| 1. |
- Pejner, Margaretha Norell, 1958-
(författare)
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The bright side of life : support in municipal elderly home care
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Registered nurses in municipal elderly home care have in some occasionsdifficulties in identifying the patients’ needs and prioritize intervention inaccordance with the patients’ preferences, which is to obtain social and emotional support. The overall aim was to explore and describe which supportive interventions registered nurses use in municipal elderly home care settings and if it is in agreement with the patient’s preferences. Methods: A retrospective descriptive study (I ) were conducted and followed up by a qualitative approach with Grounded Theory as a method (II IV ). Sample to study; I , registered nurses (62) performed interventions to 6138 patients between 80- 109 years. II , 12 registered nurses, who performed 36 home visits to patients between 80- 102 years. III , 16 registered nurses. IV , 18 patients between 80- 96 years. Data was collected by; I , between 2004- 2008, during the months of April and October using a web- based form which was filled in by registered nurses. II , through nonparticipant observations when the registered nurse made a home visit. III and IV , using informal conversational interviews. Results: Combined, the four studies show that emotional support is important to a group of older patients because it helps them to experience serenity. Serenity is a state of relief and the moment required for the patient to be able to move forward in a dignify way. Patients lost or reduced ability to process their emotions makes so that they get stuck in a state, which fatigue them with additional experience of disease and illness. To get out of their state the patient uses the registered nurse as a reliever whose mission is to identify their needs and guide them into a state of serenity. Registered nurses on the other hand, makes priorities based on patients preferences. Registered nurses strengths was their profession that contributed to the patient's emotions became available to them. Weaknesses was registered nurses workload and lack of knowledge about the identification of emotions. Emotional support should be developed as a nursing intervention and be integrated as a part of nursing.
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| 2. |
- Walldén, Jakob, 1968-
(författare)
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The influence of opioids on gastric function : experimental and clinical studies
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Efter operation och anestesi får patienter ofta en negativ påverkan på magsäck och tarmar. Illamående och kräkningar är ett stort problem och många har svårt att komma igång med intag av föda och normal tarmfunktion då magsäcken och tarmarna ”står stilla”. Flera faktorer bidrar- bl.a. smärtan, det kirurgiska traumat och de läkemedel vi ger i samband med anestesin. Av de senare är opioider, d.v.s morfin och morfinliknande läkemedel, starkt bidragande. I detta avhandlings- arbete har opioiders effekter på magsäckens motilitet studerats. Med ett absorptionstest (paracetamolmetoden) studerades hos frivilliga hur opioiden remifentanil påverkar magsäckstömning och om kroppspositionen har betydelse för tömningshastigheten ut i tarmen. Remifentanil fördröjde magsäcks-tömningen och under pågående opioid behandling hade kroppspositionen ingen större betydelse, vilket det däremot hade under kontrollförsöken. Med samma metod jämförde vi hos patienter två anestesimetoder och studerade magsäcks-tömning direkt efter en operation. Ingen skillnad kunde påvisas mellan en opioidbaserad och en opioidfri anestesi, men inom respektive grupp var det en stor variation i magsäckstömning mellan individerna. Med en barostat studerades tonus i övre delen av magsäcken. Hos hälften av de frivilliga orsakade remifentanil en ökning av tonus och hos den andra hälften en minskning av tonus. Vidare undersöktes hos en grupp patienter opioiden fentanyls påverkan på den elektriska aktiviteten i magsäcken. Med en elekroga-strograf (EGG) registrerades de långsamma elektriska vågor som koordinerar muskelrörelserna i magsäcken. Hos hälften av de undersökta påverkades aktiviteten av fentanyl med en sänkt vågfrekvens eller upphörande av vågor, medan aktiviteten var opåverkad hos den övriga hälften. För att finna en förklaring till variationen gjordes genetiska analyser av genen för opioidreceptorn hos de undersökta i barostat och EGG studierna. Variationer i genomet, s.k. polymorfism, var inte associerad till utfallen i studierna. Studierna har visat på att opioider har en uttalad effekt på magsäckens motilitet och att den varierar kraftigt mellan individer. Polymorfism i genen för opioid- receptorn förklarade inte skillnaden mellan individer. Direkt efter operation bidrar sannolikt andra faktorer än anestesimetod till det variabla utfallet i magsäckstömning.
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| 3. |
- Ahl, Rebecka, 1987-
(författare)
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The Association Between Beta-Blockade and Clinical Outcomes in the Context of Surgical and Traumatic Stress
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic injury and major abdominal surgery are areas in general surgery associated with high rates of morbidity and mortality. The overall colorectal cancer surgery mortality rate is around 4%, with that for emergency surgery more than twice as high as for planned. Surgical morbidity varies between 25% and 45%. Around half of trauma patients develop low mood. In one quarter of patients this becomes permanent. Depression is known to impede physical rehabilitation and recovery. The onset of physiological stress, driven by adrenergic hyperactivity following traumatic and surgical injury is hypothesized to contribute to these adverse outcomes. Interest has therefore been sparked into blocking adrenergic receptor activation.Papers I and II investigated the role of beta-blocker therapy in preventing post-traumatic depression following severe traumatic brain injury (Paper I) and severe extracranial injury (Paper II). The Karolinska University Hospital Trauma Registry was used to identify patients admitted between 2007 and 2011. In Paper I (n = 545), patients on pre-injury beta-blocker therapy were matched to beta-blocker naïve patients with equivalent injury burden. Results revealed that beta-blocked patients exhibited a 60% reduced risk of needing antidepressant therapy within one year of trauma. In Paper II (n = 596), the lack of beta-blocker use before extracranial trauma was linked to a three-fold increase in the risk of antidepressant initiation.Papers III-V explored the role of pre-operative beta-blocker therapy in patients undergoing surgery for colorectal cancer between 2007 and 2016, identified using the nationwide Swedish Colorectal Cancer Registry. Paper III (n = 3,187) identified a 69% reduction in the risk of 30-day mortality in beta-blocked patients. Paper IV (n = 22,337) outlined long-term survival benefits for patients on beta-blocker therapy prior to undergoing elective surgery for colon cancer. Beta-blocked patients showed a risk reduction of 42% for 1-year all-cause mortality and 18% for 5-year cancerspecific mortality. Similarly, patients on beta-blocker therapy who underwent surgery for rectal cancer demonstrated improved survival up to one year after surgery with a risk reduction of 57% and a reduction in anastomotic failure and infectious complications in Paper V (n = 11,966).
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| 4. |
- Ahlsson, Anders, 1962-
(författare)
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Atrial fibrillation in cardiac surgery
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, one-third of the patients experience episodes of AF during the first postoperative days (postoperative AF), and patients with preoperative AF (concomitant AF) can be offered ablation procedures in conjunction with surgery, in order to restore ordinary sinus rhythm (SR). The aim of this work was to study the relation between postoperative AF and inflammation; the long-term consequences of postoperative AF on mortality and late arrhythmia; and atrial function after concomitant surgical ablation for AF. In 524 open-heart surgery patients, C-reactive protein (CRP) serum concentrations were measured before and on the third day after surgery. There was no correlation between levels of CRP and the development of postoperative AF. All 1,419 patients with no history of AF, undergoing primary aortocoronary bypass surgery (CABG) in the years 1997–2000 were followed up after 8.0 years. The mortality rate was 191 deaths/1,000 patients (19.1%) in patients with no AF and 140 deaths/419 patients (33.4%) in patients with postoperative AF. Postoperative AF was an age-independent risk factor for late mortality, with a hazard ratio (HR) of 1.56 (95% CI 1.23–1.98). Postoperative AF patients had a more than doubled risk of death due to cerebral ischaemia, myocardial infarction, sudden death, and heart failure compared with patients without AF. All 571 consecutive patients undergoing primary CABG during the years 1999–2000 were followed-up after 6 years. Questionnaires were obtained from 91.6% of surviving patients and an electrocardiogram (ECG) from 88.3% of all patients. In postoperative AF patients, 14.1% had AF at follow-up, compared with 2.8% of patients with no AF at surgery (p<.001). An episode of postoperative AF was found to be an independent risk factor for development of late AF, with an adjusted risk ratio (RR) of 3.11 (95% CI 1.41–6.87). Epicardial microwave ablation was performed in 20 open-heart surgery patients with concomitant AF. Transthoracic echocardiography was performed preoperatively and at 6 months postoperatively. At 12 months postoperatively 14/19 patients (74%) were in SR with no anti-arrhythmic drugs. All patients in SR had preserved left and right atrial filling waves (A-waves) and Tissue velocity echocardiography (TVE) showed preserved atrial wall velocities and atrial strain. In conclusion, postoperative AF is an independent risk factor for late mortality and later development of AF. There is no correlation between the inflammatory marker CRP and postoperative AF. Epicardial microwave ablation of concomitant AF results in SR in the majority of patients and seems to preserve atrial mechanical function.
