| 31. |
- Wide, Peter, 1972-
(författare)
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Neurogenic bladder and bowel dysfunction : Clinical aspects in children with spinal dysraphism
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinal dysraphism (SD) is a congenital malformation that to a varying extent, often severely, affects the life of the child and the family. Most individuals with SD suffer from neurogenic bladder and bowel dysfunction—with the risk of urinary tract infections, renal deterioration, urinary and fecal incontinence—that affects social participation and quality of life negatively. In newborns with SD, early detection of neurogenic bladder dysfunction and determination of post-void residual urine are required to determine the need of clean intermittent catheterization (CIC) and follow-up.The non-invasive method of four-hour voiding observation with provocation test (VOP) was used to evaluate bladder function in 50 newborn children with SD. Voiding patterns for the children were described and compared with those of 50 healthy newborns evaluated with VOP in an earlier study. Comparison revealed significant differences among several variables. In particular, leakage at provocation test and not voiding with a stream were common in newborns with SD but did not occur in healthy newborns. VOP is a non-invasive standardized method to determine residual urine in newborns with SD. It also adds information on voiding pattern, frequency, voiding with a stream and leakage at provocation.Findings in neonatal VOP of the same cohort of newborns with SD were then related to radiology, presence of urinary tract infections during the first year, and urodynamic findings and use of CIC at the age of one year. It was found that, in children with SD, not voiding with a stream may have a predictive value for the need of CIC at the age of one year, followed probably by lifelong CIC. Despite this, the presence of an open SD per se has stronger predictive value, and each child needs to be evaluated individually while considering a number of factors. The main value of VOP may be as a structured non-invasive screening method to uncover neurogenic bladder-sphincter dysfunction in the newborn. Studies with a larger number of subjects than the present are needed to evaluate the potential of VOP in newborns with closed spinal dysraphism in whom the neurological consequences vary.A retrospective analysis detected renal damage on DMSA scintigraphy in 5 of 41 children with SD who were followed according to a proactive national program with minimal use of surgery. Median follow-up time was 10 years. High baseline pressure was confirmed as a risk factor for renal damage. Compliance with treatment and follow-up is likely to be an important factor for renal health. Therefore, efforts to support children and their families are crucial. A questionnaire-based study of 107 children with SD (age 6–16y) in Sweden and Norway examined aspects of treatment for neurogenic bowel dysfunction focusing on incontinence, independence, general satisfaction and quality of life. It was found that transanal irrigation (TAI) and antegrade colonic enemas (ACE) are effective treatments, but are time-consuming and difficult to perform independently. The majority of children using TAI (72%) and ACE (63%) never went to the toilet alone to empty their bowels. As children achieving independence on the toilet reported higher quality of life, efforts to support independence are beneficial.Continent, self-managing children with healthy kidneys enjoy high quality of life and contribute more fully to society. Therefore, further research is required to investigate and develop existing and new technologies and methods that mitigate the problems related to SD, and to make them accessible to all children with spinal dysraphism.
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| 32. |
- Wolgast, Emelie, 1982-
(författare)
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Drug use during pregnancy with focus on antidepressants
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: More than half of pregnant women use at least one prescribed medication during pregnancy, and almost all pregnant women use some kind of over-the-counter medication. Depression is one of the most common diseases in the world today, also during the peripartum period. The prevalence of pregnant women using antidepressant medication is increasing. General knowledge about the use of medication during pregnancy needs to improve. The overall aim of the studies on which this thesis is based is therefore to examine different aspects of medication use during pregnancy, with a focus on antidepressants.Material and methods: Study I was a questionnaire study where 850 pregnant women were asked about their perceptions on medication use during pregnancy. In Study II, plasma samples from 200 women were obtained at gestational weeks 10-12 and 25, and screened for drugs. The results of the analysis were compared with medication use noted in antenatal medical care records. Study III was a national register‐based cohort study including 262,329 pregnant women, and their first child born in 2012-2015. Maternal obstetric and neonatal outcomes were studied in three groups: women diagnosed with depression and who had redeemed an antidepressant before becoming pregnant and women who were diagnosed with depression and who had redeemed an antidepressant both before and during pregnancy, were compared with each other and with women who had neither been diagnosed with depression nor been prescribed antidepressants. Study IV was a pharmacokinetic study that included 81 pregnant women with ongoing antidepressant medical treatment. Antidepressant drug and metabolite concentrations were measured throughout pregnancy. Participants were genotyped for enzymes involved in antidepressant drug metabolism, i.e. CYP2D6 and CYP2C19. Results and conclusions: The majority of pregnant women in our study considered the use of medication during pregnancy as either “probably harmful” or “harmful”, and this perception was associated with non-use of medication. The women had high confidence in health care professionals when seeking advice about medication.There was a good coherence between reported drug intake in antenatal care records and presence of the drug in the pregnant women’s blood. For drugs prescribed for continuous use the coherence was 100%; thus, the reported use of medication in antenatal records is reliable. Women with major depressive disorder and antidepressant medication prior to becoming pregnant were at increased risk for adverse obstetric and neonatal outcomes compared with women without major depressive disorder. Continuation of antidepressant medication during pregnancy somewhat increased the risk of adverse obstetric and neonatal outcomes. The dose-adjusted concentrations of sertraline and citalopram and their metabolites, did not change significantly throughout pregnancy. Observed concentrations of escitalopram, mirtazapine and venlafaxine did not appear to change.
