| 1. |
- Allbrand, Marianne, 1958-
(author)
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Gene expression of inflammatory markers and growth factors in placenta in relation to maternal obesity and foetal and postnatal growth
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Maternal obesity is a growing health problem, that contributes to obstetrical complications in pregnancy, as well as neonatal morbidity and mortality. The placenta serves for gas and nutrient exchange between the mother and the foetus, and obesity may influence and modify placental growth and function. The aims of this thesis were to investigate associations between maternal obesity without associated morbidity and gene expression of inflammatory markers and growth factors in the placenta, as well as offspring birth weight and postnatal growth. Study I and III were designed as matched case-control studies including 32 obese women with an early pregnancy body mass index (BMI) ≥ 35.0 kg/m2, study II was an experimental study examining twelve placentas of normal weight women, and study IV was a cohort study including 109 obese women with a BMI ≥ 34.5 kg/m2. In studies I-IV analyses of gene expression were performed and in study III additionally cord blood concentrations were determined. No difference was found in the occurrence of placental gene expression of inflammatory markers or growth factors between obese and normal weight women, nor did the sampling site in placentas of normal weight women influence gene expression of these markers, except for leptin gene (LEP) and insulin receptor gene (INSR) expression. Ghrelin gene (GHRL) and LEP expression, as well as cord blood ghrelin and adiponectin levels, was not altered in maternal obesity, and a negatively U-shaped relationship between LEP expression and infant birth weight (BW) z-scores was observed in the placentas of obese women.In conclusion, no statistically significant difference in gene expressions of inflammatory markers and growth factors in the placenta between severely obese and normal weight women was found. These results are in contrast with earlier studies and could be due to the fact that we examined mainly healthy obese women. The correlations we found between gene expression of leptin in the placenta and the birth weight of the infants warrants further studies.
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| 2. |
- Alm, Fredrik, 1983-
(author)
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Postoperative recovery in children after tonsil surgery : with a focus on pain and pain management from the child's, caregivers', and professionals' perspectives
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Tonsil surgery is one of the most common surgical procedures in children. Although there are several health benefits associated with this surgery, the recovery can be challenging. The overall aim of this thesis was to explore varied perspectives of the recovery process following pediatric tonsil surgery, with a focus on postoperative pain and pain management at home. Study I used data from the National Tonsil Surgery Register in Sweden (n=32,225) to investigate factors affecting pain after pediatric tonsil surgery. Age, surgical method, and indication for surgery influenced the outcome of the patient-reported pain-related outcome measures. In Study II, children (n=299) and their caregiver(s) filled in a diary containing age-appropriate instruments, up to 12 days postoperatively. Data were then analyzed to explore the severity and duration of postoperative pain, the management of analgesics, and postoperative recovery. Children and caregivers reported significant pain for several days, along with a range of physical symptoms and impact on daily activities and emotional state. There was a lack of regular administration of analgesics in the home, particularly during late evening and night. In Study III, interviews with children (n=20) and their caregivers were performed to explore experiences and management of postoperative recovery at home. The results showed that the families struggled to establish resilience during the challenging recovery. The families used both pharmacological and complementary strategies to manage this period. Some families reported insufficient analgesia in preventing breakthrough pain, a lack of preparedness, inadequate information, and insufficient support from the healthcare. In Study IV, nurses and physicians (n=139) from Swedish ear, nose, and throat departments (n=48) responded to a questionnaire covering their opinions of and adherence to the Swedish guidelines for the treatment of pain in pediatric tonsil surgery. In accordance with the guidelines, the departments provided instructions for a multimodal analgesic regimen to manage pain in the home after tonsil surgery. Still, differences were noted between the departments regarding doses and routines around rescue analgesics. Overall, the experience of pain was significant, and often complex to manage. Besides pain, the postoperative period included several troublesome experiences for which neither the children nor the caregivers were informed or prepared. These findings offer knowledge to multidisciplinary teams which can help them improve the support they give to families and increase the child’s participation during the recovery process after tonsil surgery.