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| 5. |
- Ahlstrand, Erik, 1974-
(författare)
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Coagulase-negative staphylococci in hematological malignancy
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.
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| 6. |
- Ahlstrand, Rebecca, 1973-
(författare)
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Effects of anasthesia on esophageal sphincters
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The esophageal sphincters constitute the anatomical protection against pulmonary aspiration. The aim of this thesis was to study the esophageal sphincters and how they are affected by different components of emergency anesthesia using high-resolution solid-state manometry.The effect of propofol (0.3 mg/kg) was studied in young and elderly volunteers. Propofol can be given as an anxiolytic agent for manometric studies of the lower esophageal sphincter (LES) without affecting the results. However, propofol is not recommended for studies of the upper esophageal sphincter (UES).The effects of cricoid pressure (CP) and peripheral pain were studied in awake volunteers, with and without remifentanil infusion (5 ng/ml). Pain did not affect pressure in the LES, but CP or remifentanil induced a significant decrease in LES pressure. However, neither CP nor remifentanil affected the barrier pressure (LES-intra gastric pressure). When CP was applied during ongoing remifentanil infusion, no further decrease in LES pressure was measured. CP induced high pressures in the area of the UES independent of remifentanil infusion, indicating that CP is effective in preventing gastroesophageal regurgitation.Barrier pressure was also studied in anesthetized patients after rocuronium (0.6 mg/kg) administration and no decrease was measured. In addition, alfentanil (20 μ/kg) added during anesthesia induction with propofol did not decrease the barrier pressure.In conclusion, CP seems to be effective in preventing regurgitation and does not affect barrier pressure. Muscle relaxation with rocuronium does not risk gastro-esophageal integrity. In addition, opioids can be integrated, even during emergency anethesia, without increasing the risk for pulmonary aspiration.
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| 7. |
- Allbrand, Marianne, 1958-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 8. |
- Allvin, Renée, 1956-
(författare)
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Postoperative recovery : development of a multi-dimensional questionnaire for assessment of Recovery
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to present a multi-dimensional instrument for self-assessment of progress in postoperative recovery. The author employs different research paradigms and methodologies to achieve this aim. Walker and Avant’s approach to concept analysis was used to examine the basic elements of postoperative recovery (Study I). The analysis identified different recovery dimensions and developed a theoretical definition showing postoperative recovery to be an energy-requiring process of returning to normality and wholeness, defined by comparative standards. Fourteen patients and 28 staff members participated in individual and focus group interviews aimed at describing patient and staff experiences of patient recovery (Study II). The essence of the postoperative recovery process was described as a desire to decrease unpleasant physical symptoms, reach a level of emotional wellbeing, regain functions, and re-establish activities. In Study III, 5 dimensions and 19 items were identified as a part of the operationalization process of the concept postoperative recovery. Fifteen staff members and 16 patients participated in the evaluation of content validity. On average, 85% of the participants considered the items as essential to the recovery process. In a test run of the questionnaire, 14 of 15 patients considered the questionnaire to be easy to understand and easy to complete. Twenty-five patients participated in the evaluation of intra-patient reliability. Percentage agreement (PA), systematic disagreement (RP, RC), and individual variability (RV) between the two assessments were calculated. PA measures ranged from 72% to 100%. The observed disagreement could be explained mainly by systematic disagreement. In total, 158 patients participated in the evaluation of construct validity, the ability to discriminate between groups, and the investigation of important item variables (Study IV). A rank-based statistical method for evaluation of paired, ordered categorical data from rating scales was used to evaluate consistency between the assessments of the Postoperative Recovery Profile (PRP) questionnaire and a global recovery scale. The number of months needed by participants to be regarded as fully recovered was studied by means of recovery profiles displayed by the cumulative proportion of recovered participants over time. A ranking list based on the participant’s appraisal of the five most important item variables in the PRP questionnaire was compiled to illustrate the rank ordering of the items. In comparing the assessments from the PRP questionnaire and the global recovery scale, 7.6% of all possible pairs were disordered. Twelve months after discharge 73% in the orthopaedic group were regarded as fully recovered, compared to 51% of the participants in the abdominal group (95% CI: 6% to 40%). The pain variable appeared among the top five most important items on eight measurement occasions, of eight possible, in both study groups. In conclusion, the PRP questionnaire was developed and support was given for validity and reliability. The questionnaire enables one to evaluate progress in postoperative recovery.
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| 9. |
- Alm, Fredrik, 1983-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 10. |
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| 11. |
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| 12. |
- Alshamari, Muhammed, 1975-
(författare)
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Low-dose computed tomography of the abdomen and lumbar spine
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Radiography is a common radiologic investigation despite abundant evidence of its limited diagnostic value. On the other hand, computed tomography (CT) has a high diagnostic value and is widely considered to be among the most important advances in medicine. However, CT exposes patients to a higher radiation dose and it might therefore not be acceptable simply to replace radiography with CT, despite the powerful diagnostic value of this technique. At the expense of reduced CT image quality, which could be adjusted to the diagnostic needs, low-dose CT of abdomen and lumbar spine can be performed at similar dose to radiography. The aim of the current thesis project was to evaluate low-dose CT of the abdomen and lumbar spine and to compare it with radiography. The hypothesis was that CT would give better image quality and diagnostic information compared to radiography at similar dose levels. Firstly, the diagnostic accuracy of low-dose CT of the abdomen was evaluated. Results showed that low-dose CT of abdomen has a high sensitivity and specificity compared to radiography, i.e., it has higher diagnostic accuracy. Similar results were obtained from our systematic review. Secondly, in a phantom study, an ovine phantom was scanned at various CT settings. The image quality was evaluated to obtain a protocol for the optimal settings for low-dose CT of lumbar spine at 1 mSv. This new protocol was then used in a clinical study to assess the image quality of low-dose CT of the lumbar spine and compare it to radiography. Results showed that low-dose CT has significantly better image quality than radiography. Finally, the impact of Iterative reconstruction (IR) on image quality of lumbar spine CT was tested. Iterative reconstruction is a recent CT technique aimed to reduce radiation dose and/or improve image quality. The results showed that the use of medium strength IR levels in the reconstruction of CT image improves image quality compared to filtered back projection. In conclusion, low-dose CT of the abdomen and lumbar spine, at about 1 mSv, has better image quality and gives diagnostic information compared to radiography at similar dose levels and it could therefore replace radiography.
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| 13. |
- Amcoff, Karin, 1975-
(författare)
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Serological and faecal biomarkers in inflammatory bowel disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.
