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. 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. Analysen på meganivån genomfördes utifrån nätverksteorin, teorin om idésystem och socialpsykologi. I analysen på marknadsnivån tillämpades konkurrensstrategier, involveringsteorin, faktorer som påverkar köpbeslut och nätverksteorin. 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. 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. / 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. 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. 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. 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. 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.

Chlamydia trachomatis (CT) can cause infertility and is the most common sexually transmitted infection (STI) of bacterial origin in Europe. Surveys in seven countries estimated a population prevalence of 1.4-3.0 % in people 18 to 44 years. Approximately 87% of those diagnosed in Sweden are 15-29 years. Since 1997, with the exception of 2009-2010, despite all efforts, CT has increased steadily in many European countries including Sweden. That made us investigate risk factors associated with catching STIs, especially CT. In Sweden partner notification is mandatory by law when a patient is diagnosed with CT. Centralised partner notification, performed by a few experienced counsellors, and evaluation of the sexual history for at least 12 months back in time, shows superior results compared to other studies. Phone-interviews are a good option in remote areas. “The Västerbotten model” for partner notification fulfils these criteria and our evaluation has functioned as a model for changing recommendations of partner notification in Sweden. Preventing CT by primary prevention such as information and counselling is, however, still of great importance. We investigated whether it was necessary to test for CT in the throat. We found that patients testing positive for pharyngeal CT neither had more symptoms or signs nor a sexual history that differed from others. We therefore believe that we will find most or all of these patients by conventional testing of urine and cervical/vaginal samples. We wanted to further identify risk factors among patients attending a clinic for sexually transmitted infections to enable individualized care depending on risk. None or inconsistent use of condoms with new/temporary partners in combination with having at least one new/temporary partner within the past 6 months could identify persons with risk behaviour and at increased risk of CT (re)infection. Additional information about whether the condom was used during the whole intercourse did not add any risk of infection. A drop-in reception is a good contribution to an opportunistic screening approach. The rate of CT infected is high and the clinic attracts men and individuals ≥25 years old at risk of infection, groups which usually have a reduced test rate. The mean age was 28 years and 58% of the patients were men. The figure of correct condom usage is very low indicating the need for risk reducing counselling also in this grown-population. Among adult STI patients anxiety was common and depression uncommon. Neither was linked to high risk sexual behaviour nor ongoing CT infection. Hazardous alcohol consumption, however, was common and linked to anxiety and high risk sex. We conclude that preventive work can not only focus on STI prevention, but must consider the high frequency of hazardous alcohol consumption, which probably is contributing to sexual risk behaviour.

