The severity of illness was scored in a cohort of 11751 non-surgical patients presenting at the Emergency Department (ED) during 12 consecutive months and followed for 4.7 years. The scoring system Rapid Acute Physiology score (RAPS) (including blood pressure, respiratory rate, pulse rate and Glasgow coma scale) was calculated for all arrivals at the ED. The RAPS system was also additionally developed by including the peripheral oxygen saturation and patient age, resulting in the new Rapid Emergency Medicine Score, (REMS). REMS was superior to RAPS in predicting in-hospital mortality according to ROC-curve analysis. An increase of one point in the 26 point REMS scale was associated with an Odds ratio of 1.40 for in-hospital death (95% CI 1.36-1.45, p<0.0001). Similar results were obtained in the major patient groups (chest pain, stroke, coma, dyspnea and diabetes). The association between REMS and length of stay in hospital was modest. Charlson Co-morbidity Index could add prognostic information to REMS in a long-term (4.7 years), but not in a short-term perspective (3 and 7 days). REMS was shown to be as powerful a predictor of in-hospital mortality as the more complicated APACHE II. REMS at the ED could also predict long-term mortality (4.7 years) in the total cohort (Hazard ratio 1.26, p<0.0001). REMS is a potentially useful prognostic tool for non-surgical patients at the ED, regarding both in-hospital and long-term mortality. It is less complicated to use than APACHE II and has equal predictive accuracy.

Moisturizers are used in various types of dry skin disorders, but also by people with healthy skin. It is not unusual that use of moisturizers is continued for weeks, months, or even years. A number of moisturizers have been shown to improve the skin barrier function, while others to deteriorate it, but the reason for observed effects remains unknown. Further understanding of the mechanism by which long-term treatment with moisturizers influences the skin barrier would have clinical implications, as barrier-deteriorating creams may enhance penetration of allergens or irritants and predispose to dry skin and eczema, while barrier-improving ones could reduce many problems. The present research combined non-invasive techniques with analyses of skin biopsies, allowing studies of the epidermis at molecular and cellular level. Test moisturizers were examined on healthy human volunteers for their effect on the skin barrier, with regard to such factors as pH, lipid type, and presence of a humectant, as well as complexity of the product. After a 7-week treatment with the moisturizers, changes in transepidermal water loss, skin capacitance, and susceptibility to an irritant indicated a modified skin barrier function. Moreover, the mRNA expression of several genes involved in the assembly, differentiation and desquamation of the stratum corneum, as well as lipid metabolism, was altered in the skin treated with one of the moisturizers, while the other moisturizer induced fewer changes. In conclusion, long-term use of moisturizers may strengthen the barrier function of the skin, but also deteriorate it and induce skin dryness. Moisturizers have also a significant impact on the skin biochemistry, detectable at molecular level. Since the type of influence is determined by the composition of a moisturizer, more careful selection of ingredients could help to design moisturizers generating a desired clinical effect, and to avoid ingredients with a negative impact on the skin.

