| 21. |
- Ranebo, Mats, 1970-
(författare)
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Rotator Cuff Tears : Short- and long-term aspects on treatment outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rotator cuff tear is a common disorder and there is a lack of knowledge of appropriate treatment and consequences of different treatment modalities. The overall aim of this thesis was to examine short- and long-term results of rotator cuff tear treatment.In Paper I we did a retrospective 21 to 25-year follow-up of a consecutive series of patients with partial and full-thickness rotator cuff tears, treated with acromioplasty without cuff repair. The cuff status had been documented in a specific perioperative protocol in all patients at the index operation. We did x-ray, ultrasonography and clinical scores with Constant score and Western Ontario Rotator Cuff index (WORC) at follow-up. We identified 111 patients with either a partial or a full-thickness tear, but at follow-up 21 were deceased and 11 were too ill from medical conditions unrelated to their shoulder. Out of the remaining 78 eligible patients, 69 were examined (follow-up rate 88 %) and they had a mean age at the index operation of 49 years (range 19-69 years). Forty-five had a partial tear and 24 a full-thickness tear at the index operation. At follow-up, 74% of patients with full-thickness tear had cuff tear arthropathy grade 2 or more according to the arthropathy classification of Hamada (grade 1 to 5) and 87% had developed tear progression (i.e. a larger tear). Corresponding numbers in those with a partial tear was 7 % arthropathy and 42 % tear progression, and the differences between the full-thickness group and the partial tear group was significant for both outcome measures (P<0.001 for both analyses). In those with arthropathy, the mean Constant score was 47 (standard deviation [SD], 23), the mean age and gender-adjusted Constant score 62 (SD, 27) and the mean WORC 58 % (SD, 26). Patients with a partial tear at follow-up had mean Constant score and WORC within the normal range. In multivariable analysis with logistic regression, having a full-thickness tear at the index operation was a risk factor for arthropathy (odds ratio [OR] 37.8; 95% confidence interval [CI], 8.2-175.0) and for tear progression (OR 6.09; 95% CI, 1.41-26.29).In Paper II we examined the contralateral shoulder in the same patients as in paper I and with the same methodology. Sixty-one patients were examined and 38 had had a partial tear at the index operation 21-25 years ago and 23 a full-thickness tear. The overall rate of contralateral full-thickness tears was 50.8 %, which is higher than the 16-35 % rate found in previous studies of newly diagnosed cuff patients. The rate of contralateral full-thickness tear ranged from 13.6 % in patients with a partial tear in the index shoulder at follow-up, to 90 % in patients with a full-thickness tear and arthropathy in the index shoulder. There was a significant correlation regarding conditions between shoulders in the same patient, with a Spearman coefficient of 0.72 for the number of ten-dons with a full-thickness tear, 0.31 for Hamada grade of arthropathy and 0.65 for Constant score. The number of tendons with a full-thickness tear in the index shoulder at follow-up was a risk factor for a contralateral full-thickness tear (OR 3.28; 95% CI, 1.67-6.44) in a multi-variable logistic regression model. We also found that cuff tear arthropathy was significantly more common in patients who had undergone an acromioplasty (P<0.001), a finding which is not confirmatory but may generate a hypothesis.Paper III addressed 17 to 20-year results after operation with a synthetic interposition graft for irreparable cuff tears. We used X-ray, ultrasonography and clinical scores at follow-up. We identified a consecutive series of 13 patients, one of whom was deceased at follow-up. Ten of the remaining 12 participated in a complete follow-up and 2 did only x-ray examination. Nine out of 12 (75 %; 95% CI, 43-95 %) had cuff tear arthropathy Hamada grade 2 or more in the index shoulder at follow-up. The mean Constant score was 46 (SD, 26) and the mean WORC 59 % (SD, 20). Seven out of 12 had contralateral cuff tear arthropathy, and the difference in frequency of arthropathy between shoulders was not statistically significant (P=0.667).In Paper IV we tested whether early repair of small cuff tears, involving mainly supraspinatus, would give a superior clinical result com-pared to physiotherapy without repair in a prospective randomised trial with 12 months follow-up. We used Constant score as the primary out-come, and WORC, EQ-VAS and Numerical Rating Scale for pain (NRS) as secondary outcomes. We also aimed at assessing the rate of tear progression in unrepaired shoulders and the healing rate in repaired shoulders by Magnetic Resonance Imaging (MRI) performed at 12 months. With a high grade of follow-up (100 % for 12 months Constant score and 95 % for 12 months MRI), the repair group had a 12 months median Constant score of 83 (Quartile range [QR], 25) and the conservative group 78 (QR, 22). This between-group difference in medians of 4.5 (95% CI,-5 to 9; P=0.68) was not statistically significant and we did not detect any significant differences in the secondary outcomes at 12 months. The retear rate was 6.5 % in repaired patients and 29 % of unrepaired patients had a tear enlargement >5 mm.The results in this thesis indicate that patients with small, traumatic, full-thickness tears of mainly supraspinatus have no clinical benefit of early surgical repair compared to physiotherapy alone, but in the long-term, patients with full-thickness tears have an increased risk of tear progression, cuff tear arthropathy and low clinical scores. These results are especially important in the treatment decision of repair or not in younger patients. Having a full-thickness tear is also a risk factor for having a contralateral cuff tear, a phenomenon that underlines the importance of endogenous factors in the development of rotator cuff tears. If a cuff tear is not repairable to bone, the addition of a synthetic inter-position graft does not seem to prevent cuff tear arthropathy.