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| 14. |
- Amer, Ahmed, 1984-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 15. |
- Ander, Fredrik, 1978-
(författare)
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Perioperative complications in obese patients : A thesis on risk reducing strategies
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aspiration of gastric content and delayed or failed intubation are the leading causes of anesthesia-related mortality and morbidity. In the recovery period, airway obstruction with subsequent hypoxia is a relatively common cause of morbidity, and is highly associated to the amount of opioids administered, especially in obese patients.The overall aim of this thesis was to study these risk factors for airway complications and postoperative hypoxia in obese patients, and to evaluate possible strategies for their prevention.In Study I, intubation times and incidence of failed intubation in obese patients were compared between direct laryngoscopy and videolaryngoscopy with the Stortz® C-MAC™. In Studies II and III, the effect of esmolol vs. remifentanil on the esophageal junction, and the possible analgesic properties of low-dose esmolol vs. placebo were evaluated using high-resolution manometry and the cold pressor test, respectively. Finally, in Study IV, the possible opioid-sparing effect of esmolol after laparoscopic gastric bypass surgery was evaluated.The use of videlaryngoscopy did not shorten intubation times, however appeared to reduce the incidence of failed intubation. Our results also show that esmolol has a favorable profile, compared to remifentanil, with regard to the protection against passive regurgitation and aspiration of gastric content. No analgesic effect of low-dose esmolol was however demonstrated. The intraoperative administration of esmolol instead of remifentanil also did not reduce the requirement of morphine for treatment of post-operative pain.The use of Stortz® C-MAC™ may be recommended for intubation of obese patients. Further studies are however required to clarify the possible role of esmolol in anesthesia.
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| 16. |
- Andersson, Anneli, 1992-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 17. |
- Andersson, Gunnel, 1958-
(författare)
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Urinary incontinence : prevalence, treatment seeking behaviour, experiences, and perceptions among persons with and without urinary leakage
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis is to describe urinary incontinence (UI) from a population perspective and to describe experiences and perceptions of UI from an individual perspective. This includes assessing the prevalence of urinary incontinence as well as describing treatment seeking and experiences of living with UI. A secondary aim was to describe the perception of UI among cultures other than the Swedish mainstream, exemplified in this case by Syrian women living in Sweden. Both quantitative and qualitative methods were used, including questionnaires and interviews. Studies I and II were quantitative studies based on a population-based study. Together with a postal survey on general health and living conditions “Life & Health”, a questionnaire on urinary incontinence was sent out to 15 360 randomly-selected residents aged 18-79 in Orebro County, Sweden. In Study I, UI was found to affect 19%. The majority of the respondents experienced minor problems, and only 18% of those reporting UI wanted treatment. However, there was also a group who reported severe problems, but despite this 42% of them did not want treatment. Study II investigated why people with UI refrain from seeking care and treatment. It was found that the desire for treatment was regulated by the frequency of UI, being restricted from participating in various activities, the degree of inconvenience, and the type of UI. Studies III and IV were both qualitative interview studies, describing older women’s experiences of living with UI (Study III) and Syrian women’s perceptions of UI (Study IV). There were similarities between the results of these two studies; the women described UI as a normal and expected problem, and they knew that the district nurse could prescribe incontinence protections and that treatments existed. In both studies, the women expressed difficulties in making contact with the health care service, while the women who did not speak Swedish (Study IV) also had difficulties due to different communication problems. In conclusion, it is important that health care resources are optimized to identify and meet the needs of those who experience major problems with UI, and that there is awareness of the communication difficulties that can be present in meeting with people who speak other languages. However it is also important not to medicalize those who experience minor problems and who have the desire to manage on their own.
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| 18. |
- Andersson, Karin, 1989-
(författare)
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Metal artifacts in computed tomography : impact of reduction methods on image quality and radiotherapy treatment planning
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Degradation of image quality by metal artifacts is a common problem in computed tomography (CT) imaging, which can limit the diagnostic value of a CT examination and also introduce inaccuracies in radiotherapy (RT) treatment planning. In recent years, commercial metal artifact reduction (MAR) methods have been launched by several CT vendors. The overall aim of this thesis was to evaluate MAR methods in diagnostic imaging and RT treatment planning.Evaluations of hip prosthesis phantom CT images showed that MAR algorithms in general improved image quality, based on both visual grading analysis and quantitative measures, while the application of virtual monoenergetic reconstructions insufficiently reduced metal artifacts. In some cases additional artifacts were introduced by the MAR algorithms. MAR algorithms were also evaluated in hip prosthesis phantom CT imaging used for proton therapy treatment planning, where improvements in dose calculation accuracy were observed.Studies of Head & Neck (H&N) implant CT images in RT treatment planning were also performed. By visual grading of anatomy visualization with respect to target delineation in dental implant patient images, MAR algorithms were shown to significantly improve image quality. However, only minor effects of H&N implant artifacts on proton dose distributions were seen. The impact might be greater for more severe artifacts than those studied here, and thus further investigations of such cases are needed.In conclusion, MAR algorithms have been shown to enhance image quality for diagnostic applications and to improve anatomy visualization in RT treatment planning. The MAR algorithms led to increased proton dose calculation accuracy in some cases, while in other situations only minor changes were seen.
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| 19. |
- Andersson, Tommy, 1970-
(författare)
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Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.
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| 20. |
- Anderzén-Carlsson, Agneta, 1966-
(författare)
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Children with cancer : focusing on their fear and on how their fear is handled
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Various fears in children with cancer have previously been identified as a result of studying e.g. symptom experiences, distress and uncertainty within this population. Studies of the meaning the children give to their fear, as well as the handling of their fear seem to be sparse, however. Also, fear has not been an exclusive focus in previous studies. Professionals in clinical practice have pointed to the need for such research, which has prompted the present research work. The overall aim of this thesis was therefore twofold; firstly, the aim was to elucidate fear in children and adolescents with cancer in order to gain an understanding from the perspective of adolescents and parents. Secondly, it was to elucidate parents’ and professionals’ handling of the fear. This in order to gain a deeper understanding of what performances and manners the children and adolescents can face when being fearful. A qualitative descriptive design was adopted in the five included studies. The methods used in the data analysis were phenomenological hermeneutical method (studies I–III) and qualitative content analysis (studies IV–V). In study I six adolescent girls, aged 14–16 years, with experiences of various cancer diagnoses, but now declared fit, were interviewed. The results reveal that they experience their fear as embodied, which in the comprehensive understanding of the results was interpreted as a threat to their personal self, their whole existence. Their fear was seen as a holistic intertwined experience, including fear related to the physical body and to the social self. Also, existential fear was described. Their described experience was interpreted as suffering. Studies II and III share the same data. Fifteen parents of children at various ages with various cancer diagnoses were interviewed in focus groups about their experience of their child’s fear. In study II the result reveals how the parents experienced and understood their child’s fear. The fear was described as a multidimensional phenomenon, which was not always easy to identify. It was contrasted to feelings of unease and to absence of fear. In the comprehensive understanding the fear was interpreted as a suffering, as that was regarded to be what was the common meaning in the narratives. The suffering was interpreted as an ethical demand to the parents to take action. In study III the parents described their actions, i.e. they described how they dealt with the fear. Their actions were described as acting in the best interests of the child, which included striving to make the child feel secure and experience wellbeing, up to a certain point. However, after this point the parents used their parental authority to maintain the child’s physical health rather than trying to prevent or relieve the child’s fear. In the comprehensive understanding the parents’ handling of their child’s fear was interpreted as revealing mercy and as being synonymous with meeting the ethical demand put on them. In study IV ten experienced nurses and physicians were individually interviewed about how they handled fear in children with cancer. The result reveals that the existential issues were dealt with within the relationship with the child, on a sliding scale between closeness and distance, and that the fear related to medical procedures occurred on a continuum between support and lack of support. The various actions involved, and the manner in which these actions were performed, was described. In the observational study (study V) eleven parents and their children as well as eleven health professionals participated. They were observed at children’s routine visits at the outpatient clinic. The aim was to study the interactions related to fear. The result reveals that when children were fearful they expressed this both verbally and non-verbally. The parents’ and professionals’ actions and interactions in these situations were found to be characterized by recognition of the fear or lack of attention to the fear. The findings can contribute to a broadened knowledge on fear in children and adolescents with cancer. Awareness and understanding of the meaning adolescents give to their fear, and furthermore, of the parents’ experience and understanding of their child’s fear can provide tools for interacting with these groups. The findings on how fear is dealt with by the ones children have claimed as important sources for support, can give insights into what the child may face when being fearful. These insights can form the basis for individual, as well as collegial, reflections on what is done when children face fear, how fear is handled on an everyday basis and why it is handled in this way. Such reflections could lead to an ethical awareness of handling fear in children with cancer.