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| 33. |
- Wåhlén, Karin, 1986-
(författare)
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The pain profile in fibromyalgia : Painomic studies of pain characteristics and proteins in blood
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic widespread pain (CWP), including fibromyalgia (FM), is a complex pain condition, where little is known about the molecular mechanisms contributing to its pathophysiology. To date, there are no established biomarkers for CWP/FM. This thesis has investigated potential molecular mechanisms and biomarkers in blood for chronic pain in women with CWP/FM. Furthermore, investigations are made to evaluate whether common pain characteristics such as pain intensity, sensitivity, and psychological distress in CWP/FM are correlated with specific proteins in blood.The pain profile of CWP/FM, which includes the plasma proteome and clinical characteristics, is analyzed using proteomics, advanced multivariate statistics, and bioinformatics. The results from paper I, III, and IV indicate that there are prominent systemic changes related to immunity, inflammation, and metabolic processes in women with CWP/FM compared to healthy controls. Furthermore, paper II and III show that in CWP/FM, pain intensity is related to protein profiles involved in immunity processes, psychological distress with metabolic and immunity processes, and pain sensitivity with inflammatory processes.In paper IV, the plasma proteome is investigated before and after a 15 weeks resistance exercise intervention in FM and healthy controls. Both at baseline and post exercise in FM and controls, prominent protein alterations are found that are involved in immunity, stress, mRNA stability, and muscle structure development. Exercise seems to influence clinical characteristics and circulating proteins in FM. Furthermore, specific plasma proteome profile is found related to grade of chronification, pain sensitivity, and improved muscle force of the quadriceps muscle.To summarize, the results from this thesis suggest that in CWP/FM there might be a dysregulation in the biological processes involved in the immune system and metabolic processes, which are tightly linked to several proteins in the complement system and blood coagulation cascade. These results shed light on potential ongoing mechanisms involved in the pathophysiology of the complex pain condition CWP/FM. This type of biomarker research has a large potential in increasing knowledge about mechanisms involved in CWP/FM and can hereby open for better clinical understanding and management of this and other chronic pain states. The clinical value of collecting a blood sample and measuring stable pain mechanism markers in combination with evaluation of anamnesis and clinical examination would in the future help clinicians and patients receive a faster and more precise diagnosis and ultimately better treatment strategies.
