Search

Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination. Trial Registration : The study was registered at clinicaltrials.gov # NCT04163107., Competing Interests: Tobias S. Slørdahl has received honoraria from Takeda, Celgene, Amgen, Janssen, AbbVie, Pfizer; consultancy for Bristol Myers Squibb, GSK, Pfizer, Menarini Group, Sanofi; advisory board consultancy: Bristol Myers Squibb, Sanofi, Amgen, Celgene, GSK, Janssen. Frida Bugge Askeland has received consulting fees from Janssen, Sanofi, and Amgen, honoraria/payment from Janssen and Sanofi, participated in advisory boards for Janssen and Sanofi, and received research support from Sanofi. Fredrik Schjesvold has received grants from Targovax, consulting fees from GSK, BMS, Oncopeptides, XNK Therapeutics, Takeda, Janssen, Sanofi, and Galapagos, honoraria/payment from Amgen, BMS, Takeda, Sanofi, Menarini, AbbVie, Janssen, Oncopeptides, and GSK, and participated in advisory boards for AbbVie, Janssen, Regeneron, and Sanofi. The other authors declare no conflicts of interest., (© 2025 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Genomic collision at the LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) locus between donor and heart recipient was examined for the association with diagnosis of acute cellular or antibody-mediated allograft rejection, ACR or ABMR, respectively. In this single center retrospective study, 129 heart transplanted patients and donors were genotyped for the LIMS1 rs893403 variant, where the G-allele is in almost complete linkage disequilibrium with a loss of function deletion. A total of 14 cases with genomic collision (recipient genotype GG and donor genotype AA/AG) were identified. After a median follow-up time of 723 days, the multivariate adjusted hazard ratio for ACR of 1.64 (95 % CI 0.66-4.1) indicated that genomic collision indeed was a risk factor, while the risk of ABMR was less affected by genotype. Although statistically not significant, due to low power, this study indicates that LIMS1 is a minor histocompatibility antigen in heart transplantation, associated with allograft rejection., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Medication errors (MEs) pose risks to patient safety, resulting in substantial economic costs. To enhance patient safety and learning from incidents, health care and pharmacovigilance organizations systematically collect ME data through reporting systems. Despite the growing literature on MEs in reporting systems, an overview of methods used to analyze them is lacking. The authors aimed to identify, explore, and map available literature on methods used to analyze MEs in reporting systems., Methods: The review was based on Joanna Briggs Institute's methodology. The authors systematically searched electronic databases Embase, Medline, CINAHL, Cochrane Central, and other sources (Google Scholar, health care safety and pharmacovigilance centers' websites). Literature published from January 2017 to December 2023 was screened and extracted by two independent researchers., Results: Among the 59 extracted publications, analyses most often focused on MEs occurring in hospitals (57.6%), included both adult and pediatric patients (79.7%), and used national patent safety monitoring systems as a source (69.5%). We identified quantitative (39.0%), qualitative (11.9%), mixed methods (37.3%), and advanced computerized methods (11.9%). Descriptive quantitative analyses for categorized data were common; however, disproportionality analysis constituted a newer approach to address issues with reporting bias. Free-text data were commonly managed by content analysis, while mixed methods analyzed both categorized and free-text data. In addition, text mining, natural language processing, and artificial intelligence were used in more recent studies., Conclusion: This scoping review uncovered a notable span and diversity in methodologies. Future research should assess the use, applicability, and effectiveness of newer methods such as disproportionality analysis and advanced computerized techniques., (Copyright © 2024 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: Adequate nutrition is important for recovery after critical illness. Even so, our knowledge of patients' nutritional intake after intensive care unit (ICU) discharge is scarce., Objectives: We aimed to explore nutritional planning and achieved nutritional intake in ICU patients who transfer from the ICU to general wards., Methods: A retrospective quality assurance study., Inclusion Criteria: adult ICU patients transferring to a general ward at Copenhagen University Hospital-Herlev from May to August 2021. Primary outcomes were as follows: having a nutritional plan on the day of ICU transfer. A nutritional plan was defined as follows: (i) individual assessment of energy and protein requirement; (ii) intake, documented as achieved percentage of energy and protein requirements; (iii) prescribed type of nutrition. If using enteral or parenteral nutrition; (iv) the prescribed doses; and (v) the prescribed product. Secondary outcomes were as follows: achieved percentage of energy and protein requirements from day -1 before ICU transfer until day +1 and day +3 after ICU transfer., Results: We included 57 patients; the mean age was 64 years (±11.1); 43 (75%) patients were male; the median ICU stay was 6 days (interquartile range: 3-11). One (2%) patient had a full nutritional plan according to listed criteria. Patients' median percentage of requirements met declined significantly from the day before to the day after ICU discharge (energy: from 94% to 30.5%; p = 0.0051; protein: from 73% to 27.5%; p = 0.0117). The decline in percentage of requirements met remained unchanged from day 1 to 3 after ICU transfer., Conclusions: In conclusion, few patients had a nutritional plan when transferring from the ICU to a general ward. After ICU discharge, percentage of energy and protein requirements met declined significantly and remained insufficient during the first 3 days at the general ward., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: We developed the Melacare nurse-led intervention, which combines education in skin self-examination as a resource-conscious approach to detecting recurrence and management of fear of cancer recurrence in patients treated for melanoma. This publication presents the Melacare study protocol and evaluates the feasibility and acceptability of Melacare prior to a larger randomised controlled trial., Material and Methods: Feasibility and acceptability of Melacare were evaluated in an intervention-only feasibility study, in which patients attended two nurse-led intervention sessions coupled with an educational booklet. Participants completed patient-reported outcome (PRO) questionnaires at baseline and before each session. After the intervention, participants completed a study-specific feedback questionnaire. Feasibility was evaluated in terms of recruitment, adherence, and attendance. Self-reported outcomes from the study-specific questionnaire on intervention effects were also collected. Results of the feasibility study: Fourteen patients (nine stage IA, five stage IB melanoma) participated. Attendance and recruitment rates were 100%, all participants completed the baseline and PRO questionnaires, and 100% read at least half of the educational booklet. In terms of intervention effects, all patients reported improved knowledge of performing skin self-examination and coping with the fear of cancer recurrence., Interpretation: Results indicate that the Melacare nurse-led intervention is highly feasible and acceptable for use with patients treated for early-stage melanoma. Prior to clinical trial commencement, minor refinements include changing the method of recruiting by telephone and offering.