In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy. The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances. In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer. Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals. Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated. / Under de senaste årtiondena har insjuknandet i hudcancer ökat dramatiskt i västvärlden, detta till stor del beroende på förändrade solvanor. Exponering för solens ultravioletta strålning (UVstrålning) samt den individuella ljuskänsligheten i huden utgör två viktiga faktorer av betydelse för uppkomsten av hudcancer. Individer med ökad benägenhet att bli rödbrända i solen löper också ökad risk för hudcancer av solexponering, och behöver således vara extra noga med att skydda sig mot solen. Hur känslig man är mot solljuset kan bedömas antingen genom självskattning (klassificering enligt Fitzpatrick), eller genom att använda ett ljustest. Det sistnämnda är en betydligt mer objektiv metod, men används ändå relativt sparsamt, sannolikt ofta beroende på brist på resurser, tid eller klinisk rutin. Det övergripande syftet med avhandlingen var att utveckla och förbättra aspekter på ljustestningsförfarandet med inriktning på att kunna bredda användningen av ljustest inom forskning, klinisk verksamhet och hudcancerprevention. Som ett första steg undersöktes och utvärderades en ny ljustestteknik, baserad på en divergent (spridd) UV-stråle. Genom att belysa huden med ett cirkulärt UV-ljusfält framkallas en cirkulär rodnad (erytem), där diametern på rodnaden står i relation till den individuella ljuskänsligheten i huden. I jämförelse med traditionell ljustestningsmetodik visade sig metoden resultera i en noggrannare uppskattning av ljuskänslighet, samt möjligheten att beskriva ett dos-responsförhållande inom det rodnade hudområdet. Eftersom kanten på den framkallade rodnaden tenderade att bli ganska diffust avgränsad framkom dock, med undantag för speciellt tränade avläsare, svårigheter att läsa av testet med enbart ögats hjälp. Av den anledningen krävdes mer objektiv, hudfysiologisk mätmetodik. I de genomförda studierna användes så kallad Laser Doppler perfusion imaging (LDPI) för detta. Förutom uppskattning av ljuskänsligheten testades den divergenta UV-strålen också som modell för skattning av anti-inflammatorisk effekt av ämnen som appliceras på huden, exempelvis cortison, och visade sig användbar för detta. I syfte att öka förutsättningarna för bredare användning av ljustest, genomfördes en studie där försökspersonerna själva fick avläsa ett traditionellt ljustest och rapportera in testresultatet. Resultaten jämfördes med avläsningar utförda av en kunnig avläsare, och visade på god tillförlitlighet. Slutligen, med hjälp av den beskrivna självavläsningsproceduren, undersöktes i en primärvårdspopulation, om ljustestning kan vara användbart för att förebygga hudcancer, med inriktning på att påverka individers solvanor, solskyddsbeteende och attityder gentemot solning. I studien jämfördes även olika modeller för att presentera ett preventionsbudskap, och där ett muntligt sådant, förmedlat vid ett läkarbesök, hade ett betydligt bättre genomslag än motsvarande, enbart skriftlig, information. För individer med hög ljuskänslighet bidrog ljustestet till ökat solskyddsbeteende, vilket indikerar att ljustest skulle kunna vara ett användbart verktyg i eftersträvan att förebygga hudcancer speciellt i denna grupp av individer med förhöjd hudcancerrisk. Sammanfattningsvis utgör ljustestning med divergent UV-stråle, självavläsning av ljustest samt användning av ljustest vid hudcancerprevention tre nya, tidigare sparsamt undersökta aspekter på ljustestning, för vilka den här avhandlingen visar lovande resultat.

Neural stem cells are the precursors of neurons, astrocytes and oligodendrocytes. During neural development, the division of stem cells takes place close to the lumen of the neural tube, after which they migrate to their final positions within the central nervous system (CNS). Soluble factors, including growth factors, regulate neural stem cell proliferation, survival, migration and differentiation towards specific cell lineages. This thesis describes the function of platelet-derived growth factor (PDGF) and stem cell factor (SCF) in neural stem cell regulation. PDGF was previously suggested to stimulate neuronal differentiation, but the mechanisms were not defined. This study shows that PDGF is a mitogen and a survival factor that expands a pool of immature cells from neural stem cells. The PDGF-treated cells can be stained by neuronal markers, but need further stimuli to continue their maturation. They can become either neurons or glia depending on the secondary instructive cues. Moreover, neural stem cells produce PDGF. Inhibition of this endogenous PDGF negatively affects the cell number in stem cell cultures. We find that SCF stimulates migration and supports the survival of neural stem cells, but that it has no effect on their proliferation or differentiation into neurons and glia. Intracellular signaling downstream from the receptors for PDGF and SCF includes activation of extracellular signal-regulated kinase (ERK). This investigation shows that active ERK is not needed for the differentiation of stem cells into neurons, at least not during early stages. Neural stem cells have a future potential in the treatment of CNS disorders. To be able to use neural stem cells clinically we need to understand how their proliferation, differentiation, survival and migration are controlled. The results presented in this thesis increase our knowledge of how neural stem cells are regulated by growth factors.

No description available.

