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Coming dissertations at MedFak

  • Before Being Born : Studies on Preconception Health and Unplanned Pregnancies in Low- and High-Income Settings Author: Jenny Niemeyer Hultstrand Link: Publication date: 2021-02-05 12:39

    Nearly half of all pregnancies globally are unplanned. They represent a failure to meet individuals’ reproductive health needs and are associated with adverse maternal and child outcomes. Preconception and contraception care can help improving outcomes of pregnancies that are desired, and preventing those that are undesired. The aim of this thesis was to investigate factors that affect individuals and their children before they are born: parental preconception health and pregnancy planning. These phenomena were studied in Sweden and in Eswatini. Furthermore, a counseling tool to improve preconception care called the Reproductive Life Plan (RLP) was evaluated in Eswatini.

    In Sweden, baseline data from a cohort on pregnant women (n=3,389) of different origin were used. Many Nordic-born women drank alcohol (80% n=2,400) and smoked (20% n=607) preconception. Women born outside Europe were less likely to have these habits but more likely to have an unplanned pregnancy compared with Nordic-born women (AOR 1.37; 95% CI 1.01, 1.88).

    In Eswatini, data from client records were used (n=1,436). Seven out of ten pregnancies were unplanned (789/1,124). Adolescents had more than two-fold increased odds of unplanned pregnancy compared with women aged 20 or older (AOR 2.39; 95% CI 1.53, 3.75). Women with unplanned pregnancies were less likely to attend antenatal care (AOR 0.68; 95% CI 0.49, 0.95). 

    We collected qualitative data on unplanned pregnancy using focus groups discussions (n=3) with health workers called mentor mothers (n=29). Unplanned pregnancies were thoroughly perceived as negative events with major social and health implications. Driven by poor socioeconomic conditions, young women often engaged in sexual relationships characterized by violence and gender inequality, resulting in unplanned pregnancies. These pregnancies often resulted in neglected children growing up to become vulnerable adolescents at risk of becoming pregnant unintendedly, thus generating a perpetuating cycle of unplanned childbearing.

    The RLP was used by the mentor mothers in client counseling (n=29). Focus groups discussions (n=7) and a questionnaire were used to collect data. The mentor mothers were key persons in implementing the RLP. Using this tool, they observed progress in pregnancy planning among their clients and thought it improved quality of contraceptive care. The clients' ability to form and achieve their reproductive goals was hindered by contextual factors such as intimate partner violence and limited reproductive health and rights.

  • Phosphoinositides control insulin secretion through multiple routes Author: Phuoc My Nguyen Link: Publication date: 2021-02-01 12:15

    Glucose-stimulated insulin secretion from pancreatic beta cells is the sequence of events that starts with glucose uptake and ends with the fusion of insulin granules with the plasma membrane through Ca2+-triggered exocytosis. Phosphoinositides are minor components of all cellular membranes, yet play fundamental roles as regulators of many cellular processes. PI(4,5)P2 is the most abundant phosphoinositide in the plasma membrane, where it controls the activity of ion channels, endo- and exocytosis and cytoskeletal rearrangements. However, its role in the regulation of insulin secretion is unclear and there are support for both direct stimulatory and inhibitory effects. Using an optogenetic approach to acutely recruit a PI(4,5)P2 phosphatase to deplete the plasma membrane of PI(4,5)P2 in living beta cells, we found that this lipid was required to support voltage-dependent Ca2+-influx and glucose-stimulated insulin secretion. Consistently, depolarization-induced Ca2+-influx was instead augmented when the plasma membrane PI(4,5)P2 concentration was increased by light-dependent recruitment of a PI(4,5)P2-synthesizing enzyme. PI(4)P is another phosphoinositide residing in the plasma membrane and other intracellular membranes. In addition to serving as a precursor for PI(4,5)P2, PI(4)P is used to fuel lipid exchange reactions at membrane contacts sites, such as the PI(4)P/cholesterol exchange at the ER-Golgi interface catalyzed by OSBP. Sac2 is a PI(4)P phosphatase that is highly expressed in neuronal tissues and the pancreas, where it localizes to endosomes and participates in endosome maturation. We found that Sac2 additionally binds to insulin granules through interactions with granule PI(4)P and Rab3. Loss of Sac2 resulted in accumulation of both PI(4)P and cholesterol on the granule surface, impaired insulin granule docking to the plasma membrane and reduced insulin secretion. The cholesterol levels on insulin granules were normalized in cells with reduced OSBP expression, indicating that Sac2 and OSBP cooperate at insulin granules. Acute inhibition of OSBP by OSW-1 resulted in the redistribution of OSBP, and its ER localized receptor VAP-A, from the ER-Golgi interface to insulin granules. Similar to loss of Sac2, both siRNA-mediated knockdown and pharmacological inhibition of OSBP resulted in decreased insulin secretion. Together, these results show that Sac2, by negatively regulating granule PI(4)P, limits OSBP-mediated cholesterol transfer to insulin granules at ER–insulin granule contact sites. Type-2 diabetes is associated with impaired insulin granule docking and exocytosis as well as altered cholesterol homeostasis. We found that Sac2 expression was reduced in patients with type-2 diabetes, which may help to explain some of the hallmarks of this disease at the level of the beta cell and also form the basis for future interventions.