Background/Objectives: Co-delivering dual-drug systems have proven to be effective in, for example, anticancer therapy or HIV prophylaxis due to a higher target selectivity and therapeutic efficacy from compound synergism. However, various challenges regarding physical stability can arise during the formulation definition when multiple drug compounds are included in the same formulation. In this work, the focus was on aqueous suspensions, which could be applied as long-acting injectable formulations to release the drug compounds over weeks to months after administration. Methods: It was possible to gain insights into dual-drug nano- and microsuspensions containing two acidic compounds (indomethacin and naproxen) prepared by milling with dual centrifugation. Information regarding the physical stability of individual suspensions was subtracted and compared to dual-drug suspensions when prepared with the same milling conditions and stored at elevated temperatures of 40 °C. Results: Distinct particle size profiles after milling were obtained dependent on the stabilizer used in both individual and dual-drug suspensions. Most notably, the combination of indomethacin and naproxen in one formulation resulted in smaller sizes of drug particles compared to individual suspensions under the presence of some stabilizers. The obtained particle size profiles further indicated that at least one of the model compounds needed to be sufficiently stabilized from a stabilizer to obtain physically stable dual-drug suspensions over 28 days when stored at 40 °C. Similarly, the particle size distribution was dependent on the individual distribution of the suspensions, which showed a monomodal distribution could be achieved for dual-drug suspensions when at least one of the individual suspensions demonstrated a monomodal distribution in the presence of the stabilizer alone. Over a 28-day period, the smallest particle size was obtained in dual-drug suspensions stabilized with a combination of polysorbate 85 and poloxamer 338 compared to dual-drug suspensions stabilized with only a single stabilizer during preparation, indicating tendencies towards stabilization synergism from a combination of stabilizers as well as the model compounds. Conclusion: Overall, the study showed insights into the preparation and physical stability of dual-drug suspensions containing indomethacin and naproxen.

No reviews so far have been conducted to define the constructs of patient-experienced quality in healthcare transitions or to identify existing generic measures of patients' experience of the quality within healthcare transitions. Our aim was to identify domains relevant for people experiencing healthcare transitions when evaluating the quality of care they have received, map the comprehensiveness of existing patient-reported experience measures (PREM), and evaluate the PREMs' content validity. The method was guided by the Joanna Briggs Institutes' guidance for scoping reviews. The search was performed on 07 December 2021 and updated 27 May 2024, in the electronic databases Medline (Ovid), Embase (Ovid), and Cinahl (EBSCO). The search identified 20,422 publications, and 190 studies were included for review. We identified 30 PREMs assessing at least one aspect of adults' experience of transitions in healthcare. Summarising the content, we consider a model with two domains, organisational and human-relational, likely to be adequate. However, a more comprehensive analysis and adequate definition of the construct is needed. None of the PREMs were considered content valid., (© 2024. The Author(s).)

Background: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive., Results: In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes., Conclusion: Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface., (© 2024. The Author(s).)

Introduction The use and consumption of "products", such as cosmetic procedures and confectionery, is on a rise in the Danish population. However, it has never been evaluated if the same tendency can be observed among the providers of these products. In view of the upcoming Christmas, we decided to investigate this delicate matter. Methods This study was a survey-based cross-sectional study examining demographics, professional backgrounds, as well as frequency and preferences regarding confectionery and cosmetic procedures among confectioners and plastic surgeons. Results A total of 90 persons answered the questionnaire. Results showed that consumption of confectionery was high among both confectioners and plastic surgeons, and that the use of cosmetic procedures was higher among both confectioners and plastic surgeons than among the background population. Both groups preferred to know the person who provided "the product" within their respective area. Conclusion Most plastic surgeons do not need to know their confectioner but would like to know their cosmetic procedure provider. So, if you, as part of the department management, or simply as a well-meaning colleague, want to treat your staff/colleagues, you can safely order cake from a random confectioner but not cosmetic procedures from a random surgeon! Funding none. Trial registration not relevant., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Objective: To determine if the administration of atropine would reduce the measured minimum anaesthetic concentration of isoflurane (MAC isoflurane ) in freshwater turtles - the yellow-bellied slider (Trachemys scripta scripta)., Study Design: Paired, blinded, randomized, prospective studies of 1) the effect of atropine in isoflurane anaesthetized freshwater turtles (T. scripta scripta) and 2) the effect of atropine in yellow-bellied sliders in which anaesthesia was induced with propofol and maintained with isoflurane., Animals: T. scripta scripta (n = 8), female, adult., Methods: Atropine (2 mg kg -1 ) or an isovolumetric control injection of saline was administered intraperitoneally 15 minutes prior to induction of anaesthesia with isoflurane. Individual MAC isoflurane was then determined by end-tidal gas analysis in a bracketing design by an experimenter blinded to the administered drug, with a 2 week washout period. The experiment was repeated, with atropine (2 mg kg -1 ) or saline administered intravascularly in combination with propofol for anaesthetic induction. Linear mixed modelling was used to determine the effects of atropine and propofol on the individual MAC isoflurane . Data are presented as mean ± standard deviation., Results: Premedication with atropine significantly reduced MAC isoflurane (p = 0.0039). In isoflurane-induced T. scripta scripta, MAC isoflurane decreased from 4.2 ± 0.4% to 3.3 ± 0.8% when atropine had been administered. Propofol as an induction agent had a MAC-sparing effect (p < 0.001) such that MAC isoflurane following propofol and a control injection of saline was 2.3 ± 1.0%, which decreased further to 1.5 ± 0.8% when propofol was combined with atropine., Conclusions and Clinical Relevance: Atropine, presumably by inhibiting parasympathetically mediated pulmonary artery constriction, decreases right-to-left cardiac shunting and the MAC isoflurane in yellow-bellied sliders, and thereby may facilitate control of inhalant anaesthesia. Propofol can be used for induction of anaesthesia and reduces the required concentration of inhaled anaesthesia assessed 1.5 hours following induction., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF)., Objective: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA)., Methods: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA., Results: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 μV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively)., Conclusion: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction. Patients with severe aortic stenosis (AS) undergoing surgery are at increased risk of hypotension and hypoperfusion. Although treatable with inotropic agents or fluid, little is known about how these therapies affect central hemodynamics in AS patients under general anesthesia. We measured changes in central hemodynamics after dobutamine infusion and fluid bolus among patients with severe AS and associated these changes with preoperative echocardiography. Methods. We included 33 patients with severe AS undergoing surgical AVR. After induction of general anesthesia, hemodynamic measurements were obtained with a pulmonary artery catheter, including Cardiac index (CI), stroke volume index (SVi) and pulmonary capillary wedge pressure (PCWP). Measurements were repeated during dobutamine infusion, after fluid bolus and lastly after sternotomy. Results. General anesthesia resulted in a decrease in CI and SVi compared to preoperative values. During dobutamine infusion CI increased but mean SVi did not (38 ± 12 vs 37 ± 13 ml/m 2 , p  = .90). Higher EF and SVi before surgery and a larger decrease in SVi after induction of general anesthesia were associated with an increase in SVi during dobutamine infusion. After fluid bolus both CI, SVi (48 ± 12 vs 37 ± 13 ml/min/m 2 , p  < .0001) and PCWP increased. PCWP increased mostly among patients with a larger LA volume index. Conclusion. In patients with AS, CI can be increased with both dobutamine and fluid during surgery. Dobutamine's effect on SVI was highly variable and associated with baseline LVEF, and an increase in CI was mostly driven by an increase in heart rate. Fluid increased SVi at the cost of an increase in PCWP.

