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Aim To describe the co-designing process of an online support programme with and for informal carers of people with heart failure.Design A co-design process built on core concepts and ideas embedded in co-design methodology.Data sources Our co-design process included three phases involving 32 informal caregivers and 25 content creators; (1) Identification of topics and content through literature searches, focus group interviews and user group sessions; (2) Development of the online support programme and; (3) Refinement and finalization which included testing a paper prototype followed by testing the online version and testing and approval of the final version of the support programme.Outcomes The co-design process resulted in a support programme consisting of 15 different modules relevant to informal carers, delivered on a National Health Portal.Conclusion Co-design is an explorative process where researchers need to balance a range of potentially conflicting factors and to ensure that the end users are genuinely included in the process.Relevance to clinical practice Emphasizing equal involvement of end users (e.g. carers or patients) in the design and development of healthcare interventions aligns with contemporary ideas of person-centred care and provides a valuable learning opportunity for those involved. Furthermore, a co-designed online support programme has the capacity to be both accessible and meet end users information and support needs, thereby optimizing their self-care abilities. Additionally, an online support programme provides the opportunity to address current challenges regarding scarce resources and the lack of healthcare personnel.Reporting methods Consolidated criteria for reporting qualitative research (COREQ).Patient or public contribution Both informal carers and content creators were involved in developing the support programme., Funding Agencies|Swedish Research Council for Health, Working Life and Welfare [dnr 2014-4100]; Swedish Research Council; Familjen Kamprads stiftelse [2014-34016-113474-48]; [20210130]

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC50, 11.5 nM and ADB-4en-PINACA (EC50, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC50, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation., Funding Agencies|Linkopings Universitet; Dubai Police Force [2427681]; Leverhulme TrustLeverhulme Trust [RC-2015-01]; Scottish Prison Service [01865]; Linkoping University; VINNOVAVinnova [2019-03566]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [E! 113377]

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a good death. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure., Funding Agencies|Patient Forum of the European Society of Cardiology

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: center dot Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin have consistently demonstrated to be effective for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. The specifically listed agents are recommended. center dot Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction, already receiving guideline-directed medical therapy, regardless of the presence of type 2 diabetes mellitus.

Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts opinions, for all emergency medical services health providers involved in the pre-hospital management of acute cardiovascular care.

Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.

Skin microdialysis (SMD) is a versatile sampling technique that can be used to recover soluble endogenous and exogenous molecules from the extracellular compartment of human skin. Due to its minimally invasive character, SMD can be applied in both clinical and preclinical settings. Despite being available since the 1990s, the technique has still not reached its full potential use as a tool to explore pathophysiological mechanisms of allergic and inflammatory reactions in the skin. Therefore, an EAACI Task Force on SMD was formed to disseminate knowledge about the technique and its many applications. This position paper from the task force provides an overview of the current use of SMD in the investigation of the pathogenesis of chronic inflammatory skin diseases, such as atopic dermatitis, chronic urticaria, psoriasis, and in studies of cutaneous events during type 1 hypersensitivity reactions. Furthermore, this paper covers drug hypersensitivity, UVB-induced- and neurogenic inflammation, and drug penetration investigated by SMD. The aim of this paper is to encourage the use of SMD and to make the technique easily accessible by providing an overview of methodology and applications, supported by standardized operating procedures for SMD in vivo and ex vivo., Funding Agencies|EAACI

The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the destination therapy indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described.

Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the destination therapy indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patients pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.

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Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF.

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. (c) 2019 The Authors. The Journal of Pathology published by John Wiley amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Heart failure (HF) and frailty are two distinct yet commonly associated conditions. The interplay between the two conditions is complex, due to overlaps in underlying mechanisms, symptoms and prognosis. The assessment of frailty in patients with HF is crucial, as it is associated with both unfavourable outcomes and reduced access and tolerance to treatments. However, to date a consensus definition of frailty in patients with HF remains lacking and the need for a validated assessment score, for identifying those HF patients with frailty, is high and timely. This position paper proposes a new definition of frailty for use by healthcare professionals in the setting of HF and creates a foundation for the design of a tailored and validated score for this common condition.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and similar to 10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patients functional capacity. However, the existing evidence in support of ET in these patients remains limited. After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patients needs. Finally, gaps in our knowledge are discussed.