  • Equity in Treatment and Outcomes among Heart Failure Patients in Sweden : The role of gender, age and socioeconomic factors in access to treatment and mortality Author: Anna Ohlsson Link: Publication date: 2021-01-29 07:57

    There is extensive empirical evidence for inequity in health and health care between and within countries across all economic levels worldwide. In Sweden, the Health and Medical Services Act states that health care should provide good health and equal health care for the entire population, but this goal has yet to be fulfilled. Equity has been defined as “differences which are unnecessary and avoidable, but in addition are considered unfair and unjust”. Equity in health is closely linked with the so-called social determinants of health, or the conditions in which people are born, grow, live, work, and age.

    Heart failure (HF) is a common disease globally, carrying high morbidity and mortality, and is one of the major causes of hospitalisations in Sweden. There is a strong evidence base for renin angiotensin system blockers (RASb) as well as beta-blockers (BB) reducing mortality in HF, and long-standing recommendations for these medications in treatment guidelines. However, not all eligible patients receive this first-line treatment. There has been some evidence of inequity by gender and age in treatment of HF, but evidence regarding socioeconomic risk factors has been scarce.

    In this thesis, differences in access to pharmacological therapy by demographic and socioeconomic factors were investigated.

    Observational studies with cohort designs were performed. In Study I–III large national population-level interlinked register materials were investigated, and in Study IV a well characterised cohort including clinical and prescription data from the SwedeHF, a Swedish HF quality register, was analysed.

    In Study I, we investigated differences in access to angiotensin-converting enzyme inhibitors (a type of RASb) by gender, age, educational level, employment status, income and immigration status among hospitalised HF patients in Sweden. In Study II we aimed to investigate effectiveness, i.e., the association between RASb exposure and mortality, among hospitalised HF patients in Sweden, and whether effectiveness varied with gender and age. In Study III, RASb access and mortality by employment status and educational level among hospitalised HF patients in Sweden of working age was analysed, along with possible excess mortality among non-employed patients without access to RASb. In Study IV, medication adherence to mortality-reducing HF medications, i.e., RASb and BB, was examined by age, gender, educational level, marital status and income.

    In conclusion, the studies in the thesis showed that access to RASb treatment appeared inequitable for women, the non-employed, and the elderly among hospitalised HF patients, although this treatment was associated with lower mortality for all these groups. Furthermore, RASb treatment was associated with similar reductions in mortality for women and men, but the association was somewhat weaker among older compared with younger hospitalised HF patients. In addition, non-employment and lower educational level were associated with higher mortality in hospitalised HF patients, and non-employment was associated with less access to RASb treatment. Finally, lower income and single status were associated with lower adherence to mortality-reducing treatment with BB and RASb in a quality register HF cohort, while associations were more unclear regarding gender and age.