Aim: Treatment with certain drugs can augment the risk of developing malignant arrhythmias (e.g. torsades de pointes [TdP]). Hence, we examined the overall TdP risk drug use before out-of-hospital cardiac arrest (OHCA) and possible association with shockable rhythm and return of spontaneous circulation (ROSC)., Methods: Patients ≥18 years with an OHCA of cardiac origin from the Danish Cardiac Arrest Registry (2001-2014) and TdP risk drug use according to www.CredibleMeds.org were identified. Factors associated with TdP risk drug use and secondly how use may affect shockable rhythm and ROSC were determined by multivariable logistic regression., Results: We identified 27,481 patients with an OHCA of cardiac origin (median age: 72 years [interquartile range 62.0, 80.0 years]). A total of 37% were in treatment with TdP risk drugs 0-30 days before OHCA compared with 33% 61-90 days before OHCA (p < 0.001). Most commonly used TdP risk drugs were citalopram (36.1%) and roxithromycin (10.7%). Patients in TdP risk drug treatment were older (75 vs 70 years) and more comorbid compared with those not in treatment. Subsequently, TdP risk drug use was associated with less likelihood of the presenting rhythm being shockable (odds ratio [OR] = 0.63, 95% confidence interval [CI]:0.58-0.69) and ROSC (OR = 0.73, 95% CI:0.66-0.80)., Conclusion: TdP risk drug use increased in the time leading up to OHCA and was associated with reduced likelihood of presenting with a shockable rhythm and ROSC in an all-comer OHCA setting. However, patients in TdP risk drug treatment were older and more comorbid than patients not in treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Medication errors (MEs) are associated with patient harm and high economic costs. Healthcare authorities and pharmacovigilance organisations in many countries routinely collect data on MEs via reporting systems to improve patient safety and for learning purposes. Different approaches have been developed and used for the ME analysis, but an overview of the scope of available methods currently is lacking. This scoping review aimed to identify, explore and map available literature on methods used to analyse MEs in reporting systems., Methods and Analyses: This protocol describes a scoping review, based on the Joanna Briggs Institute methodological framework. A systematic search will be performed in MEDLINE (Ovid), Embase (Ovid), Cinahl (EBSCOhost), Cochrane Central, Google Scholar, websites of the major pharmacovigilance centres and national healthcare safety agencies, and citation search in Scopus in August 2022. All retrieved records are to be independently screened by two researchers on title, abstract and full text, involving a third researcher in case of disagreement. Data will be extracted and presented in descriptive and tabular form. The extraction will be based on information about methods of ME analyses, type of reporting system and information on MEs (medication name, ATC codes, ME type, medication-event categories and harm categories)., Ethics and Dissemination: Ethical approval is not required. The results will be disseminated via publication in peer-reviewed journals, scientific networks and relevant conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fascicular heart blocks can progress to complete heart blocks, but this risk has not been evaluated in a large general population., Objective: The purpose of this study was to investigate the association between various types of fascicular blocks diagnosed by electrocardiographic (ECG) readings and the risk of incident higher degree atrioventricular block (AVB), syncope, pacemaker implantation, and death., Methods: We studied primary care patients referred for ECG recording between 2001 and 2015. Cox regression models were used to estimate hazard ratios (HRs) as well as absolute risks of cardiovascular outcomes., Results: Of 358,958 primary care patients (median age 54 years; 55% women), 13,636 (3.8%) had any type of fascicular block. Patients were followed up to 15.9 years. We found increasing HRs of incident syncope, pacemaker implantation, and third-degree AVB with increasing complexity of fascicular block. Compared with no block, isolated left anterior fascicular block (LAFB) was associated with 0%-2% increased 10-year risk of developing third-degree AVB (HR 1.6; 95% confidence interval [CI] 1.25-2.05), whereas right bundle branch block combined with LAFB and first-degree AVB was associated with up to 23% increased 10-year risk (HR 11.0; 95% CI 7.7-15.7), depending on age and sex group. Except for left posterior fascicular block (HR 2.09; 95% CI 1.87-2.32), we did not find any relevant associations between fascicular block and death., Conclusion: We found that higher degrees of fascicular blocks were associated with increasing risk of syncope, pacemaker implantation, and complete heart block, but the association with death was negligible., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESS sep ) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESS sep for clinical outcome after CRT., Methods: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESS sep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization., Results: Two-thirds (65%) of patients had a positive SLICE-ESS sep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESS sep were at lower risk to reach the primary end point (hazard ratio 0.36; P <0.001) and heart failure hospitalization (hazard ratio 0.41; P =0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P =0.272). Clinical outcome of class II patients with a positive ESS sep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; P =0.396)., Conclusions: Strain assessment of the septum (SLICE-ESS sep ) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESS sep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESS sep negative patients have poor prognosis after CRT implantation.

