differences in ScO 2 on the skull and ScO 2 on the skin and the dura mater, respectively. Data were described with median (5%-95% range) and analysed with the Wilcoxon signed-rank test., Results: ScO 2 values on the dura mater were obtained in 11 patients, and median ScO 2 (48%, 29%-95%) did not differ significantly from ScO 2 on the skin (73%, 49%-92%; p = .052), median difference -25% (-35.6% to -1.2%). ScO 2 on the skull (N = 16) was lower than that on the skin (63% [43%-79%] vs. 75% [61%-94%]; p = .0002), median difference -10% (-20.8 to -3.0)., Conclusion: In adults undergoing craniotomy, NIRS-based ScO 2 measured on the dura mater did not reach statistically significantly lower values than ScO 2 measured on the skin, whereas values on the skull were lower than on the skin, indicating a contribution from scalp tissue to the signal., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Butyrate, a gut microbial metabolite, has beneficial effects on glucose homeostasis and has become an attractive drug candidate for type 2 diabetes (T2D). Recently, we showed that butyrate protects pancreatic beta cells against cytokine-induced dysfunction. In this study, we explored the underlying mechanisms of butyrate action. Pancreatic mouse islets were exposed to a non-cytotoxic concentration of interleukin-1β (IL-1β) for 10 days to mimic low-grade inflammation in T2D. Similar to the effect of butyrate, an isoform-selective histone deacetylase 3 (HDAC3) inhibitor normalized IL-1β-reduced glucose-stimulated insulin secretion and insulin content. In contrast, free fatty acid receptor 2 and 3 (FFAR2/3) agonists failed to normalize IL-1β-induced beta cell dysfunction. Furthermore, butyrate inhibited HDAC activity and increased the acetylation of histone H3 and H4 by 3- and 10-fold, respectively. Genome-wide analysis of histone H3 lysine 27 acetylation (H3K27ac) revealed that butyrate mainly increased H3K27ac at promoter regions (74%), while H3K27ac peaks regulated by IL-1β were more equally distributed at promoters (38%), introns (23%) and intergenic regions (23%). Gene ontology analysis showed that butyrate increased IL-1β-reduced H3K27ac levels near several genes related to hormone secretion and reduced IL-1β-increased H3K27ac levels near genes associated with inflammatory responses. Butyrate alone increased H3K27ac near many genes related to MAPK signaling, hormone secretion, and differentiation, and decreased H3K27ac at genes involved in cell replication. Together, these results suggest that butyrate prevents IL-1β-induced pancreatic islet dysfunction by inhibition of HDACs resulting in changes in H3K27ac levels at genes relevant for beta cell function and inflammatory responses., (© 2023 Federation of European Biochemical Societies.)

The 12-item version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was originally developed for patients with heart failure but has been used and tested among patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation. Whether the instrument is suitable for patients with AS who underwent surgical aortic valve replacement (SAVR) is currently unknown. Thus, we aimed to investigate the psychometric properties of the KCCQ-12 before and after SAVR among patients with severe AS. We conducted a prospective cohort of 184 patients with AS who completed the KCCQ-12 and the EuroQol 5 Dimension 5 Levels before and 4 weeks after surgery. Construct validity was investigated with hypothesis testing and an analysis of Spearman's correlation between the two instruments. Structural validity was investigated with explorative and confirmatory factor analyses and reliability with Cronbach's α. All analyses were conducted on data from the two time points (preoperatively and four weeks after surgery). The hypothesis testing revealed how the New York Heart Association class was significantly correlated with the preoperative KCCQ-12 total score (higher New York Heart Association class, worse score). A longer length of hospital stay and living alone were significantly associated with poorer postoperative KCCQ-12 total score. KCCQ-12 and EuroQol 5 Dimension 5 Levels were moderately correlated in most domains/the total score/Visual Analogue Scale score. Principal component analyses revealed two 3-factor structures. The confirmatory factor analyses did not support the original model at any time point. Cronbach's α ranged from 0.22 to 0.84 in three preoperative factors and from 0.39 to 0.76 in the postoperative factors. The total Cronbach's α was 0.83 for the suggested preoperative 3-factor model and 0.83 