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| 34. |
- Zhang, Hui
(författare)
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Learning from Experience : The Use of Structured Video-Assisted Debriefing Among Nursing Students
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Simulation enhances experiential learning through creating experience to form the basis of learning, and it has been recognized as an effective pedagogy in current health professions education. As an integral element of simulation, debriefing contributes to transforming the created experience to new knowledge. Video-assisted debriefing (VAD) refers to adding audio-visual capture and review to traditional verbal debriefing (VD). Despite being regarded as ‘gold standard’ for simulation, evidence reporting educational effects of VAD is mixed and its best practice remains absent.Aims: The aims of this thesis were to develop a framework for VAD, to test and compare its effects on prelicensure nursing students’ debriefing experiences, reflective abilities and nursing competencies with VD without video, as well as to explore its potential impact on facilitators’ perceptions and practices following high-fidelity simulation.Design and methods: This thesis comprised of four studies with different research designs. Study I was a systematic review which synthesized the characteristics of existing VAD practices in health professions education and evaluated its effectiveness on learners’ reactions, learning and behaviors. Study II was a proof-of-concept study which developed of a three-phase framework for VAD and tested its preliminary effects on nursing students’ debriefing experiences, reflective abilities, and nursing competencies using a pretest-posttest design. Study III adopted a qualitative method to explore nursing students’ experiences and perspectives of a structured VAD using focus groups. Data were analyzed using thematic analysis approach. Study IV employed a mixed-method research design to investigate the impact of a three-phase VAD on nursing students’ debriefing experiences, perceived stress, as well as facilitators’ perceptions and debriefing practices.Results: Study I showed that existing VAD offered comparable educational effects as VD in terms of learners’ experiences, attitudes, and performance, except on knowledge acquisition. Video did not demonstrate its continuous advantage in debriefing, which informed the absence of best practice. The preliminary results of Study II reported that a three-phase VAD significantly improved students’ debriefing experiences (p<0.001), reflective abilities (p<0.01), and nursing competencies (p<0.001). Study III disclosed an emotional roller coaster experienced by nursing students in VAD, from unwillingness and fear of being judged, followed by stress and defensiveness, to sense of appreciation and satisfaction. Most students agreed that VAD provided a good learning experience with few preferred not to receive peer feedback after video review. Study IV demonstrated that VAD improved nursing students’ debriefing experiences (p=0.01) and caused comparable stress as VD. Repeated exposure to VAD significantly reduced stress levels. VAD also enhanced facilitators’ perceptions and debriefing practices.Conclusions: This project developed a three-phase framework for VAD, and affirmed its educational effects on improving nursing students’ debriefing experiences, reflective abilities, and competencies following high fidelity simulation, with comparable stress experienced as in VD. The finding of an emotional roller coaster experienced by nursing students in VAD challenged the snapshot of negative emotions reported in other studies, offering some clarity to the inconsistent evidence regarding learners’ experiences of VAD and contributing to its best practice. This thesis also proved that this three-phase VAD held the potential to enhance facilitators’ debriefing practices towards student-centered learning.
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| 35. |
- Zimdahl, Anna, 1987-
(författare)
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Pharmacogenetic studies of thiopurine methyltransferase genotype-phenotype concordance and effect of methotrexate on thiopurine metabolism
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thiopurines (6-mercaptopurine [6-MP], 6-thioguanine and azathioprine) are cytotoxic drugs used in the treatment of acute lymphoblastic leukemia (ALL), inflammatory bowel diseases, certain autoimmune diseases and after transplantation. The metabolism of thiopurines is complex with several enzymes involved in the conversion into active drug metabolites. One of the enzymes, thiopurine methyltransferase (TPMT), is one of the best examples of implemented pharmacogenetics so far. Due to lowered TPMT enzyme activity caused by genetic polymorphism, carriers of heterozygous or homozygous defective TPMT alleles need dose reduction to avoid cytotoxic adverse reactions like myelosuppression or hepatotoxicity if treated with thiopurines.To determine TPMT status before the start of treatment, genotyping (for the three most occurring TPMT alleles) and/or phenotyping (TPMT enzyme activity measurements) are used in the clinical setting. In the focus of this thesis, concordance of these methods was investigated in a large cohort of unique samples (n=12,663) collected in the routine analysis service of TPMT status determinations in Linköping. By sequencing all exons in samples where the results of the two methods differed, rare or novel TPMT alleles were discovered. Four TPMT alleles (TPMT*41, *42, *43, *44), not previously described, were characterized in terms of clinical in vivo data as well as protein structure and stability data obtained from recombinant human TPMT (rTPMT) produced by E. Coli and biophysical methods.The clinical cohort was also used in the search for other factors (except genetic factors) that influence TPMT enzyme activity, and both age and gender turned out to affect TPMT enzyme activity level. In addition, TPMT enzyme activity in the early treatment of ALL was investigated and shown to be significantly lower at time of ALL diagnosis.In the treatment protocol of ALL, the combined treatment using 6-MP and methotrexate (MTX) has increased the positive outcomes since the start in the 1950s. Despite this, the synergistic effect of these drugs is not yet fully understood. To evaluate the effect of MTX on thiopurine metabolism specifically, TPMT enzyme activity, TPMT gene expression, and thiopurine metabolite levels were determined before and after MTX infusions in vivo and after cotreatment in lymphoblasts in vitro. In the presence of MTX, TPMT enzyme activity and metabolite levels decreased, both in vivo and in vitro, although dose- and time-dependent. In addition, MTX bound to rTPMT and caused inhibition of rTPMT enzyme activity.The results found in the scope of this thesis may be used for further individualization of thiopurine treatment.