Background: There is increasing awareness that regardless of the proven value of clinical interventions, the use of effective strategies to implement such interventions into clinical practice is necessary to ensure that patients receive the benefits. However, there is often confusion between what is the clinical intervention and what is the implementation intervention. This may be caused by a lack of conceptual clarity between intervention and implementation, yet at other times by ambiguity in application. We suggest that both the scientific and the clinical communities would benefit from greater clarity; therefore, in this paper, we address the concepts of intervention and implementation, primarily as in clinical interventions and implementation interventions, and explore the grey area in between. Discussion: To begin, we consider the similarities, differences and potential greyness between clinical interventions and implementation interventions through an overview of concepts. This is illustrated with reference to two examples of clinical interventions and implementation intervention studies, including the potential ambiguity in between. We then discuss strategies to explore the hybridity of clinical-implementation intervention studies, including the role of theories, frameworks, models, and reporting guidelines that can be applied to help clarify the clinical and implementation intervention, respectively. Conclusion: Semantics provide opportunities for improved precision in depicting what is intervention and what is implementation in health care research. Further, attention to study design, the use of theory, and adoption of reporting guidelines can assist in distinguishing between the clinical intervention and the implementation intervention. However, certain aspects may remain unclear in analyses of hybrid studies of clinical and implementation interventions. Recognizing this potential greyness can inform further discourse.

Background: Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management. Aim: The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB. Sources: This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations. Implications: The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved., Funding Agencies|EU INTERREG OKS

Immunization is highly effective in preventing infectious diseases and therefore an indispensable public health measure. Allergic patients deserve access to the same publicly recommended immunizations as nonallergic patients unless risks associated with vaccination outweigh the gains. Whereas the number of reported possible allergic reactions to vaccines is high, confirmed vaccine-triggered allergic reactions are rare. Anaphylaxis following vaccination is rare, affecting less than 1/100,000, but can occur in any patient. Some patient groups, notably those with a previous allergic reaction to a vaccine or its components, are at heightened risk of allergic reaction and require special precautions. Allergic reactions, however, may occur in patients without known risk factors and cannot be predicted by currently available tools. Unwarranted fear and uncertainty can result in incomplete vaccination coverage for children and adults with or without allergy. In addition to concerns about an allergic reaction to the vaccine itself, there is fear that routine childhood immunization may promote the development of allergic sensitization and disease. Thus, although there is no evidence that routine childhood immunization increases the risk of allergy development, such risks need to be discussed. This article is protected by copyright. All rights reserved.

Evaluation of quality of care is an integral part of modern healthcare, and has become an indispensable tool for health authorities, the public, the press and patients. However, measuring quality of care is difficult, because it is a multifactorial and multidimensional concept that cannot be estimated solely on the basis of patients' clinical outcomes. Thus, measuring the process of care through quality indicators (QIs) has become a widely used practice in this context. Other professional societies have published QIs for the evaluation of quality of care in the context of acute myocardial infarction (AMI), but no such indicators exist in Europe. In this context, the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) has reflected on the measurement of quality of care in the context of AMI (ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI)) and created a set of QIs, with a view to developing programmes to improve quality of care for the management of AMI across Europe. We present here the list of QIs defined by the ACCA, with explanations of the methodology used, scientific justification and reasons for the choice for each measure.

Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level., Funding Agencies|Boehringer Ingelheim

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The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., Funding Agencies|European Society of Cardiology Funding Source: Medline

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., Funding Agencies|European Society of Cardiology Funding Source: Medline

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., Funding Agencies|European Society of Cardiology Funding Source: Medline

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., Funding Agencies|European Society of Cardiology Funding Source: Medline

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., Funding Agencies|European Society of Cardiology Funding Source: Medline

The allocation of resources is a crucial part of political decision-making in healthcare, but explicit priorities are rarely set when resources are distributed. Two areas that have received some attention in research about legitimacy and priority-setting decisions in healthcare are the role of technical expert agencies as mediating institutions and the role of elected politicians. This paper investigates a political priority-setting advisory committee within a regional authority in Sweden. The aim is to explore how a political body can serve as a mediating institution for priority-setting in healthcare by disentangling the arrangements of its work in terms of what role it performs in the organisation and what it should do. The findings illustrate that promoting the notion of explicit priority-setting and the political aspects inherent in priority-setting in political healthcare management can contribute to consolidating political governance and leadership. There is, however, a complex tension between stability and conflicting values which has implications for the role of politicians as citizens' democratic representatives. This paper enhances our understanding of the role of mediating institutions and political properties of healthcare priority-setting, as well as our understanding of political and democratic healthcare governance in local self-government., Funding Agencies|Swedish National Centre for Priorities in Health

