Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and subsequent destruction of synovial joints. Although its causes remain largely unknown, a substantial genetic contribution is known to exist. During the last decades the benefits of early aggressive treatment have become evident, and more potent therapeutic options have become available. These advances have increased the demands for rapid accurate diagnosis and prognostic markers of disease course and therapy response. The ‘rheumatoid factor’ (RF) has long been used as a diagnostic and prognostic marker of RA. In this thesis, the utility of measuring antibodies to cyclic citrullinated peptides (CCP) was investigated. In a population-based arthritis incidence study, 69 very early arthritis patients (symptom duration < 3 months) were identified. The anti-CCP test, performed at baseline and related to diagnosis at the 2-year follow-up, had a diagnostic specificity for RA of 96% and a sensitivity of 44%, both of which were superior to RF. In a prospective cohort of 242 incident cases of RA (symptom duration < 1 year), 64% of the patients tested positive for anti-CCP at baseline (equal to RF). Despite receiving more active anti-rheumatic therapy, the anti-CCP-positive patients had a more aggressive disease course during 3 years as compared to those testing negative. The 158VV genotype of Fcγ Receptor type IIIA (FcγRIIIA), which binds IgG with higher affinity than 158FF, was associated with an increased susceptibility to RA in men, but not in women. Previous studies report conflicting results, and none stratified according to gender. The 158V/F polymorphism of FcγRIIIA was not found to influence outcome of anti-tumour necrosis factor therapy in 282 RA patients, contradicting hints from previous studies. Genetic variation in proteins of the inflammasome, an interleukin-1 (IL-1) regulating intracellular protein complex, is associated with rare autoinflammatory conditions and possibly with Crohn’s disease. In this first study on genetic variation of the inflammasome in RA, we describe a compound polymorphism of the genes CIAS1 and TUCAN that associates both with susceptibility to RA and to the severity of the disease. Hypothetically, these genes may identify a subgroup of RA patients that would benefit from anti-IL-1 therapy. This thesis work emphasizes the benefits of testing for anti-CCP in the diagnosis and outcome prediction in early arthritis. FcγRIIIA genotype is likely to affect RA susceptibility and further work should apply a gender perspective. Inflammasome genetics may influence the risk of developing RA. Additional studies are warranted to settle whether it also identifies a subgroup of RA patients benefiting from IL-1 targeted therapy.

The overall aim of the present thesis was to explore and describe the health experiences of men and women with musculoskeletal problems. The specific aims of the four papers were: (I) to explore the experience of illness and wellness among ambulance personnel with musculoskeletal symptoms; (II) to explore the experience of illness and wellness among female health care personnel with musculoskeletal symptoms; (III) to explore the experience of bodily illness among people with musculoskeletal problems in the neck-shoulder region, and; (IV) to investigate the symptoms described by people with non-specific neck-shoulder problems, to investigate the method of development of neck-shoulder questionnaires that assesses pain and other symptoms, to analyse the content and items of these questionnaires, and to compare the findings. The overall findings show that the occupationally active men and women with MSDs were “striving for balance” (I-II), that the disease course of chronic neck-shoulder disorders was characterised by “uncontrollable fluctuations” (III), and that most neck-shoulder questionnaires had a low correspondence to the variety of symptoms experienced during this course (IV). In the process of striving for balance (I-II), the informants’ health experiences were not a state of either wellness or illness, but of both, in varying degrees at different times. The balancing started when illness became too intrusive, and was a process of minimising the impact of illness by accepting and handling it, while attaining and maintaining wellness to feel well enough. When striving for balance, the interviewees kept on working to continue being nurtured at the same time as they made different efforts directed at minimising the impact of their illness. For both men and women, illness was characterised by disembodiment, vulnerability, and exhaustion. The illness experiences were counterbalanced by wellness, where some differences could be recognised between the men and the women. Study III further explored the experiences of bodily illness, focusing on people with chronic musculoskeletal disorders in the neck-shoulder region. The course of the disorder was described as characterised by uncontrollable fluctuations, and it usually developed from insidious symptoms to a state of constant discomfort. The participants experienced calmer periods during the course, but intermittent events of increasing illness were always lying in wait, with periodic moments of consuming intensity. In the interviews included in study IV a variety of symptoms were expressed, which indicated a bodily, mental, and emotional engagement, which included more general and more severe symptoms than are usually related to neck-shoulder disorders. Few of the questionnaires were developed using the experiences of the affected. Taken as a whole, did the questionnaires cover many of the symptoms of the interviewees, but each individual questionnaire only included a few. The fluctuations and nuances of symptoms were rarely considered. The correspondence between individual questionnaires and the experiences of those affected was most often low. This thesis reveals other aspects of health than just bodily experiences as important among occupationally active people with MSDs. It also provides a description of the disease course, and an indication of possibilities for improvement of neck-shoulder questionnaires.