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| 36. |
- Zötterman, Johan, 1975-
(författare)
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Laser Speckle Contrast Imaging in Reconstructive Surgery
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesReconstructive surgery aims to restore function or normal appearance by reconstructing defective organs after trauma or disease. In patients undergoing reconstructive surgery, previous trauma, surgery or radiotherapy can result in compromised blood supply. This will affect the viability of the tissue and increases the risk for postoperative complications, such as ischemia and infection. It is therefore important to assess the tissue viability, both before, during and after the surgery. This can be done using different techniques that monitor the perfusion of the skin covering the affected area. In this thesis, LSCI have been evaluated for tissue monitoring in reconstructive surgery. The technique allows for a fast and noninvasive assessment of superficial tissue perfusion over a wide field. Based on previous work on the technology, we have seen clear advantages with LSCI compared to other methods, for example laser Doppler flowmetry (LDF). We have evaluated laser speckle contrast imaging (LSCI) as a tool for tissue monitoring in reconstructive surgery in four studies.MethodsIn study I we used a bench top model and healthy subjects to address methodological concerns subjected to the LSCI technology. We investigated the effect of motion distance and angle on the assessed perfusion value In study II we used a porcine model to compare LSCI and LDF as tools to detect partial and full venous outflow obstruction. We used both methods to assess a flap based on the cranial gluteal artery perforator with partial and complete occlusion of the vein and artery. In study III we used the same porcine model as in study II to investigate the possibility to use LSCI intraoperatively to identify flap areas with compromised circulation and thereby predict areas with a high risk of postoperative necrosis. In study IV we used LSCI for intraoperative evaluation of tissue viability during deep inferior epigastric perforator (DIEP) free flap surgery and to investigate the perfusion distribution according to the Hartrampf zones, as measured with LSCI, in relation to the selected perforator in the deep inferior epigastric perforator free flap.ResultsIn study I we saw that tissue perfusion as measured with LSCI increases with increasing tissue motion, independent of frame rate, number of images, and tissue perfusion. Measured perfusion will decrease when images are acquired at an angle larger than 45° but distances between 15 and 40 cm do not affect the measured perfusion. In study II we observed significant decreases in perfusion during both partial and complete venous occlusion with both LSCI and LDF. However, higher variability seen with LDF, measured as % coefficient of variation. In study III a decrease in perfusion during the first 30 min after raising the flap and a perfusion value below 25 PU after 30 min was a predictor for tissue morbidity 72h after surgery. In study IV the highest perfusion values were found in zone I and higher perfusion in zone II compared to zone III, directly after the flap was raised. No remaining significant difference between zone I, II and III could be seen after anastomosis of the vessels. All flaps with a minimum perfusion <30 PU, measured after the flap was shaped and inserted, later suffered from partial flap necrosis.ConclusionLSCI is a technology that has the potential to contribute to tissue monitoring in reconstructive surgery. It has many advantages over other techniques, such as the fast acquisition time, the spatial resolution and the fact that it is completely non-invasive. However, the current system is still too bulky to be easily introduced into a clinical setting and the technology is also subject to certain drawbacks which limit its usability. It is sensitive to motion artefacts; only superficial tissue is assessed and cannot offer absolute perfusion data. If these disadvantages could be addressed, LSCI could contribute to a more accurate survey of tissue perfusion and thus better outcome in reconstructive surgery.
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| 37. |
- Ågren, Axel, 1985-
(författare)
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Loneliness and Dying as Issues of Public Concern in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Loneliness among older people and how the dying should be cared for are issues that evoke public debate. These issues are often described as universal and existential aspects of the human experience. Societal understandings of loneliness and dying have, however, changed dramatically over the past decades. Loneliness among older people and how we die are surrounded with ideals of how to "age well" and "good deaths", where failure to meet these expectations is associated with tabus, stigma and personal and societal failures. Consequently, studying loneliness among older people and care of the dying gives rise to the question of to what degree loneliness and dying are personal or public concerns. The aim of this dissertation is to study how loneliness among older people is constructed in the Swedish news press and how care of the dying is constructed in policies and through the perspectives of experts in palliative care. Specifically, the analysis explores to what extent these issues have become public concerns, and how "old and lonely" and "the dying" are positioned and constructed. In Paper I, the focus is on identifying overall discourses on loneliness among older people in the Swedish news press. Paper II is an analysis of how the responsibility for reducing loneliness is designated in the Swedish news press. Paper III explores how policies on palliative care have emerged and developed in Sweden over time since the 1970s up until today. Paper IV highlights the perspectives of experts, in palliative care, on the development and current state of palliative care, and the role of policymaking in this context. The findings of Paper I illustrate that although loneliness among older people have seemingly gained increased attention, much of the news