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| 21. |
- Andrén, Ove, 1963-
(författare)
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Natural history and prognostic factors in localized prostate cancer
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects. The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden. Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer. The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment. Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.
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| 22. |
- Arinell, Karin, 1982-
(författare)
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Immobilization as a risk factor for arterial and venous thrombosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: Immobilization and a sedentary lifestyle are correlated with an elevated risk of both arterial and venous thrombosis. The goal of this research was to investigate whether markers associated with cardiovascular disease risk are altered during long term immobilization in a human model and in the brown bear, which survives annual cycles of long-term immobilization.Methods: In study populations assigned to 20-60 days of strict head-down-tilt bed rest 24h a day, we analysed blood levels of the emerging cardiovascular disease marker cystatin C, soluble markers of in vivo platelet activation P-selectin and PDGF-BB, and platelet aggregation. Blood samples were taken from free-ranging brown bears in summer and again during hibernation for analysis of lipid profile and platelet aggregation. Histological examination was performed on the left anterior descending coronary artery and aortic arches of bears harvested during the hunting season.Results: During prolonged bed rest in humans, levels of cystatin C and platelet aggregation remained unchanged, but we observed a significant decrease in platelet activation markers. Brown bear plasma lipids were elevated during hibernation compared with the active state and cholesterol levels were generally considerably higher than normal human values. The arterial specimens showed no signs of atherosclerosis. Platelet aggregation was halved during hibernation compared to the active state.Conclusions: Long-term immobilization has effects on several cardiovascular risk factors in both humans and bears. Increased knowledge and understanding of the protective mechanisms that allows the brown bear to survive repeated periods of immobilization could contribute to new strategies for prevention and treatment of cardiovascular disease in humans.
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| 23. |
- Asfaw Idosa, Berhane, 1977-
(författare)
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Inflammasome polymorphisms and the Inflammatory Response to Bacterial Infections
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- NLRP3 inflammasome; a key component of the innate immune system, can be activated by a number of pathogens and other threats of the body. Activation of the NLRP3 inflammasome triggers caspase-1 mediated maturationof IL-1β and IL-18. Polymorphisms Q705K and C10X are two gene variants of the NLRP3 inflammasome that combined or per se have been associated with higher risk and severity of chronic inflammation and excessive production of IL-1β. Host genetic factors have been found an important determinants of susceptibility of infectious diseases and disease outcome. The aims of this thesis were to investigate the association between polymorphisms Q705K and C10X with bacterial infections and the inflammatory response, moreover to determine the inflammasome activation state in healthy carriers of these polymorphisms. The data of the thesis show higher levels of IL-1β and IL-33 in healthy carriers of combined polymorphisms of Q705K and C10X as compared to non-carrier controls. This may provide individuals with combined polymorphisms a more robust innate immune response against pathogens, but could also lead to the onset of chronic inflammation, and excessive inflammation during acute infection. In addition, individuals with C10X polymorphism per se showed association with the presence of bacteremia as compared withhealthy blood donors. No association was found in severely ill patients with negative blood culture bottle. In addition, the results show that LOS of N. meningitidis is responsible for the priming and activating steps of the inflammasome. The non-LOS components were found to contribute to the priming step. A higher inflammatory response to N. meningitidis was found in individuals who were non-carriers of the polymorphisms than individuals with the Q705K and C10X per se or combined regardless of the strain of bacteria. Taken together, the gene variations of the NLRP3 inflammasome are of importance in explaining inter-individual variation in susceptibility to infectious diseases.
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| 24. |
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| 25. |
- Axer, Stephan, 1971-
(författare)
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Revisional bariatric surgery : more than a moral obligation
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 26. |
- Baban, Bayar, 1973-
(författare)
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Colorectal cancer and surgery : Insights into insulin resistance and inflammatory markers
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 27. |
- Basic, Vladimir, 1982-
(författare)
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Molecular mechanisms mediating development of pulmonary cachexia in COPD
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cigarette smoking (CS) represents the main causative agent underlying development and progress of COPD. Recently, involvement of CS in the pathogenesis of COPDassociated muscle abnormalities is becoming increasingly evident. Nevertheless, involved triggers and underlying mechanisms remain largely unknown. This study was conceived in order to examine effects of cigarette smoke exposure on skeletal muscle morphology, vascular supply and function. For this purpose, we have specifically designed murine COPD/emphysema model and gastrocnemius muscle was examined, while in vitro experiments were conducted using murine C2C12 skeletal muscle myocytes.In addition to the mild emphysematous changes present in the lungs of CS-exposed mice, our results demonstrated evident signs of muscle atrophy reflected by decreased fiber cross-sectional area, profound fiber size variation and reduced body mass. Furthermore, we have observed impairment in terminal myogenesis and lower number of myonuclei in skeletal muscles of CS-exposed animals despite evident activation of muscle repair process. Additionally, our results demonstrate capillary rarefaction in skeletal muscles of CS-exposed animals which was associated with deregulation of hypoxia-angiogenesis signaling, reduced levels of angiogenic factors such as HIF1-α and VEGF and enhanced expression of VHL and its partner proteins PHD2 and Ube2D1. The results of our in-vitro experiments demonstrated that VHL and its ubiquitination machinery can be synergistically regulated by TNF and hypoxia consequentially impairing angiogenic potential of skeletal muscle myocytes. Finally, we have shown that CS elicits chronic ER stress in murine skeletal muscles which is associated with activation of ERAD and apoptotic pathways as mirrored by elevated expression of Usp19, caspase 12 and caspase 3 in skeletal muscles of CSexposed animals. Moreover, molecular and morphological alterations in CS-exposed mice resulted in impairment of muscle function as reflected by their impaired exercise capacity.Taken together, from our results it is evident that cigarette smoke exposure elicits set of morphological, vascular and functional changes highly resembling those observed in COPD. Additionally, CS induces wide range of molecular alterations and signaling pathway deregulations suggesting profound effects of cigarette smoke exposure on skeletal muscle cell homeostasis.
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| 28. |
- Befekadu Wodajo, Rahel, 1968-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 29. |
- Bergemalm, Per-Olof, 1951-
(författare)
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Audiologic and cognitive long-term sequelae from closed head injury
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives – Head injury is an important health problem all over the world. Previous studies have shown that peripheral hearing impairment (HI) is a common sequel of closed head injury (CHI), but in most cases it will subside within the first posttraumatic months. However, in some cases, the HI persists and in other cases there can even be progress. The objective of the present study was to analyse long-term audiologic and cognitive consequences of CHI.There were four main issues:1. To study the presence and progress of sensorineural hearing loss (SNHL) after CHI and whether prediction of progress is possible. Autoimmunity as a possible cause of progress is also investigated, and the question of sympathetic cochleolabyrinthitis is discussed.2. To study the presence of central auditory processing disorders (CAPD) after CHI; the question of a King-Kopetzky syndrome should be discussed.3. To study the presence of cognitive impairments.4. To evaluate self-assessed hearing, cognition and quality of life from a long-term perspective.Material and methods – During a period of 14 years, around 2000 patients with head injuries were admitted to the emergency ward at Lindesberg County Hospital and Örebro Medical Centre Hospital. Six hundred subjects suffered from skull fracture and/or brain contusion and diagnosis was established using a computed tomography scan (CT). The degree of initial brain injury was estimated using the Swedish Reaction Level Scale (RLS). Sixty-six subjects were investigated with pure tone audiometry in close proximity to the trauma, and this gave an opportunity to study the issue of progress. The investigation took place two to 14 years after trauma, and the results were compared to matched control groups. A battery of different audiological methods was used to investigate peripheral and central auditory function, and a specially designed acoustic environmental room was also utilized. Cognition was investigated using a computer-based test-battery, text information process system (TIPS). Self-assessed hearing, cognition and quality of life were explored using different questionnaires.Results – A high percentage of peripheral and central auditory impairments and also cognitive shortcomings were demonstrated. Progress of SNHL was a common finding, and fracture, high age at trauma and large initial hearing loss predicted progress. Antibody-mediated autoimmunity as a mechanism behind posttraumatic progress of SNHL or clear evidence for sympathetic cochleolabyrinthitis could not be demonstrated. Binaural auditory deficits could be demonstrated when tested in a realistic acoustic environment. Tinnitus, vertigo and memory shortcomings proved to be common sequelae, even in a long-term perspectiveCognitive shortcomings were found in several of these well-rehabilitated subjects.On a group level, there was a good correlation between self-assessments and audiometric results, even if some individuals had a tendency to over- or underestimate their abilities.Conclusion – Auditory and cognitive long-term sequelae of CHI are a common finding even in well-rehabilitated and socially well-functioning subjects, as are vertigo and tinnitus. Vertigo and tinnitus are also common sequelae after CHI, therefore a basic audiovestibular investigation after CHI is recommended, at least in selected cases.Early awareness of the risk for hearing and cognitive sequelae after CHI could lead to measurements taken to prevent tension-related symptoms.Early detection of HI offers an opportunity to try immunosuppressive treatment in cases with a large initial SNHL.
