Coming dissertations at MedFak
-
Trauma Care - Implementation, Evaluation and Validation
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-521759
Trauma is a major cause of death and morbidity in all ages, which makes continuous improvement of trauma care a high priority. During the last decades, Sweden’s trauma system has evolved with initiation of a national trauma registry (SweTrau) in 2011 and the Swedish National Trauma Triage criteria (SNTTC) in 2017. However, the Swedish trauma panorama has evolved as well, something this thesis aimed to explore, alongside with evaluating the safety and accuracy of the SNTTC and performing the first validation of SweTrau. Paper I is a prospective stepped-wedge cohort study, showing unchanged 30-day mortality, over- and undertriage after the implementation of the SNTTC, as well as a reduction of the lowest level of trauma call by almost 50%, proving that the SNTTC are safe to use. In Paper II, a retrospective multicentre cohort study, the SNTTC are further investigated, displaying a sensitivity of almost 85% while also assessing specificity, positive predictive value (PPV) and positive likelihood ratio (LR+). With no additional enhancing criteria found, the SNTTC are concluded to efficiently identify severely injured patients. Paper III reports the first validation of SweTrau; an on-site re-registration compared with the original registration in SweTrau. It demonstrates that the data in SweTrau is reliable, with high accuracy (85.8%), correctness (89.7%), data completeness (88.5%) and correlation (87.5%), while being comparable to international trauma registries using the Utstein template of trauma. Case completeness and timeliness are identified as areas of improvement. In Paper IV, nine-year trauma trends in two major trauma centres are analysed in a retrospective cohort study. A sharp reduction in intensive care unit admissions is seen, as well as a worrying increase in penetrating trauma (>50%) and mortality for patients with a low injury severity score (1.3%-2.7%, p=0.005), all of which require further investigation. In conclusion; this thesis has confirmed that the SNTTC are safe and efficient, as well as pin-pointed important trauma areas to focus on in the future. Finally, it has established the validity of the data in SweTrau - a major source of Swedish trauma research.
-
Role of MYCN in retinoblastoma : From carcinogenesis to tumor progression
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-523595
Retinoblastoma, a pediatric malignancy of the retina, is primarily driven by the bi-allelic inactivation of the RB1gene. However, a subset of cases are characterized by proficient RB1 functions but with MYCN copy number mutations, suggesting an alternative oncogenic mechanism in the absence of RB1 mutations. The aim of this thesis is to investigate the intricate molecular and cellular pathways implicated in retinoblastoma, with a particular focus on the role of MYCN expression and its interplay with the cell cycle and apoptotic pathways.
In Paper I, we explored the regulatory mechanisms underpinning MYCN-induced retinoblastoma using aRB1-proficient MYCN-overexpressing in vivo model in embryonic chicken retina and MYCN-transformed cells in culture. Our findings revealed that MYCN overexpression led to a significant upregulation of E2F levels, thereby dysregulating the cell cycle and mimicking the mechanistic phenotype of RB1-deficient tumors. Inhibition on E2f DNA-binding activity efficiently normalized growth and apoptosis in MYCN-transformed cells in culture. Despite RB1 proficiency, the elevated E2F levels induced a neoplastic behavior in retinal cells, indicating a novel mechanism of retinoblastoma carcinogenesis independent of RB1 inactivation.
Paper II employed single-cell RNA sequencing to dissect the cellular composition of MYCN-driven retinoblastoma in chicken in vivo model, revealing a predominant origin in cone photoreceptor progenitors. This finding suggested a cell-type-specific vulnerability to MYCN-induced transformation. The research further identifies a notable heterogeneity within the MYCN-transformed cells, with a subset of cells exhibiting non-cone photoreceptor features but features of other neurons like ganglion cells. A cluster was also identified withelevated expression of genes related to malignancy and tumor progression, including UBE2C and TOP2A. This suggested a link between MYCN overexpression and tumor development, potentially mediated through the E2F pathway.
In Paper III, the focus shifted to the interplay between MYCN expression, E2f activity, and the p53 pathway in human retinoblastoma cell lines exhibiting both RB1 deficiency and MYCN amplification. By modulating E2f and p53 pathway activities using chemical inhibitors, we demonstrated the essential role of MYCN expression level in mediating p53-driven growth inhibition and highlighted the independent effects of E2f inhibition and p53 activation by a Mdm2 inhibitor.
Together, these studies illuminate the intricate molecular pathways involved in MYCN-amplified retinoblastoma, emphasizing the pivotal role of MYCN in disrupting cell cycle regulation and promoting tumorigenesis. These insights not only advance our understanding of retinoblastoma pathogenesis but also provide potential therapeutic targets within the MYCN-E2F axis, offering novel treatment strategies in MYCN-amplified retinoblastoma.
-
Patients’ Access to Their Mental Health Records : Understanding Policy, Access, and Patient Experiences
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-522720
ORA is the concept of patients' access to clinical information, which has become more widespread worldwide. When patients are provided online record access (ORA) to their health records, concerns have been raised by healthcare professionals, especially when it comes to patients with mental health diagnoses. In the general population, positive aspects appear to outweigh the negative, yet limited research has so far explored the impact of ORA in mental healthcare.
The overall aim of this thesis was to explore how patients experience ORA in mental healthcare through four studies: 1) a literature review aimed to explore the current literature on the experiences of ORA among mental healthcare patients, care partners, and healthcare professionals, 2) a document analysis combined with key stakeholder email interviews that aimed to explore to what extent ORA in mental healthcare has been implemented in Sweden including national and local policy regulations, 3) an online patient survey study aimed to understand mental healthcare patients' experiences with ORA in Sweden, Estonia, Finland, and Norway, and 4) an online patient survey study aimed to understand if and how patients with mental health conditions experiences of ORA differs from patients in other healthcare settings.
More patients reported positive experiences with ORA in mental healthcare than negative experiences. Common benefits of ORA included, among others, a greater sense of control over their care, improved understanding of their mental health diagnosis, and better adherence to appointments. Despite patients' predominant positive experiences, only 17 out of 21 regions in Sweden offered ORA in mental healthcare in 2021. Additionally, many patients experienced errors and omissions and felt offended by the content of their health records. Mental healthcare patients experienced this at a higher rate than patients in other healthcare settings.
In conclusion, mental healthcare patients have higher rates of negative experiences of ORA compared to patients in other healthcare settings. However, patients' experiences of ORA are still predominantly positive among both patient groups. Yet, in 2021, only 17 regions offered patients ORA in mental healthcare. Denying mental healthcare patients ORA to protect them from negative experiences could instead increase stigma in this patient group.