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| 3. |
- Amer, Ahmed, 1984-
(author)
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Cross-cultural adaptation and psychometric properties of two questionnaires for the assessment of occupational performance in children with disability : Children's Hand-use Experience Questionnaire (CHEQ) and Pediatric Evaluation of Disability Inventory (PEDI)
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Globally, 93–150 million children live with some form of disability, most of them live in developing countries. Occupational performance describes a person’s ability to execute tasks that are meaningful, in the context in which the person lives. The Children’s Hand-use Experience Questionnaire (CHEQ) and the Pediatric Evaluation of Disability Inventory (PEDI) are measurement tools developed to measure different aspects of occupational performance. However, before using these tools in another cultural context, evidence of validity in that context should be established.The overall aim of this thesis was to investigate the evidence of validity for CHEQ and the Uganda version of PEDI (PEDI-UG).Study I established the validity of revised CHEQ 1.0 for children with unilateral cerebral palsy (CP). The study suggested improvements and inclusion of younger children. This led to the development of CHEQ 2.0, which was culturally adapted and validated for Jordan in Study II. Study III indicated that PEDI-UG had good psychometric properties when tested on typically developing children, and it suggested improvements and further analysis in children with disability. Therefore, study IV investigated the psychometric properties on Ugandan children with CP and confirmed the instrument’s validity. However, the differential item functioning analysis comparing children with CP and typically developing children, and the developmental trajectories for both groups, suggested that a separate conversion table should be used to transform the total sum score from raw scores to a 0–100 scaled score. This thesis shows the importance of cultural adaptations and psychometric validation of measurement tools before they can be used in new cultural contexts. The Arabic CHEQ 2.0and PEDI-UG can be used in the evaluation of rehabilitation interventions and will help to fill the need for measurement tools in these countries.
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| 4. |
- Andersson, Anneli, 1992-
(author)
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How is ADHD associated with comorbidities and health related outcomes? : The role of familial factors and ADHD during pregnancy
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired attention and hyperactivity/impulsivity. ADHD is associated with several comorbidities and health-related outcomes. However, it is uncertain whether ADHD is more strongly associated with certain disorder domains, and whether ADHD-related comorbidities and health-related outcomes is important to consider during pregnancy. Aims: To expand the knowledge regarding the genetic overlap between ADHD and other psychiatric disorder symptoms, and to increase the awareness and understanding related to ADHD in women, with a focus on adverse health behaviors, mental health problems, and pregnancy outcomes. Methods: The present thesis includes one systematic review and metaanalysis (Study I), and three studies based on population-based register data from Sweden (Study II, III, and IV), and Norway (Study II).Results: Individuals with ADHD have an increased liability to meet criteria for externalizing, internalizing and neurodevelopmental disordersymptoms, and these co-occurrences are partly due to shared genetic risks. Further, ADHD is an important risk factor to consider before, during and after pregnancy, as ADHD increases the risk of smoking during pregnancy, mental health problems postpartum, and adverse pregnancy outcomes.Conclusions: The genetic overlaps between ADHD and other psychiatric disorder symptoms were similar across disorder dimensions. Further, results demonstrated that ADHD is an important risk factor to consider in women surrounding pregnancy. These findings point towards the importance of recognizing that women diagnosed with ADHD need to be prioritized and allowed more attention and support by the healthcare system, specifically during their fertile years.
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| 5. |
- Axer, Stephan, 1971-
(author)
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Revisional bariatric surgery : more than a moral obligation
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Growing awareness of biological, genetic, environmental, and behavioural factors contributed to the recognition of obesity as a chronic disease. Nowadays, obesity and its medical/surgical treatment is widely acknowledgedin the medical curriculum. Bariatric surgery has long been shown to provide superior induction and maintenance of weight loss, together with improvement or resolution of obesity-related diseases. The role of revisional bariatric surgery for treatment of procedure-related complications is accepted. However, its role as second-line treatment of patients with primary or secondary non-response is still a matter of debate. This prompted Dr Henry Buchwald in 2015 to publish his article “Revisional Metabolic/Bariatric Surgery: A Moral Obligation”. Studies I and II in this doctoral thesis covered issues that fuel the ongoing controversy, namely effects and risks of revisional surgery. Conversion to gastric bypass is the most common revisional procedure in Sweden. In Studies I and II, we found revisional gastric bypass to give inferior weight loss with a higher risk for perioperative complications compared to primary gastric bypass. However, the beneficial effects on obesity-related disease were similar (Papers I and II). In Study III, the theoretical need for revisional bariatric surgery in patients with primary or secondary weight non-response was evaluated. When applying four different indication criteria, more than 13% of patients met the criteria for second-line treatment, with a significant higher probability after sleeve gastrectomy compared to gastric bypass (Paper III). To gain a clearer picture, a systematic review of the literature on revisional bariatric surgery after sleeve gastrectomy was inevitable. However, an evidence-based treatment strategy for patients with primary or secondary weight non-response could not be deduced from the current literature (Paper IV).