Vegetables rich in bitter-tasting phytochemicals may exert enhanced beneficial effects against key factors associated with type two diabetes (T2D). This study investigates whether selected cultivars of bitter and strong-tasting (BST) Brassica and root vegetables exert greater health benefits on T2D patients compared to equivalent modern mild and sweet tasting (MST) vegetables. A 12-week randomized, controlled, parallel intervention study involved 92 T2D patients, who were allocated three different diets: (1) 500 g daily of bitter and strong-tasting (BST) vegetables; (2) 500 g daily of mild and sweet-tasting (MST) vegetables; (3) 120 g daily MST normal diet (control). Both vegetable diets contained root vegetables and cabbages selected based on sensory differences and content of phytochemicals. Prior to and after the study, all participants underwent an oral glucose tolerance test (OGTT), 24 h blood pressure measurements, DEXA scans, and fasted blood samples. Both diets high in vegetables significantly reduced the participants' BMI, total body fat mass, and HbA1c levels compared to control, but in the BST group, significant differences were also found regarding incremental area under the curve glucose 240 min (OGTT) and fasting glucose levels. A high daily intake of root vegetables and cabbages showed significant health improvements in both vegetable groups. BST vegetables had the greatest impact on insulin sensitivity, body fat mass, and blood pressure compared to control; moreover, they further improved glycemic control compared to MST vegetables.

Aims: To examine socioeconomic differences in care and outcomes in a 1-year period beginning 30 days after hospital discharge for first-time atrial fibrillation or flutter (AF) hospitalization., Methods and Results: This nationwide register-based follow-up cohort study investigated AF 30-day discharge survivors in Denmark during 2005-2014 and examined associations between patient's socioeconomic status (SES) and selected outcomes during a 1-year follow-up period beginning 30 days post-discharge after first-time hospitalization for AF. Patient SES was defined in four groups (lowest, second lowest, second highest, and highest) according to each patient's equivalized income. SES of the included 150 544 patients was: 27.7% lowest (n = 41 648), 28.1% second lowest (n = 42 321), 23.7% second highest (n = 35 656), and 20.5% highest (n = 30 919). Patients of lowest SES were older and more often women. Within 1-year follow-up, patients of lowest SES were less often rehospitalized or seen in outpatient clinics due to AF, or treated with cardioversion or ablation and were slightly more often diagnosed with stroke and heart failure (HF) and significantly more likely to die (16.1% vs. 14.9%, 11.3% and 8.1%). Hazard ratios for all-cause mortality were 0.64 (95% confidence interval 0.61-0.68) for highest vs. lowest SES, adjusted for CHA2DS2-VASc score, chronic obstructive pulmonary disease, rate- and rhythm-controlling drugs, and cohabitation status., Conclusion: In 30-day survivors of first-time hospitalization due to AF, lowest SES is associated with increased 1-year all-cause and cardiovascular mortality and fewer cardioversions, ablations, readmissions, and outpatient contacts due to AF. Our findings indicate a need for socially differentiated rehabilitation following hospital discharge for first-time AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Increased bleeding and blood product transfusions during cardiac surgery are associated with poor outcomes. The patient's ABO blood group is related to hemostatic balance, although it is unclear whether this influences bleeding during cardiac surgery. This study aimed to evaluate whether ABO blood group is related to bleeding during cardiac surgery., Methods: This retrospective study evaluated data from 17,058 cardiac surgical procedures that were performed in four Danish cardiosurgical centers. Data regarding chest tube drainage and transfusion volumes were retrieved from a clinical database and combined with information regarding ABO group. The primary outcome was chest tube drainage volume and the secondary outcomes were transfused volumes of various blood products., Results: Blood group O had the largest chest tube drainage volume (mean: 745 mL, 95% CI: 720-771 mL) and blood group AB had the smallest volume (mean: 664 mL, 95% CI: 598-731 mL). The inter-group difference in the mean drainage volume was 81 mL (95% CI: 8-154 mL, P < .05). Patients with blood group A or blood group B had mean drainage volumes that were between the volumes for groups AB and O. Relative to group O, group AB received smaller mean volumes of all blood products. The most pronounced difference was in platelet concentrates, with mean values of 170 mL for group O (95% CI: 157-184 mL) and 63 mL for group AB (95% CI: 34-92 mL)., Conclusion: The patient's ABO group appears to be related to volumes of chest tube drainage and transfused blood products during cardiac surgery., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival., Methods: From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders., Results: We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups., Conclusion: Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors., Competing Interests: Competing interests: LK has received lecture fees from Sanofi and Novartis., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Left bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data., Methods and Results: Using ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p < 0.001). There was no association between the PR interval and HF after adjustment., Conclusion: Prolonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF., Competing Interests: Competing interests: KHK reports to have received speaker’s honoraria from Novartis and research grant from the Laerdal Foundation. SMH has received support from the Danish Heart Foundation, The Danish Foundation Trygfonden and AstraZeneca. PS reports having received research grants from GE Health Care and BIOTRONIK. CP reports receiving speaking fees from H Lundbeck., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage., Materials and Methods: In one pig and six mice, three different methods were used to create ischemic conditions in the lower extremity, producing symptoms similar to what is observed in ACS. In each condition, perfusion to the distal extremity was measured with the hemodynamic detection device (HDD; Odin Technologies), an optical assessment tool for perfusion and blood flow quality., Results: We observed a profound decrease in extremity perfusion immediately after onset of ischemia in all three models. In the porcine model, the HDD's measurements demonstrated similar characteristic flow between the various measurement locations. After the tourniquet was applied, the HDD revealed a 95% decrease in normalized perfusion value (npv) while the intracompartmental pressure rose from 5 to 52 mmHg (a 47mmHg increase). After the tourniquet was removed during reperfusion, the normalized blood flow returned to baseline and the intracompartmental pressure dropped from 20 to 6 mmHg in less than 5 minutes. For each mouse, the HDD test leg demonstrated a measurement of 0.97 npv before femoral ligation and 0.05 npv after femoral ligation, an 89% decrease (P < .01) in flow. Pulsed-wave Doppler ultrasound (PWDU) measurements on the test leg had pre-ligation measurement of 0.84 npv and a post-ligation measurement of 0.001 npv, a 99% decrease. These PWDU measurements revealed almost complete stoppage of blood flow during ischemia, followed by a substantial increase after the femoral artery ligation was removed., Conclusions: Here, we show that a novel, optics-based sensing system can be used to diagnose and assess ACS in animal models. This technology is comparable to other standards used to monitor ACS and nonobvious hemorrhage and may also be a plausible alternative to prolonged invasive monitoring of patients with sustained extremity trauma., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Biventricular (BiV) pacing increases transmural repolarization heterogeneity due to epicardial to endocardial conduction from the left ventricular (LV) lead. However, limited evidence is available on concomitant changes in ventricular depolarization and repolarization and long-term outcomes of BiV pacing. Therefore, we investigated associations of BiV pacing-induced concomitant changes in ventricular depolarization and repolarization with mortality (i.e., LV assist device, heart transplantation, or all-cause mortality) and sustained ventricular arrhythmia endpoints., Methods: Consecutive BiV-defibrillator recipients with digital preimplantation and postimplantation electrocardiograms recorded between 2006 and 2015 at Duke University Medical Center were included. We calculated changes in QRS duration and corrected JT (JTc) interval and split them by median values. For simplicity, these variables were named QRS decreased (≤ -12 ms), QRS increased (> -12 ms), JTc decreased (≤22 ms), and JTc increased (> 22 ms) and subsequently used to construct four mutually exclusive groups., Results: We included 528 patients (median age, 68 years; male, 69%). No correlation between changes in QRS duration and JTc interval was observed (P = .295). Compared to QRS decreased /JTc increased , increased risk of the composite mortality endpoint was associated with QRS decreased /JTc decreased (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.09-2.43), QRS increased /JTc decreased (HR = 1.86; 95% CI = 1.27-2.71), and QRS increased /JTc increased (HR = 2.25; 95% CI = 1.52-3.35). No QRS/JTc group was associated with excess sustained ventricular arrhythmia risk (P = .400)., Conclusion: Among BiV-defibrillator recipients, QRS decreased /JTc increased was associated with the most favorable long-term survival free of LV assist device, heart transplantation, and sustained ventricular arrhythmias. Our findings suggest that improved electrical resynchronization may be achieved by assessing concomitant changes in ventricular depolarization and repolarization., (© 2020 Wiley Periodicals LLC.)

