Coming dissertations at MedFak
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Contextualising a South African social innovation for maternal and child health to mothers with experiences of migration in Sweden
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524965
Despite a universally accessible and high-quality welfare system, disparities in health and wellbeing persist between families who have migrated to Sweden and the native population. The South African Mentor Mother programme, a social innovation for maternal and child health among socially disadvantaged communities, was transferred and adapted to benefit mothers and pregnant women with experiences of migrating to Sweden.
This thesis aims to explore the adaptation, implementation and further development of the South African Mentor Mother programme in two locations in Sweden, based on professional and lived experience among various groups of stakeholders.
In Study I, three workshops and eleven interviews were held with stakeholders to explore central aspects of the adaptation process. These aspects entailed prioritising social determinants of health over health behaviour change, using indirect mechanisms and social ripples to achieve change, prioritising referring clients over intervening directly, recruiting peer supporters with competencies responding to a heterogeneous socio-cultural context, and allowing flexibility in programme content and methods.
In Study II, nineteen interviews with different stakeholders and digital field logs of peer support meetings (n=1,294) were used to evaluate the implementations of the programme. Contextual factors of importance included institutional mistrust, gender norms, unpredictable funding, and the organisation's third sector affiliation. Peer supporters prioritised linking clients to welfare services over educational intervention components, and sometimes experienced blurring between professional and personal roles. Practical support and trustful relationships emerged as important entry points to support more sensitive issues.
In Study III, the photovoice method was used to conduct a focus group discussion and six interviews with Mentor Mothers and their coordinator in Gothenburg, exploring how they developed empowerment strategies perceived to be relevant, feasible and effective. These strategies consisted of various aspects of using both informative, practical, psychosocial and motivational support to meet community health and social needs.
In Study IV, twenty-one interviews with Mentor Mothers, client mothers and other stakeholders were conducted to explore the emergence and management of mistrust in welfare services in Gothenburg. Mistrust was described to arise through rumours, unclear interactions with services, and lack of familiarity with the welfare system. Mentor Mothers used various strategies to build trusting relations with clients, which enabled them to promote institutional trust through information and humanisation of service providers.
This thesis illustrates how innovative community-based solutions to complex societal problems can be transferred between contexts, implemented and further developed to ensure their relevance to the target group.
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Polycystic ovary syndrome and pregnancy complications : Focus on hyperandrogenism and comorbidity
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524847
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women, affecting their lives in many ways. PCOS is characterised by ovulatory dysfunction, polycystic ovary morphology and hyperandrogenism, either clinical or biochemical. Women with PCOS face a higher risk of obstetric complications than women without PCOS. There are many factors that contribute to these complications, such as metabolic disturbances, insulin resistance, chronic inflammation, hyperandrogenism and factors related to infertility.
The overall aim of the research presented in this thesis was to study factors that might affect the association between PCOS and pregnancy complications. The thesis consists of matched cohort studies based on data from the Uppsala Biobank of Pregnant Women (Papers I and II) and national register-based cohort studies (Papers III and IV). In the first two studies, we included women with PCOS (n = 159) and BMI-matched controls (n = 320), and the aim was to study the effect of high anti-Müllerian hormone (AMH) and testosterone on pregnancy complications. The third study (n = 138 219) explored whether the association between PCOS and preeclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of preeclampsia. In the fourth study (n = 281 806), the aim was to explore association and risk estimates for pregnancy outcomes in women with either or both PCOS and gestational diabetes mellitus (GDM).
The main results were that women with PCOS have higher levels of AMH and testosterone and a higher free androgen index during second trimester pregnancy than non-PCOS controls. High AMH levels were not associated with adverse pregnancy outcome or birthweight. PCOS women with the highest testosterone levels had the highest risk for preeclampsia. Compared to non-PCOS controls, women with PCOS have increased risk of preeclampsia, especially the more severe subtypes of preeclampsia, early onset or with a birth of an infant born small for gestational age. With available data, we were unable to determine whether hyperandrogenism affects the risk of preeclampsia. The combination of PCOS and GDM exacerbates the risk of adverse pregnancy outcomes for both mother and infant compared with women with either PCOS or GDM alone.
In conclusion, the research presented in this thesis adds important information about the association of PCOS and the more severe subtypes of preeclampsia and underpins the importance of an increased awareness of PCOS in antenatal care along with early screening for diabetes and hypertensive disorders.
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Clinical and Genetic studies in Chronic Myeloid Leukaemia
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524571
This thesis explores strategies to enhance deep molecular response (DMR) rates and treatment-free remission (TFR) eligibility in chronic myeloid leukaemia (CML), investigates factors linked to treatment milestone failures, describes tyrosine kinase inhibitor (TKI) discontinuation outcomes in a population-based cohort, and examines TFR probabilities after a second TKI discontinuation. In paper I we examined data from the Swedish CML registry on 128 CML patients in chronic phase with a reported TKI discontinuation of ≥1 month due to DMR. Findings indicate that patients discontinuing a 2nd generation TKI had a higher probability of remaining treatment-free, and 11% of patients with a diagnosis of CML in chronic phase were treatment free by last follow-up. Paper II involved a long-term follow-up of 40 patients treated initially with a 2nd generation TKI, dasatinib, combined with a low dose of pegylated interferon α2b as part of the phase II study NordCML007. The combination had an acceptable toxicity profile, and the occurrence of late dasatinib-related adverse events was not increased compared with previous studies of single treatment with dasatinib. The proportion of patients achieving major and DMR were high in comparison with historical cohorts of patients treated with dasatinib. In paper III, an interim analysis was conducted on CML patients attempting a second TKI discontinuation within the DAstop2 study, after a prior molecular relapse. After a median 27 months from the second discontinuation attempt, 50% had re-initiated TKI therapy, and TFR rate after 12 months was 56%. Those with a short (<6 months) TFR duration after the first discontinuation attempt were more likely to experience a molecular relapse after the second discontinuation attempt. Paper IV retrospectively analysed 20 patients newly diagnosed with CML in chronic phase and primary refractory to TKI treatment without BCR::ABL1 kinase domain mutations. Diagnostic samples were analysed for pathogenic variants in a panel of 54 genes recurrently mutated in myeloid neoplasms. Pathogenic variants were seen in 50% with AXL1 being the most frequently affected gene. All patients with truncating ASXL1 variants exhibited resistance to multiple TKIs. Overall, this thesis highlights the potential of TKI discontinuation in selected CML patients, the promising combination of dasatinib and pegylated interferon α in achieving high DMR rates, and the importance of genetic profiling in understanding TKI resistance.