Background: The stiffness of the abdominal aorta is considered a significant factor affecting the morbidity and mortality of cardiovascular disease. Estimating vascular stiffness is an integral part in cardiovascular risk assessment. Wall stress of the abdominal aorta appears to be a crucial factor in the remodeling of the arterial wall and the growth of aneurysms. Consequently, arterial mechanics plays a vital role in the function of the cardiovascular system. Therefore, there is a need for comprehensive studies of mechanical forces in the vessel wall to better understand the mechanisms behind normal and pathological changes that are significant for hypertension, atherosclerosis, and the development of arterial aneurysms. The aim of this study was to explore the blood pressure-induced forces in the aortic wall using a computational mechanical model, with particular attention to the effects of age, sex, and blood pressure on the remodeling process of the vessel wall. Methods: A computational model, comprising a solid mechanical model and a parameter identification process known as the Parameter Identification Method for Mechanical Parameters (PIMMP), was used to investigate the mechanical properties of the abdominal aortic vessel wall. Data for the model were obtained from the human abdominal aorta of volunteers: 30 healthy individuals, females (n=15) and males, divided into three age groups with an equal number of females and males (n=5 in each age group). Invasive blood pressure, measured via catheter, and diameter variation in the abdominal aorta, measured via ultrasound, were acquired to be used as input data for PIMMP. This dataset was utilized in Papers I, III, and IV. In Paper II, 24 datasets were generated, based on model parameters presented in the scientific literature. Results: Paper I reveals that elderly males exhibit both higher aortic wall stress and higher isotropic stress component, than females. With age, males show an increase in isotro, Funding agencies: • Residents Physician Grants, Region Östergötland, Sweden• ALF Grants, Region Östergötland, Sweden• Swedish Heart Lung Foundation (Grants), Sweden• Swedish Research Council Grant, Sweden

Deep learning has the potential to be used to improve and streamline EEG analysis. At the present, classifiers and supervised learning dominate the field. Supervised learning depends on target labels which most often are created by human experts manually classifying data. A problem with supervised learning is intra- and interrater agreement which in some instances are far from perfect. This can affect the training and make evaluation more difficult. This thesis includes three papers where self-supervised deep neural networks were developed. In self-supervised learning, the input data to the networks themselves contain structures that are used as targets for the training and no labeling is necessary. In paper I, deep neural networks were trained to increase the number of-, or to recreate missing EEG-channels. The performance was at least on the same level as that of spherical interpolation, but unlike in the case of interpolation, missing data does not have to be identified manually first. Papers II and III involved developing deep neural networks for clustering analysis. The networks produced two-dimensional representations of EEG data and the training strategy was based on the principle of t-distributed stochastic neighbor embedding (t-SNE). In paper II, comparisons were made to parametric t-SNE and EEG-features obtained from time-frequency methods. The deep neural networks produced more distinct clustering when tested on data annotated for epileptiform discharges, seizure activity, or sleep-wakefulness. In paper III, the newly developed method was used to compare annotations of epileptiform discharges. Two experts performed independent annotations and classifiers were trained on these, using supervised learning, which in turn produced new annotations. The agreement when comparing two sets of annotations was not larger between the two experts than between an expert and a classifier. The analysis showed that differences in the annotations by the experts infl, Funding: The work was funded by Saad Nagi (grants RÖ-974228, RÖ-962769, and RÖ-941377), Magnus Thordstein (grant RÖ-986017), and Håkan Olaus-son (grants LIO-936017 and RÖ-941359).

The rising incidence of skin cancer globally makes it important to emphasize preventive measures that promote sun protection, particularly among individuals with phenotypic predisposition and/or risky sun habits. Actinic keratosis (AK) is the predominant actinic lesion observed in fair-skinned populations, recognized as a sign of actinic skin damage and as an occasional precursor to squamous cell carcinoma (SCC). The aim of this thesis was to explore, from a primary care perspective, how an enhanced understanding of risk factors for skin cancer development can aid in identifying individuals for patient education on prevention and early detection of skin cancer. Paper I suggests that personalized sun protection advice delivered in person by the GP can result in both short-term and long-lasting improvements in sun protective behaviour. Paper II demonstrated that individuals diagnosed with AK face a significantly elevated risk of developing SCC, basal cell carcinoma (BCC), or malignant melanoma (MM) in the following decade compared to sex- and age-matched controls. Paper III highlighted the fact that the presence of chronic lymphocytic leukaemia, and to a lesser degree hypertension and Parkinson's disease, independently raises the risk of skin cancer. This underscores the importance of providing tailored preventive guidance to individuals with these conditions. Paper IV showed that both age and male gender were factors found to be associated with an increased risk of developing skin cancer in AK patients while no risk increase was identified for any of the other variables studied. In conclusion, personalized sun protection advice from general physicians (GPs) can bring about lasting improvements in sun protective behaviour. Reinforcing this advice during medical consultations, such as nevi checks, is important to sustain this effect over a long period. This is encouraging for the accepted practice of giving sun protection advice to patients with MM, SCC and BCC., Den ökande förekomsten av hudcancer globalt gör det viktigt att betona förebyggande åtgärder som främjar solskydd, särskilt bland individer med solkänslig hudtyp och/eller riskfyllda solvanor. Aktinisk keratos är en mycket vanlig typ av hudförändring hos ljushyade personer, välkänd för att vara ett tecken på hudskada orsakad av långvarig solexponering, och som också kan utgöra ett förstadium till skivepitelcancer. Syftet med denna avhandling var att utforska, ur ett primärvårdsperspektiv, hur ökad förståelse för riskfaktorer för utveckling av hudcancer kan hjälpa till att identifiera individer för patientutbildning om förebyggande och tidig upptäckt av hudcancer, med särskilt fokus på just individer med aktinisk keratos. Artikel I föreslår att individuellt utformade solskyddsråd som ges personligen av allmänläkare kan resultera i både kortsiktiga och långvariga förbättringar av solskyddsbeteendet. Artikel II visade att individer som diagnostiserats med aktinisk keratos löper en signifikant ökad risk att utveckla någon av de tre viktigaste hudcancertyperna skivepitelcancer, basal-cellscancer eller malignt melanom, under det följande decenniet jämfört med individer i en köns- och åldersmatchad kontrollergrupp. Artikel III påvisade att förekomsten av kronisk lymfatisk leukemi, och i mindre grad högt blodtryck och Parkinsons sjukdom, självständigt ökar risken för hud-cancer. Detta understryker vikten av att ge skräddarsydd förebyggande vägledning till individer med dessa tillstånd. Artikel IV visade att både ålder och manligt kön var faktorer som visade sig vara associerade med en ökad risk att utveckla hudcancer hos patienter med aktinisk keratos, medan ingen riskökning identifierades för någon av de andra variablerna som studerades, såsom antal och storlek på förändringarna. Sammanfattningsvis kan personliga solskyddsråd från allmänläkare leda till bestående förbättringar av solskyddsbeteendet. Att återupprepa sådana råd i samband med läkarbesök, såsom vid kontr