<p>Socioeconomic inequalities in health and disability are found in all countries where social gradients have been studied. Despite rapid economic growth and expanding health care systems, aiming at providing services to people according to need rather than according to wealth, persistent and even widening health inequalities are found in Europe after the second World War.</p><p>In this research project we wanted to establish a method for measuring socioeconomic status based on occupational groups and education in the HUNT Study, thereby providing tools for research in social medicine. A social gradient scale based on the occupational grouping from the HUNT study questionnaires had not been established. When this study was planned however, educational level, which might serve as a proxy for socioeconomic status, had been monitored in both HUNT I and HUNT II.</p><p>Disability pension has been a central element in social security legislation in Norway, established as a universal right for all citizens in 1967. This public income-maintenance program protects workers in case of disability, and comprises both universal and earningrelated programs. The main eligibility criterion has been permanent impaired earning ability by at least 50 % for reasons of illness or disease, injury or disability. Despite objective health improvement in the population the last decades, incidence of disability pension has increased.</p><p>In epidemiology, socioeconomic status is not only an important variable in itself. It is also a confounder that should be taken into consideration in discussing almost all causal relationships. Thus, in population based health studies, measures of socio-economic status are essential. Occupation, education and income together determine the socioeconomic status of a person. However, these factors are sufficiently distinct to require that they should also be studied separately in relation to health. To study them separately is often preferable since this can suggest hypotheses on causal relationships between exposure and disease.</p>

<p>Atherosclerosis is a progressive inflammatory disease that is characterized by the accumulation of lipids, infiltrated cells and fibrous elements in large arteries.</p><p>This thesis focuses on the molecular mechanisms behind foam cell formation and inflammation, two central processes in the development of atherosclerosis. More specific, we studied the effects of proinflammatory cytokines on CXCL16 expression and its role as scavenger receptor on macrophages and smooth muscle cells in atherogenesis. CXCL16 is defined as a chemokine and a scavenger receptor, regulating adhesion and chemoattraction of CXCR6 expressing cells and uptake of oxLDL. We show that the expression of CXCL16 and its receptor CXCR6 are more pronounced in human atherosclerotic lesions compared with non-atherosclerotic vessels. Increased expression of CXCL16 was also seen in atherosclerotic aortas of apoE-/- mice compared with aortas of non-atherosclerotic, age-matched C57BL/6 mice. In vitro, IFN gamma induced CXCL16 expression in primary human monocytes and smooth muscle cells which resulted in an increased uptake of oxLDL. Treatment of mice with IFN gamma also induced CXCL16 expression in atherosclerotic lesions. Thus, we have demonstrated a role for IFN gamma in foam cell formation through upregulation of CXCL16. The expression of CXCR6 was defined to the same regions as for CXCL16 in the lesion, indicating the presence of cells able to respond to CXCL16. Consequently, CXCL16 could serve as a molecular link between lipid metabolism and immune activity in atherosclerotic lesion.</p><p>CD137 belongs to the TNF family and mediates several important processes in inflammation. CD137 is involved in the activation of T cells, NK cells, B cells and monocytes and regulate cytokine production, proliferation and apoptosis in these cells. A limited number of studies have demonstrated CD137 expression on smooth muscle cells and endothelial cells. Our results show that CD137 mRNA is higher expressed in human atherosclerotic lesions compared with unaffected vessels. We found that endothelial cells express CD137 in atherosclerotic lesions and that cultured endothelial cells and smooth muscle cells express CD137 and CD137 ligand in vitro. CD137 was regulated differentially by proinflammatory cytokines (i.e. IFN gamma, TNF alpha, IL-1 beta) and bacterial lipopolysaccharide depending on cell type. Furthermore, we investigated the effects of CD137 signalling, demonstrating that binding of the CD137 ligand to its receptor increases proliferation and migration of smooth muscle cells.</p><p>In summary, this thesis has focused on the expression, regulation and role of CXCL16 and CD137, two genes that have not been described earlier in the concept of atherosclerosis. The findings demonstrate some of the molecular mechanisms involved in vascular inflammation and may increase our knowledge about the development of atherosclerosis.</p>