for the postoperative model. In conclusion, the Danish version of the KCCQ-12 tested in a population of patients with AS who underwent SAVR appears to have acceptable construct validity, whereas structural validity cannot be confirmed for the original four-factor model. Overall reliability is good., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Approximately 20-30% of patients with a cardiac disease suffer from anxiety and/or depression, leading to poor health outcomes. To identify this subgroup, clinical guidelines recommend screening for anxiety and depression in cardiac rehabilitation (CR). It is unknown how screening practice is delivered post-COVID., Methods: This observational study used data from the National Audit of Cardiac Rehabilitation from April 2018-March 2022. Descriptive statistics were used to assess screening rates and prevalence, while a multivariate logistic regression model was performed to analyse determinants for screening for anxiety and depression among patients participating in cardiac rehabilitation., Results: The population consisted of 245,705 patients, where 128,643 (52.4%) were screened and 117,062 (47.6%) were not. Patients attending CR during first year of COVID-19 were less likely to be screened. Patients with female gender, living alone, non-white ethnicity, living in the most deprived areas, current smoking, and physical inactivity were less likely to be screened, while patients who were revascularized, having an objective physical fitness test, and attending a certified CR center were more likely to be screened. For patients attending CR during COVID-19, the prevalence of anxiety and depression decreased significantly. For anxiety the prevalence dropped from 34.4% to 15.8%, for depression the prevalence dropped from 33.5% to 16.5%., Conclusion: CR service provision was negatively impacted during COVID-19, leading to much lower screening for anxiety and depression in the CR setting. Prevalence of anxiety and depression decreased during COVID-19 for this population, possibly because psychologically affected patients refrained from attending CR., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Modern clinical management of patients with an implantable cardioverter defibrillator (ICD) largely consists of remote device monitoring, although a subset is at risk of mental health issues post-implantation. We compared a 12-month web-based intervention consisting of goal setting, monitoring of patients' mental health-with a psychological intervention if needed-psychoeducational support from a nurse, and an online patient forum, with usual care on participants' device acceptance 12 months after implantation., Methods and Results: This national, multi-site, two-arm, non-blinded, randomized, controlled, superiority trial enrolled 478 first-time ICD recipients from all 6 implantation centres in Denmark. The primary endpoint was patient device acceptance measured by the Florida Patient Acceptance Survey (FPAS; general score range = 0-100, with higher scores indicating higher device acceptance) 12 months after implantation. Secondary endpoints included symptoms of depression and anxiety. The primary endpoint of device acceptance was not different between groups at 12 months [B = -2.67, 95% confidence interval (CI) (-5.62, 0.29), P = 0.08]. Furthermore, the secondary endpoint analyses showed no significant treatment effect on either depressive [B = -0.49, 95% CI (-1.19; 0.21), P = 0.17] or anxiety symptoms [B = -0.39, 95% CI (-0.96; 0.18), P = 0.18]., Conclusion: The web-based intervention as supplement to usual care did not improve patient device acceptance nor symptoms of anxiety and depression compared with usual care. This specific web-based intervention thus cannot be recommended as a standardized intervention in ICD patients., Competing Interests: Conflict of interest: J.C.N. received institutional grants from the Novo Nordisk Foundation and the Danish Heart Foundation. J.B.J. is a consultant for Medtronic. M.V. serves on conduction system pacing advisory boards for Medtronic and Abbott. K.G.S. reports unrestricted research grants from Philips, Abbott, Merck, and Johnson & Johnson, and she is a consultant for Optum Labs and Abbott, Happify, and Haemonetics. K.G.S. is supported by NIH grants 1R21AT012430-01 (NCCIH) and 1R01HL163640-01A1 (NHLBI). J.A.S. has no conflicts of interest for the study but discloses providing consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Meyers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare. He holds research grants from Bristol Meyers Squibb, Abbott Vascular, and Janssen. