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Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand ( p  < .001) with no interaction ( p  = .405) by treatment group (reductions by ramipril and doxazosin were 8.7 ± 30.8 ng/L, p  = .044, and 13.4 ± 25.5 ng/L, p  = .002, respectively). There were no changes in P-selectin by treatment within ( p  = .556) or between ( p  = .256) treatment groups. No changes were observed in E-selectin, hyaluronan, syndecan-1, or thrombomodulin by antihypertensive treatment ( p  = .091-.991), or between ramipril and doxazosin ( p  = .223-.999). Our results show a potential reduction of platelet activity by ACE inhibitor treatment. Also, the alpha 1-adrenoceptor antagonist doxazosin may reduce platelet activation. Neither drug influenced eGCX markers.

Since both top and bottom illuminations are widely used in infrared transmission measurements, in this paper, we study the effects of different illuminations on the signatures in infrared microspectroscopy. By simulating a series of dielectric samples, we show that their extinction efficiency, Q ext , remains unchanged when the direction of the incident plane wave is reversed, even though the field distributions both inside and outside of the sample may be dramatically different. We find features in Q ext that are correlated with whispering gallery modes for one beam direction and correspond to completely different field distributions for the opposite beam direction. In addition, by linking the optical theorem and the reciprocity relation of far-field scattered field, we rigorously prove the invariance of Q ext for arbitrary dielectric targets under opposite plane-wave illuminations. Furthermore, we show the difference in the apparent absorbance spectrum for opposite beam directions when considering numerical apertures., (© 2024 The Author(s). Journal of Biophotonics published by Wiley‐VCH GmbH.)

Aims: The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL)., Methods and Results: A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015-2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new-onset HF, 482 (88%) had complete iron data at baseline. Median age was 70 years (interquartile range 61-77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41-49%, and 26% had HF with preserved EF (HFpEF) [Correction added on 26 June 2024, after first online publication: The 'Mean age was 70 years' has been corrected to 'Median age was 70 years' in this version.]. At baseline, 163 patients (34%) had ID defined as ferritin <100 μg/L or ferritin 100-299 μg/L and transferrin saturation <20%. After 12 months of follow-up, 119 (32%) had ID of the 368 patients who had complete iron data both at baseline and after 12 months and did not receive intravenous (i.v.) iron during follow-up. During the first year after HF diagnosis, 19% had persistent ID, 13% developed ID, 11% resolved ID, and 57% never had ID, consequently 24% changed their classification. Anaemia at baseline was the strongest independent predictor of ID 1 year after diagnosis [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.88-8.13, P < 0.001], followed by HF hospitalization (OR 2.21, 95% CI 1.24-3.95, P < 0.01), female sex (OR 2.04, 95% CI 1.25-3.32, P < 0.01), HFpEF (OR 1.96, 95% CI 1.13-3.39, P < 0.05), and diabetes mellitus (OR 1.92, 95% CI 1.06-3.48, P < 0.05). ID was associated with low QoL at baseline (MLHFQ score mean difference 7.4 points, 95% CI 3.1-11.7, P < 0.001), but not at follow-up., Conclusions: About one third of patients with new onset HF had ID both at the time of HF diagnosis and after 1 year, though a quarter of the patients changed their ID status. Patients with anaemia, HF hospitalization, female gender, HFpEF, or diabetes mellitus at baseline were more likely to have ID after 1 year implying that these should be carefully screened for ID to find those in need of i.v. iron treatment., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Irritable bowel syndrome (IBS) is a common and debilitating disorder. When dietary and pharmacological interventions are not satisfactory, psychological treatment may produce good results. However, the access to such treatment is scarce, and therefore, it is of importance to make use of technical solutions. In this study, we wanted to investigate the real-world effectiveness of an Internet-delivered exposure-based cognitive behavior therapy (ECBT) for IBS and to replicate an earlier finding regarding the working mechanism of the treatment., Methods: A total of 309 consecutively recruited patients from the Internet Psychiatry Clinic in Stockholm received ECBT for 12 weeks. The patients' IBS symptoms, quality of life, avoidance behaviors, and gastrointestinal symptom-specific anxiety were monitored, and we used a bivariate cross-lagged panel model to investigate time-related change in symptoms and avoidance behaviors., Results: IBS symptoms, measured with the Gastrointestinal Symptom Rating Scale for IBS, were reduced from 48.06 (SD = 11.26) before treatment to 33.06 (SD = 10.81) 6 months after treatment ( P < 0.001). The effect size (calculated by Cohen d ) was 1.30 (1.08-1.51). There was a significant ( P < 0.001) cross-lagged effect from reduction in avoidance behavior to reduction in symptoms but not in the reverse direction, indicating that the treatment effect is mediated by behavioral change., Discussion: We conclude that ECBT is effective under real-world conditions, also when delivered through the Internet, and that an important treatment mechanism is the reduction of avoidance behaviors., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable., Materials and Methods: Blood samples from patients on dabigatran ( n  = 23), rivaroxaban ( n  = 26), or apixaban ( n  = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin., Results: Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors., Conclusions: Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.