Background: Gestational weight gain (GWG), affects almost 50% of pregnant women and effective and scalable interventions are needed and should be inclusive for all irrespectively of origin. The overall aim of this thesis was to evaluate the HealthyMoms app targeting GWG as well as dietary and physical activity behaviors and how the app may be adapted to also reach women of migrant backgrounds. The first part evaluated the effectiveness of the HealthyMoms trial and the dietary assessment method used in it (Paper I-II). The second part aimed to explore how the HealthyMoms app could be adapted to reach Arabic- and Somali-speaking women (Paper III-IV). Methods: Paper I was a randomized controlled trial in healthy pregnant women (n=305). After baseline assessment (week 14), women were randomized to the intervention (n=152) or control group (n=153). The intervention group received standard care and the HealthyMoms app. The primary outcome was GWG between baseline and follow-up measurement (week 37). Secondary outcomes included body fatness (air displacement plethysmography), dietary habits (SHEI score), moderate-to-vigorous physical activity (accelerometry), glycemia and insulin resistance. Paper II: Nested validation study of RiksmatenFlex (dietary assessment method in HealthyMoms) in a subsample of the trial. Three days of dietary data (energy, foods groups, macronutrients and SHEI score) from RiksmatenFlex was compared to 24 h telephone dietary recalls (n=52). Total energy expenditure (TEE) was measured with the doubly labelled water method (n=24). Paper III: A qualitative exploration of healthcare professionals’ views on supporting healthy lifestyle behaviors in pregnant migrant women was performed through individual interviews over phone or in person with healthcare professionals working in maternity healthcare (n=14). An inductive thematic analysis was performed. Paper IV: Individual interviews with Arabic (n=10) and Somali women (n=9) exploring what support is n, Funding: The studies in this thesis were primarily supported by the Swedish Research Council (VR) and the Swedish Research Council for Health,Working Life and Welfare (Forte). The studies also received additional funding from several funding agencies (for details see the individual Papers I-IV).

Resilient performance is a crucial characteristic of complex socio-technical systems, enabling them to sustain essential functionality during changing or stressful conditions. Resilience Engineering (RE), a sub-field of safety research, focuses on this perspective of resilience. RE emphasises its “cornerstone model”, presenting the REsystem goals of “anticipating, monitoring, responding and learning”. The cornerstone of learning remains fragmented and undertheorized in the existing literature. This paper aims to enrich RE research and its practical implications by developing a nuanced and comprehensive understanding of the role of learning from resilient performance. To achieve this aim, a scoping literature review was conducted to assess how learning is conceptualised in the RE literature and the theoretical foundations on which previous work rests. The main findings show that RE researchers view learning as the process of understanding the system, sharing knowledge, and re-designing system properties. The application of established learning theories is limited. This paper contributes to research by proposing an organisational process for the RE cornerstone of learning, paving the way for deeper discussions in future studies about learning from resilient performance within complex sociotechnical systems.