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| 22. |
- Samefors, Maria, 1980-
(författare)
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Aspects of Vitamin D Deficiency in Elderly People in Nursing Homes and in Patients with Type 2 Diabetes : with Emphasis on Mortality, Cardiovascular Morbidity and Mental Health
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundInstitutionalised elderly people living in northern latitudes may be at elevated risk for vitamin D deficiency. They are recommended to take oral vitamin D supplements, but the main source of vitamin D is sunlight. Previous studies have shown an association between low levels of vitamin D and several diseases, but important knowledge about vitamin D in elderly people in nursing homes and in patients with type 2 diabetes is lacking. The aims of this thesis were to study aspects of vitamin D deficiency in these two populations and to explore whether low vitamin D levels were associated with mortality, cardiovascular morbidity and mental health. Also, we aimed to examine whether an intervention with encouragement to spend time outdoors during summer could increase vitamin D levels in the elderly in nursing homes.MethodsThe present thesis is based on four papers. Papers I and IV are confined to nursing home residents >65 years. Paper I is based on data from SHADES (The Study of Health and Drugs in the Elderly). Paper IV is based on the study Sunlight and Vitamin D in Older People in Nursing Homes. Papers II and III are based on data from CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes—a Prospective Study in Primary Care), with patients with type 2 diabetes aged 55-66 years. Papers I-III were prospective observational cohort studies and Paper IV was a cluster randomised intervention trial.In Paper I, serum 25-hydroxyvitamin D3 (25(OH)D3) was analysed on three occasions. The vital status of the subjects was ascertained and hazard ratios (HRs) for mortality according to baseline 25(OH)D3 quartiles (Q) were calculated.In Paper II, serum 25(OH)D3 was analysed at baseline. HRs for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D3 were calculated.In Paper III, serum 25(OH)D3 was analysed at baseline. The SF-36 questionnaires measuring vitality and mental health were administered at baseline and after four years.In Paper IV, the intervention group was encouraged to go outside for 20-30 minutes every day for two months during the summer of 2018. Before and after the summer, serum 25(OH)D was analysed and SF-36 questionnaires measuring vitality and mental health were administered.ResultsIn Paper I, 80% of the participants had 25(OH)D3 < 50 nmol/l. Vitamin D deficiency was associated with an increased mortality risk. Compared with Q4 (25(OH)D3 >48 nmol/l), the HR (with a 95% confidence interval (CI)) for mortality was 2.02 (1.31-3.12) in Q1 (25(OH)D3 <29 nmol/l) (p<0.05), 2.03 (1.32-3.14) in Q2 (25(OH)D3 30-37 nmol/l) (p<0.05) and 1.6 (1.03-2.48) in Q3 (25(OH)D3 38-47 nmol/l) (p<0.05).In Paper II, serum 25(OH)D3 was inversely associated with the risk of cardiovascular morbidity and mortality. The HR per nmol/l was 0.98 (95% CI: 0.96-0.99) (p=0.001), when adjusted for age, sex and season.In Paper III, serum 25(OH)D3 was inversely associated with poor mental health at baseline. The odds ratio (OR) for 10 nmol/l increase in 25(OH)D3 was 0.90 (95% CI: 0.83-0.96) (p=0.003), but not at follow-up (p>0.05). Serum 25(OH)D3 was not associated with vitality at baseline (p>0.05), nor at follow-up after adjustments.In Paper IV, the 25(OH)D levels increased significantly in the intervention group during the summer: from a median (interquartile range (IQR)) of serum 25(OH)D of 42.5 (23.0) nmol/l to 53.5 (33.0) nmol/l (p=0.011). The 25(OH)D levels increased in the control group as well, but the increase was not significant. The intervention group reported better mental health after the summer compared to before the summer (p=0.015), unlike the control group.ConclusionsLow vitamin D levels were associated with increased mortality in elderly people in nursing homes, and with cardiovascular morbidity/ mortality and poor mental health in patients with type 2 diabetes. From our studies, we cannot draw conclusions about causality. The results indicate that the vitamin D levels give prognostic information. Active encouragement to spend time outdoors during summer improved the vitamin D levels and mental health in elderly people in nursing homes, and such activity could be considered as a complement to oral vitamin D supplementation in the summer.