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| 30. |
- Bergengren, Lovisa, 1972-
(författare)
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Cervical screening with primary HPV : from research to clinical effectiveness
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 31. |
- Bergh, Cecilia, 1972-
(författare)
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Life-course influences on occurrence and outcome for stroke and coronary heart disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.
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| 32. |
- Berglund, Carolina, 1980-
(författare)
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Molecular epidemiology of methicillin-resistant staphylococcus aureus : epidemiological aspects of MRSA and the dissemination in the community and in hospitals
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Methicillin-resistenta Staphylococcus aureus (MRSA) som bär på genen mecA, har förekommit och spridit sig över hela världen, främst i sjukhusmiljö, och orsakat utbrott av vårdrelaterade (så kallade nosokomiala) infektioner. Dessa infektioner kan inte behandlas med stafylokock-penicilliner och MRSA-bakterierna är ofta resistenta även mot flera andra grupper av antibiotika vilket medför att infektionerna ofta är påtagligt svårbehandlade. Under senare år har emellertid allt fler fall beskrivits av samhällsförvärvad MRSA infektion, det vill säga uppträdande av MRSA hos personer som tidigare ej har haft kontakt med sjukhusvård eller behandlats med antibiotika. Det har länge varit oklart om de samhällsförvärvade MRSA [community-acquired (CA-MRSA)] representerar spridning av bakterier från sjukhusmiljön ut till samhället eller om dessa MRSA är spontant uppträdande. Många av dessa stammar har dessutom visat sig bära på sjukdomsrelaterade gener som vanligen inte återfinns hos S. aureus, t.ex. Panton Valentine leukocidin (PVL) som associeras med hudinfektioner och allvarlig lunginflammation med hög dödlighet hos unga och annars friska individer. Denna avhandling beskriver den molekylära epidemiologin hos MRSA med fokus på samhällsförvärvade MRSA som utgjorde mer än hälften av samtliga fall av MRSA i Örebro län och som dessutom ofta producerade PVL toxinet, vars funktion vidare analyserades i detalj. Undersökning av ursprung och släktskap hos samtliga MRSA som isolerats i Örebro län, samt karaktärisering av det genetiskt element som kallas staphylococcal cassette chromosome mec (SCCmec) vilket innehåller genen mecA och ibland även andra resistensgener, visade att CA-MRSA inte är relaterade till de nosokomiala MRSA, och att dessa har uppstått oberoende av varandra. Flertalet MRSA visade sig dessutom bära på SCCmec, och resistensmekanismer, som tidigare inte beskrivits. Troligen har dessa MRSA uppstått genom ett genetiskt utbyte av SCCmec mellan methicillin-resistenta koagulas-negativa stafylokocker (MR-KNS), som utgör huvudparten av normalfloran på huden, och methicillin-känsliga S. aureus som därvid erhåller genen mecA och resistensmekanismer mot samtliga stafylokockantibiotika. I den här avhandlingen framläggs bevis för att ett sådant genetiskt utbyte har skett på Barnkliniken på Universitetssjukhuset i Örebro i slutet på 1990-talet, vilket resulterade i uppkomsten av en ny klon av MRSA som därefter orsakade ett allvarligt utbrott. Kartläggning av DNA-sekvensen hos flertalet unika SCCmec från svenska MRSA gav dessutom en bättre förståelse för hur resistens uppkommer och sprider sig, samt mekanismerna bakom detta. Dessa nya kunskaper kan bidra till en förbättrad diagnostik av MRSA. Detta är framför allt av stor betydelse eftersom nya effektiva kloner av MRSA verkar kunna uppstå ute i samhället med potential att orsaka svårbehandlade infektioner men även att sprida sig bland den friska befolkningen.
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| 33. |
- Björk, Tabita
(författare)
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Measuring eating disorder outcome : definitions, dropout and patients' perspectives
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite a plethora of research, there are serious limitations in our knowledge of outcome in eating disorders. Almost all studies have been compromised by the problem of treatment dropout or non-participation in follow-ups. There exists a lack of consensus in definitions of outcome and choice of outcome measures, and there is a dearth of studies focusing on how patients subjectively perceive recovery. The overall aim of this thesis was to address problems in measuring outcome after treatment for eating disorders, with an emphasis on methodological issues. Specific areas of investigation included non-participation in long-term follow-ups, the role of self-image in treatment dropout, outcome among patients who drop out, patients’ subjective perspectives of recovery, and the impact of different methods of measuring outcome. Method: Four quantitative studies (I, II, III and V) were conducted within the framework of a large Swedish multi-centre study of eating disorders, which adopted a prospective, longitudinal and naturalistic design. Study IV was a qualitative investigation encompassing interviews with former ex-patients who were considered recovered. Results: Study I suggested that the reasons for non-participation in research were mainly patient related (69%). Those declining further participation in follow-ups were reported significantly lower levels of obsession-compulsion and anxiety, while those not traceable reported significantly higher levels of hostility at admission. Study II suggested that patients who dropped out from treatment initially presented with less negative self-image and fewer psychological problems compared to those who remained in treatment. Low levels of self-blame discriminated dropouts from completers and remainers, and significantly predicted treatment dropout. Study III found no significant differences between dropouts and completers at follow-up, with the exception that dropouts were more dissatisfied with treatment. However, patterns of treatment response revealed that those who completed treatment made significantly greater changes in terms of reduced eating disorder symptoms, fewer psychological problems and a more positive self-image compared to dropouts. Study IV found that patients who had recovered from an eating disorder tended to describe other dimensions of outcome than those usually reported in follow-ups. Patients tended to view recovery in terms of being able to relate in a relaxed and accepting manner to food, their bodies, themselves as individuals, and their social environment. Some perceived recovery in terms of coping better with emotions, while others experienced themselves as healthier than people generally regarding food and weight. Study V applied some of the most frequently used outcome measures for eating disorders and found marked variations in the number of patients who could be considered in remission. Overall remission rates varied from 24.3% to 77.8%, depending on the outcome measure used. Discussion: The results suggest that non-participation and dropout are not unitary phenomena. There is also a need for greater consensus on how eating disorder outcome should be measured. This is necessary in order to make comparisons between different outcome studies meaningful, and to elucidate the overall picture of eating disorders outcome.