Background: Adolescent idiopathic scoliosis (AIS) is a three-dimensional distortion of spinal curvature of unknown cause that develops during puberty. If the frontal plane curvature exceeds a Cobb angle of 24°, full-time bracing is recommended to prevent curve progression, negative health consequences or need for surgery. However, many patients decline full-time bracing, and limited evidence exists regarding alternative conservative treatments. Increasing knowledge of risk factors enables better identification of high-risk patients, thereby reducing the risk of over- or undertreatment. The overall aim of this thesis was to evaluate evidence of association between scoliosis and postural stability to inform a potential treatment target, to investigate the effectiveness of three alternative conservative treatments for patients who declined full-time bracing, and to develop a prognostic model for future risk of increased curvature in AIS. Methods: Data collection is based on one systematic literature review and meta-analysis, and one randomised controlled trial (RCT) for patients with AIS. In Paper I, literature was reviewed, and utilized posturography data to assess static postural stability to identify potential differences between patients with AIS and the control group (CON). In Papers II and III, patients were randomly assigned to either physical activity combined with hypercorrective Boston scoliosis night brace (NB), scoliosis-specific exercises (SSE), or a control group with physical activity alone (PA). Effects on trunk rotation, Cobb angle, self-reported physical activity, spinal appearance, and health-related quality of life were evaluated. Likewise, adherence, capability, and motivation in performing self-managed treatment were assessed. Follow-up was conducted at 6 months intervals until endpoint. The endpoint was defined as non-progression if the curvature increased by 6° or less at skeletal maturity, i.e., less than 1cm of growth over 6 months, or pro, Bakgrund: Idiopatisk skolios (AIS) är en tredimensionell ryggradskrökning som uppstår under puberteten utan känd orsak. Om kröken i frontalplanet når en Cobbsvinkel över 24 grader rekommenderas korsettbehandling under större delen av dygnet för att förhindra att kröken blir större och leder till negativa hälsokonsekvenser eller kirurgi. Många har svårt att acceptera dygnskorsett och det saknas kunskap om alternativa icke-kirurgiska behandlingsmetoder. Ökad kunskap om riskfaktorer möjliggör bättre identifiering av högriskpatienter och minskar därmed risken för över- eller underbehandling. Övergripande syfte med avhandlingen var att utvärdera evidens om sambandet mellan skolios och postural stabilitet vilket skulle kunna påverka behandlingen, att undersöka effektiviteten avseende tre alternativa icke kirurgiska behandlingar för patienter som avböjt dygnskorsett, samt att utveckla en prognostisk modell för framtida risk av ökad krök vid AIS. Metod: Datainsamlingen baserades på en systematisk litteraturöversikt med metaanalys och en randomiserad kontrollerad studie (RCT) för patienter med AIS. Delarbete I granskade litteratur och sammanvägde data från posturografi där postural stabilitet undersöktes för att kunna diagnostisera möjliga skillnader mellan patienter med AIS jämfört med kontrollgrupp (CON). I delarbete II och III lottades patienterna till endera fysisk aktivitet i kombination med nattkorsett (NB), eller skolios-specifik träning (SSE), eller kontrollgrupp med enbart fysisk aktivitet (PA). Effekter på bålrotation, Cobbsvinkel, samt självrapporterad fysisk aktivitet, ryggens utseende och hälso-relaterad livskvalité utvärderades. Likaså följsamhet, motivation och egenförmåga att genomföra behandlingen. Uppföljning utfördes var sjätte månad fram till studiens slut. Slutpunkten definierades som ej progress om kröken ökade med 6° eller mindre vid skelettmognad (mindre än 1 cm längdtillväxt under 6 månader) eller progress om kröken ökade mer än 6° före skelettmo