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| 23. |
- Sandstedt, Mårten, 1972-
(författare)
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Computed Tomography of the Coronary Arteries : Developmental and Prognostic Investigations
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Computed tomography (CT) is an increasingly used modality for investigations of patients with suspected coronary artery disease (CAD). Technical advances could improve diagnostic accuracy and lead to clinical workflow improvements. Also, more prognostic information can optimize clinical follow-up strategies and treatments.The general aim of this thesis was to explore the use of CT for CAD investigations. Three studies aimed to examine new technologies, including the evaluation of an on-site, computed tomography-based fractional flow reserve (CT-FFR) software (study I), the evaluation of an AI-based, calcium scoring computed tomography (CSCT) software (study III), and the evaluation of an photon-counting detector (PCD)-CT (study IV). One study aimed to evaluate the long-term prognostic value of coronary computed tomography angiography (CCTA) in symptomatic patients with no history of CAD (study II).The software evaluation studies (study I and III) and the prognostic study (study II) utilized CT data from clinical patients, while the PCD-CT evaluation study (study IV) used CT data from cadaveric specimens. The performances of both software programs were compared with standard references, being represented by fractional flow reserve (FFR) measurements (study I), and coronary artery calcification (CAC) scores from a semi-automatic software (study III), respectively. The PCD-CT performance on CAC quantification was compared with corresponding results from an energy integrating detector (EID)-CT, using micro-CT as the standard reference (study IV). The prognostic study merged registries to identify major adverse cardiac events (MACE), having a follow-up time of up to 7.5 years (study II).The CT-FFR and CSCT software correlation and agreement to corresponding standard references were good and excellent, respectively. Also, both software programs had time-saving potential (study I and III). The CAC quantification was more accurate using PCD-CT than EID-CT (study IV). The prognosis was excellent in patients with normal coronary arteries, and progressively impaired in non-obstructive and obstructive CAD (study II).The results in this thesis convey developmental, technical CT technology advances for CAD investigations. In addition, prognostic follow-up data is communicated. The results may benefit patients by an increased accuracy in the CT evaluation of CAD and can contribute to improve clinical follow-up strategies. Furthermore, the results suggest possibilities to improve the workflow in clinical radiology, which potentially could impact health care costs.
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| 24. |
- Serreyn Lundin, Evelyn, 1969-
(författare)
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On Quality Improvement in Gynaecological Cancer Surgery
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The overall purpose of this thesis was to find medical and surgical treatment methods of improving the perioperative care of gynaecological cancer patients. The specific objectives were to determine whether a single dose tranexamic acid given immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and the need for blood transfusions, and to determine whether postoperative recovery, tissue damage, and inflammatory response markers differ between women operated with robotic and abdominal hysterectomy for low-risk endometrial cancer in an enhanced recovery after surgery (ERAS) programme, and to evaluate costs for hospital stay and postoperative recovery in relation to health impact. Material and Methods: The thesis was based on two randomised trials. The first trial was a randomised double-blind placebo-controlled multicentre study conducted in four hospitals in the southeast and central of Sweden between March 2008 and May 2012. One hundred women with presumed advanced ovarian cancer who had been scheduled for radical debulking surgery were included; 50 received tranexamic acid and 50 received a placebo. The main outcomes were blood loss and red blood cell transfusions. The second trial was a randomised open single centre trial at a Swedish university hospital, which included 50 women with low-risk endometrial cancer scheduled for radical surgery between February 2012 and May 2016; 25 women underwent robotic hysterectomy and 25 had abdominal hysterectomy. Anaesthesia and perioperative care followed an ERAS protocol in both groups. The EuroQol Group form EQ-5D-3L and the Short Form-36 evaluated the health-related quality of life. The Swedish Postoperative Symptoms Questionnaire assessed symptoms perioperatively until six weeks postoperatively. Venous blood samples were collected on several occasions until six weeks postoperatively and were analysed for markers reflecting inflammatory response and tissue damage. In addition, a health economic evaluation was conducted comparing total costs, qualityadjusted life years (QALYs) and cost per QALY between the surgical methods. Results: Total blood loss volume and transfusion rate following surgery in advanced ovarian cancer were significantly lower in the tranexamic group compared with the placebo group. Women with early endometrial cancer treated by robotic hysterectomy recovered significantly faster in the EQ-5D health index, and reached their preoperative level nearly two weeks earlier than the abdominal group. Differences regarding improvement in health-related quality of life (Short Form-36) comprising general health and social functioning were more favourable in the robotic hysterectomy group. Consumption of analgesics, pain intensity, postoperative symptom sum score and length of hospital stay were equal between the groups. The occurrence of complications was an independent risk factor and influenced most of the outcome measures adversely. Postoperative inflammatory response and tissue damage were lower after robotic hysterectomy compared with the abdominal approach. The robotic group gained more QALYs until six weeks after surgery than the abdominal group but the total costs were higher. The total cost per QALY gained was quite high for the robotic procedure. Conclusions: A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates in advanced ovarian cancer surgery. Robotic hysterectomy in an ERAS programme treating early endometrial cancer leads to a faster recovery in the health-related quality of life than abdominal hysterectomy, the latter being strongly influenced by perioperative complications. Less tissue damage and inflammation might contribute to a faster recovery in the robotic group. Robotic hysterectomy provides more QALYs until six weeks postoperatively but with a substantially higher total cost for the society.