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| 34. |
- Björkenheim, Anna, 1980-
(författare)
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Catheter ablation for atrial fibrillation : effects on rhythm, symptoms and health-related quality of life
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: AF ablation is an increasingly used treatment in patients with AF to improve patient-reported outcomes (PROs). Atrioventricular junction ablation (AVJA) is a palliative treatment option in therapy refractory AF that improves PROs but renders the patient pacemaker dependent.Aims: To evaluate rhythm control and PROs before and up to two years after AF ablation. To analyze the long-term incidence of and predictors of hospitalization for HF and all-cause mortality in patients who underwent AVJA and right ventricular pacing.Methods and Results: Fifty-four patients underwent AF ablation and both continuous rhythm monitoring via an implantable loop recorder (ILR) and intermittent rhythm monitoring three, six, 12 and 24 months after ablation. 76 % of patients had at least one AF recurrence, of whom 24 % were only detected by ILR. One third of symptom recordings did not show AF. The AF-specific AF6 scores, physician-assessed EHRA symptom class and both SF-36 summary scores all improved significantly from before to two years after ablation. There was a weak correlation between the change in AF6 scores and EHRA class from before to six and 12 months but not to 24 months after ablation. Responders to ablation (AF burden < 0.5 %), reached age- and sex-matched norms in all SF-36 domains, but non-responders only in social functioning and MCS. All AF6 scores showed at least moderate improvement in both responders and non-responders. Higher AF burden was independently associated with poorer PCS and AF6 scores. In 162 patients who underwent AVJA, hospitalization for HF occurred in 20 % of patients (two-year cumula-tive incidence 9.1 %) and 22 % died (two-year cumulative incidence 5.2 %) during a median follow-up of five years. QRS ≥ 120 ms and left atrial diame-ter were independent predictors of hospitalization for HF, and hypertension and previous HF of death.Conclusions: Continuous rhythm monitoring was superior to intermittent monitoring. The AF-specific AF6 was more sensitive to changes related to AF burden after AF ablation than both EHRA class and the SF-36. The long-term hospitalization rate for HF and all-cause mortality was low after AVJA.
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| 35. |
- Björkman Hjalmarsson, Louise, 1984-
(författare)
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Aspects of neonatal septicaemia : prevention and complications
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Study I was part of the Extremely Preterm Infants in Sweden Study (EXPRESS), a prospective national study including all infants born <27 weeks in Sweden in 2004-2007 that survived their first year of life (n=497). Neonatal sepsis was evaluated as a risk factor for neonatal morbidities. Definite sepsis was associated with severe bronchopulmonary dysplasia and prolonged hospital stay, but not with a higher risk of retinopathy of prematurity or intraventricular haemorrhage.Study II was a non-randomized single-centre intervention study evaluating possible preventive effects on coagulase-negative staphylococci (CoNS) sepsis when the scrub the hub method was used. During the intervention period, the incidence of CoNS sepsis decreased from 1.5% to 0% (CI: 0.53-2.58%, p=0.06).Study III was an in-vitro study evaluating leakage of isopropanol (IPA) and ethanol when alcohol caps and scrub the hub were used to disinfect hubs. Alcohol leakage was measured using gas chromatography. IPA was detected in all samples from cap circuits, and mean leakage increased over time. Ethanol levels were low, and scrub the hub therefore seems safe to use.Study IV was a survey study evaluating reported hygiene routines from Swedish neonatal intensive care units (NICUs) included in the EXPRESS study. Routines were compared between the EXPRESS period (2004- 2007) and 2013. Improvements were seen regarding basic hygiene routines, routines for work clothing, and follow-up of compliance. Antibiotic prophylaxis decreased while fungal prophylaxis increased, but the empiric treatment of suspected late-onset sepsis (LOS) showed heterogeneity.Study V investigated the association between incidence in LOS in the EXPRESS cohort and the hygiene routines previously evaluated in Study IV. Strict catheter routines, blood culture routines, and non-use of antibiotic prophylaxis were associated with decreased sepsis risk.
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| 36. |
- Björksved, Margitha, 1964-
(författare)
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Open vs closed exposure of palatally displaced canines : clinical, patient-related outcomes and health economics
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 37. |
- Bohr Mordhorst, Louise, 1958-
(författare)
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Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A series of 131 women with cervical carcinoma FIGO stage I-IV were treated with external radiotherapy and intracavitary brachytherapy. In 47 patients (36%) concomitant chemotherapy was given. One hundred and twenty-one tumors (92%) achieved complete remission. Addition of chemotherapy increased primary cure rate to 98%. Tumor stage, tumor size, and histology were significant predictive factors for primary cure. Treatment related factors were: brachytherapy dose and interruption of irradiation.Thirty-nine recurrences (30%) were recorded. Tumor stage, histology, and concomitant chemotherapy were significant predictive factors.The 5-year cancer-specific survival rate of the complete series was 65%. Tumor size was a strong prognostic factor in multivariate analysis.Serum samples from 44 patients were analyzed. Ten candidate biomarker proteins with regard to tumor recurrences were identified.Five Hedgehog proteins were analyzed with immunohistochemistry. Residual tumor, local and distant recurrences and survival rate were associated with PTCH, SMO and GLI2. In the Wnt-β-catenin study intense staining of the membranes and nuclear staining > 5% were of significant predictive and prognostic value. Intense nuclear APC staining was associated with recurrences and cancer-specific survival rate.Conclusion: Histology, tumor size and brachytherapy dose were important clinical predictive and prognostic factors. Multiprotein analysis identified ten biomarker proteins associated with tumor recurrences. Three proteins (PTCH, SMO, and GLI2) in the Hedgehog pathway were of predictive and prognostic value. In the Wnt-β-catenin pathway intensity of β-catenin membrane staining and accumulation in the nuclei as well as nuclear APC-expression were of predictive and prognostic value.
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| 38. |
- Bozorg, Soran Rabin, 1993-
(författare)
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Various Aspects of Gastrointestinal Disease : Examining Validity and Health Economic Outcomes
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)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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| 39. |
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| 40. |
- Brocki, Barbara C, 1957-
(författare)
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Physiotherapy interventions and outcomes following lung cancer surgery
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to evaluate the effect of exercise training and inspiratory muscle training and to describe pulmonary function, respiratory muscle strength, physical performance and health-related quality of life (HRQoL) following lung cancer surgery.Study I was a randomised controlled trial including 78 patients radically operated for lung cancer. The intervention group received 10 sessions of supervised exercise training in addition to home-based exercise; the control group was instructed on home-exercise alone. Supervised compared to non-supervised exercise training did not result in differences between groups in HRQoL, except for the SF-36 bodily pain domain four months after the surgery. No effects of supervised training were found for any outcome after one year.Study II was descriptive and was based on the study I sample. We evaluated the course of recovery of HRQoL and physical performance up to one year following surgery. All patients improved HRQoL and physical performance one year after the surgery, reaching values comparable to a reference healthy population. The walked distance was positively associated with the SF-36 domain for physical functioning.Study III was descriptive, included 81 patients and evaluated the influence of surgery on respiratory muscle strength, lung function and physical performance two weeks and six months after surgery. We found that respiratory muscle strength was not affected after the second postoperative week and that muscle-sparring thoracotomy did not deteriorate respiratory muscle strength, compared to video-assisted thoracic surgery. Compared to preoperative values, physical performance was recovered, whereas lung function remained reduced six months postoperatively.Study IV was a randomised controlled trial including 68 patients at high risk of developing postoperative pulmonary complications (PPC). This study evaluated the effects of two weeks of postoperative inspiratory muscle training in addition to breathing exercises and early mobilisation on respiratory muscle strength and the incidence of PPC. Additional inspiratory muscle training did not increase respiratory muscle strength, but improved postoperative oxygenation. Respiratory muscle strength was recovered in both groups two weeks postoperatively.