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Involving patients and carers in the development of blended collaborative care (BCC) interventions for multimorbid heart failure (HF) patients is recommended but rarely practised, and research on the patient perspective is scarce. The aim of this study is to investigate patients' and carers' care-related needs and preferences to better customize a novel international BCC intervention., Methods: A qualitative study design using framework analysis was employed. The study was performed in accordance with the EQUATOR standards for reporting qualitative research (SRQR). Patients aged at least 65 years with HF and at least two other physical diseases as well as their carers completed semistructured interviews in Germany, Italy, and Denmark. Based on these interviews, personas (prototype profiles of patients and carers) were created., Results: Data from interviews with 25 patients and 17 carers were analysed. Initially, seven country-specific personas were identified, which were iteratively narrowed down to a final set of 3 personas: (a) the one who needs and wants support, (b) the one who has accepted their situation with HF and reaches out when necessary, and (c) the one who feels neglected by the health care system. Carers identifying with the last persona showed high levels of psychological stress and a high need for support., Discussion: This is the first international qualitative study on patients' and carers' needs regarding a BCC intervention using the creation of personas. Across three European countries, data from interviews were used to develop three contrasting personas. Instead of providing "one size fits all" interventions, the results indicate that BCC interventions should offer different approaches based on the needs of individual patients and carers. The personas will serve as a basis for the development of a novel BCC intervention as part of the EU project ESCAPE (Evaluation of a patient-centred biopSychosocial blended collaborative CAre Pathway for the treatment of multimorbid Elderly patients)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Engelmann, Eilerskov, Thilsing, Bernardini, Rasmussen, Löwe, Herrmann-Lingen, Gostoli, Andréasson, Rafanelli, Pedersen, Jaarsma and Kohlmann.)

Aims: The aim of this study was to evaluate if a combination of World Health Organization-5 (WHO-5), Anxiety Symptom Scale-2 (ASS-2), and Major Depression Inventory-2 (MDI-2) can replace the Hospital Anxiety and Depression Scale (HADS) as screening tool for anxiety and depression in cardiac patients across diagnoses and whether it is feasible to generate crosswalks (translation tables) for use in clinical practice., Methods and Results: We used data from the Danish 'Life with a heart disease' survey, in which 10 000 patients with a hospital contact and discharge diagnosis of ischaemic heart disease, heart failure, heart valve disease, or atrial fibrillation in 2018 were invited. Potential participants received an electronic questionnaire including 51 questions on health, well-being, and evaluation of the health care system. Crosswalks between WHO-5/ASS-2 and HADS anxiety dimension (HADS-A) and between WHO-5/MDI-2 and HADS depression dimension (HADS-D) were generated and tested using item response theory (IRT). A total of 4346 patients responded to HADS, WHO-5, ASS-2, and MDI-2. Model fit of the bi-factor IRT models illustrated appropriateness of a bi-factor structure and thus of essential uni-dimensionality [root mean square error of approximation (RMSEA) (P value) range 0.000-0.053 (0.0099-0.7529) for anxiety and 0.033-0.061 (0.0168-0.2233) for depression]. A combination of WHO-5 and ASS-2 measured the same trait as HADS-A, and a combination of WHO-5 and MDI-2 measured the same trait as HADS-D. Consequently, crosswalks (translation tables) were generated., Conclusions: Our study shows that it is feasible to use crosswalks between HADS-A and WHO-5/ASS-2 and HADS-D and WHO-5/MDI-2 for screening cardiac patients across diagnoses for anxiety and depression in clinical practice., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement., Methods: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024., Conclusions: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT., Gov Identifier: NCT03280862., Competing Interests: Conflict of interests JCN is supported by grants from the Novo Nordisk Foundation (NNF16OC0018658, NNF17OC0029148), JHS reports membership of advisory committee in Medtronic, research grant