Artros - en sjukdom som drabbar både djur och människa, en komparativ studie med kaninen som modelldjur.

SAMMANFATTNING Artros och skador i ledbrosk är vanliga problem hos både människor och djur, som orsakar stora fysiska besvär i form av smärta och nedsatt rörelseförmåga. Idag finns ett flertal olika behandlingsmetoder mot artros, men ännu finns ingen bra behandlingsmetod för att åstadkomma läkning av ett skadat ledbrosk. I den här studien användes kanin som modelldjur för att utvärdera en ny behandling mot artros på människa. Målet var att stimulera nybildning av ledbrosk via rekrytering av mesenkymala stamceller. Studien utfördes på 20 kaniner av rasen New Zeeland White, 6-7 månader gamla honor med en kroppsvikt på ca 4 kg. En ledskada skapades med borr på den mediala femurkondylen i kaninernas vänstra knäled under anestesi. Därefter injicerades en hyaluronsyragel enbart eller tillsammans med tillväxtfaktorn bone morphogenic protein-2 (BMP-2) i leden. En likadan skada skapades i den högra knäleden, men i denna injicierades istället koksaltlösning som kontrollbehandling. De två första veckorna postoperativt undersöktes kaninerna dagligen avseende allmäntillstånd och vikt. Knälederna undersöktes särskilt efter tecken på infektion och graden av hälta uppskattades på en 4-gradig skala. Efter tre månader (n=5) och sex månader (n=10) avlivades kaninerna och knälederna undersöktes histologiskt samt med magnetkamera (MRI) för att utvärdera nybildning av ledbrosk. Studien utgör den kliniska delen av forskningsprojektet och i detta arbete presenteras resultaten från operationen och den postoperativa perioden.SUMMARY Osteoarthritis and articular cartilage lesions are common problems affecting both people and animals, causing large amounts of pain and functional disability. Many different strategies have been used to treat osteoarthritis, but no good treatment to accomplish regeneration of damaged articular cartilage is available today. In this study rabbits were used as a model for finding a new treatment against osteoarthritis in humans. The goal was to stimulate regeneration of damaged articular cartilage by recruitment of mesenchymal stem cells from subchondral bone. The study was performed on 20 New Zealand White rabbits. A cartilage defect was induced on the medial femoral condyle in the left knee joint. The defects were treated with hyaluronan hydrogel containing the growth factor bone morphogenic protein-2 (BMP-2) or hyaluronan hydrogel itself. The same defect was induced in the rabbits’ right knee joint which was injected with isotonic saline to serve as a control. The first weeks postoperatively the rabbits were examined every day. The knees were examined for signs of infection and the grade of lameness was estimated on a scale from 0 to 3. After surgery the animals were kept for three months (n=5) or six months (n=10) until they were euthanized. A pathological examination and a magnetic resonance imaging (MRI) of the knee joints were performed to evaluate the regeneration of articular cartilage. The study is a part of a larger research project and in this assignment the results from the clinical part are presented

Sharing is caring: integrating health information systems to support patient-centred shared homecare

In the light of an ageing society with shrinking economic resources, deinstitutionalization of elderly care is a general trend. As a result, homecare is increasing, and increasingly shared between different health and social care organizations. To provide a holistic overview about the patient care process, i.e. to be patient-centred, shared homecare needs to be integrated. This requires improved support for information sharing and cooperation between different actors, such as care professionals, patients and their relatives. The research objectives of this thesis are therefore to study information and communication needs for patient-centered shared homecare, to explore how integrated information and communication technology (ICT) can support information sharing, and to analyze how current standards for continuity of care and semantic interoperability meet requirements of patient-centered shared homecare. An action research approach, characterized by an iterative cycle, an emphasis on change and close collaboration with practitioners, patients and their relatives, was used. Studying one specific homecare setting closely, intersection points between involved actors and specific needs for information sharing were identified and described as shared information objects. An integration architecture making shared information objects available through integration of existing systems was designed and implemented. Mobile virtual health record (VHR) applications thereby enable a seamless flow of information between involved actors. These applications were tested and validated in the OLD@HOME-project. Moreover, the underlying information model for a shared care plan was mapped against current standards. Some important discrepancies were identified between these results and current standards for continuity of care, stressing the importance of evaluating standardized models against requirements of evolving healthcare contexts. In conclusion, this thesis gives important insights into the needs and requirements of shared homecare, enabling a shift towards patient-centered homecare through mobile access to aggregated information from current feeder systems and documentation at the point of need

"You have to know why you're doing this" : a mixed methods study of the benefits and burdens of self-tracking in Parkinson's disease

Background: This study explores opinions and experiences of people with Parkinson's disease (PwP) in Sweden of using self-tracking. Parkinson's disease (PD) is a neurodegenerative condition entailing varied and changing symptoms and side effects that can be a challenge to manage optimally. Patients' self-tracking has demonstrated potential in other diseases, but we know little about PD self-tracking. The aim of this study was therefore to explore the opinions and experiences of PwP in Sweden of using self-tracking for PD. Method: A mixed methods approach was used, combining qualitative data from seven interviews with quantitative data from a survey to formulate a model for self-tracking in PD. In total 280 PwP responded to the survey, 64% (n = 180) of which had experience from self-tracking. Result: We propose a model for self-tracking in PD which share distinctive characteristics with the Plan-Do-Study-Act (PDSA) cycle for healthcare improvement. PwP think that tracking takes a lot of work and the right individual balance between burdens and benefits needs to be found. Some strategies have here been identified; to focus on positive aspects rather than negative, to find better solutions for their selfcare, and to increase the benefits through improved tools and increased use of self-tracking results in the dialogue with healthcare. Conclusion: The main identified benefits are that self-tracking gives PwP a deeper understanding of their own specific manifestations of PD and contributes to a more effective decision making regarding their own selfcare. The process of self-tracking also enables PwP to be more active in communicating with healthcare. Tracking takes a lot of work and there is a need to find the right balance between burdens and benefits.FORTE, the Swedish Research Council for Health, Working Life and Welfare, grant number 2014-4238Vinnova, the Swedish Governmental Agency for Innovation SystemsPublishe