Background: Research regarding out-of-hospital cardiac arrest (OHCA) survival of diabetes patients is sparse and it remains unknown whether initiatives to increase OHCA survival benefit diabetes and non-diabetes patients equally. We therefore examined overall and temporal survival in diabetes and non-diabetes patients following OHCA., Methods: Adult presumed cardiac-caused OHCAs were identified from the Danish Cardiac Arrest Registry (2001-2014). Associations between diabetes and return of spontaneous circulation upon hospital arrival and 30-day survival were estimated with logistic regression adjusted for patient- and OHCA-related characteristics., Results: In total, 28,955 OHCAs were included of which 4276 (14.8%) had diabetes. Compared with non-diabetes patients, diabetes patients had more comorbidities, same prevalence of bystander-witnessed arrests (51.7% vs. 52.7%) and bystander cardiopulmonary resuscitation (43.2% vs. 42.0%), more arrests in residential locations (77.3% vs. 73.0%) and were less likely to have shockable heart rhythm (23.5% vs. 27.9%). Temporal increases in return of spontaneous circulation and 30-day survival were seen for both groups (return of spontaneous circulation: 8.8% in 2001 to 22.3% in 2014 (diabetes patients) vs. 7.8% in 2001 to 25.7% in 2014 (non-diabetes patients); and 30-day survival: 2.8% in 2001 to 9.7% in 2014 vs. 3.5% to 14.8% in 2014, respectively). In adjusted models, diabetes was associated with decreased odds of return of spontaneous circulation (odds ratio 0.74 (95% confidence interval 0.66-0.82)) and 30-day survival (odds ratio 0.56 (95% confidence interval 0.48-0.65)) (interaction with calendar year p =0.434 and p =0.243, respectively)., Conclusion: No significant difference in temporal survival was found between the two groups. However, diabetes was associated with lower odds of return of spontaneous circulation and 30-day survival.