As our societies have grown larger, and communications have become global and fast-paced, our bodies and minds have been subjected to a mental stress different from the "fight or flight" situations we have adapted to through evolution. Furthermore, mental health issues are now seen to be on the rise all over the world. Globalisation has enabled social crises of different origins, e.g. financial or biological, to influence nations worldwide and spread faster than ever before. This thesis aims to investigate how populations are affected in regard to stress and mental health by the extraordinary circumstances of the global financial crisis of 2008 and the COVID-19 pandemic of 2020-2023. The first two studies in this thesis focus on the effects of the financial crisis on young adults (Paper I) and adults in working ages (Paper II). Greece was severely affected by the global financial crisis of 2008 and went into a decade long recession, whereas Scandinavian countries were less affected. University students were recruited from the psychology and medicine programs in Athens, Greece and Linköping, Sweden. Primary care visitors were recruited consecutively at primary health care centres (PHCC) in Greece, Sweden, and Norway. Data was collected in connection to recruitment. All participants filled out the same short questionnaire and gave hair samples that were analysed for cortisol concentrations (HCC) as a biological measure of stress. Papers III and IV are based on the Healthy OLD-study and investigate mental health, stress, and coping in older adults (70-80 years) during the COVID-19 pandemic. This age group was particularly vulnerable to the virus and therefore subjected to protective restrictions like social isolation. Participants were randomly recruited from five PHCC in south-east Sweden. Data was collected during one visit at the participant’s own PHCC and consisted of a comprehensive questionnaire, biometrics, and samples of blood, hair, and saliva. In Paper III on, I och med att våra samhällen har blivit allt större och vår kommunikation allt snabbare och mer global, så utsätts våra kroppar och sinnen för en mental stress som skiljer sig från de "fight and flight" situationer som vi evolutionärt är anpassade till. Dessutom ökar mental ohälsa över hela världen. Globaliseringen har möjliggjort att sociala kriser av olika slag, t.ex. finansiella eller biologiska, påverkar länder över hela världen och sprids fortare än någonsin tidigare. Den här avhandlingen har till syfte att undersöka hur befolkningen påverkas avseende stress och mental hälsa i samhällen som exponeras för svåra händelser, mer specifikt den globala finansiella krisen 2008 och COVID-19 pandemin 2020–2023. De två första studierna i den här avhandlingen fokuserar på effekterna av finansiell kris på unga vuxna (Studie I) och vuxna i arbetsför ålder (Studie II). Grekland drabbades särskilt hårt av den globala finansiella krisen 2008 och gick in i en recession som varade ett decennium, medan skandinaviska länder blev mindre drabbade. Universitetsstudenter rekryterades från psykolog- och läkarprogrammen i Aten, Grekland, och Linköping, Sverige. Vårdcentralsbesökare rekryterades konsekutivt vid vårdcentraler i Grekland, Sverige och Norge. Data samlades in i samband med rekryteringen. Alla deltagare fyllde i samma korta enkät och gav ett hårprov, vilket analyserades för kortisolkoncentrationer (HCC) som ett biologiskt mått på stress. Studie III och IV baseras på Healthy-OLD-studien och undersöker mental hälsa, stress och coping hos äldre (70–80 år) under COVID-19-pandemin. Denna åldersgrupp var särskilt sårbar för viruset, varför förebyggande restriktioner, som social isolering, i synnerhet riktades mot de äldre. Deltagare rekryterades randomiserat från fem vårdcentraler i sydöstra Sverige. Data insamlades vid ett besök på deltagarnas egna vårdcentraler och utgjordes av en omfattande enkät, biometriska värden, blodprov, hår och saliv. I Studie III användes endast enkäten

Cancer is the second leading cause of death globally and is one of the most pressing health issues today. While significant advances have been made in cancer treatment, drug resistance and toxicity remain formidable obstacles to successful therapy. Thus, there is a need to find novel targets that pave the way for new cancer therapeutics. Ubiquitination, the process of tagging substrate proteins with ubiquitin molecules, regulates many of the pathways that underlie cancer progression. This thesis aims to explore innovative strategies for combating cancer by focusing on crucial elements within the ubiquitination machinery, specifically the Ubiquitin-Proteasome System (UPS) and deubiquitinases (DUBs). In Paper I, we employed the Connectivity Map to discern UPS inhibitors by analyzing the gene expression patterns of various compounds in comparison to those induced by proteasome perturbation. In Paper II, we employed orthogonal methods to identify the primary mechanism for the cytotoxicity of b-AP15. Here, we showed that pharmacologic doses of b-AP15 resulted in strong proteasome inhibition and that cytotoxicity is mediated through the mitochondria and influenced by the proteasome-associated DUB, USP14. In Paper III, we explored the role of USP14 in colorectal cancer cells and evaluated its potential as a cancer target. We found that the genetic deletion of USP14 confers a quiescent phenotype to cancer cells. In Paper IV, we used CRISPR-based screens to search for new deubiquitinase targets. We identified deubiquitinase interactions essential for cancer and explored the possibility of combinatorial deubiquitinase targeting. We pinpointed highly-networked deubiquitinases (PSMD14, USP9X, USP39, and USP7) and deubiquitinase pairs represent promising drug targets. This thesis underscores the importance of the ubiquitination process in the search for novel cancer therapeutics and provides new avenues to explore in developing therapies based on the inhibition of deubiquitinase

Bleeding is a serious and common complication in cardiac surgery. Complicated surgery together with alterations in hemostatic conditions from the use of cardiopulmonary bypass (CPB), presents challenges in how to preserve hemostasis in the patient. CPB is thought to affect platelet function and coagulation in many ways. Before connecting the patient to the CPB system, heparin is used as anticoagulation. With the connection between the patient and the CPB tubing there is a dilution of platelets and coagulation proteins and despite anticoagulation there is an activation of coagulation and inflammation resulting in consumption of coagulation factors and triggering of fibrinolysis. After disconnection of the CPB system, protamine is used to reverse the effect of heparin and restore the coagulation capacity of the patient. When protamine binds to heparin, the anticoagulant effect of heparin is removed but protamine is known to affect both platelet function and coagulation. There is uncertainty about how to best dose protamine to limit the negative effects from protamine without risking remaining heparin effect. A lot is known about how and to what extent cardiac surgery with the use of CPB affect the hemostasis in the patient, but there are still many uncertainties. The aims of this thesis were to examine how platelets are affected by CPB and protamine and to investigate if dosing of protamine had an impact on the risk of remaining or reappearing heparin after cardiac surgery. We also wanted to investigate whether sampling site matters when studying platelet function. In paper I, we found that protamine in vitro interacts with platelets by both a direct activating effect and by a secondary impairment of function when exposed to other activators. The impairment of platelet function from protamine could also be seen in vivo and is described in paper III. In paper III, we also conclude that, in contrast to prior studies, there was no increase in activation in pla

