Coming dissertations at MedFak
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”Det är liksom en stor grej som händer just nu i våra liv” : Psykisk hälsa och stigma bland ungdomar
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-535659
Adolescents’ mental health is a current public health issue. However, research, on adolescents’ views on different aspects of mental health, and the prevalence of mental well-being, mental illness and related stigma, among adolescents is limited in Sweden. The overall aim of this thesis was to explore perceptions and status of mental health and stigma related to mental health problems among adolescents in a Swedish context.
Study I and II were based on qualitative interviews with 32 adolescents on the Swedish island Gotland. Study I indicated that the adolescents had a complex understanding of various mental health concepts but labelled mental well-being as ‘feeling good’ and mental illness as ‘feeling bad’. In Study II, the adolescents described mental health problems as common due to current living conditions, e.g. stress related to school performance and social media and an increased openness about mental health problems. Stigmatisation of people with mental health problems was perceived as problematic, caused by lack of experience and knowledge, but also as related to rumour spreading and stereotypical gender norms.
Study III and IV were based on the Life and Health Youth survey, conducted in secondary schools located on Gotland. In study III, the results according to the dual-factor model of mental health showed that most adolescents had vulnerable mental health status (47.5%), while 36.2% had complete mental health. A smaller proportion had troubled (13,9%) or symptomatic but content (2,5%) mental health status. Associations were observed between mental health status and gender, grades, truancy, stress level, resilience, and subjective social status in school.
In study IV, the factor structure and internal consistency was acceptable for the modified Attitudes About Mental Illness and its Treatment scale, but the adolescents perceived it as difficult to answer. Further, negative attitudes towards people with mental health problems were present, and more common among boys and foreign-born adolescents.
The findings of this thesis suggests the two-factor model of mental health and the three-part description of stigma, including stereotypes, prejudice and discrimination, to be applicable among adolescents. Further, the findings suggest a need for promotion of mental well-being and prevention of mental health problems such as interventions to reduce school-related stress, increase resilience and promote societal knowledge about mental health, stigma and gender stereotypes among adolescents. The findings also motivate support to adolescents with low mental wellbeing and minor mental health problems as well as to adolescents who have friends with mental health problems.
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Novel biomarkers and their relation to clinical outcomes and pathophysiology in anticoagulated patients with atrial fibrillation
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-536026
Atrial fibrillation (AF) is a common arrhythmia and is associated with an increased risk of cardiovascular (CV) outcomes, including mortality and heart failure (HF).
The overall aim of this thesis was to evaluate the association of novel and established biomarkers with cardiovascular outcomes in patients with AF. Baseline levels of apolipoproteins A1 (ApoA1) and B (ApoB) were investigated in relation to CV outcomes. The geographic consistency of Growth differentiation factor 15 (GDF-15) and the ABC-AF risk scores in predicting bleeding and mortality were investigated. Proteomic analyses were employed to screen for novel biomarkers associated with CV death and hospitalization for HF in AF and biomarker profile differences between HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) were also explored.
The study population consisted of patients with AF on anticoagulation included in the biomarker substudies from the large randomized clinical controlled trials RE-LY (n=6,187) and ARISTOTLE (n=14,954) with a median follow up of 2.0 and 1.9 years. Biomarker levels were measured at baseline.
Higher levels of ApoA1 were independently associated with a lower risk of ischemic events, whereas ApoB was not. Neither apolipoprotein was significantly associated with major bleeding. The predictive value of GDF-15 and the biomarker-based ABC-AF risk scores for bleeding and mortality across various geographic regions was consistent. In the screening investigation for novel markers, the biomarkers most strongly and consistently associated with CV death were: NT-proBNP, cTnT-hs, IL-6, GDF-15, FGF-23, uPAR, TFF3, TNFR1, TRAILR2 and CTSL1. The biomarkers most strongly associated with HF hospitalization were NT-proBNP, BNP, cTnT-hs, FGF-23, spon1, IGFBP-7, u-par, OPN, PTX3 and TR. In comparison of HFrEF versus HFpEF, levels of NT-proBNP, BNP, cTnT-hs, renin, ACE-2, GDF-15 and IL-6 were higher in HFrEF, whereas levels of SCF and leptin were higher in HFpEF.
In conclusion, this thesis underscores the pivotal role of biomarkers in better understanding AF and its complications. The insights from this thesis suggest potential therapeutic targets and strategies for personalized management in AF, possibly enhancing risk stratification and improving patient outcomes.
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Invasive Candida infections : Treatment of the critically ill and patients with infective endocarditis
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-535842
Invasive Candida infections have a major impact on morbidity and mortality in critically ill patients. Prompt initiation of effective antifungal therapy and source control are cornerstones in management. The echinocandin caspofungin is first-line treatment in invasive Candida infections and dosage is based on the Child-Pugh liver scoring system, developed for patients with chronic liver disease. Pathophysiological changes in the critically ill, e.g. hypoalbuminemia, may affect antifungal pharmacokinetics (PK) and drug exposure, calling into question if dosage regimens are adequate for this group. Candida infective endocarditis (CIE) is a rare but serious form of deep-seated Candida infection, burdened with high mortality rates. The standard of care has been antifungal therapy combined with cardiac valve surgery.
The overall aim of this thesis was to study aspects of invasive Candida infections in relation to caspofungin pharmacokinetics and pharmacodynamics (PK/PD) and the management of patients with CIE.
In a prospective study of critically ill patients, we investigated the prevalence of hepatic impairment, the effect of Child-Pugh score on caspofungin PK and whether caspofungin PK/PD targets were achieved. The prevalence of patients with pathological liver function tests was high, but the Child-Pugh score did not significantly impact caspofungin PK. The PK/PD target was reached, but with small margins. No dose reduction is warranted in critically ill patients with hepatic impairment, in the absence of chronic liver disease.
The impact of plasma protein levels on the antifungal activity of caspofungin at clinically relevant concentrations was studied in time-kill experiments. Reduced plasma protein levels in vitro increased caspofungin’s fungicidal effect on Candida glabrata.
In a retrospective observational study, we compared the effect of echinocandins, mainly caspofungin, on the outcome in patients with CIE with those of other antifungal regimens. We found no significant differences in outcome between regimens.
Further investigation of the CIE cohort showed that Candida parapsilosis was overrepresented in CIE compared with candidemia, indicating a higher propensity to cause CIE. In the overall CIE cohort, surgery did not improve outcome. Therefore, the recommendation of surgery in all patients with CIE may be questioned. Long-term suppressive antifungal therapy reduced the number of relapses.