outside this work from Medtronic and speakers’ honorarium from Medtronic. LK report speakers’ honorarium from AstraZeneca, Bayer, Boehringer, Novartis and Novo, not related to this manuscript. MHJPF reports speakers’ honorarium from Medtronic outside submitted work. Remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is often associated with troubling symptoms leading to impaired quality of life (QoL) and high health care use. Symptom preoccupation, that is, fear of cardiac-related symptoms and avoidance behavior, potentially contributes to disability in AF but is not targeted by current interventions., Objectives: We sought to evaluate the effect of online cognitive behavior therapy (AF-CBT) on QoL in patients with symptomatic paroxysmal AF., Methods: Patients with symptomatic paroxysmal AF (n = 127) were randomly assigned to receive AF-CBT (n = 65) or standardized AF education (n = 62). Online AF-CBT lasted 10 weeks and was therapist guided. The main components were exposure to cardiac-related symptoms and reduction of AF-related avoidance behavior. Patients were evaluated at baseline, posttreatment, and at the 3-month follow-up. Primary outcome was AF-specific QoL as assessed by the Atrial Fibrillation Effect on Quality of Life summary score (range: 0-100) at the 3-month follow-up. Secondary outcomes included AF-specific health care consumption and AF burden assessed by 5-day continuous electrocardiogram recording. The AF-CBT group was followed for 12 months., Results: AF-CBT led to large improvements in AF-specific QoL (Atrial Fibrillation Effect on Quality of Life summary score) by 15.0 points (95% CI: 10.1-19.8; P < 0.001). Furthermore, AF-CBT reduced health care consumption by 56% (95% CI: 22-90; P = 0.025). The AF burden remained unchanged. Results on self-assessed outcomes were sustained 12 months after treatment., Conclusions: In patients with symptomatic paroxysmal AF, online CBT led to large improvements in AF-specific QoL and reduced health care use. If these results are replicated, online CBT may constitute an important addition to AF management. (Internet-Delivered Cognitive Behavior Therapy for Atrial Fibrillation; NCT03378349)., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from the Swedish Research Council (2016–013792016-01379); Region Stockholm; the ALF project (20160260); Mats Kleberg’s Foundation (2015-00088); and Karolinska University Hospital, Stockholm, Sweden. None of the funding bodies had any influence on the study design, implementation, data analysis, or interpretation. Dr Braunschweig has received personal fees for trial committee participation and lectures by Medtronic, Biotronik, Biosense Webster, Impulse Dynamics, Novartis, Orion, Boehringer, and Pfizer. Dr Ljótsson owns shares in DahliaQomit, which specializes in online services for symptom assessment (outside the submitted work); and holds intellectual property rights to a cognitive behavioral treatment manual for irritable bowel syndrome, with royalties paid from Pear Therapeutics. Dr Skúladóttir has received lecture fees from Novo Nordisk and AstraZeneca. Drs Axelsson and Ljótsson have coauthored a self-help book based on exposure-based cognitive behavior therapy for health anxiety that is available in the public marketplace. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review focuses on the efficacy of internet-based psychological interventions for patients with cardiovascular disease (CVD) and comorbid anxiety and depression. Anxiety and depression comprise barriers for treatment adherence and are associated with poorer patient-reported and clinical outcomes, and greater health care costs., Recent Findings: Internet-based, therapist-assisted interventions targeting anxiety and depression can be as efficacious as face-to-face therapy and may have some advantages, as patients can do it from their own laptop/smartphone at home at a time of their convenience, which may facilitate a better integration in their lives. To enhance the field of internet-based therapy for patients with CVD, we need to involve patients in the development of interventions, focus on developing standards for adherence and assessment of fidelity, and assess and augment health literacy in patients to safeguard equality in health care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Escape: Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multimorbid elderly patients., Therapeutic Area: Healthcare interventions for the management of older patients with multiple morbidities., Aims: Multi-morbidity treatment is an increasing