Hjärtsvikt är ett kroniskt tillstånd som ofta leder till stor symtombörda och nedsatt livskvalitet. Trots behandling har hjärtsvikt hög mortalitet. Sjukdomsförloppet är individuellt med gradvis försämring och övergången till den palliativa fasen kan vara svår att identifiera. Kommunikation om prognos och sjukdomsförlopp bör ske i tidigt skede för att underlätta patientens möjlighet att hantera hela sjukdomsförloppet. Syftet var att belysa kommunikationen om prognos och sjukdomsförlopp mellan patienten med hjärtsvikt och vårdpersonalen. Litteraturöversikt valdes som metod för att svara mot syftet. Sökningar utfördes i PubMed, Cinahl och PsycINFO och utifrån dessa sökningar inkluderades 15 artiklar publicerade 2007–2019. Kvalitetsgranskningen gjordes utifrån Sophiahemmet högskolas bedömningsunderlag och artiklarna analyserades med integrerad analys. Resultatet visade att kommunikation om prognos, sjukdomsförlopp och vård vid livet slut förekommer i låg utsträckning och möjligheter till kommunikation missas ofta av sjukvårdspersonalen. Dessutom finns det flera hindrande faktorer för kommunikation som svårigheten att förutsäga prognos, gemensam syn på när rätt tidpunkt är och patientens bristande kunskap om hjärtsvikt. Patienterna önskar att kommunikationen vid livets slut ska präglas av positivitet och de önskar få veta sanningen trots att den kan skapa en rädsla. Kommunikation om prognos behöver även balanseras med hopp. Slutsatsen är att patienter med hjärtsvikt har olika önskemål om hur kommunikationen bör gå till och att en ökad kunskap om hjärtsvikt är en förutsättning för en bra kommunikation om prognos och sjukdomsförlopp. Patientens individuella önskan om kommunikation behöver bemötas på ett personcentrerat sätt för att skapa möjlighet för patienten att bli delaktig i vården. / Heart failure is a chronic condition that often leads to a high burden of symptoms and impaired quality of life. Despite treatment, heart failure still has a high mortality rate. The pattern of the disease is individual with gradual deterioration and the transition to the palliative phase can be difficult to identify. Communication on prognosis and disease progression should be made at an early stage to facilitate the patient's ability to manage the entire disease pattern. The aim was to explore communication about prognosis and progress of disease between the patient with heart failure and the healthcare professionals. To answer the purpose, a literature review were conducted by using the databases PubMed, Cinahl and PsycINFO and 15 articles were included, published between 2007–2019. The quality of the articles where surveyed with the Sophiahemmet university’s assessment and the articles were analyzed using integrated analysis. The result shows that communication of prognosis, disease progression and end-of-life care occurs to a low extent and opportunities for communication are often missed by the healthcare professionals. In addition, there are several factors that detain communication including the difficulty in predicting prognosis, a common view of when the right time is for communication and the patient’s lack of knowledge of heart failure. The patients want the communication at the end of life to be characterized by positivity and they want to know the truth even though it could create fear. Communication about prognosis also needs to be balanced by hope. The conclusion is that patients with heart failure have different preferences for communication and the patient’s knowledge about heart failure is provided for communication about prognosis and disease progression. The care should be designed in person-centered way to create the opportunity for the patient to become involved in their care.