articles are about the deficiencies in the organisation of eldercare and volunteer work with aims of reducing loneliness. In Paper II, the main finding is that the task of reducing loneliness is discussed, defined, and designated by and to those who were "non-old" and "non-lonely", where ambitions of inclusion result in constructing old people as the "others". Paper III shows how policies on palliative care have changed, from an emphasis on psychological end-of-life care and an overarching critique of the hospice care philosophy, to claims for care to be instead inspired by the very same philosophy. Furthermore, ideals of dying at home have lost their significance as palliative care should be universal and carried out everywhere. Based on interviews with experts in palliative care, the results of Paper IV highlight the complex development of palliative care in between deficiencies in end-of-life care of the past and improvements of the present. These improvements resulted, however, in risks of too much bureaucracy.The overall findings of this dissertation indicate that loneliness among older people and care of the dying serve as symbols for criticising the idea of the development of "modern society", which is altogether viewed as individualistic, bureaucratised and medicalised. Throughout the studies included in this dissertation, the issues of individual autonomy and activity as well as responsibility have shown to be central. In the context of palliative care, the concept of autonomy has a key position and responsibility is on the dying person to make choices in order to achieve "good palliative care". Regarding loneliness among older people, emphasis is on how to make older people physically and socially active. Loneliness is constructed as a problem which should be avoided and solved by "society" bearing the responsibility for enabling older people not to be lonely.
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| 38. |
- Åhlund, Kristina, 1978-
(författare)
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Physical Fitness in Hospitalized Frail Elderly Patients
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Demographic research shows that the proportion of older people in society is increasing. More people age well, but there are also more people getting old with disability and multimorbidity. The large diversity in functioning illustrates the heterogeneity of aging. Accelerated aging may lead to frailty, which is a geriatric syndrome, often used as a marker of biologic age and associated with decreased physiologic reserves, increased vulnerability and the risk of adverse health out- comes. Frail elderly people are frequent visitors within emergency hospital care and physical decline is common. Unfortunately, elderly patients with substantial multimorbidity are often excluded from clinical trials.Physical fitness comprises a set of measurable health- and skill-related outcomes, such as cardiorespiratory endurance and muscle strength. A decrease in physical fitness may affect the prognosis negatively. However, previous research indicates that it may be possible to reverse frailty and improve physical fitness. It is therefore of the utmost interest to identify frailty and study how care is best provided, in order to prevent, reduce and postpone adverse health consequences.The overall aim of this thesis is to study physical fitness in a group of frail elderly patients, within clinical hospital health care. The patients’ physical fitness will be evaluated and compared in different care settings during and after hospitalization. The aim is also to study the long-term consequences of changes in physical fitness in relation to mortality. To better understand the underlying factors for partici- pation in physical activity and exercise, patients’ perceptions of the phenomena will be explored.This thesis consists of four papers based on two studies comprising frail elderly patients with substantial multimorbidity, in connection with an in-hospital episode. Paper 1 was an observational study with a cross-sectional design (n=408). Different components of physical fitness were measured during an index hospital stay and the results showed that hospitalized frail elderly patients performed below previously described age-related reference values. Furthermore, physical fitness was associated with the degree of frailty, rather than the chronological age. Paper 2 was a prospective controlled trial, with two parallel groups. The patients included in the intervention group (n=206) were cared for at an emergency medical care unit providing care according to Comprehensive Geriatric Assessment and care (CGA). The control group (n=202) was cared for at conventional emergency medical care units. The multi-professional care approach at the CGA unit was shown to be beneficial, in terms of a greater proportion of patients who preserved or improved their function during the first three months after discharge from hospital, compared with conventional care. Paper 3 had a prospective approach when evaluating the association between physical fitness and oneyear mortality in those 390 patients discharged alive from a hospital care episode. The results showed that physical fitness during in-hospital care and the change in physical fitness during the first months after discharge were associated with one-year mortality.In Paper 4, the patients’ perspective in terms of physical activity and exercise was explored. The theme of “Meaningfulness and risk of harm in an aging body” emerged, followed by the three categories of physical activity as part of daily life, goals of physical activity and exercise and prerequisites for physical activity and exercise.These studies highlight the importance of a greater focus on physical fitness in hospitalized elderly patients. A careful assessment and a multi-professional approach may lead to beneficial results and better survival even in a group of frail elderly patients with severe multimorbidity. To increase physical activity and exercise in this group of patients, health care probably needs to improve the means of communicating the benefits and goals of exercise and facilitating them so that the risk of harm is reduced.
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