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Coming dissertations at MedFak

  • Internet-based Psychosocial Support : Design, Effects and User Experience in the Cancer Setting Author: Anna Hauffman Link: Publication date: 2020-05-20 08:42

    Background and Aim Being diagnosed with cancer is often described as a major loss of control leading to severe psychological distress and symptoms of anxiety and depression can continue to affect the individual in the long term. The cancer and its treatment may influence all dimensions of health, thus the psychosocial support provided needs to be multifaceted and easy accessed. Internet-based interventions may be one way to provide such support, but evidence is limited. This thesis aimed to investigate the design, effects, and experiences of internet-based psychosocial support in cancer.

    Methods and Results Study 1 encompassed a co-creation development process resulting in the interactive support provided as the first step in an internet-based stepped care intervention (iCAN-DO). The effects of iCAN-DO were investigated in a randomised controlled trial, targeting individuals newly diagnosed with cancer and concurrent self-reported symptoms of anxiety and depression (according to the Hospital Anxiety and Depression Scale). Step 1 had a psycho-educative content involving self-care strategies and was available to the intervention group during the ten-month study period. Step 2 comprised a guided internet-based cognitive behavior therapy (iCBT) program and was offered those without improvement in anxiety and depression after using Step 1. The results showed that iCAN-DO improved symptoms of depression compared with standard care, while symptoms of anxiety were largely unaffected. Most participants used Step 1, while only a few used Step 2.

    In Study 2, aspects of usefulness, relevance, and usability in iCAN-DO were explored through qualitative interviews, analysed using content analysis. Results showed that standard healthcare did not meet the individuals' needs and iCAN-DO was used as complement, providing access to relevant, trustworthy information and support. Usability was affected by the perceived usefulness and ease of use of the intervention, as well as by the user´s circumstances in life and consequences of the cancer. The co-creation process in the development of Step 1 added relevance, but both steps 1 and 2 would have gained from being provided earlier, integrated into standard healthcare and more adaptable to the individual.

    Conclusion The thesis concluded that the internet-based intervention had positive effects on symptoms of depression in individuals newly diagnosed with cancer. Individuals with cancer experience several unmet needs in standard healthcare and since psycho-educative support including self-care advice seems feasible in this group, efforts are needed to incorporate internet-based support in regular oncology care. Since the intervention did not target all symptoms (i.e. anxiety) further research is needed on how to enhance efficacy and how to make iCBT more feasible for this group.

  • Social Stratification of Children's Diet and Nutrition: Understanding Women's Situation in Addis Ababa Author: Hanna Yemane Berhane Link: Publication date: 2020-05-19 10:50

    Background: Childhood undernutrition is the cause of nearly half of all deaths in under-five children. In sub-Saharan African countries, this problem is further complicated by the rising prevalence of overweight. Mothers play a key role in child care and nutrition, however, in cities that are undergoing rapid social and economic changes, little is known about their lived experiences and challenges. Moreover, little is known about the influence of the neighbourhood food environment and family socio-economic conditions of food acquisition and intake in sub-Saharan Africa. Therefore, the study aims to understand the nexus between mothers’ child care and feeding experiences, neighbourhood food environment, diet diversity, and family socioeconomic status. Methods: A mixed qualitative and quantitative study design was used. The qualitative component involved thirty-six in-depth interviews with mothers who had children under the age of five years. A thematic analysis approach was used to analyse verbatim transcripts. For the quantitative component, two rounds of cross-sectional household surveys were conducted. The sample was drawn from all districts of Addis Ababa; a total of 5467 households with mother-child pairs. Data were analysed using a generalised estimating equation (GEE) and mixed-effect logistic regression model. Results: Urban mothers are under pressure to ensure their child gets adequate care and food; the changes in their environment owing to the reconstruction of city and migration further limit their ability to do so. Mothers expressed that their decision of what to feed their children is influenced by children’s preferences, perceived safety of the food, familiarity with the food, and affordability.

    Children receiving the recommended minimum diet diversity totaled 59.9% (58.5–61.3). Having an adequately diverse diet was associated with having an educated mother, and being from the wealthier and more food-secure households. Animal source and vitamin-A-rich food groups are the least affordable and consumed food groups in the study settings. Families with uneducated mothers, in the lowest wealth group and those who perceived food groups to be unaffordable, consumed a less diverse diet.

    The prevalence of stunting was 19.6% (18.5–20.6) and that of over-weight/obesity was 11.4% (10.6–12.2). Maternal education level was associated with both forms of malnutrition; children with uneducated mothers were more likely to be stunted (AOR: 1.8; 1.4–2.2) and less likely to be overweight/obese (AOR: 0.61; 0.44–0.84), while being from the highest wealth household and from a severely food insecure household were associated with a higher likelihood of obesity and stunting, respectively. Conclusion: Child nutritional outcomes and diet quality vary by the socioeconomic status of the family; particularly that of mothers. Therefore, efforts to improve diet and nutritional outcomes of children need to consider mechanisms to strongly support mothers.

  • The activation and regulation of plasmacytoid dendritic cells in SLE : and possible therapeutic interventions Author: Karin Hjorton Link: Publication date: 2020-05-18 14:03

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by the presence of anti-nuclear antibodies and the formation of nucleic acid containing immune complexes (ICs), which can cause organ damage by deposition in tissues. ICs strongly trigger the plasmacytoid dendritic cells (pDCs) to produce interferon (IFN)-α, which potently activates the immune system. An activated type I IFN system is seen in a majority of SLE patients. Natural killer (NK) cells enhance the IC triggered response of pDCs. Other NK cell alterations are described in SLE. Standard SLE treatment, hydroxychloroquine (HCQ), reduces flare risks, and HCQ concentration measurement can optimize its dosing. However, new treatments are needed.

    In paper I, we screened for autoantibodies to lectin-like NK cell receptors. In 3.4% of SLE patient sera, autoantibodies to CD94/NKG2A and CD94/NKG2C were found, which interfered with HLA-E mediated regulation of NK cell cytotoxicity, and facilitated elimination of target cells expressing expressing these receptors. Autoantibody levels correlated with SLE disease activity and with a more severe disease phenotype.

    In paper II, we found that RNA-IC triggered proinflammatory cytokine production in immune cells from healthy blood donors and SLE patients. After RNA-IC stimulation of pDCs, RNA sequencing detected 975 differentially expressed genes, connected to cytokine pathways, cell regulation and apoptosis. An IRAK4i had a broader inhibitory effect on RNA-IC triggered cytokine production and pro-inflammatory pathways than HCQ.

    In paper III we showed that RNA-IC induced type III IFN production in a subset of pDCs (3%) which also produced type I IFN. Type III IFN production by pDCs was enhanced by NK and B cells, as well as by IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6 and GM-CSF. Type III IFN production by RNA-IC stimulated immune cells of SLE patients was detected in a minority. IFN-α2b and GM-CSF increased the proportion of responders to RNA-IC from 11 to 33%.

    In paper IV a LC-HRMS method, was evaluated for HCQ concentration measurement in whole blood (WB), serum and plasma from 26 SLE patients. The levels in WB were approximately 2-fold compared to serum and plasma, and correlated with weekly HCQ-dose. Large inter-individual variations were observed, despite equal doses. The WB matrix showed superior reproducibility in patient samples (CV<5%).

    These findings add to the knowledge of how cytokine production by pDCs in SLE is regulated, and support a role for NK cells in the pathogenesis of SLE. Moreover WB was the superior matrix for HCQ measurement in SLE patients.