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| 25. |
- Sten, Sebastian, 1993-
(författare)
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Mathematical modeling of neurovascular coupling
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The brain is critically dependent on the continuous supply of oxygen and glucose, which is carried and delivered by blood. When a brain region is activated, metabolism of these substrates increases rapidly, but is quickly offset by a substantially higher increase in blood flow to that region, resulting in a brief oversupply of these substrates. This phenomenon is referred to as functional hyperemia, and forms the foundation of functional neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI), which captures a Blood Oxygen Level-Dependent (BOLD) signal. fMRI exploits these BOLD signals to infer brain activity, an approach that has revolutionized the research of brain function over the last 30 years. Due to the indirect nature of this measure, a deeper understanding of the connection between brain activity and hemodynamic changes — a neurovascular coupling (NVC) — is essential in order to fully interpret such functional imaging data. NVC connects the synaptic activity of neurons with local changes in cerebral blood flow, cerebral blood volume, and cerebral metabolism of oxygen, through a complex signaling network, consisting of multiple different brain cells which release a myriad of distinct vasoactive messengers with specific vascular targets. To aid with this complexity, mathematical modeling can provide vital help using methods and tools from the field of Systems Biology. Previous models of the NVC exist, conventionally describing quasi-phenomenological steps translating neuronal activity into hemodynamic changes. However, no mechanistic mathematical model that describe the known intracellular mechanisms or hypotheses underlying the NVC, and which can account for a wide variety of NVC related measurements, currently exists. Therefore, in this thesis, we apply a Systems Biology approach to develop such intracellular mechanisms based models using in vivo experimental data consisting of different NVC related measures in rodents, primates, and humans.Paper I investigates two widely discussed hypotheses describing the NVC: the metabolic feedback hypothesis, and the vasoactive feed-forward hypothesis. We illustrate through multiple model rejections that only a model describing a combination of the two hypotheses can capture the qualitative features of the BOLD signal, as measured in humans. This combined model can describe data used for training, as well as predict independent validation data not previously seen by the model before.Paper II extends this model to describe the negative BOLD response, where the blood oxygenation drops below basal levels, which is commonly observed in clinical and cognitive studies. The model explains the negative BOLD response as the result of neuronal inhibition, describing and adequately predicting experimental data from two different experiments.In Paper III, we develop a first model including the cell-specific contributions of GABAergic interneurons and pyramidal neurons to functional hyperemia, using data of optogenetic and sensory stimuli in rodents for both awake and anesthesia conditions. The model captures the effect of the anesthetic as purely acting on the neuronal level if a Michaelis-Menten expression is included, and it also correctly predicts data from experiments with different pharmacological inhibitors.Finally, in Paper IV, we extend the model in Paper III to describe and predict a majority of the relevant hemodynamic NVC measures using data from rodents, primates, and humans. The model suggests an explanation for observed bi-modal behaviors, and can be used to generate new insights regarding the underpinnings of other complicated observed behaviors. This model constitutes the most complete mechanistic model of the NVC to date.This new model-based understanding opens the door for a more integrative approach to the analysis of neuroimaging data, with potential applications in both basic science and in the clinic.