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| 6. |
- Baban, Bayar, 1973-
(author)
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Colorectal cancer and surgery : Insights into insulin resistance and inflammatory markers
- 2024
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Doctoral thesis (other academic/artistic)abstract
- The art of surgery has progressively extended from the realm of anatomy to encompass physiology and beyond, in search of further refinement and optimal recovery. Integral to this is a deeper understanding of the body’s essential metabolic and inflammatory responses to surgical trauma.This thesis aims to provide insights into the intricate interplay between insulin resistance, inflammation and surgical interventions in colorectal cancer patients, as each has an influence on postoperative recovery. Particular emphasis is placed on the role of inflammasomes – central mediators of the innate immune response, adept at detecting and responding to a diverse range of triggers, yet insufficiently explored in these specific contexts.Study I is a comparative analysis of the hyperinsulinemic–euglycaemic clamp and homeostatic model assessment (HOMA) in determining postoperative insulin resistance in 113 patients undergoing various elective surgeries. The findings establish the clamp as the accurate method, detecting key physiological distinctions missed by HOMA.Study II, an exploratory case–control study, assesses insulin sensitivity and inflammatory markers in 20 colorectal cancer patients compared to 10 matched healthy controls. Results indicate insulin resistance, reduced inflammasome activity in circulating immune cells and elevated systemic IL-1β and IL-6 levels in patients.Study III, a pilot exploratory study of 17 patients from Study II, assesses the impact of surgical technique, open versus minimally invasive surgery, on postoperative insulin resistance and inflammation in colorectal cancer resections. It indicates a differential inflammatory response with higher levels in open surgeries, yet a consistent degree of insulin resistance across both surgical techniques.Study IV explores the perioperative temporal sequencing of inflammation and inflammasome action in 18 patients from Study II undergoing elective colorectal cancer resections. It points to a more immediate and pronounced inflammatory response in open surgery compared to minimally invasive surgery, though both techniques show reduced intraoperative caspase-1 activity.In conclusion, the hyperinsulinemic euglycaemic clamp is the accurate method in determinations of postoperative insulin resistance. Patients with colorectal cancer, in comparison to matched healthy controls, exhibit insulin resistance and higher levels of inflammation, but decreased inflammasome (caspase-1) activity in circulating immune cells. Finally, colorectal cancer resections induce both insulin resistance and inflammation; however, the surgical technique utilized only significantly affects the latter, with generally higher inflammatory / inflammasome responses in open surgery.