Aims: The usefulness of mortality statistics relies on the validity of death certificate diagnosis. However, diagnosing the causal sequence of conditions leading to death is not simple. We examined diagnostic support for fatal acute myocardial infarction (AMI) and investigated its association with regional variation., Methods and Results: From Danish nationwide registers, we identified the study population (N = 3,244,051) of whom 36,669 individuals were recorded with AMI as the underlying cause-of-death between 2002 and 2015. We included clinical diagnoses, procedures, and claimed prescriptions related to atherosclerotic disease to evaluate the level of diagnostic support for fatal AMI in three diagnostic groups (Definite; Plausible; Uncertain). Adjusted mortality rates, rate ratios, and odds ratios were estimated for each AMI category, stratified by hospital region using multivariable regression models. More than one-third (N = 12,827, 35%) of deaths reported as fatal AMI had uncertain diagnostic support. The largest regional variation in AMI mortality rate ratios, varying from 1.16 (95%CI:1.02;1.31) to 1.62 (95%CI:1.43;1.83), was found among cases with uncertain diagnostic supportive data. Substantial inter-regional differences in the degree to which death occurs outside hospital [OR: 1.01 (95%CI:0.92;1.12) - 1.49 (95%CI:1.36;1.63)] and general practitioners determining the cause-of-death at home were present. Minor regional differences [OR: 0.96 (95%CI:0.85;1.07) - 1.16 (95%CI:1.04;1.29)] in in-hospital AMI mortality were observed., Conclusion: There is significant regional variation associated with recording AMI as a cause-of-death. This variation is predominately based on death certificate diagnoses without diagnostic supportive evidence. Studies of fatal AMI should include a stratification on supportive evidence of the diagnosis., Competing Interests: MTS reports grants from the Danish Heart Foundation and the Maria Pedersen and Jensine Heiberg Foundation, during the conduct of the study. STM reports grants from Trygfonden, the Laerdal Foundation, the Danish Heart Foundation outside the submitted work. CTP reports grants from Bayer and Novo Nordisk outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The general cardiovascular health has improved throughout the last few decades for middle-aged and older individuals, but the incidence of several cardiovascular diseases is reported to increase in younger people. We aimed to assess the age-specific incidence and mortality rates associated with out-of-hospital-cardiac-arrest (OHCA) between 2002 and 2014., Methods: We used the Danish Cardiac Arrest Register to identify patients with OHCA of presumed cardiac etiology. We calculated the annual incidence rates (IR) and 30-day mortality rates (MR) in 7 age groups (18-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years, 75-84 years and ≥85 years, and ≤50 vs. >50 years)., Results: Between 2002 and 2014, IR of OHCA decreased in individuals aged 65-74 and 75-84 years (158.08 to 111.2 and 237.5 to 217.09 per 100,000 person-years) and increased in the oldest from 201.01 to 325.4 pr. 100.000 person-years. In 18-34-years incidence of OHCA increased from 1.7 to 2.6 per 100.000 person-years. When stratifying into age ≤50 vs. >50 years, the IR deviated in those >50 years (from 117.8 in 2002 to 91 in 2008 to 117.4 in 2014100,000 person-years). The prevalence of acute myocardial infarction and heart failure prior to OHCA increased in the younger patient group in contrast to the older segment (AMI: ≤50 years: 10% to 16%, vs. >50 years: 25% to 23%, heart failure: ≤50 years 6% to 14%, vs. >50 years: 21% to 24%)., Conclusion: Over the last decades, incidence rates of OHCA decreased in individuals aged 65-84, but increased in individuals older than 85. An increase was also observed in younger individuals, potentially indicating a need for better cardiovascular disease prevention in younger adults., (Copyright © 2020 Elsevier B.V. All rights reserved.)

High-dose prednisolone is used in first-line treatment for lymphoma, but the potential adverse impact on bone health is unclear. Danish patients with diffuse large B-cell lymphoma or follicular lymphoma diagnosed between 2000 and 2012 were matched to the background population. Osteoporotic events (osteoporosis treatment or low-energy fracture) were identified using the Danish National Patient Registry and Prescription Registry. In total, 2589 patients and 12,945 controls were included. Lymphoma patients had increased risk of osteoporotic events compared to the matched population (hazard ratio 1.61 [95% confidence interval 1.40;1.84]). The 5- and 10-year cumulative risks of osteoporotic events for lymphoma patients were 10.0% [8.6;11.4] and 16.3% [13.8;18.7], whereas corresponding risks in the background population were 6.8% [6.3;7.3] and 13.5% [12.4;14.6]. Patients without osteoporotic event in the first two years after treatment were not at higher risk of osteoporotic events in subsequent years. Risk factors for osteoporotic events were female sex and age >70 years.

Background: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome., Methods: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and <1 mm or <30 ms and ≥1 mm), patients had lenient Q waves. If another contiguous Q wave occurred, patients had strict Q waves., Results: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads., Conclusions: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: A low electrocardiogram (ECG) lead one ratio (LOR) of the maximum positive/negative QRS amplitudes is associated with lower left ventricular ejection fraction (LVEF) and worse outcomes in left bundle branch block (LBBB); however, the impact of LOR on cardiac resynchronization therapy (CRT) outcomes is unknown. We compared clinical outcomes and echocardiographic changes after CRT implantation by LOR., Methods: Consecutive CRT-defibrillator recipients with LBBB implanted between 2006 and 2015 at Duke University Medical Center were included (N = 496). Time to heart transplant, left ventricular assist device (LVAD) implantation, or death was compared among patients with LOR <12 vs ≥12 using Cox-proportional hazard models. Changes in LVEF and LV volumes after CRT were compared by LOR., Results: Baseline ECG LOR <12 was associated with an adjusted hazard ratio (HR) of 1.69 (95% CI: 1.12-2.40, P = .01) for heart transplant, LVAD, or death. Patients with LOR <12 had less reduction of LV end diastolic volume (ΔLVEDV -4 ± 21 vs -13 ± 23%, P = .04) and LV end systolic volume (ΔLVESV -9 ± 27 vs -22 ± 26%, P = .03) after CRT. In patients with QRS duration (QRSd) ≥150 ms, LOR <12 was associated with an adjusted HR of 2.01 (95% CI 1.21-3.35, P = .008) for heart transplant, LVAD, or death, compared with LOR ≥12., Conclusions: Baseline ECG LOR <12 portends worse outcomes after CRT implantation in patients with LBBB, specifically among those with QRSd ≥150 ms. This ECG ratio may identify patients with a class I indication for CRT implantation at high risk for poor postimplantation outcomes., (© 2020 Wiley Periodicals, Inc.)