<p>Irradia AB tillverkar och säljer terapeutiska, kirurgiska och kosmetiska lasrar. Företaget har hittills inte lyckats skapa utbyte med den offentliga sjukvårdsmarknaden. Syftet med undersökningen var därför att analysera och utvärdera hinder för Irradia AB:s introduktion på den offentliga svenska sjukvårdsmarknaden. Fokus lades på de terapeutiska lasrarna. På grund av undersökningsområdets natur gjordes en separation av mega- och marknadsnivå. På meganivån undersöktes ett expertnätverk, som skall acceptera nya medicinsktekniska produkter inom sitt verksamhetsområde, och på marknadsnivån undersöktes Irradia AB och den offentliga sjukvårdsmarknaden. </p><p>Författarna valde fallstudien som metod. För att samla in primärdata ansåg författarna att intervjuer var den mest relevanta metoden. På marknadsnivån intervjuades Lars Hode, VD för Irradia AB, och Jan Svenonius, tidigare upphandlingschef på Huddinge sjukhus och Mikael Wickström, upphandlingschef, Karolinska Universitetssjukhuset. På meganivån fick Audio Laser-Kliniken representera Irradia, då företagets produkter används till behandling av hörselsjukdomar på kliniken. Med hjälp av ett anvisningsurval lyckades författarna snabbt identifiera och intervjua respondenter som varit kritiska till behandlingsformen som tillämpas på kliniken. </p><p>Analysen på meganivån genomfördes utifrån nätverksteorin, teorin om idésystem och socialpsykologi. I analysen på marknadsnivån tillämpades konkurrensstrategier, involveringsteorin, faktorer som påverkar köpbeslut och nätverksteorin. </p><p>Resultatet visar att Irradia möter hinder på marknadsnivån, framför allt när det gäller relationers betydelse i upphandlingsprocessen. Irradia AB har goda förutsättningar för att bemästra de flesta hindren, men relativt lite nätverkande har varit svagheten i den strategi som tillämpats hittills. Resultatet på meganivån visar att aktörerna anser att Mikael Bäckmans verksamhet på Audio Laser-Kliniken inte svarar mot vetenskap och beprövad erfarenhet. Därmed har experterna kunnat förklara laserbehandling av hörselsjukdomar som illegitim. Undersökningen visar dock att andra behandlingsmetoder på hörselområdet inte möter samma krav utifrån vetenskap och beprövad erfarenhet. Resultatet visar framför allt att liten tilltro till produkterna i expertnätverket sänker möjligheten till utbyte med den offentliga sjukvården. </p><p>Frågeställningen hade fokus på faktorer som är viktiga för nyetablerare på sjukvårdsmarknaden. Slutsatserna är att differentiering kan vara en lämplig strategi för företag med små resurser, och att utbildning som mervärde kan vara lämpligt om produkterna är komplexa. Nyetablerare bör satsa på löpande bearbetning av aktörer både på mega- och marknadsnivå. Undersökningen tyder dock på att bearbetningen på meganivå bör ske i första hand, för att nyetablerare skall kunna sälja nya produkter på den offentliga sjukvårdsmarknaden. </p> / <p>Irradia AB is a manufacturer and seller of medical, surgical and cosmetical laser instruments. So far the company has failed in establishing exchange with the public health services in Sweden. The purpose of this studie was to analyse and evaluate obstacles in the way of Irradias introduction on the public health service market. The medical lasers were chosen as the primary products to study. Due to the nature of the area of investigation, mega level marketing was separated from the market level. On the mega level, new and complex medical products must be approved by experts. On the market level, a comparison was made between Irradia and the public health service market. </p><p>The case study was chosen as a main method. Qualitative primary data was collected by interviewing. On the market level, interviews were conducted with Lars Hode, managing director of Irradia AB, Jan Svenonius, former director of purchasing at Huddinge Sjukhus and Mikael Wickström, director of purchasing at Karolinska Sjukhuset. On the mega-level, Audio Laser-Kliniken was chosen to represent Irradia, since their medical lasers are used for treatment of hearing disorders at the clinic. By using directive selection, the authors could quickly identify and interview persons who are negative when it comes to laser treatment of hearing disorders. </p><p>Competitive strategies, the involvement theory, network theory and factors influencing buyer behavior were applied in the market level analysis. The mega level analysis is based on the network theory, the theory of dominant ideas and social psychology. </p><p>Results of the market level analysis show that relations are of great importance in public health service purchasing processes. Irradia meets most of the basic conditions that are required for establishing exchange with the public health service market, but a relatively low degree of networking has been a flaw in the strategy that Irradia has had so far. Results of the mega level analysis show that the laser treatment of hearing disorders at Audio Laser-Kliniken does not comply with the requirements for an evidence-based medicine, according to the interviewees. Therefore laser treatment of hearing disorders has been announced illegitimate by the experts. The results also show that other treatment forms of hearing disorders can be difficult to evaluate regarding to the requirements of an evidence-based medicine. The results show, above all, that any possible distrust to the products among experts will have a negative impact on the possibility to establish exchange with the public health service market. </p><p>The question at issue focused on factors that are of importance for companies trying to establish exchange with the public health service market. Conclusions of the study show that differentiation can be a suitable strategy for establishers with new products, and that customer academies can be a relevant way to reduce risks if the products are complex. New companies should try to create relations on both the mega level and market level. The study shows that relations with experts on the mega level are critical for companies trying to sell new products to the public health service market. </p>

