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- Nerpin, Elisabet, 1962-
(författare)
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The Kidney in Different Stages of the Cardiovascular Continuum
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.
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| 2. |
- Byrskog, Ulrika, 1970-
(författare)
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’Moving On’ and Transitional Bridges : Studies on migration, violence and wellbeing in encounters with Somali-born women and the maternity health care in Sweden
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the latest decade Somali-born women with experiences of long-lasting war followed by migration have increasingly encountered Swedish maternity care, where antenatal care midwives are assigned to ask questions about exposure to violence. The overall aim in this thesis was to gain deeper understanding of Somali-born women’s wellbeing and needs during the parallel transitions of migration to Sweden and childbearing, focusing on maternity healthcare encounters and violence. Data were obtained from medical records (paper I), qualitative interviews with Somali-born women (II, III) and Swedish antenatal care midwives (IV). Descriptive statistics and thematic analysis were used. Compared to pregnancies of Swedish-born women, Somali-born women’s pregnancies demonstrated later booking and less visits to antenatal care, more maternal morbidity but less psychiatric treatment, less medical pain relief during delivery and more emergency caesarean sections and small-for-gestational-age infants (I). Political violence with broken societal structures before migration contributed to up-rootedness, limited healthcare and absent state-based support to women subjected to violence, which reinforced reliance on social networks, own endurance and faith in Somalia (II). After migration, sources of wellbeing were a pragmatic “moving-on” approach including faith and motherhood, combined with social coherence. Lawful rights for women were appreciated but could concurrently risk creating power tensions in partner relationships. Generally, the Somali-born women associated the midwife more with providing medical care than with overall wellbeing or concerns about violence, but new societal resources were parallel incorporated with known resources (III). Midwives strived for woman-centered approaches beyond ethnicity and culture in care encounters, with language, social gaps and divergent views on violence as potential barriers in violence inquiry. Somali-born women’s strength and contentment were highlighted, and ongoing violence seldom encountered according to the midwives experiences (IV). Pragmatism including “moving on” combined with support from family and social networks, indicate capability to cope with violence and migration-related stress. However, this must be balanced against potential unspoken needs at individual level in care encounters.With trustful relationships, optimized interaction and networking with local Somali communities and across professions, the antenatal midwife can have a “bridging-function” in balancing between dual societies and contribute to healthy transitions in the new society.
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| 3. |
- Granström, Therese, 1969-
(författare)
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Patient-reported and medical outcomes in patients treated for diabetic macular edema : A real-world longitudinal study
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Diabetes mellitus can lead to complications, when the complication affects the eyes it is called retinopathy. This can affect the macula and lead to severe loss of vision, diabetic macular edema (DME). This condition has traditionally been treated with laser. However, in 2011, anti-vascular endothelial growth factor (anti-VEGF) injections in the eye were approved as a treatment for diabetic macular edema, and started to be used in eye clinics.Aim The overall aim of this thesis was to describe patient-reported outcomes and medical outcomes (PRO) in people treated for diabetic macular edema in a real-world setting in a long-time follow-up study in Sweden.Methods Participants were enrolled at two eye clinics at two county hospitals in Sweden between 2012 and 2014. Patient-reported outcomes were measured using a vision-specific questionnaire, the 25-question National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and a generic questionnaire, the Short Form-36 Health Survey (SF-36). Completed questionnaires, medical data such as visual acuity (EDRS), macula swelling (OCT) and social background characteristics were collected before treatment start, at one-year and four-year follow up points. The data was analyzed, descriptive statistics developed and comparative analyses were performed. Interviews were performed before treatment start and were analyzed using qualitative content analysis.Results A total of 59 participants were included at baseline. The mean age was 69 years, with an equal gender distribution. At baseline, the participants scored a low general health with the vision-specific questionnaire. In total, 21 participants were interviewed, and a theme emerged of ‘being at a crossroads and a crucial phase in life with an uncertain outcome’. The participants expressed thoughts and concerns at different levels, including practical concerns about the treatment procedure and more existential thoughts about hope for improved visual acuity or fear of deterioration. The results at the one-year follow up showed that 30 patients had improved visual acuity and reported an improvement in several subscales in the NEI VFQ-25. The remaining 27 participants had no improvement in visual acuity or in the vision specific questionnaire. The four-year follow-up involved 37 people, and the result showed significant improvement in subjective near-vision activities and improved distance visual acuity.Conclusion: Before treatment, the participants reported low general health and expressed concerns about the injection treatment and their vision. One year after treatment started, the results showed significant improvement in several NEI VFQ-25 subscales, decreased macula swelling and improved visual acuity. These positive results remained at the four-year follow-up point.
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| 4. |
- Jobs, Elisabeth
(författare)
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Cathepsin S as a Biomarker of Low-grade Inflammation, Insulin Resistance, and Cardiometabolic Disease Risk
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations.