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| 7. |
- Befekadu Wodajo, Rahel, 1968-
(author)
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Analysis of new biomarkers and their kinetics in connection with ST-elevation myocardial infarction and percutaneous coronary intervention
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This thesis studies different biomarkers in a cohort of patients suffering from ST-elevation myocardial infarction (STEMI) who underwent Percutaneous coronary intervention (PCI) in Örebro in 2011-2012. Blood samples were collected at three time points, at the arrival at the hospital, 1-3 days after PCI and for a smaller group of patients also 3 months after PCI. The study is a sub-study of the TASTE study, so half of the patients were also randomized to thrombus aspiration in conjunction with their PCI. For all patients, it was also recorded whether the culprit coronary vessel was totally occluded or partially patent. In total, there are samples from 165 patients, but not all markers have been measured in all patients, and 3-month samples are only available from those who had their follow-up in Örebro. The plasma levels of the biomarkers have also been measured in plasma from blood donors for comparison. In March 2019, a follow-up was made of the patients' survival, and the time of death was noted in cases where this had occurred.The markers studied are the lysosome protein Cathepsin S (Cat-S), the platelet granule protein thrombospondin 1 (TSP-1), the pentraxins C-reactive protein (CRP) and pentraxin 3 (PTX3), the endopeptidase neprilysin, the soluble forms of TNF-receptor 1 and 2 (sTNFR1 and sTNFR2), markers showing activation of the lectin pathway for complement activation (MASP-1/AT, MASP-1/C1-INH, MASP-2/C1-INH, MASP-2/AT) and common activation markers for complement activation (C3a and sC5b-9).In summary, the thesis shows that the plasma levels of all markers, except neprilysin and sC5b-9, are elevated at the time of arrival compared to healthy blood donors. Neprilysin is at the same level, and sC5b-9 is lower compared to blood donors. 1-3 days after PCI, the levels for CRP, sTNFR1 and sC5b-9 have risen strongly (>50%) compared to the levels at arrival. MASP-1/AT and MASP-2/AT have fallen moderately (about 50%), Cat-S and TSP-1 have decreased strongly, while the remaining markers are relatively similar to the levels at arrival (± 25%). The levels for CRP, PTX3, sTNFR1, sTNFR2 and neprilysin decreased even further between 1-3 days and 3 months, sC5b-9 rises slightly while the other markers remain at roughly the same levels. At 3 months, most markers still show higher levels compared to corresponding levels in blood donors, only MASP-2/C1-INH has the same level, while neprilysin is slightly lower and TSP-1 much lower compared to blood donors (the latter presumably an effect of ongoing medication with platelet inhibitors in the patients). No relevant differences were observed between patients with and without thrombus aspiration, and few differences were seen between patients with occluded or partially patent vessels. This may indicate that these factors were of minor importance for the levels of the analyzed markers. In contrast, analysis of survival showed that individuals with plasma levels above the median value for PTX3, sTNFR1 and sTNFR2 at admission and/or at 1-3 days had a significantly increased mortality compared to those with levels below the median value, which indicates that these markers could be interesting for further studies in a material where also analysis of possible interfering factors can be implemented.
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| 8. |
- Bergengren, Lovisa, 1972-
(author)
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Cervical screening with primary HPV : from research to clinical effectiveness
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Organized cervical screening has greatly reduced the incidence of cervical cancer where implemented. Human papilloma virus (HPV) is the cause of cervical cancer, and in later years, convincing evidence has led to cervical screening with HPV as the primary method being implemented around the world. The overall aim of this thesis is to improve cervical screening, with focus on HPV screening.Papers I–III were performed with focus on postmenopausal women. Women aged, 55–59 years, excluded from the screening with a normal cytology cervical sample were found to have a high-risk HPV (hrHPV) prevalence of 5.5% in paper II. In a follow-up sample, 56% (71/126) had a persistent infection with the same genotype. Nineteen per cent of the women had dysplasia, where the majority of the high-grade squamous intraepithelial lesions (HSILs) were associated with HPV types other than HPV 16/18.Women 55-59 has a lower attendance rate in the study region, and since self-sample has been proven to increase attendance, paper I was performed to compare self-sample and professionally collected samples in these postmenopausal women. The concordance between the sampling methods was 83%, and both tests detected all histological HSILs. When including a study with older women (aged 70 years) in paper III, 23% of histological HSILs were found in hrHPV-positive women.Paper IV is a scientific evaluation of an implemented HPV-based screening programme, comparing clinical effectiveness and cost with cytology screening. More HSIL+ were detected in the new programme but at a higher cost than the old cytology-based programme. The screening visits for sampling accounted for two thirds of the costs.Altogether, the results indicate the importance of having a negative HPVtest before exiting screening. Data also present the necessity to find biomarkers that are more specific than cytology and HPV 16/18 for triaging women with hrHPV to further follow-up, both among postmenopausal women and other age groups when screening with HPV, since many women without HSIL are coming for clinical follow-up and treatment. Extending the screening interval between hrHPV-negative tests as well as implementing selfsampling to a greater extent can be important changes, since two thirds of the costs in the programme come from screening visits for sampling.