Nickel allergy is the most prevalent contact allergy and has been discussed as a possible riskfactor for hand eczema. However, hand eczema is one of the most frequently occurring skindiseases and has multifactorial origin. The aim of this thesis was to study the association between nickel allergy and hand eczema in the general population. There are only a fewpopulation-based studies previously published, that include patch testing. In addition, this thesis aimed to evaluate methods to follow the prevalence of nickel allergy.The study cohort consisted of 908 women who had been patch tested for the occurrence of nickel allergy as schoolgirls. Twenty years later, they were invited to participate in a follow-up questionnaire study. The response rate was 81%. In total, 17.6% of respondents reported handeczema after the age of 15 years and there was no statistically significant difference in the occurrence of hand eczema between those who were nickel-positive and those who were nickel negativeas schoolgirls. To further investigate possible links, another study was performed,which included a second questionnaire, a clinical investigation and patch testing. All schoolgirls from the baseline study who were still living in the area as adults were invited to participate and the participation rate was 77%. Patch test showed 30.1% nickel-positive individuals.When all participants were included in the analysis, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. Adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 in relation to nickel patch testresults was 1.03 (95% CI 0.71--1.50) and in relation to childhood eczema 3.68 (95% CI 2.45--5.54). When women with and without history of childhood eczema were analyzed separately, the hand eczema risk was doubled in nickel-positive women without history of childhood eczema. In conclusion, the risk of hand eczema in nickel-positive women may previously havebeen overestimated. Next, the validity of self-reported nickel allergy was investigated. In the established cohort; two questions regarding nickel allergy were compared with patch test results. The validity of self-reported nickel allergy was low, and the questions regarding nickel allergy overestimated the true prevalence of nickel allergy. The positive predictive values were 59% and 60%. Another method for estimating the prevalence of nickel allergy, namely self-patch testing, was validated in the last study. In total, 191 patients from three different dermatology departments participated. The validity of self-testing for nickel allergy was adequate, with sensitivity 72%and proportion of agreement 86%. / Nickelallergi är vanligt förekommande. Prevalensen i Skandinavien är 15--25% hos kvinnor och cirka 3% hos män. Sambandet mellan nickelallergi och uppkomst av handeksem har tidigare diskuterats och i vissa studier anges att 30--45% av alla individer med nickelallergi får handeksem. Det finns dock endast ett fåtal publicerade studier där personer ur normalbefolkningen har lapptestats för nickel. Handeksem ärvanligt och har ofta flera olika kombinerade orsaker. Det övergripande syftet med avhandlingen var att studera nickelallergins betydelse för uppkomst av handeksem. Detfinns ett intresse av att följa förekomsten av nickelallergi över tid, speciellt sedan det i början av 2000-talet infördes ett EU-direktiv som begränsar nickelinnehåll i klockor,smycken, metallknappar etc. Ytterligare ett syfte med avhandlingen var att utvärderaepidemiologiska metoder för att följa förekomsten av nickelallergi.Den första studien var en uppföljningsstudie av 908 flickor ur normalbefolkningen,vilka i skolåldern lapptestats med nickel. Tjugo år senare skickades en enkät till dessa kvinnor, svarsfrekvensen var hög (81%). Förekomsten av självrapporterat handeksemefter 15 års ålder var 17.6%. Det förelåg ingen signifikant skillnad i förekomst avhandeksem mellan de kvinnor som var nickelallergiska som barn jämfört med dem som inte var nickelallergiska. År 2006 utfördes ytterligare en studie, som inkluderade de kvinnor som fortfarande bodde i Örebro län. Studien omfattade en klinisk undersökning av händerna samt ett lapptest. 30% av kvinnorna var positiva för nickel.Det förelåg ingen signifikant skillnad i förekomst av handeksem mellan de som var positiva för nickel och de som var negativa. Vid separat analys av de kvinnor som angav tidigare barneksem jämfört med dem som aldrig hade haft barneksem visade det sig att risken för handeksem var dubbelt så stor hos nickelallergiker i den gruppen som aldrig hade haft barneksem. Båda studierna visade att barneksem var den största riskfaktorn för att få handeksem som vuxen, med en 3-4 gånger ökad risk. Den tredje studien var en validering av självrapporterad nickelallergi. Överensstämmelsen var låg mellan enkätfrågor gällande nickelallergi och lapptestverifierad nickelallergi. Av dem som själva bedömde sig vara nickelallergiska var endast 59% positiva enligt lapptest. För att följa förekomsten av nickelallergi i befolkningen behövs därför andra metoder. I den fjärde studien utvärderades ett självtest för nickelallergi. 191 patienter från tre olika hudkliniker i Sverige deltog i studien. Validiteten för metoden självtest var tillfredsställande, sensitiviteten var 72%och graden av överensstämmelse var 86%.

The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period. The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999. In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%. Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course. 69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. Conclusion: A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.