Background and Aims: Heated tobacco products (HTPs) are novel alternative tobacco products being promoted as an alternative to cigarettes. To evaluate the impact of HTP use on vascular function, we investigated the effects of a brief HTP usage on arterial stiffness and platelet thrombus formation in healthy volunteers., Methods: In a randomised crossover study, twenty-four healthy young adults with occasional tobacco use smoked the HTP IQOS 3 Multi (Phillip Morris Int.) and "no-exposure" was used as a control, with a wash-out period of at least one week in-between. Arterial stiffness was assessed through pulse wave velocity and pulse wave analysis. Blood samples, collected at baseline and 5 min following exposure, were analysed with the Total-Thrombus-formation analysis system evaluating platelet and fibrin-rich thrombus formation tendency., Results: HTP exposure caused immediate heightened pulse wave velocity (+0.365 m/s, 95% CI: +0.188 to 0.543; p = 0.004) and enhanced augmentation index corrected to heart rate (+6.22%, 95% CI: +2.33 to 10.11; p = 0.003) compared to the no-exposure occasion. Similarly, blood pressure and heart rate transiently increased immediately following HTP inhalation. Platelet thrombus formation significantly increased following HTP exposure (area under the curve +59.5, 95% CI: +25.6 to 93.4; p < 0.001) compared to no-exposure. No effect was seen on fibrin-rich thrombus formation following HTP-exposure., Conclusions: Brief HTP use in healthy young adults had immediate adverse effects on vascular function resulting in increased arterial stiffness and platelet thrombus formation, known risk factors for the development of atherosclerosis. Further research is needed to address long term health impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association., Methods: A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1-3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+)., Results: The concentrations of nine biomarkers-endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)-were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19-1.50). None of the biomarkers showed an interaction with CKD., Conclusions: The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD., Competing Interests: B.S. has received lecture honorarium from Boehringer Ingelheim and advisory board honoraria and a grant from AstraZeneca. J.S. has received speaker honoraria from Bayer, AstraZeneca and Medtronics and holds minor shares in Beat Vascular Health, all outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

While Coronavirus Disease in 2019 (COVID-19) may no longer be classified as a global public health emergency, it still poses a significant risk at least due to its association with thrombotic events. This study aims to reaffirm our previous hypothesis that COVID-19 is fundamentally a thrombotic disease. To accomplish this, we have undertaken an extensive literature review focused on assessing the comprehensive impact of COVID-19 on the entire hemostatic system. Our analysis revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly enhances the initiation of thrombin generation. However, it is noteworthy that the thrombin generation may be modulated by specific anticoagulants present in patients' plasma. Consequently, higher levels of fibrinogen appear to play a more pivotal role in promoting coagulation in COVID-19, as opposed to thrombin generation. Furthermore, the viral infection can stimulate platelet activation either through widespread dissemination from the lungs to other organs or localized effects on platelets themselves. An imbalance between Von Willebrand Factor (VWF) and ADAMTS-13 also contributes to an exaggerated platelet response in this disease, in addition to elevated D-dimer levels, coupled with a significant increase in fibrin viscoelasticity. This paradoxical phenotype has been identified as 'fibrinolysis shutdown'. To clarify the pathogenesis underlying these hemostatic disorders in COVID-19, we also examined published data, tracing the reaction process of relevant proteins and cells, from ACE2-dependent viral invasion, through induced tissue inflammation, endothelial injury, and innate immune responses, to occurrence of thrombotic events. We therefrom understand that COVID-19 should no longer be viewed as a thrombotic disease solely based on abnormalities in fibrin clot formation and proteolysis. Instead, it should be regarded as a thromboinflammatory disorder, incorporating both classical elements of cellular inflammation and their intricate interactions with the specific coagulopathy., Competing Interests: None of the authors have financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (© 2024 The Author(s). Published by Upsala Medical Society.)