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| 41. |
- Brus, Ole, 1982-
(författare)
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Prognostic factors of electroconvulsive therapy for depression
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depression is a severe disorder that can be difficult to treat. One approach to treating depression is electroconvulsive therapy (ECT), whereby electricity is administered through electrodes fastened to the patient’s head. This procedure is effective, however not all patients respond. Moreover, ECT can induce side effects, such as memory problems. In addition, even after achieving remission patients are likely to relapse at a later date. Thus, it is important to optimize ECT in terms of treatment effectiveness while minimizing its side effects. A further crucial issue is to prevent relapses by developing effective follow-up treatments. This thesis encapsulates four studies with the following goals: 1) to identify which factors that are associated with the worsening of subjective memory, 2) to identify factors that are associated with remission, 3) to quantify the effect of lithium on relapse after ECT for unipolar depression, 4) to investigate whether the difference in time to relapse between continuation ECT (C-ECT) with medication and medication alone during the first year of treatment changes over 10 years following the end of C-ECT treatment in patients with depression.The studies were performed using the Swedish national register data. The first two studies used the outcomes of subjective memory worsening and remission respectively. The third and fourth studies used time to relapse as the outcome.Several factors were associated with the outcomes: in the first, second, and third studies, it was found that older patients were associated with a positive outcome. In both the second and fourth studies, psychotic depression and not having anxiety disorder were associated with positive outcomes. The third study showed that patients who used lithium were less likely to relapse: the hazard ratio with 95% confidence interval among lithium users compared to non-lithium users was 0.84 (0.75–0.93). The fourth study indicated that the beneficial effect of C-ECT and medication compared with medication alone during the first year post-ECT was maintained for several years.In conclusion, it is important to identify factors that are associated with beneficial treatment, and the studies conducted for this thesis contribute to such knowledge.
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| 42. |
- Böttiger, Anna, 1977-
(författare)
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Genetic variation in the folate receptor-alpha and methylenetetrahydrofolate reductase genes as determinants of plasma homocysteine concentrations
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and neurocognitive disease such as dementia. The B vitamins folate and B12 are the main de terminants of tHcy. tHcy concentration can also be affected by mutations in genes coding for receptors, enzymes and transporters important in the metabolism of Hcy. This thesis focuses on mutations in the genes for folate receptor-alpha and methylenetetrahydrofolate reductase (MTHFR) and the effect they have on tHcy concentrations. Six novel mutations in the gene for folate receptor-alpha were described in Paper I. Taken together they exist in a population with a prevalence of approximately 1% and thus are not unusual. There may be an association of –69dupA and –18C>T to tHcy but for the 25-bp deletion, –856C>T, –921T>C and –1043G>A there is probably no association to tHcy. Mutation screening was continued and four additional mutations, 1314G>A, 1816delC, 1841G>A and 1928C>T, were described in Paper II. The prevalences for the heterozygotes were between 0.5% and 13% in an elderly population. There was no significant difference in prevalence between the elderly subjects and patients with dementia. The 1816(–)-allele and the 1841A-allele were in complete linkage and the haplotype 1816(–)-1841A may possibly have a tHcy raising effect. The 1314G>A and 1928C>T mutations had no association to tHcy. The genotype prevalences and haplotype frequencies of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms were determined in a population sample of Swedish children and adolescents (Paper III). The MTHFR 677T-allele was associated with increased tHcy concentrations in both children and adolescents. A small elevating effect of the 1298C-allele and a small lowering effect of the 1793A-allele could be shown. In an epidemiological sample of adults from the Canary Islands, Spain, data for serum folate and vitamin B12 were used for a broader study of the nutrigenetic impact on tHcy (Paper IV). The 677T-allele had a significant tHcy increasing effect in men but not in women. The 1298C-allele had a minor elevating effect on tHcy in men with the 677CT genotype. It was not possible to document any effect of the 1793A-allele on tHcy due to its low prevalence. A slightly superior explanatory power for the genetic impact was obtained using the MTHFR haplotypes in the analysis compared to the MTHFR 677C>T genotype-based approach in both the Swedish children and adolescents and in the Spanish adults. Therefore MTHFR haplotypes should be considered when analysing the impact of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms on tHcy. Notwithstanding the large geographical distance between our study populations the haplotype composition is quite similar. The MTHFR 677T-allele is slightly more prevalent in Spain compared to Sweden but it has only an effect on tHcy in the Spanish men. Age, gender and factors linked to the ethnicity of the studied subjects, seem to be able to override the nutrigenetic impact of tHcy-raising genotypes or haplotypes in particular settings, such as in the Spanish women in our study. Gene-nutrient interactions on plasma tHcy levels thus may or may not exist in a certain population. The transferability of nutrigenetic findings may therefore be limited, and must be re-evaluated for each particular setting of age-gender-ethnicity.
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| 43. |
- Cajander, Per, 1976-
(författare)
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Risk of pulmonary aspiration during anesthesia and sedation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary aspiration is a feared complication in anesthesia practice. Even if it is a rare event it is the most common cause of anesthesia related death. There are two different types of pulmonary aspiration, macroaspirationwhere large amounts of gastric content are inhaled to the lungs, and the silent, often unnoticed, microaspiration, where small amounts of gastric or oropharyngeal contents are aspirated. Micro aspirations is much more common and can occur at any time during the perioperative period, presenting as postoperative pulmonary complications, often several days after the anesthesia procedure. Human physiology features multiple mechanisms of protection against pulmonary aspiration, including the esophageal sphincters that prevent gastric regurgitation and complex laryngeal reflex systems protecting the airway. An additional vital defense against pulmonary aspiration is an intact swallowing function, with dysphagia being the primary cause of aspiration pneumonia. Anesthetic agents affect these protective mechanisms to various extent.The aim of this thesis was to study the effects of sedative agents on swallowing function, and different ventilatory techniques during anesthesia induction in healthy volunteers. In study I, the use of positive end expiratory pressure during mask ventilation after anesthesia induction was studied in regard of risk of gastric insufflation. In study II and IV the pharmacological effects of the opioid remifentanil on swallowing function were studied. Study III was the first study on effects of dexmedetomidine on human swallowing physiology. The experiments in this thesis has led to a deeper understanding in how different anesthetic agents affects the physiological protective mechanisms against pulmonary aspiration, both during anesthesia induction and sedation. The findings may facilitate clinical decisions, leading to better risk management in terms of macroaspiration during anesthesia and sedation, and postoperative pulmonary complications related to microaspirations.
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| 44. |
- Cajander, Sara, 1980-
(författare)
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Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression.In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control.In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.
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| 45. |
- Calais, Fredrik, 1971-
(författare)
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Coronary artery disease and prognosis in relation to cardiovascular risk factors, interventional techniques and systemic atherosclerosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To evaluate the prognosis associated with location and severity of coronary and systemic atherosclerosis in patients with coronary artery disease (CAD) in relation to risk factors and interventional techniques.Methods: The thesis comprised six longitudinal studies based on three patient cohorts: The Swedish Coronary Angiography and Angioplasty Registry, the Västmanland Myocardial Infarction Survey, and the Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia study, to evaluate clinical outcome relative to coronary lesion location and severity, extracoronary artery disease (ECAD), intervention techniques, and leisuretime physical inactivity (LTPI).Results: Stent placement in the proximal left anterior descending artery (LAD) was more often associated with restenosis than was stenting in the other coronary arteries. The use of drug-eluting stents in the LAD was associated with a lower risk of restenosis and death compared to baremetal stents. Thrombus aspiration in in the LAD during acute ST elevation myocardial infarction (MI) did not improve clinical outcome, irrespective of adjunct intervention technique. Clinical, but not subclinical, ECAD was associated with poor prognosis in patients with MI. Longitudinal extent of CAD at the time of MI was a predictor of ECAD, and coexistence of extensive CAD and ECAD was associated with particularly poor prognosis following MI. Self-reported LTPI was associated with MI and all-cause mortality independent of ECAD.Conclusions: Drug-eluting stents, but not thrombus aspiration, improved prognosis following percutaneous coronary intervention in the proximal LAD. Self- reported LTPI, clinical ECAD, and systemic atherosclerosis defined groups with poor prognosis after MI.