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| 9. |
- Björksved, Margitha, 1964-
(author)
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Open vs closed exposure of palatally displaced canines : clinical, patient-related outcomes and health economics
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The maxillary permanent canine usually erupts in the mouth between the ages of 11 and 12 years. Sometimes the canines are displaced toward the palatal side of the dental arch and eruption is disturbed. Palatally displaced canines (PDCs) are a frequent dental anomaly, present in 2% of the young population. If untreated, there is risk of damage to the roots of the adjacent teeth and potential tooth loss. Thus, early interceptive treatment with extraction of the deciduous canine should be undertaken, with the aim to improve the PDC eruption path. If the eruption path does not improve within about a year, surgical exposure and orthodontic treatment is indicated.The two different main techniques of surgical exposure in PDCs are the open and the closed techniques. Retrospective studies of the exposure techniques have shown differences in outcomes, which high-lights the need for evidence-based research.The overall aim of this thesis was to compare outcomes of treatment duration, complications and side effects, patients’ perceptions and health economic aspects of the two surgical techniques, in PDCs. Moreover, a comparison of PDC position between the two radiographic methods commonly used in PDC cases; panoramic radiograph and CBCT, aimed to evaluate agreement between the actual measures. This thesis was based on a multicentre randomised controlled trial with two parallel groups, including 120 consecutive patients, aged 9 to 16 years, who were randomly allocated to open or closed surgical exposure. The following conclusions were drawn:The agreement of PDC mesiodistal position was fair (weighted kappa 0.36 (95%CI0.24–0.49) and the mean difference in angle to midline was almost 7˚ (95%CI 5.9˚–7.9˚) higher in panoramic radiographs compared with CBCT. Surgery time, treatment time, root resorption or periodontal measures showed no clinically significant differences between the exposure groups. The open group reported higher pain intensity up to one week post surgery. A higher proportion of bilateral open group cases experienced complications, and weremore frequently wakened at night post surgery. The closed group reported higher pain and discomfort during the orthodontic traction. All PDCs were successfully aligned in the dental arch. A cost-minimization analysis showed no differences in healthcare or societal costs.
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| 10. |
- Bozorg, Soran Rabin, 1993-
(author)
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Various Aspects of Gastrointestinal Disease : Examining Validity and Health Economic Outcomes
- 2022
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Licentiate thesis (other academic/artistic)abstract
- Introduction: Recent years have seen significant research advances within the gastroenterological field. Some of these consist of the recognition of serrated polyps as a precursor to colorectal cancer, and the realization of the health economic burden associated with gastrointestinal diseases.Aim: In this thesis, we aim to validate the specificity of serrated polyps in the ESPRESSO cohort (Paper I). We also aim to estimate work loss in patients with celiac disease, including the temporal relationship of work loss before and after diagnosis (Paper II).Method: By using the ESPRESSO cohort, we collected data on patients with serrated polyps and patients with celiac disease. In Paper I, the specificity of serrated polyps in the ESPRESSO cohort were validated by a structured retrospective review of patient chart. In Paper II, we estimated work loss in patients with celiac disease as compared withgeneral-population comparators matched on age, sex, county of residence and year of diagnosis.Result: The presence of a serrated polyp was confirmed in 101 out of 106 individuals identified through the ESPRESSO cohort, yielding a positive predictive value of 95% (95% confidence interval: 89-98%). Patients with celiac disase had 42.5 lost work days as compared to 28.6 days in comparators (mean difference, 14.7; 95% confidence interval, 13.2-16.2), corresponding to a relative increase of 49%. Excess work loss in patients with celiac disease was observed even 5 years before diagnosis and remained eleveated during the years after diagnosis this loss. Notebly, the excess work loss was concentrated to a small proportion while most celiac patients did not have any work loss before or after diagnosis. Conclusion: The ESPRESSO cohort has a high specificity for serrated polyps. Patients with celiac disease miss more work days than the general population even before diagnosis, and this loss persists after diagnosis.
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