Background: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. The optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis, and elevated biomarkers of NET formation are associated with poor prognosis., Objectives: To investigate the association between NET formation and occult cancer in patients with VTE., Methods: Blood biomarkers associated with NETs and neutrophil activation (nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) were quantified in patients with VTE. The primary outcome was cancer diagnosed during a one-year follow-up., Results: This study included 460 patients with VTE, of which 221 (48%) had isolated deep vein thrombosis. Forty-three patients had active cancer at inclusion and were excluded from the primary analysis Cancer during follow-up was diagnosed in 29 of 417 (7.0%) patients. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/mL increase of H3Cit-DNA was 1.79 (95% CI, 1.03-3.10). Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA than cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, previous cancer, and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/mL increase of H3Cit-DNA [95% CI, 1.35-3.13])., Conclusions: H3Cit-DNA is an independent predictor for occult cancer in patients with VTE and elevated in cancer-associated VTE, suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE and that elevated NET formation is a hallmark of cancer-associated VTE., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Electronic cigarette (EC) vaping is increasingly popular, despite growing evidence of adverse health effects. To further evaluate the impact of EC use on vascular health, we investigated the effects of brief EC inhalation on flow-dependent thrombus formation and microcirculation in healthy volunteers. The study was performed with a randomised double-blind crossover design. Twenty-two healthy subjects aged between 18 and 45 years with occasional tobacco use were recruited. Subjects inhaled 30 puffs of EC aerosol with and without nicotine on two occasions separated by a wash-out period of at least 1 week. Blood samples were collected at baseline and at 15 and 60 min following exposure and analysed with the Total-Thrombus-formation analysis system evaluating fibrin-rich thrombus formation and platelet thrombus formation in whole blood under flow. Microvascular function was assessed at baseline and 30 min after exposure by laser speckle contrast imaging and iontophoresis of acetylcholine and sodium nitroprusside (SNP) to evaluate the endothelium-dependent and independent pathways of vasodilation. Compared with nicotine free EC aerosol, exposure to EC aerosol with nicotine significantly increased platelet thrombus formation and fibrin-rich thrombus formation at 15 min (p = 0.017 and p = 0.037, respectively) with normalisation after 60 min. Peak SNP-mediated microvascular perfusion, i.e. endothelium-independent vasodilation, was reduced following EC vaping with nicotine compared with baseline (p = 0.006). Thirty puffs of EC aerosol with nicotine increased platelet and fibrin-dependent thrombus formation and reduced microvascular dilatation capacity. No compelling effects of EC vaping without nicotine were observed, indicating nicotine as the main effector. Trial registration: ClinicalTrials.gov Identifier: NCT04175457 URL: https://clinicaltrials.gov/ct2/show/NCT04175457., (© 2023. The Author(s).)

Background: Risks of antithrombotic switching is not investigated in elderly atrial fibrillation patients., Objectives: To investigate the effectiveness and safety of antithrombotic treatment and switching of antithrombotic treatment in elderly patients (aged 75 years or older) with atrial fibrillation (AF)., Methods: We conducted a cohort study of 2943 patients with AF (Carrebean-elderly), hospitalized during 2010-2017. Cox models were used to estimate the association of antithrombotic treatment (warfarin, direct oral anticoagulants [DOAC] and non-guideline-recommended therapy [NG], i.e., aspirin and low-molecular-weight heparin) at discharge and antithrombotic treatment switching during follow-up with the risk of a composite and single end points of thromboembolism, bleeding, and cardiac death. Crude and adjusted risk estimates were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). All-cause death was evaluated, with competing risk regression and estimates expressed as subhazard ratios and 95% CIs., Results: We observed an increased risk for the composite end point associated with NG as compared to warfarin at discharge (HR, 1.18; 95% CI, 1.01-1.38) with congruent competing risk regression results, while no significant risk difference was seen for DOACs compared to warfarin (HR, 1.12; 95% CI, 0.92-1.36). Switching from NG to warfarin/DOAC and from warfarin to DOAC occurred in 30.4% and 33.1% of respective antithrombotic treatment groups at discharge and was associated with a decreased risk for the composite end point with an adjusted HR of 0.45 (95% CI, 0.32-0.63) and a HR of 0.50 (95% CI, 0.38-0.65), respectively., Conclusions: Antithrombotic treatment switching is common in the elderly AF population. Importantly, switching to guideline-recommended treatment has a favorable impact on both effectiveness and safety., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Aims: Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype., Materials and Methods: Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function ( n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)]., Results: Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans -coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups., Conclusion: Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans -coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury., 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., (Copyright © 2022 Matan, Mobarrez, Löfström, Corbascio, Ekström, Hage, Lyngå, Persson, Eriksson, Linde, Persson and Wallén.)