challenge for healthcare systems in ageing societies. This comprehensive cohort study with embedded randomized controlled trial tests an integrated biopsychosocial care model for multimorbid elderly patients., Hypothesis: A holistic, patient-centred pro-active 9-month intervention based on the blended collaborative care (BCC) approach and enhanced by information and communication technologies can improve health-related quality of life (HRQoL) and disease outcomes as compared with usual care at 9 months., Methods: Across six European countries, ESCAPE is recruiting patients with heart failure, mental distress/disorder plus ≥2 medical co-morbidities into an observational cohort study. Within the cohort study, 300 patients will be included in a randomized controlled assessor-blinded two-arm parallel group interventional clinical trial (RCT). In the intervention, trained care managers (CMs) regularly support patients and informal carers in managing their multiple health problems. Supervised by a clinical specialist team, CMs remotely support patients in implementing the treatment plan-customized to the patients' individual needs and preferences-into their daily lives and liaise with patients' healthcare providers. An eHealth platform with an integrated patient registry guides the intervention and helps to empower patients and informal carers. HRQoL measured with the EQ-5D-5L as primary endpoint, and secondary outcomes, that is, medical and patient-reported outcomes, healthcare costs, cost-effectiveness, and informal carer burden, will be assessed at 9 and ≥18 months., Conclusions: If proven effective, the ESCAPE BCC intervention can be implemented in routine care for older patients with multiple morbidities across the participating countries and beyond., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Poly(ethylene terephthalate) polyester represents the most common class of thermoplastic polymers widely used in the textile, bottling, and packaging industries. Terephthalic acid and ethylene glycol, both of petrochemical origin, are polymerized to yield the polyester. However, an earlier report suggests that polymerization of methoxyterephthalic acid with ethylene glycol provides a methoxy-polyester with similar properties. Currently, there are no established biobased synthetic routes toward the methoxyterephthalic acid monomer. Here, we show a viable route to the dicarboxylic acid from various tree species involving three catalytic steps. We demonstrate that sawdust can be converted to valuable aryl nitrile intermediates through hydrogenolysis, followed by an efficient fluorosulfation-catalytic cyanation sequence (>90%) and then converted to methoxyterephthalic acid by hydrolysis and oxidation. A preliminary polymerization result indicates a methoxy-polyester with acceptable thermal properties., Competing Interests: The authors declare the following competing financial interest(s): Troels Skrydstrup is co-owner of SyTracks a/s, which commercializes the two-chamber reactor, COware., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: New dietary proteins are currently introduced to replace traditional animal protein sources. However, not much is known about their bioaccessibility and ability to stimulate muscle protein synthesis compared to the traditional protein sources. We aimed to compare effects of ingesting a protein bolus (0.25 g/kg fat free mass) of either cricket (insect), pea, or whey protein on circulating amino acid levels and activation of the mTORC1 signaling pathway in the skeletal muscle at rest and after exercise., Methods: In a randomized parallel controlled trial, young males (n = 50) performed a one-legged resistance exercise followed by ingestion of one of the three protein sources. Blood samples were collected before and in the following 4 h after exercise. Muscle biopsies were obtained at baseline and after 3 h from the non-exercised and exercised leg., Results: Analysis of blood serum showed a significantly higher concentration of amino acids after ingestion of whey protein compared to cricket and pea protein. No difference between protein sources in activation of the mTORC1 signaling pathway was observed either at rest or after exercise., Conclusion: Amino acid blood concentration after protein ingestion was higher for whey than pea and cricket protein, whereas activation of mTORC1 signaling pathway at rest and after exercise did not differ between protein sources., Trial Registration Number: Clinicaltrials.org ID NCT04633694., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)