Little is known about the occurrence of hypokalemia due to combination therapy for hypertension. Using data from Danish administrative registries, we investigated the association between different combinations of antihypertensive therapy and risk of developing hypokalemia. Using incidence density matching, 2 patients without hypokalemia were matched to a patient with hypokalemia (K, <3.5 mmol/L) on age, sex, renal function, and time between index date and date of potassium measurement. Combination therapies were subdivided into 10 groups including β-blockers (BB)+thiazides (BB+thiazides), calcium channel blockers (CCB)+renin angiotensin system inhibitors (RASi)+thiazides (CCB+RASi+Thiazides), calcium channel blockers+thiazides (CCB+thiazides), and β-blockers+renin angiotensin system inhibitors+thiazides (BB+RASi+thiazides). We used conditional logistic regression to estimate the odds of developing hypokalemia for different combinations of antihypertensive drugs within 90 days of combination therapy initiation. We matched 463 patients with hypokalemia to 926 patients with normal potassium concentrations. The multivariable analysis showed 5.82× increased odds of developing hypokalemia if administered CCB+thiazides (95% CI, 3.06-11.08) compared with CCB+RASi. Other combinations significantly associated with increased hypokalemia odds were BB+thiazides (odds ratio, 3.34 [95% CI, 1.67-6.66]), CCB+RASi+thiazides (odds ratio, 3.07 [95% CI, 1.72-5.46]), and BB+RASi+thiazides (odds ratio, 2.78 [95% CI, 1.41-5.47]). Combinations of thiazides with CCB, RASi, or BB were strongly associated with increased hypokalemia risk within 90 days of treatment initiation.

Background: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia., Methods: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs)., Results: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39)., Conclusions: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This is a case report of two patients, who had accidental self-inflicted chainsaw lacerations of the face. The injuries were remarkably similar with jagged soft tissue lacerations and soft tissue parts of questionable vitality. These cases and their treatment are presented to show examples of the handling of soft tissue injuries of the face in an emergency department setting and to show, that very conservative debridement of these injuries is the recommended approach.

Objective: To examine the association between time from emergency medical service vehicle dispatch to hospital arrival and 1-day and 30-day mortality., Design: Register-based cohort study., Setting: North Denmark Region (≈8000 km 2 , catchment population ≈600 000)., Participants: We included all highest priority dispatched ambulance transports in North Denmark Region in 2006-2012., Interventions: Using logistic regression and the g-formula approach, we examined the association between time from emergency dispatch to hospital arrival and mortality for presumed heart, respiratory, cerebrovascular and other presumed medical conditions, as well as traffic or other accidents, as classified by emergency dispatch personnel., Main Outcome Measures: 1-day and 30-day mortality., Results: Among 93 167 individuals with highest priority ambulances dispatched, 1948 (2.1%) were dead before the ambulance arrived and 19 968 (21.4%) were transported to the hospital under highest priority (median total prehospital time from dispatch to hospital arrival 47 min (25%-75%: 35-60 min); 95th percentile 84 min). Among 18 709 with population data, 1-day mortality was 10.9% (n=2038), and was highest for patients with dyspnoea (20.4%) and lowest for patients with traffic accidents (2.8%). Thirty-day mortality was 18.3% and varied between 36.6% (patients with dyspnoea) and 3.7% (traffic accidents). One-day mortality was not associated with total prehospital time, except for presumed heart conditions, where longer prehospital time was associated with decreased mortality: adjusted OR for >60 min vs 0-30 min was 0.61 (95% CI 0.40 to 0.91). For patients with dyspnoea, OR for >60 min vs 0-30 min was 0.90 (95% CI 0.56 to 1.45), for presumed cerebrovascular conditions OR 1.41 (95% CI 0.53 to 3.78), for other presumed medical conditions OR 0.84 (95% CI 0.70 to 1.02), for traffic accidents OR 0.65 (95% CI 0.29 to 1.48) and for other accidents OR 0.84 (95% CI 0.47 to 1.51). Similar findings were found for 30-day mortality., Conclusions: In this study, where time from emergency dispatch to hospital arrival mainly was <80 min, there was no overall relation between this prehospital time measure and mortality., Competing Interests: Competing interests: SMH is supported by the Danish foundation TrygFonden. CT-P has received grants from Bayer and Biotronic and has received speaker honorarium from Bayer. PS reports research grants and personal fees from Biotronik, personal fees from Novartis, personal fees from AstraZeneca, research grants from GE Healthcare and research grants from EBR Systems. KK has received grants from the Laerdal Foundation and has received speaker’s honoraria from Novartis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: PR interval prolongation is associated with poor outcome after cardiac resynchronization therapy (CRT) among patients with left bundle branch block (LBBB) but the mechanisms are unknown. We investigated clinical outcomes, electrocardiogram (ECG), and echocardiogram changes after CRT by PR interval., Methods: This is a retrospective study of CRT recipients with a baseline ejection fraction ≤35% and ECG showing sinus rhythm and LBBB. Patients were stratified by baseline PR interval quartile and the primary combined endpoint was time to heart transplantation, left ventricular assist device (LVAD) implantation, or death. ECG, echocardiogram, and clinical variables were compared to identify mechanisms for observed differences in outcomes., Results: Of 291 eligible patients, the mean age was 65 years, 60% were male, and 19% had prior atrial fibrillation. Patients with PR prolongation (quartile 4, PR > 200 ms) more frequently had a history of atrial fibrillation, coronary artery bypass graft surgery, prior implantable cardioverter defibrillator implantation, and use of amiodarone than patients in PR quartiles 1-3. A PR > 200ms was associated with an adjusted hazard ratio of 1.7 (95% CI: 1.1-2.5) for the primary endpoint. Patients with PR > 200 ms had less reduction in QRS duration and QRS area after CRT while having more increase in QT and QTc intervals than patients with PR ≤ 200 ms. No major differences were observed in echocardiography by baseline PR interval quartiles., Conclusions: PR prolongation predicts shorter survival free of heart transplantation or LVAD implantation in patients with LBBB. This may be due to inadequate ventricular resynchronization., (© 2019 Wiley Periodicals, Inc.)