Meeting the burden of self-management : qualitative study investigating the empowering behaviors of patients and informal caregivers

Background: Patient empowerment is an important concept and a movement toward person-centered care of patients with chronic conditions. Nevertheless, to date, most research on empowered patients or informal caregivers has been conducted from a narrow clinical perspective. Such research has mainly focused on how health care professionals can empower patients to increase self-care or compliance with treatment. Research on empowered patient and informal caregiver needs and self-empowering activities is scarce. Objective: We aimed to explore empowering behaviors from a patient and informal caregiver perspective in the context of self-management and to understand how health care can support such behaviors better. Methods: We used an exploratory, qualitative study design. A total of 15 semistructured interviews and 6 focus group interviews were conducted with 48 patients and informal caregivers. We analyzed the interviews using thematic analysis and used a directed content analysis to analyze the focus group interviews. Results: A total of 14 patterns of empowering behaviors were identified that were characterized by several exploratory and influencing activities performed by the participants. The participants expressed a desire to be more active in their care than what is expected and supported by health care professionals. The participants also desired better support for activities imposed on them by health care professionals. Conclusions: To enable a transformation of the health care system to better support self-empowering behaviors, there is a need to develop self-management approaches from a patient and informal caregiver perspective.Vinnova, the Swedish Governmental Agency for Innovation Systems (grant 2017-01221)Forte, the Swedish Research Council for Health, Working Life and Welfare (grant 2016-07324 and grant 2018-01472)Publishe

From information seekers to innovators : qualitative analysis describing experiences of the second generation of e-patients

Background: Current health care systems are rarely designed to meet the needs of people living with chronic conditions. However, some patients and informal caregivers are not waiting for the health care system to redesign itself. These individuals are sometimes referred to as e-patients. The first generation of e-patients used the internet for finding information and for communicating with peers. Compared with the first generation, the second generation of e-patients collects their own health data and appears to be more innovative. Objective: The aim of this study was to describe the second generation of e-patients through exploration of their active engagement in their self-care and health care. Methods: Semistructured interviews were conducted with 10 patients with chronic conditions and 5 informal caregivers. They were all recruited through a Web-based advertisement. Data were analyzed according to the framework analysis approach, using the 3 concepts of the self-determination theory-autonomy, relatedness, and competence-at the outset. Results: Study participants were actively engaged in influencing their self-care and the health care system to improve their own health, as well as the health of others. This occurred at different levels, such as using their own experience when giving presentations and lectures to health care professionals and medical students, working as professional peers in clinical settings, performing self-tracking, contributing with innovations, and being active on social media. When interaction with health care providers was perceived as being insufficient, the participants sought support through their peers, which showed strong relatedness. Competence increased through the use of technology and learning experiences with peers. Their autonomy was important but was sometimes described as involuntary and to give up was not an option for them. Conclusions: Like the first generation of e-patients, the participants frequently searched for Web-based information. However, the second generation of e-patients also produce their own health data, which they learn from and share. They also engage in the innovation of digital tools to meet health-related needs. Utilizing technological developments comes naturally to the second generation of e-patients, even if the health care system is not prepared to support them under these new circumstancesVinnova, the Swedish Governmental Agency for Innovation Systems (grant number 2017-01221)Publishe

The Limits of Lawyering: Legal Opinions in Structured Finance

Significant controversy surrounds the issuance of legal opinions in structured finance transactions, particularly where accountants separately use these opinions, beyond their traditional primary use, for determining whether to characterize the transactions as debt. Reflecting at its core the unresolved boundaries between public and private in financial transactions, this controversy raises important issues of first impression: To what extent, for example, should lawyers be able to issue legal opinions that create negative externalities? Furthermore, what should differentiate the roles of lawyers and accountants in disclosing information to investors? Resolution of these issues not only helps to demystify the mystique, and untangle the morass, of legal-opinion giving but also affects the very viability of the securitization industry, which dominates American, and increasingly global, financing

The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage

The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue. This tyrosine and key residues surrounding the oxygen pocket are conserved in enzymes from related bacteria, including pathogens such as Staphylococcus aureus. Photo-sensitivity may thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria

The barley grain thioredoxin system - an update.

Thioredoxin reduces disulfide bonds and play numerous important functions in plants. In cereal seeds, cytosolic h-type thioredoxin facilitates the release of energy reserves during the germination process and is recycled by NADPH-dependent thioredoxin reductase. This review presents a summary of the research conducted during the last ten years to elucidate the structure and function of the barley seed thioredoxin system at the molecular level combined with proteomic approaches to identify target proteins

Effects of exergaming on exercise capacity in patients with heart failure: results of an international multicentre randomized controlled trial

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