Objectives: To investigate the association of the heart rate-corrected QT interval (QTc) with the risk of atrial fibrillation (AF) and ischaemic stroke., Methods: We estimated the risk of AF and ischaemic stroke associated with QTc duration (ms) by Cox regression in study participants from the cohort of 60-year-old men and women from Stockholm (60YO) (n=4232). Univariate and multivariate adjusted risk estimates were expressed as HR and 95% CI. Main results were validated in elderly patients with AF, included in the Carebbean-e study, where an ECG in sinus rhythm (SR) (ECG-SR) recorded before the ECG diagnostic for (ECG-AF) was available (n=803). We estimated the correlation between the time interval (years) between the ECG-SR and ECG-AF with the QTc duration, by the Spearman correlation coefficient (rho)., Results: In the 60YO, the highest QTc duration quartile (>427 ms) associated with the AF risk (n=435) with a multivariable adjusted HR of 1.68 and 95% CI (1.26 to 2.24). No association was observed with ischaemic stroke. In the Carebbean-e study, no significant association was observed between the QTc duration measured on the ECG-SR and risk of ischaemic stroke during follow-up. QTc duration showed an inverse correlation (rho: -0.26, p<0.0001) with the time interval intercurred between ECG-SR and ECG-AF., Conclusions: The association of QTc duration with AF risk might depend on the time interval between the QTc measurement and the clinical diagnosis of AF. No association was observed between QTc duration and ischaemic stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background  A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis. Objective  This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV). Method  ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20-500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CT diff ). Results  Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CT diff data were similar. Patient sample data were obtained within 20 minutes from sampling. Conclusion  Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Patients with irritable bowel syndrome (IBS) may benefit from psychological treatment when diet changes and medications do not sufficiently reduce symptoms. Our research team has developed an exposure based cognitive behavioral therapy protocol (ECBT), which has been shown to be effective in several randomized controlled trials., Aim: To investigate the effectiveness of ECBT in clinical routine care at a gastroenterological clinic in Stockholm and to find predictors for treatment outcome., Method: A ten session ECBT based on our protocol was given face to face by licensed psychologists in groups of 4-6 patients. A total of 129 patients provided information regarding IBS symptoms, quality of life, gastrointestinal symptom-specific anxiety (GSA), and depression pre and post-treatment. We used linear regression analyses to identify patient characteristics that predicted treatment outcome., Results: The primary outcome was symptom severity measured with The Gastrointestinal Symptom Rating Scale for IBS (GSRS-IBS). Average pre-and post-treatment GSRS-IBS scores were 49.24 (SD = 11.54) and 37.03 (SD = 10.03), corresponding to a 34.0% reduction in symptom severity ( p  < .001). Reductions were also found in GSA, 43.9% ( p  < .001) and depression, 38.6% ( p  < .001). IBS-related quality of life was on average increased by 68.2% ( p  < .001). The effect sizes were large and varied between (Cohen's d) 0.95 and 1.84. None of the patients' pre-treatment characteristics predicted outcome., Conclusion: We conclude that ECBT for IBS delivered face-to-face in a group-format is very effective, also in a routine care setting. We did not find any reliable predictors for treatment outcome. The trial was registered at Clinicaltrials.gov with ID: NCT04756414.

Aim: We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology., Methods and Results: New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015-2018 and characterized by N-terminal pro brain natriuretic peptide (NT-proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41-49%) and with HF with reduced LVEF (HFrEF; LVEF ≤ 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70-81 years; median; interquartile range) than HFrEF (67; 58-74; P < 0.001), more often women (49% vs. 30%; P < 0.001), and had significantly higher comorbidity burden. They more often had atrial fibrillation, hypertension, and renal dysfunction. NT-proBNP was lower in HFpEF (896; 462-1645 ng/L) than in HFrEF (1160; 563-2370; P = 0.005). In HFpEF, left ventricular (LV) diameters and volumes were smaller (P < 0.001) and septal and posterior wall thickness and relative wall thickness higher (P < 0.001). E/é ≥ 14 was present in 26% of HFpEF vs. 32% of HFrEF (P = 0.017) and left atrial volume index > 34 mL/m 2 in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/é., Conclusions: Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology., Clinical Trial Registration: Clinicaltrials.gov identifier: NCT03671122., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)