After colectomy there are four options available. The least complicated and most common is to leave the end ileostomy and not go for any reconstructive surgery. Then there is the ileal pouch anal anastomosis (IPAA) in which the rectum is removed, but the anal canal and a small rectal “cuff” is preserved. The pouch is created from the distal ileum and anastomosed to the rectal cuff. In the ileorectal anastomosis (IRA) the rectum is spared, and the distal ileum is anastomosed to the top of the rectum. In the continent ileostomy (CI), also referred to as the Kock pouch, the fecal flow is let out through the abdominal wall, but a pouch and a nipple valve mechanism is created making the stoma continent which needs to be manually emptied. This thesis aims to investigate function, quality of life, satisfaction, complications, and aspects associated with the chance of having reconstructive surgery after colectomy for inflammatory bowel disease (IBD), i.e. ulcerative colitis (UC) or Crohn’s disease (CD). The first two papers focus on the continent ileostomy, the most uncommon of the options after colectomy. In Paper 1 all patients who have received a CI at our center were identified and medical charts were reviewed for complications and CI patency. Function and quality of life were evaluated with the 36-item short form survey (SF-36), short health scale (SHS) and a local CI specific questionnaire for function and satisfaction. In Paper II, the Swedish national patient register (NPR) was used to identify all patients with an IBD diagnosis who had received a CI and data on diagnosis, demographics, reoperations, and excisions were obtained from the register. Paper III describes an ongoing prospective non-randomized, multi-center, open-label, controlled trial between IRA and IPAA in UC patients subjected to colectomy. The primary endpoint is satisfaction but Quality of Life (QoL), sexual function, bowel function and complications are also evaluated. In Paper IV, we invest

IntroductionInternet-based psychological treatments for depression have been around for more than 20 years. There has been a continuous line of research with new research questions being asked and studies conducted.Areas coveredIn this paper, the author reviews studies with a focus on papers published from 2020 and onwards based on a Medline and Scopus search. Internet-based cognitive behavior therapy (ICBT) programs have been developed and tested for adolescents, older adults, immigrant groups and to handle a societal crisis (e.g. COVID-19). ICBT works in regular clinical settings and long-term effects can be obtained. Studies on different treatment orientations and approaches such as acceptance commitment therapy, unified protocol, and tailored treatments have been conducted. Effects on quality-of-life measures, knowledge acquisition and ecological momentary assessment as a research tool have been reported. Factorial design trials and individual patient data meta-analysis are increasingly used in association with internet intervention research. Finally, prediction studies and recent advances in artificial intelligence are mentioned.Expert opinionInternet-delivered treatments are effective, in particular if therapist guidance is provided. More target groups have been covered but there are many remaining challenges including how new tools like artificial intelligence will be used when treating depression., Funding Agencies|Linkoping University

BackgroundFlywheel resistance training has become more integrated within resistance training programs in a variety of sports due to the neuromuscular, strength, and task-specific enhancements reported with this training.ObjectiveThis paper aimed to present the consensus reached by internationally recognized experts during a meeting on current definitions and guidelines for the implementation of flywheel resistance training technology in sports.MethodsNineteen experts from different countries took part in the consensus process; 16 of them were present at the consensus meeting (18 May 2023) while three submitted their recommendations by e-mail. Prior to the meeting, evidence summaries were developed relating to areas of priority. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of flywheel resistance training technology in sports. The process to gain consensus had five steps: (1) performing a systematic review of systematic reviews, (2) updating the most recent umbrella review published on this topic, (3) first round discussion among a sample of the research group included in this consensus statement, (4) selection of research group members-process of the consensus meeting and formulation of the recommendations, and (5) the consensus process. The systematic analysis of the literature was performed to select the most up-to-date review papers available on the topic, which resulted in nine articles; their methodological quality was assessed according to AMSTAR 2 (Assessing the Methodological Quality of Systematic Review 2) and GRADE (Grading Recommendations Assessment Development and Evaluation). Statements and recommendations scoring 7-9 were considered appropriate.ResultsThe recommendations were based on the evidence summary and researchers' expertise; the consensus statement included three statements and seven recommendations for the use of flywheel resistance training technology. Thes, Funding Agencies|Spanish Ministry of Science and Innovation [RYC2021-031072-I]; State Research Agency (AEI); European Union (NextGenerationEU/PRTR)