Treatment results and clinical characteristics in adult acute lymphoblastic leukaemia (ALL) were evaluated regarding three issues: a new treatment with cytarabine up-front, stem cell transplantation and a comparison between adult and paediatric treatment protocols. All studies were conducted on a national basis. Furthermore, activity of imatinib was investigated by in vitro cytotoxicity assay. The national protocol was evaluated in 153 adult ALL patients. A high complete remission rate, 86%, was achieved with 29% overall survival at 3-years. Favourable outcome was identified in patients < 40 years with precursor B phenotype and continuous complete remission was higher for precursor B compared to T-ALL. Stem cell transplantation was evaluated in 187 patients. No differences in outcome between allogeneic and autologous transplantation were found, with the exception of Philadelphia-positive ALL, in which allogeneic transplantation was preferable. Limited chronic graft-versus-host disease (compared to none) resulted in superior disease free survival. The paediatric NOPHO-92 and the Adult protocols were evaluated for 243 ALL-patients. Superior remission rate and survival were achieved for 10-18 year-olds treated according to the Paediatric protocol compared to both 15-25 and 25-40 year-olds treated according to the Adult protocol. Treatment protocol was a significant prognostic factor for patients aged 15-20 years. Fluorometric Microculture Cytotoxicity Assey was used to analyze 15 tumour cell samples from ALL patients. High concordance was determined between in vitro sensitivity to imatinib and presence of BCR-ABL. Daunorubicin, prednisolone and cytarabine had the greatest benefit from a combination with imatinib. The national adult treatment protocol’s results were consistent with international trials regarding precursor B ALL but may be under performing for T-ALL. Adolescents may benefit from treatment according to the Paediatric protocol. No difference in outcome between allogeneic and autologous stem cell transplantation was determined except for Philadelphia-positive patients, despite the indication of a graft-versus-leukaemia effect.

The aims of the thesis were (i) to investigate the impact of repetitive low-intensity work exposure on proprioception and (ii) to examine effects of muscle stretching (especially sensory effects and effects on muscle nociception) and to relate its application to the prevention, alleviation and/or treatment of work-related neuromuscular disorders. The effects of low-intensity repetitive work on the shoulder proprioception were tested in healthy subjects. The effect of working time on the retention of subjective fatigue and their relation to changes in proprioception, and the immediate effect of stretching on shoulder proprioception were investigated. A new method to test the stretchability of the rectus femoris muscle was investigated for reliability and validity and used to assess the effects of a two-week stretching regimen on range of motion and on subjective stretch sensation. Finally, the interactions between innocuous muscle stretch and nociceptive chemical stimulation on discharge behavior of nociceptive dorsal horn neurons in the feline spinal cord were explored. The main findings were as follows: 1) The repetitive low-intensity work to fatigue diminished the shoulder proprioception; the working time as well as the retention of subjective fatigue were partly related to the extent of changed proprioception. 2) There was no effect of acute muscle stretching on the proprioception. 3) The new method for testing muscle stretchability proved valid and reliable. A two-week stretching regimen increased the tolerance to stretch torque, but the range of motion remained unchanged. 4) Half of the nociceptive dorsal horn neurons that responded to close arterial injections of bradykinin were modulated by muscle stretching applied directly after the injections. Altogether, the results give credence to the hypothesis of an involvement of sensory information distortion due to repetitive low-intensity work exposure in the development of work-related neuromuscular disorders. Increased tolerance to stretch torque may be an important mechanism in explaining improvements following stretch treatment. The spinal interactions between innocuous stretch and nociceptive muscle afferent inputs indicate a possible mechanism involved in stretching-induced pain alleviation.

<p>Studies concerning social consequences, gastrointestinal and urinary tract symptoms were conducted in a population-based cohort comprising patients with long-standing type 1 diabetes and matched control persons. Three different questionnaires were sent by mail to diabetic patients and control persons. After a mean duration of 28.7±2.6 years, compared to the controls the diabetic patients showed an almost 10 times higher mortality, a lower employment rate and greater need for welfare benefits. These differences were mainly due to diabetic late complications. Education, housing conditions, life-style, civil state, alcohol and smoking habits were similar in the two groups. The prevalence of gastrointestinal symptoms was significantly higher in the diabetic patients than in the controls, and this was found to be attributable to the female diabetic patients. Female diabetic patients had been treated with antibiotics for urinary tract infections more often than controls, they experienced more social problems than controls in daily life because of urinary tract problems and used clamps to prevent wetting more often than did controls. </p><p>Body composition and bone mineral density were evaluated in parts of the cohort with long-standing type 1 diabetes and control persons in another population-based cohort comprising diabetic females aged 16-19 years with type 1 diabetes since childhood and matched controls. Besides a tendency to reduced abdominal fat mass in diabetic males, no difference was observed in fat mass, muscle mass or bone mineral density between the patients with long-standing type 1 diabetes and controls. Significant correlations were found between insulin dosage and whole body fat mass in diabetic females and between serum cholesterol levels and abdominal fat mass in diabetic males. The female adolescents had a higher body mass index than the controls, and their overweight was shown to consist almost entirely of an increased fat mass. The distribution of fat, expressed as abdominal-to-leg ratio, correlated significantly to HbA1c and daily dosage of insulin. Bone mineral density did not differ between the groups. IGF I was significantly lower both in patients with long-standing type 1 diabetes and in the adolescent diabetic females compared with their matched controls.</p>