<p>The main purpose of this thesis was to apply the WHO and NHS palliative care approach to dementia care. </p><p>Thirty-one staff-members in mid-Sweden (studies I and II) and 20 next-of- kin (study IV) were interviewed. In study III, 316 staff-members from dementia care and 121 staff-members from palliative cancer care responded to a questionnaire about family support. The interviews were tape-recorded and analysed with a qualitative phenomenographic (I and II) and a hermeneutic approach (IV). The questionnaires (III) were analysed using qualitative and quantitative content analysis.</p><p>The staff-members stated almost unanimously that daily leadership was lacking, and consequently clear goal formulations and care planning were rare (I). Proper teamwork between the doctor and the staff who worked on a daily basis with the patients was absent (I). With respect to existential issues, education and staff discussions were lacking (II). The staff were at a loss concerning how to deal with these issues. Nevertheless, these issues are central to family-members who have to deal with an existential crisis (IV). Important questions emerged about obligation and guilt, faithfulness, responsibility, and paying back what you once received. Existential isolation could be identified e.g. in the reversal of roles experienced as "being a parent to your parent" and in the burden of "visiting a living dead person". </p><p>There were no routines for bereavement visits. The type of support suggested for dementia family members is partly similar to support in palliative cancer care, but it also differs in other respects such as feelings of guilt because the early signs of the disease are misunderstood, the need for respite because of the long trajectory of dementia diseases, and the occurrence of anticipatory grief because in the late phase family members can no longer make any contact at all with the patient (III).</p><p>A palliative approach can improve the quality of life for the dementia patient and for the family. It can be used as a basis for a clear goal formulation. Some of the suggestions listed in this thesis for improving the quality of care are more a reflection of the need for a change in attitudes rather than the need for substantial budget increases.</p>

<p>Heart failure and left ventricular dysfunction are major causes of morbidity and mortality. In this thesis, metabolic, hormonal, genetic and prognostic aspects of echocardiographically determined left ventricular function were investigated in a fairly large longitudinal population-based study of men. The participants were examined both at age 50 and 70 years and were followed for mortality using the national cause-of-death registry.</p><p>Several factors associated with the insulin resistance syndrome predicted left ventricular systolic dysfunction independent of myocardial infarction, hypertension, diabetes and the use of cardiovascular medication after twenty years follow-up. Plasma levels of N-terminal atrial natriuretic peptide (N-ANP) were significantly increased in men with left ventricular dysfunction in comparison to healthy men. However, the diagnostic accuracy was poor due to the extensive overlapping between the groups. Relations between a haplotype of the novel hUNC-93B1 gene and the E/A-ratio were found and validated in separate samples of the cohort. Myocardial performance index (a Doppler derived index of combined left ventricular systolic and diastolic function) and left ventricular ejection fraction were found to be predictors for cardiovascular mortality independent of traditional cardiovascular risk factors in a longitudinal analysis with a mean follow-up of seven years.</p><p>In conclusion, this thesis showed that left ventricular function is influenced by metabolic, hormonal and genetic factors and that echocardiographic measurements of left ventricular function, such as the myocardial performance index, are strong independent risk factors for cardiovascular mortality in elderly men.</p>