Not all ad blockers achieve the same blocking success and, depending on their implementation, they can either improve or hurt the web performance experienced by users. Borgolte and Feamster (2020) recently provided the first extensive evaluation of how privacy-focused browser extensions affect a users web performance. However, while their work provides a nice comparison of the performance impact that different extensions may have, their evaluation only considered landing pages of a single set of websites. In this paper, we focus specifically on performance comparisons when considering different sets of webpages. For example, we study the impact of whether a page is a landing page or an internal page, whether a page is popular or less popular, as well as the impact of in which country/region the company registering the website is operating (used as a proxy for the primary target market). For our evaluations, we use pairs of webpages carefully selected from the recently proposed Hispar list (Aqeel et al. 2020) and compare the performance of the most popular blocking extensions (Adblock Plus, uBlock Origin, Ghostery, and Private Badger) considered by Borgolte and Feamster with a baseline case in which we do not use any extension. While we observe clear differences in the distribution statistics of the metrics considered, several observations were consistent across all dimensions, including whether we consider landing pages or internal pages. The paper highlights some of these invariants and discusses their implications. In addition, our measurements (and the differences observed by different adblockers) also reveal new insights into how internal vs. landing pages of different webpage categories (e.g., based on popularity or region) differ in their composition and resource usage.

In this paper, we compare the performance of two BERT-based text classifiers whose task is to classify patients (more precisely, their medical histories) as having or not having implant(s) in their body. One classifier is a fully-supervised BERT classifier. The other one is a semi-supervised GAN-BERT classifier. Both models are compared against a fully-supervised SVM classifier. Since fully-supervised classification is expensive in terms of data annotation, with the experiments presented in this paper, we investigate whether we can achieve a competitive performance with a semi-supervised classifier based only on a small amount of annotated data. Results are promising and show that the semi-supervised classifier has a competitive performance when compared with the fully-supervised classifier., Funding Agencies|Vinnova (Swedens innovation agency) [2021-01699]

The COVID-19 pandemic has had a global impact om society. Different countries and organizations have chosen different approaches to manage this crisis. This paper aims to describes how public Swedish actors (county administrative boards, municipalities, and regional councils) evaluated their management of the COVID-19 pandemic. Also, the paper aims to suggest improvements for crisis management strategies. Applying a meta-evaluation approach to open reports from the public organizations means collecting evaluation reports, determining if they fit the inclusion criteria, and if so, include them in the analysis. Included reports were categorized and given points indicating different types of merits. In addition, a thematic analysis of conclusions was conducted. 110 evaluation reports from 98 different organizations are included in the analysis. The importance of evaluating, having a structure for data collection, analysis, and reporting is reflected in the quality of the reports. Four identified themes offer an understanding of areas in need for development among Swedish regional councils, municipalities, and county administrative boards.

Today, electrification is a widely discussed topic within all fields of engineering and especially in the field ofaeronautics. Whether electrification of aircraft systems is the only viable option to overcome environmentalissues is a highly complex question which involves many aspects. In this paper, fundamental differences between electrified and hydraulic aircraft actuators are mapped, compared and discussed to understand how andif these systems can be compared without misleading results. In this paper, different actuator architectures were collected from literature, classified and analyzed by usingan ontological approach. The classification was created by utilizing defined classes where the class definitioncorresponded to the functional requirements which had to be fulfilled by the actuator architecture. This work has shown that ontologies can sufficiently be used for classification of actuator architectures. Thebuilt in reasoner can be used to sort a large set of actuators into comparable classes. Meanwhile, the ontologydefines a framework where important information of the actuators and their components can be stored andstructured.

BackgroundIn a previous paper in Philos Ethics Humanit Med, the 1937 Swedish novel Somnlos (Swedish for sleepless) by Vilhelm Moberg was used as background for a thought experiment, in which last centurys progresses concerning the safety of sleeping pills were projected into the future. This gave rise to a theoretical discussion about broad medico-philosophical questions such as (among other things) the concept of pharmaceuticalisation.MethodsIn this follow-up paper, the theme of insomnia in Somnlos is complemented by a discussion of the concept of nostalgia. The core of the paper is a theoretical discussion about the benefits and risks of nostalgia, bringing together some aspects of recent psychological research about the construct of nostalgia with the main story line of the novel.Results and ConclusionNostalgia is portrayed as being, in some sense at least, ultimately beneficial for the protagonist of Somnlos. This is congruent with recent psychological research. However, the story also shows that nostalgia may lead to problematic behaviours, at least when viewed from a virtue ethics perspective. Hence, nostalgia is both what leads the protagonist into ethically problematic behaviour and that which (paradoxically) ultimately saves him from his initial lack of courage, justice, temperance and practical wisdom. Moreover, the protagonist does not only "grow" ethically but also existentially. Hence, the novel opens up the possibility that insomnia and nostalgia might be viewed as bearers of important existential information (cf. sociologist of religion Peter L. Berger and his concept of "signals of transcendence").