Aims: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels., Methods and Results: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p < 0.0001); T-wave amplitude was 43.1 μV lower for each mmol/L decrease in potassium (p < 0.0001); and MCS was 0.13 higher per mmol/L decrease in potassium (p < 0.001). Moreover, P-wave duration and PR interval were prolonged by 2.7 and 4.6 ms for each mmol/L decrease in potassium (p < 0.0001), respectively. Within the lowest potassium range (2.0-4.1 mmol/L) P-wave amplitude was 3.5 μV higher for each mmol/L decrease in potassium (p < 0.0001). Within the high potassium range associations with the above-mentioned ECG parameters were much weaker., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Changes in left ventricular (LV) activation after cardiac resynchronization therapy (CRT) influence survival but are difficult to quantify noninvasively., Methods and Results: We studied 527 CRT patients to assess whether noninvasive quantification of changes in LV activation, defined by change (Δ) in QRS area (QRSA), can predict outcomes after CRT. The study outcome was time until LV assist device(LVAD), cardiac transplant, or death. The three-dimensional QRSA was measured from clinical 12 lead ECGs which were transformed into vectorcardiograms using the Kors method. QRSA was calculated as (QRSx 2  + QRSy 2  + QRSz 2 ) 1/2 ; ΔQRSA was calculated as post-QRSA minus pre-QRSA, where a negative value represents a reduction in LV activation delay. Kaplan-Meier plots and multivariable Cox proportional hazards models were used to relate ΔQRSA area with outcomes after stratifying the population into quartiles of ΔQRSA. The median baseline QRSA of 93.6 µVs decreased to 59.7 µVs after CRT. Progressive reductions in QRSA with CRT were associated with a lower rate of LVAD, transplant, or death across patient quartiles (P < .001). In Cox regression analyses, ΔQRSA was associated with outcomes independent of QRS morphology and other clinical variables (Q1[greatest decrease] vs Q4[smallest change=reference], HR 0.45, CI, 0.30-0.70, P < .001). There was no interaction between ΔQRSA and QRS morphology., Conclusions: CRT induced ΔQRSA was associated with clinically meaningful changes in event-free survival. ΔQRSA may be a novel target to guide lead implantation and device optimization., (© 2019 Wiley Periodicals, Inc.)

Aims: To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders., Methods: We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001-2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression., Results: Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32-0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70-0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72-0.83), shockable heart rhythm (0.37 95% CI, 0.33-0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59-0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0-10.0%) in 2006 to 13.9% (CI 12.4-15.4%) in 2015 and from 7.0% (4.3-10.8%) in 2006 to 7.0% (CI 4.5-9.7%) in 2015, respectively., Conclusion: Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Social communication difficulties (SCDs) occur frequently after an acquired brain injury (ABI) and have disabling consequences, but effective interventions are scant. Group Interactive Structured Treatment (GIST) is a holistic group treatment targeting SCD that has received empirical support., Objective: To determine the efficacy of two GIST protocols, standard GIST and a newly developed intensive GIST, comparing standard GIST results to a wait-list control group (WL), as well as to intensive GIST received by participants following WL. The within subject results for WL and intensive GIST will also be examined., Methods and Analysis: Sixty adults (18-75 years) with SCD after ABI will be recruited for this randomised controlled trial. Standard GIST (n=30) will be delivered via outpatient sessions for 2.5 hours once per week for 12 weeks, plus one initial orientation session. Participants will be assessed at preintervention and postintervention and at 3-month and 6-month follow-ups (T1-T4). Intensive GIST (n=30) participants will be admitted to an inpatient rehabilitation unit for 4 weeks (two times 3 days/week, two times 4 days/week) and receive full-day sessions each week. Those participants will complete four assessments (T1-T4) in 12-week intervals as part of WL, assessments preintensive and postintensive GIST and at 3-month and 6-month follow-ups (T4-T7). The primary outcome measure is the La Trobe Questionnaire (self-report). Secondary outcome measures include the Profile of Pragmatic Impairment in Communication, a test of emotion recognition, the Goal Attainment Scale and questionnaires addressing social, emotional and cognitive functions, self-efficacy and quality of life., Ethics and Dissemination: Results will be communicated through international, peer-reviewed and popular science journals and presentations at scientific conferences. The study is approved by the Regional Committees for Medical and Health Research Ethics Norway (2017/1360). The trial will be conducted in accordance with the Declaration of Helsinki and reported in accordance with the Consolidated Standards of Reporting Trials 2010 statement and Standard Protocol Items: Recommendations for Interventional Trials recommendations., Trial Registration Number: NCT03636399., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Electrocardiographic bundle branch block (BBB) is common but the prognostic implications in primary care are unclear. We sought to investigate the relationship between electrocardiographic BBB subtypes and the risk of cardiovascular (CV) outcomes in a primary care population free of major CV disease., Methods: Retrospective cohort study of primary care patients referred for electrocardiogram (ECG) recording between 2001 and 2011. Cox regression models were used to estimate hazard ratios (HR) as well as absolute risks of CV outcomes based on various BBB subtypes., Results: We included 202 268 individuals with a median follow-up period of 7.8 years (Inter-quartile range [IQR] 4.9-10.6). Left bundle branch block (LBBB) was associated with heart failure (HF) in both men (HR 3.96, 95% CI 3.30 to 4.76) and women (HR 2.51, 95% CI 2.15 to 2.94) and with CV death in men (HR 1.80, 95% CI 1.38 to 2.35). Right bundle branch block (RBBB) was associated with pacemaker implantation in both men (HR 3.26, 95% CI 2.74 to 3.89) and women (HR 3.69, 95% CI 2.91 to 4.67), HF in both sexes and weakly associated with CV death in men. Regarding LBBB, we found an increasing hazard of HF with increasing QRS-interval duration (HR 1.25, 95% CI 1.11 to 1.42 per 10 ms increase in men and HR 1.23, 95% CI 1.08 to 1.40 per 10 ms increase in women). Absolute 10-year risk predictions across age-specific and sex-specific subgroups revealed clinically relevant differences between having various BBB subtypes., Conclusions: Opportunistic findings of BBB subtypes in primary care patients without major CV disease should be considered warnings of future HF and pacemaker implantation., Competing Interests: Competing interests: AGH is an employee of Novo Nordisk A/S., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)