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| 46. |
- Carling, Anna, 1985-
(författare)
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Impaired balance and fall risk in people with multiple sclerosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The symptoms from the neurological disease multiple sclerosis vary from person to person and over time. Impaired balance is common in people with multiple sclerosis and can lead to falls. Fall frequency is high in people with multiple sclerosis, above 50%. Multiple sclerosis affects not only the person having the disease but also their next of kin. To be able to reduce fall risk it is important to know when, why and where people with multiple sclerosis fall, and how to improve balance and reduce falls with exercise. It is also important to know how the falls affect the residing next of kin to people with multiple sclerosis.The overall aim of this thesis was to gain enhanced knowledge by investigating when and why people with MS fall and how these falls possibly affect their next of kin, and also to evaluate the effects and perceptions of participating in a specific balance exercise.Data were gathered using four different data collections, and this thesis contains both qualitative and quantitative data.The major finding in this thesis is that people with multiple sclerosis fall in the course of everyday life activities, most often in their own homes due to various intrinsic and extrinsic factors. Balance can be improved and falls reduced and everyday life may be made easier and facilitated after participating in the CoDuSe balance exercise. This is important also for the next of kin, since they are adapting, adjusting and renouncing their activities due to the falls of the PwMS, in order to make it work for the whole family.
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| 47. |
- Carlsson, Jessica, 1984-
(författare)
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Identification of miRNA expression profiles for diagnosis and prognosis of prostate cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer of the prostate (CaP) is the most common malignancy diagnosed in men in the Western society. During the last years, prostate specific antigen (PSA) has been used as a biomarker for CaP, although a high PSA value is not specific for CaP. Thus, there is an urgent need for new and improved diagnostic markers for CaP.In this thesis, the aim was to find a miRNA signature for diagnosis of CaP and to elucidate if differences in behavior between transition zone and peripheral zone tumors are reflected in miRNA expression. One of the major findings is anexpression signature based on nine miRNAs that with high accuracy (85%) could classify normal and malignant tissues from the transition zone of the prostate. The results furthermore show that the major differences in miRNA expression are found between normal and malignant tissues, rather than between the different zones. In addition, tumors arising in the peripheral zone have fewer changes in miRNA expression compared to tumors in the transition zone, indicating that the peripheral zone is more prone to tumor development compared to the transition zone of the prostate.A crucial step in pre-processing of expression data, in order to differentiate true biological changes, is the normalization step. Therefore, an additional aim of this thesis was to compare different normalization methods for qPCR array data in miRNA expression experiments. The results show that data-driven methods based on quantile normalization performs the best. The results also show that in smaller miRNA expression studies, only investigating a few miRNAs, RNU24 is the most suitable endogenous control gene for normalization.Taken together, the results in this thesis show the importance of miRNAs and the possibility of their future use as biomarkers in the field of prostate cancer.
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| 48. |
- Carlsson, Per-Inge, 1959-
(författare)
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Hearing impairment and deafness : genetic and environmental factors - interactions - consequences : a clinical audiological approach
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVES - Hearing impairment (HI) can be due to genetic or environmental factors, e.g. noise. More than 50% of HI cases are thougt to be hereditary. HI can affect social participation in different ways. How serious these problems becomes depends on several factors, for example, the type of social environment the person lives in. The objective of the present study was to point out the importance of studying HI and deafness in a broad perspective, from the molecular - biological level to the psychological - social level and to evaluate how interactions of factors at several levels form the consequences, in a long-term perspective, to witch HI and deafness can lead. MATERIAL AND METHODS - Three different study populations have been used to study the four levels in this study: Papers I - III; 1200 noise-exposed workers (molecular and biological levels), Paper IV; 50 persons with HI since early childhood, with or without a family history of HI (FHHI)(biological, psychological and social level), and in Paper V; 600 persons with early onset of deafness in two counties with differently strong Deaf communities (psychological and social level). RESULTS - The molecular genetic studies (Papers I – III) showed that the combination of smoking and having a mutation in the protective antioxidant system revealed an additional risk for noise induced hearing loss. In Paper IV, only small differences was found between subjects with and without a FHHI. The results in Paper V indicated that differences in the social environment, in terms of the strength of the Deaf community, influence family factors such as marriages, divorces and the number of children born. CONCLUSIONS - Analysing complex issues such as HI and deafness from a medical audiological perspective requires a multi- level approach at several levels. The results indicate that interactions of factors at all four levels form the consequences, in a long-term perspective, to wich HI and deafness can lead. Furthermore, this multi-level approach - here called a clinical audiological approach - is essential when using the ICF framework in audiological rehabilitation/habilitation.
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| 49. |
- Carstens, Adam, 1975-
(författare)
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Chronic inflammatory bowel diseases : studies of microbiota and its influence
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Inflammatory bowel diseases are becoming increasingly common. The underlying mechanisms are not entirely known but the gut microbiota seem to be involved in the pathogenesis. Aim: The aim of this thesis was to characterise gut microbiota related to diagnosis, disease course and response to biological treatment, taking aspects of the source of biological material into account. Materials and methods: Patients and healthy individuals from several different cohorts in Sweden and Europe were invited. Faecal samples and mucosal biopsies were analysed using different sequencing platforms to investigate the gut microbiota. In Study I the faecal microbiota was correlated to different inflammatory bowel diseases. In Study II we compared the microbiota in faeces to the microbiota in mucosal biopsies. In StudyIII we related the faecal microbiota to the outcome of biological treatment. In Study IV we investigated the diagnostic and prognostic properties of the GAmapTM Dysbiosis Test.Results: The faecal microbiota in collagenous colitis resembles the faecalmicrobiota in inflammatory bowel disease. The faecal microbiota differs from the mucosal microbiota. Faecal microbiota at initiation of biological treatment among patients with Crohn’s disease differ between responders and non-responders. The GAmapTM Dysbiosis Test discriminates patients with inflammatory bowel disease from healthy individuals.Conclusion: Collagenous colitis may share microbial underpinnings with other inflammatory bowel diseases. Conclusions about mucosal interactions with the gut microbiota should be made with caution when usingfaecal samples to characterise the microbiota. In Crohn’s disease, the faecal microbiota may be included in a model to predict the outcome of biological treatment. The GAmap Dysbiosis Test does not seem to be superior to other current diagnostic tools in clinical decision-making.
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| 50. |
- Crommert, Martin Eriksson, 1974-
(författare)
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On the role of transversus abdominis in trunk motor control
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- All trunk muscles are important contributors to spine stability. However, the deepest abdominal muscle, transversus abdominis (TrA), with its characteristically horizontal fibre orientation seems to serve a unique function in trunk motor control. The main mechanical role of TrA is believed to be to contribute to vertebral alignment during imposed moments on the trunk, executed mainly via either regulating the pressure level within the abdominal cavity and/or transmit forces to the spine via the thoracolumbar fascia. However, the complete function of TrA and what factors affect its activation are still not fully understood. The purpose of the present thesis was to investigate the role of TrA in trunk motor control, specifically in relation to the presence or absence of postural demand on the trunk.The timing and magnitude of TrA activation were investigated, in relation to other trunk muscles, with intramuscular fine-wire electrodes in different loading situations and body positions with varying postural demand.In a side-lying position, with no postural demand of keeping the trunk upright, the activation of TrA was delayed relative the superficial abdominal muscles compared to previous experiments performed in a standing position. The timing and magnitude of activation of TrA did not depend upon the direction of perturbation. In the standing position, different static arm positions revealed that the activation of TrA co-varied with variations in the degree of postural demand on the trunk and also the imposed moments, regardless of moment direction. Finally, a study on rapid arm flexion movements confirmed that TrA is part of the pre-programmed anticipatory response in advance of known perturbations. The activation magnitude of TrA was the same regardless if the arm movement induced flexion or extension moments on the trunk.In conclusion, the activation of TrA is associated with the upright postural demand on the trunk and with balancing imposed moments acting on the spine, regardless their direction. The findings are in support of the beliefs that TrA act as a general, direction non specific, stabilizer of the lumbar spine.
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