<p>Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.</p><p>We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s. </p><p>Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.</p><p>A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).</p><p>Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s. </p>

<p>In sera remitted for anti-nuclear antibody (ANA) analysis, the supplement of a sensitive anti-SSA/Ro ELISA to the conventional ANA screening by immunofluorescence (IF) revealed that one fourth of the individuals with IF-ANA negative, but SSA/Ro ELISA positive sera, had systemic lupus erythematosus (SLE) or cutaneous LE. Consequently, adding a sensitive anti-SSA/Ro ELISA to the ANA screening is valuable for the serological detection of ANA negative SLE/LE patients.</p><p>SLE patients often have measurable interferon-alpha (IFN-α) levels in serum, and IFN-α treatment of patients with non-autoimmune diseases can induce SLE. Thus, the type I IFN system seems to be important in SLE and was therefore investigated. Initially, a decreased IFN-α producing capacity, due to a 70-fold reduction in the number of circulating natural IFN-α producing cells (NIPC), was noted in peripheral blood mononuclear cells (PBMC) from SLE patients. SLE-sera contained an endogenous IFN-α inducing factor (SLE-IIF), consisting of IgG and DNA in the form of small immune complexes (300-1000 kD). The SLE-IIF selectively activated NIPC and was more common in sera from patients with active disease compared to individuals with inactive disease. IFN-α producing cells could be detected by immunohistochemistry in both lesional and unaffected skin from SLE patients, and IFN-α gene transcription could be verified by in situ hybridisation in some of the skin biopsies. A reduced number of NIPC, detected by expression of the blood dendritic cell antigen (BDCA)-2, was noted among SLE-PBMC. The IFN-α production triggered by SLE-IIF in SLE-PBMC was inhibited by monoclonal antibodies (mAbs) to BDCA-2 and markedly decreased by anti-BDCA-4 mAbs. </p><p>The observations in the present thesis may explain the ongoing IFN-α production in SLE patients, indicate an important role for the activated type I IFN system in the pathogenesis, and suggest that direct targeting of SLE-NIPC may constitute a new therapeutic principle in SLE.</p>

<p>In patients with diabetes mellitus (DM), acute myocardial infarction (AMI) is a major cause of death. We have studied two populations with respect to the relationship between DM or related glucometabolic disturbances and AMI.</p><p>In the first population, the prevalence of DM and the importance of the glycaemic state for the long-term prognosis in non-diabetic patients were investigated in patients with AMI admitted to the Coronary Care Unite at Västerås Central Hospital.</p><p>In the second population, the prevalence of impaired glucose tolerance (IGT), DM and other metabolic abnormalities was investigated in patients with AMI and without known DM admitted to the Coronary Care Units at Västerås and Karolinska Hospital, Stockholm.</p><p>21% of the patients with AMI had previously known DM and 4% had newly detected DM if diagnosis is based upon fasting blood glucose (F-BG). The glycemic state, measured as HbA1c, at a 5.5 years follow-up was a risk factor for re-infarction and/or death in non-diabetic patients after AMI.</p><p>If an oral glucose tolerance test (OGTT) is performed, 40-45% of all patients with AMI have DM and in addition about 30% have IGT. Both an OGTT and a single post-challenge blood glucose value after 60 minutes performed at hospital discharge, were independent predictors of IGT or DM at follow-up. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), decreased during hospital stay, with no further decrease from hospital discharge to follow-up.</p><p>In summary, the studies in this dissertation have revealed an unexpectedly high prevalence of abnormal glucose tolerance in patients with AMI. The glycaemic state, reflected by HbA1c, in non-diabetic patients after AMI has an impact on the long-term prognosis. Consequently, in all patients with AMI, HbA1c and casual blood glucose should be measured at admission and, at least, F-BG at hospital discharge.</p>