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| 5. |
- Malm, Mari-Cristin, 1956-
(författare)
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Fetal Movements in late Pregnancy : Categorization, Self-assessment, and Prenatal Attachment in relation to women’s experiences
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To explore how pregnant women experience fetal movements in late pregnancy. Specific aims were: to study women’s experiences during the time prior to receiving news that their unborn baby had died in utero (I), to investigate women’s descriptions of fetal movements (II), investigate the association between the magnitude of fetal movements and level of prenatal attachment (III), and to study women’s experiences using two different self-assessment methods (IV).Methods: Interviews, questionnaires, and observations were used.Results: Premonition that something had happened to their unborn baby, based on a lack of fetal movements, was experienced by the participants. The overall theme “something is wrong” describes the women’s insight that the baby’s life was threatened (I). Fetal movements that were sorted into the domain “powerful movements” were perceived in late pregnancy by 96 % of the participants (II). Perceiving frequent fetal movements on at least three occasions per 24 hours was associated with higher scores of prenatal attachment in all the three subscales on PAI-R. The majority (55%) of the 456 participants reported average occasions of frequent fetal movements, 26% several occasions and 18% reported few occasions of frequent fetal movements, during the current gestational week. (III). Only one of the 40 participants did not find at least one method for monitoring fetal movements suitable. Fifteen of the 39 participants reported a preference for the mindfetalness method and five for the count-to-ten method. The women described the observation of the movements as a safe and reassuring moment for communication with their unborn baby (IV).Conclusion: In full-term and uncomplicated pregnancies, women usually perceive fetal movements as powerful. Furthermore, women in late pregnancy who reported frequent fetal movements on several occasions during a 24-hour period seem to have a high level of prenatal attachment. Women who used self-assessment methods for monitoring fetal movements felt calm and relaxed when observing the movements of their babies. They had a high compliance for both self-assessment methods. Women that had experienced a stillbirth in late pregnancy described that they had a premonition before they were told that their baby had died in utero.
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| 6. |
- Skoglund, Lena, 1980-
(författare)
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Molecular Mechanisms of Frontotemporal Lobar Degeneration
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases.In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts.Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency.In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations.In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.
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| 7. |
- Ternström, Elin, 1982-
(författare)
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Identification and Treatment of Women with a Fear of Birth
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although a fear of birth affects many women during pregnancy and is associated with adverse birth outcomes, it is rarely measured in clinical practice and evidence-based treatments are lacking. The aim of this thesis was to assess the clinical utility of the Fear of Birth Scale, and to evaluate the effect of guided Internet-based cognitive behavior therapy compared with standard care on the levels of fear of birth in pregnant and postpartum women.This thesis consists of four papers originating from three studies. The Fear of Birth Scale was used to measure fear of birth among pregnant women in all three studies. In Study I, prevalence of fear of birth among Swedish-born and foreign-born pregnant women was measured, and in Study II, 31 pregnant women were interviewed about their thoughts when assessing fear of birth. In Study III, a multicenter randomized controlled trial was conducted to compare guided Internet-based cognitive behavior therapy (ICBT) with standard care for pregnant women with a fear of birth.Fear of birth was identified among 22% of the pregnant women. Prevalence was twice as high among the foreign-born women (37%) compared to the Swedish-born women (18%). When asking the participants what they thought when assessing their fear on the Fear of Birth Scale, they confirmed that they had understood the measurement intent of the scale. The randomized controlled trial showed that fear of birth decreased during pregnancy and postpartum in both groups. However, the levels of fear decreased more in the guided ICBT-group when measuring fear of birth up to one year postpartum. The changes in fear of birth over time did not differ between parity groups.Altogether, these results suggest that the Fear of Birth Scale is a suitable screening instrument for identifying pregnant women with a fear of birth in a clinical setting and that such screening would be beneficial, as it probably would increase the chance of achieving a more equitable care. As the effect of time during pregnancy and postpartum was most evident in reducing fear of birth, this can be communicated to pregnant women, along with a continuous dialogue about how the women experience fear during pregnancy.
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| 8. |
- Westin, Jerker, 1971-
(författare)
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Decision Support for Treatment of Patients with Advanced Parkinson’s Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to develop, deploy and evaluate new IT-based methods for supporting treatment and assessment of treatment of advanced Parkinson’s disease. In this condition a number of different motor and non-motor symptoms occur in episodes of varying frequency, duration and severity. In order to determine outcome of treatment changes, repeated assessments are necessary. Hospitalization for observation is expensive and may not be representative for the situation at home. Paper home diaries have questionable reliability and storage and retrieval of results are problematic. Approaches for monitoring using wearable sensors are unable to address important non-motor symptoms. A test battery system consisting of both self-assessments of symptoms and motor function tests was constructed for a touch screen mobile phone. Tests are performed on several occasions per day during test periods of one week. Data is transmitted over the mobile net to a central server where summaries in different symptom dimensions and an overall test score per patient and test period are calculated. There is a web application that graphically presents the results to treating clinical staff. As part of this work, a novel method for assessment of spiral drawing impairment useful during event-driven sampling was developed. To date, the system has been used by over 100 patients in 10 clinics in Sweden and Italy. Evidence is growing that the test battery is useful, reliable and valid for assessment of symptoms during advanced Parkinson’s disease. Infusion of a levodopa/carbidopa gel into the small intestine has been shown to reduce variation in plasma drug levels and improve clinical response in this patient category. A pharmacokinetic-pharmacodynamic model of this intestinal gel infusion was constructed. Possibly this model can assist the process of individualization of dosage for this treatment through in numero simulations. Results from an exploratory data analysis indicate that severity measures during oral levodopa treatment may be factors to consider when deciding candidates for infusion treatment.
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