Diploma project, the issue of informal care for a close person with Parkinson's disease from the perspective of caregivers is focused on the intensity of care and access to services that could help informal caregivers in the care of their loved ones.In the theoretical section of Parkinson's disease I am describing, its development and changes that the disease brings along. Then I followed with the care of relatives person and support from the social system - the state. In the practical part I have chosen for my research a survey, which was attended by only a small part of respondents from informal carers. Care of long-term sick family member is very difficult. Caregivers feel tired and exhausted, they report that their own health becomes wors. Care also affects cares professional life and there leisure time. Although half of the respondents are still able to find time for their hobbies. Some carers have no idea about the possibilities of helping services and just minimum of them use these services.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, which primarily affects middle-aged women. The liver histology is characterized by inflammation and destruction of the intrahepatic bile ducts as well as a high frequency of granuloma. Although the etiology is unknown, the occurrence of associated multiorganic abnormalities such as Sjogren's syndrome, scleroderma, rheumatic disorders and thyroid gland diseases have been cited as evidence favouring an autoimmune background. Addison and Gull in 1851 described the first patient with jaundice and xanthomatosis. PBC was first mentioned in 1876 as an entity by Hanot. PBC was considered to be a rare disease until in 1973 Sherlock and Scheuer described 100 patients. Since then a greater awareness of the disease combined with a wider use of laboratory screening methods has led to the discovery of an increasing number of patients with PBC. In an epidemiological investigation of PBC in the northern part of Sweden a point prevalence of 151 per 106 was found, which is the highest so far reported, and the mean annual incidence amounted to 13.3 per 106. Asymptomatic PBC was present in more than one third of the patients which is consistent with the finding in other epidemiological investigations and is supposed to explain the higher prevalence of PBC and the better prognosis. Nevertheless 25 patients died during the study period, 14 as a direct consequence of the liver disease. Chronic intrahepatic cholestasis has been reported in sarcoidosis and, moreover, a high frequency of liver granuloma is found. The implication of the present study is that a negative Kveim test in combination with positive mitochondrial antibodies is accurate in differentiating PBC from sarcoidosis. Multisystem involvement is frequently observed in PBC and the present study confirms this. In the prospective investigation of 26 PBC patients 50 % had arthropathy considered to be associated with PBC. Rheumatoid arthritis was found in 5 patients, who all had symptoms of liver disease in addition. Lung function impairment was present in 56% (1 asymptomatic PBC). Most commonly a reduced diffusion capacity was found (36%). Bronchial asthma was present in three patients, and severe lung emphysema in one. Features of Sjogren's syndrome was found in 73% (3 asymptomatic PBC). In 6 patients keratoconjunctivitis sicca (KCS) was evident with the rose bengal test demonstrating corneal staining and a Schirmer test of less than 5 mm. Radiological findings of sialectasia were demonstrated in 6 patients, of whom 5 had KCS as well. The ultimate treatment in PBC is liver transplantation and to calculate the need for that, good epidemiological surveys are needed, and also indicators of hepatocellular function. The present investigation indicates that determination of the von Willebrand factor could be used for this purpose. / <p>Härtill 6 uppsatser</p> / digitalisering@umu

IN ENGLISH Drug dependency in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), is a specific disease phenotype which determines disease prognosis and hence may be used as a prognostic marker for treatment management. Drug dependency in IBD has been well described in corticosteroid treatment and recently also in infliximab (IFX) therapy. The aims of this thesis were: 1) to assess the occurrence of IFX dependency in paediatric and adult patients with CD; further to search for clinical and genetic predictors of IFX outcome and to evaluate the impact of IFX dependency on surgical rate; 2) to assess in CD patients the outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency and to define clinical predictors of 5-ASA treatment outcome. We found that 66% of children and 29% of adults with CD became IFX dependent. The high frequency in paediatrics is in agreement with previously published studies, while the finding in adult patients indicates a lower rate of IFX dependency in the only study to date. Perianal disease and no bowel surgery prior to IFX start were predicative of IFX dependency in paediatric patients. In adult cohort, 2 genetic variants LTA c.207 A>G and CASP9 c.93 C>T were associated with IFX outcome, whereas no relevant clinical...

IN ENGLISH Drug dependency in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), is a specific disease phenotype which determines disease prognosis and hence may be used as a prognostic marker for treatment management. Drug dependency in IBD has been well described in corticosteroid treatment and recently also in infliximab (IFX) therapy. The aims of this thesis were: 1) to assess the occurrence of IFX dependency in paediatric and adult patients with CD; further to search for clinical and genetic predictors of IFX outcome and to evaluate the impact of IFX dependency on surgical rate; 2) to assess in CD patients the outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency and to define clinical predictors of 5-ASA treatment outcome. We found that 66% of children and 29% of adults with CD became IFX dependent. The high frequency in paediatrics is in agreement with previously published studies, while the finding in adult patients indicates a lower rate of IFX dependency in the only study to date. Perianal disease and no bowel surgery prior to IFX start were predicative of IFX dependency in paediatric patients. In adult cohort, 2 genetic variants LTA c.207 A>G and CASP9 c.93 C>T were associated with IFX outcome, whereas no relevant clinical...