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Coming dissertations at MedFak

  • Long-term outcome after burn : Pruritus, pain, personality and perceived health Author: Emelie Gauffin Link: Publication date: 2019-05-15 09:46

    This thesis investigated the role of burn-specific and individual-related factors for long-term outcome after burn with emphasis on pruritus, pain, personality and perceived health.

    Consecutive adult patients, admitted to the Uppsala University Burn Center between 2000 and 2009, were included. Patients were assessed during hospitalization, at 3, 6, 12 and 24 months and finally at 2-7 and 10-17 years post-burn.

    Pruritus was prevalent in half of the patients 2-7 years post-burn. Of the patients with pruritus, half had severe pruritus, which was independently related to full thickness burn and health-related quality of life (HRQoL) at 3 months post-burn. One third scratched to the point of bleeding. Such scratching was independently related to full thickness burns and the personality trait Impulsiveness, but did not necessarily imply more severe pruritus. Results suggest that many patients lack adequate treatment.

     Pain was prevalent in one third of the patients 2-7 years post-burn. Severity levels generally decreased over time and was at follow-up mostly regarded as mild to moderate. Post-burn pain has a negative effect on HRQoL and at 3 months post-burn, HRQoL was independently related to the reporting of post-burn pain at 2-7 years.

    Personality trait scores in burn patients deviated little from norm values. Personality traits remained largely stable the first year after burn injury, except for an increase in the trait Stress Susceptibility, which was scored lower during the acute care phase but normalized at 12 months post-burn.

    In qualitative interviews 10-17 years post-burn, participants reported living a near normal life. The subscales of the burn-specific health scale brief were in general still applicable at this time point. Additional areas playing an important role for post-burn health and outcome were skin-related problems, morphine de-escalation, the importance of work, stress and avoidance, mentality and the healthcare system.

    Certain subgroups of burn patients are more vulnerable and likely to develop post-burn sequalae and this is dependent on both burn severity and individual characteristics. In general, however, many former burn patients recover well in the long run.

  • Sleep-disordered breathing in women : Associations with cardiovascular disease and the significance of sleep apnea during REM sleep Author: Mirjam Ljunggren Link: Publication date: 2019-05-15 08:17

    Background: Sleep-disordered breathing (SDB) is associated with an increased risk of cardiovascular disease, but it is unclear which elements of SDB that are most harmful to the cardiovascular system and whether the associations observed in men also apply to women.

    Aim: To investigate associations between different aspects of SDB and cardiovascular disease in women

    Methods and results: All four papers were based on participants in “Sleep and Health in Women” (SHE), a population-based cohort study of women.

    Paper I is a cross-sectional study of 349 women with polysomnographic assessments of obstructive sleep apnea (OSA) and measurements of plasma BNP, clinically used as a marker of heart failure, in the morning. There was a dose-response relationship between the severity of OSA and levels of BNP.

    In Paper II, with a study population of 5,990 women, questionnaire data on symptoms of obstructive sleep apnea were combined with register data from the Swedish National Patient Register regarding a diagnosis of heart failure (mean follow-up 11.4 years). Women with the combination of snoring and daytime sleepiness had a two-fold increase in the risk of incident heart failure after adjustment for confounding.

    Paper III was based on 201 women without known cardiovascular disease, with a polysomnography at baseline, assessing OSA during REM sleep, and a carotid artery ultrasound with measurements of intima thickness at follow-up. Severe OSA during REM sleep was associated with a thicker carotid intima.

    Paper IV comprised 253 women with polysomnographic data on severe OSA and severe OSA during REM sleep, as well as proteomic analyses of cardiac and inflammatory proteins. After adjustment for confounding and multiple testing, severe OSA during REM sleep was associated with decreased levels of Sirt2, LAP-TGF-β1 and Axin1, while there were no significant associations for OSA based on a whole night and protein levels.

    Conclusions: Women with symptoms of OSA run an increased risk of developing heart failure and OSA is associated with increased levels of BNP. Severe OSA during REM sleep is associated with an early sign of atherosclerosis and reduced levels of proteins with anti-inflammatory effects linked to atherosclerosis and metabolic regulation.

  • Molecular Epidemiology of Cardiovascular Disease Author: Markus Stenemo Link: Publication date: 2019-05-14 13:52

    Cardiovascular disease is a major cause of morbidity and mortality, with increasing prevalence worldwide.

    Identification of risk markers may enable improved prevention by targeting high-risk individuals, earlier disease diagnosis and treatment, as well as stratification of disease subtypes with different treatment options, thereby minimizing side effects while increasing success rates.

    The overall aim of this thesis was to investigate associations between proteomic and metabolomic biomarkers, and the development of heart failure and ischemic stroke. Specific objectives were to examine potential causal pathways, and the added value in risk prediction of the identified risk markers.

    In Studies I–II, we performed proximity extension assay based proteomic profiling of ≥80 circulating proteins in the Swedish cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS n=901, median age 70), and the Uppsala Longitudinal Study of Adult Men (ULSAM, n=685, median age 77). In Study I, we identified nine proteins involved in apoptosis, inflammation, matrix remodeling, and fibrinolysis associated with incident heart failure, including growth differentiation factor-15 (GDF-15). In Study II, we identified several proteins associated with incident ischemic stroke, including GDF-15. Both studies revealed potential to improve disease risk prediction by using proteomic data.

    In Study III, we performed mass spectrometry-based metabolomic profiling in plasma or serum samples from PIVUS, ULSAM, and TwinGene (total n=3,924). The metabolites urobilin and sphingomyelin (30:1) were associated with incident heart failure.

    In Study IV, we followed up on the results of Studies I–II, performing Mendelian randomization analyses (a framework for causal analysis using genetic variants) in 1,053,527 individuals, with 88,448 coronary artery disease cases, 70,305 ischemic stroke cases, and 1,420 heart failure cases. This study supports a causal role of genetically elevated GDF-15 levels in heart failure development, but not in coronary artery disease or ischemic stroke.

    In conclusion, we identified multiple biomarkers associated with incident heart failure and ischemic stroke, potentially involved in early disease development. We also saw potential to improve disease risk prediction for incident heart failure and ischemic stroke using proteomics data.

    Our findings encourage further large-scale proteomic, metabolomic, and genetic studies to give new insights into heart failure and stroke pathogenesis.