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Coming dissertations at MedFak

  • Self-sampling for HPV testing in primary cervical screening : Including clinical and health economic aspects Author: Riina Aarnio Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-405864 Publication date: 2020-03-27 11:03

    Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV testing has higher sensitivity for high-grade cervical intraepithelial neoplasia (CIN2+) than cytology, resulting in more effective screening. As HPV testing also offers an opportunity for self-sampling, it could serve as an even more effective and cost-effective method of cervical screening.

    First, we compared repeated self-sampling for HPV testing with Pap smear cytology in detection of CIN2+ in primary cervical screening for women aged 30–49 years (n=36 390). We found a more than twofold higher detection rate of CIN2+ and a fourfold higher detection rate of CIN2 with self-sampling compared with cytology. However, no difference was seen between the arms in the detection rate of CIN3+. It thus seems that CIN is detected at an earlier stage with self-sampling than with cytology, but the impact of this needs to be further explored.

    Second, as management of HPV-positive women with normal cytology results is a challenge, we wanted to evaluate the proportion of cases of histological CIN2+ in these women. In this prospective study we performed LEEP and found that 15% (6/40) of the women had undetected CIN2+. These findings can be used in counseling women about the risk of cervical cancer and helping clinicians in decisions on management.

    Third, we performed a cost-effectiveness analysis on the same study population as in Study I. Self-sampling for HPV testing resulted in a higher participation rate and more detected cases of CIN2+ at a lower cost and was regarded as more cost-effective than Pap smear cytology in cervical screening. These results can guide policy-makers when planning future screening programs.

    Fourth, we compared self-sampling with sampling by medical professionals for HPV testing in detection of CIN2+, using a combination of an FTA card as storage medium and a PCR-based HPV test (hpVIR) in women aged 30–60 years (n=11 951). No difference in the detection rates of histological CIN2+ was found between the arms.

    Taken together, self-sampling resulted in a higher participation rate than sampling by medical professionals in cervical screening and that triage with repeated self-sampling resulted in high compliance and detection rate of CIN2+. As repeated self-sampling for HPV testing was also cost-effective, it could serve as an attractive alternative in the development of future cervical screening programs. More research is needed on how to refine the management of HPV-positive women by self-sampling only.

  • On potentials and limitations of perfusion MRI in neurological disorders Author: Markus Fahlström Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-404604 Publication date: 2020-03-26 13:03

    Cerebral perfusion outlines several parameters which describe the status of cerebral haemodynamics. Numerous neurological diseases affect cerebral perfusion, thus the importance of diagnostic measurements. Perfusion magnetic resonance imaging (MRI) is a collection of non-ionizing magnetic resonance-based perfusion measurement techniques that can be used for clinical assessment of cerebral perfusion. The aim of this thesis was to investigate potentials and limitations of perfusion MRI used for clinical assessment of patients with neurological disorders. Patients with glioblastoma were examined with dynamic susceptibility contrast MRI (DSC-MRI) and dynamic contrast enhanced MRI (DCE-MRI) before/after treatment with fractionated radiotherapy (FRT). Radiation-induced changes in normal-appearing brain tissue were found in the form of decreased cerebral blood volume (CBV) and cerebral blood flow (CBF) measured with DSC-MRI and increased vascular permeability and increased fraction of the extravascular extracellular space measured with DCE-MRI. Papers I–II provide valuable information regarding the possibility that radiation-induced changes could be a confounder in DSC-MRI and that DCE-MRI could potentially act as a biomarker for vascular damage secondary to radiation exposure. Additionally, CBF derived from arterial spin labelling (ASL) was compared to the reference standard 15O-water positron emission tomography (PET). Simultaneous measurements were acquired with an integrated PET/MR scanner using arterial blood sampling and zero-echo time-based attenuation correction in healthy subjects and patients with epilepsy. Correlation- and Bland–Altman analysis showed fair correlation and a negative relationship with wide limits of agreement in several cortical and subcortical regions. Thus, agreement with 15O-water is insufficient for absolute quantification with ASL, but ASL provides reliable relative measures that could potentially be rescaled to absolute values. Moyamoya disease (MMD) is characterized by progressive stenosis/occlusion in large brain arteries. A limitation of ASL is the sensitivity to prolonged arterial transit times, which is common in the collateral vessels of the brain in patients with MMD. Given the non-invasiveness and non-ionizing exposure, ASL has a pronounced potential for use in diagnostic imaging in patients with MMD. ASL was performed before and after administration of acetazolamide; CBF and cerebrovascular reserve capacity were derived for large vascular regions. Artefacts originating from prolonged arterial transit times were found to have negligible effects on CBF and cerebrovascular reserve capacity derived from ASL. This thesis adds to the understanding of potential and limitations of perfusion MRI in neurological diseases. 

  • Effectiveness and cost-effectiveness of indicated preventive interventions for depression in adolescents : An application of health economics methods Author: Richard Ssegonja Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-404547 Publication date: 2020-03-25 07:57

    Unipolar depressive disorders are commonly encountered conditions in clinical practice with about 25% reporting their first episode during adolescence. Longitudinal studies show adolescent depression to be associated with an increased risk of mental illness in adulthood, healthcare usage, poor educational outcomes, unemployment, and dependency on welfare recipiency. Therefore, adolescent depression contributes a high disease burden and impinges a considerable financial strain on society’s limited resources.

    Several preventive interventions have been developed to prevent adolescent depression. Of these interventions, group-based cognitive behavioural therapy (GB-CBT) indicated preventive interventions for depression are well studied and accepted. However, evaluations of their effectiveness and cost effectiveness have yielded conflicting and incomplete results mainly due to methodological limitations.

    Therefore, the overarching aim of this thesis was to investigate the effectiveness and cost-effectiveness of GB-CBT indicated preventive interventions for depression in children and adolescents, and estimate the additional healthcare costs and welfare burden in early to mid-adulthood associated with adolescent depression.

    In study I, GB-CBT indicated preventive interventions for depression in children and adolescents were protective against developing a depressive disorder and also reduced depressive symptoms. The intervention relative effect was noted to decay over time. Study II revealed that adolescent depression was associated with considerable increased healthcare consumption in mid-adulthood compared to the non-depressed peers at a population level. This finding was more pronounced in females with persistent depressive disorder (PDD). Study III showed adolescent depression to be associated with all the forms of social transfer payments (welfare) especially in individuals with PDD and those with early comorbid psychopathologies.

    Study IV demonstrated that GB-CBT indicated preventive interventions for adolescent depression are not only effective but also have the potential to be cost-effective compared to leaving adolescents with subsyndromal depression unattended.

    Findings from studies II and III, emphasized the large financial burden to society in terms of additional healthcare costs and welfare expenditure associated with adolescent depression. Whereas, study I and IV bring forward the message that it is possible to change the course of subsyndromal depression by offering GB-CBT indicated preventive interventions to adolescents with subsyndromal depression. Such an initiative was not only cost-effective compared to not intervening, but also largely cost-saving. Therefore, GB-CBT indicated preventive interventions could be used as part of a stepped care program linking into more specialized care services. The results of this thesis will be useful in decision-making concerning the resource allocation related to adoption and implementation of such preventive measures.

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