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| 26. |
- Strindlund, Lena, 1973-
(författare)
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The Social Dynamics of Labor Market Inclusion
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Labor market inclusion is a complex assignment that takes place through a dynamic interaction between unemployed individuals from vulnerable groups, several authority actors and employers.The overall aim of this thesis was to explore the social dynamics of labor market inclusion, with a particular focus on integration, from the perspectives of employers and authority actors. Three empirical studies have been conducted focusing on different perspectives and integration challenges, using various forms of qualitative methods and theoretical approaches.Study I was a qualitative phenomenographic interview study of employers’ perspectives on labor market inclusion and intersectoral integration. The study showed that employers’ views are multifaceted and can be categorized as constrained, independent, and conditional, and can be understood through a complex internal relationship between conceived individual-, workplace- and authority-related aspects in relation to the themes of trust, contribution, and support (paper I).Study II was a two-year longitudinal case study of an interorganizational integration project, focusing on the authority actors’ perspectives. Through ethnographic fieldwork and a practice-theory approach, two divergent rationalities (an empowerment rationality and a coordinating rationality) were identified within the project organization, and four central concepts were highlighted – communication, trust, structure, and steering – contributing to a collapse in integration (paper II). The dysfunctional group processes were further analyzed with the theory of negative effects of social capital and shadow organizing, summarized as three social dynamics: insulation, homogenization, and escalating commitment (paper III).Study III was a one-year longitudinal case study of a municipal intraorganizational integration project focusing on the perspectives of both authority actors and municipal employers. This study combined ethnographic field work with the theory of social representations, which visualized three different representations among the different professional groups – individual-, employer-, and political-oriented – which contributed to creating tensions within the project, identified as incomprehension, power struggles, expectation gaps, and distrust (paper IV).By studying two labor market inclusion projects through shadow organizing, the thesis has revealed a complex and dynamic interplay between the various views of the actors involved, as well as social processes within the project organizations and organizational aspects, referred to as social dynamics. These social dynamics constitute the key concepts in this thesis, contributing understanding about how integration and organization work within labor market inclusion projects, or rather, what makes them fail. Three social dynamics were identified: multiple and conflicting views, grouping processes, and power struggles.Greater knowledge and awareness of these complex and social dynamics of labor market inclusion may contribute to better preparedness when organizing integration projects. The results suggest that by identifying and addressing the multiple views characterizing integration projects and not letting incomprehension dominate, the destructive social dynamics may not be given as much space, or may even be avoided, which may stimulate a willingness to integrate rather than the opposite.
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| 27. |
- Svedberg, Anna, 1988-
(författare)
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Toxicity and pharmacokinetic biomarkers for personalized non-small cell lung cancer treatment
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lung cancer is the leading cause of cancer-related deaths worldwide. Unfortunately, lung cancer is usually discovered at a late stage when the curative treatment options are limited. The treatment can include surgery, radiation, chemotherapy, targeted therapy and now also immunotherapy.The challenge in cancer treatment is to eradicate cancer by the use of harsh treatments, while still, keeping the patient alive. For this purpose, treatments with severe toxicities are usually accepted but regularly lead to dose reductions or postponed treatment. Large variations in response are generally observed between patients treated with the same drug at the same dose. The dose may be adequate in one patient while ineffective or cause severe adverse drug reactions in other patients. The occurrence of drug-induced toxicities can, however, also be a positive indicator of treatment response. In personalized treatment it is of importance to select the most suitable treatment option and give it at the most favorable dose, to enable the patients to stay on treatment during the time the treatment is able to affect cancer since the tumor commonly develops resistance towards the treatment eventually.In this thesis, inter-individual variability in pharmacokinetics and toxicity for the targeted therapy erlotinib, associated with the adverse events skin rash and diarrhea was studied. Inter-individual variability in toxicity was also studied for the chemotherapy treatment gemcitabine/carboplatin linked to the hematological toxicities neutropenia and leukopenia.Erlotinib was studied in papers I-IV. Erlotinib and its metabolite concentrations were determined using a validated LC-MS/MS method. Diarrhea was associated with erlotinib and the metabolite M13, while skin rash was associated with the activity of the erlotinib metabolizing enzyme CYP3A and the ABCG2 single nucleotide polymorphism rs10856870. CYP3A was also shown to be induced during treatment. Additionally, in vitro studies showed that genetic variability in ABCG2 contributes to differences in intracellular concentrations. Genes and gene variants were found to be associated with gemcitabine/carboplatininduced toxicity in paper V. The variants were partially validated, and two models were developed to estimate the risk of leukopenia or neutropenia based on a set of genetic variants.
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| 28. |
- Toll, Rani, 1975-
(författare)
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To See or Not to See : A Study on Capillary Refill
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Assessment of the critically ill is traditionally based on vital signs (blood pressure, pulse, respiratory rate, temperature and level of consciousness). Altered vital signs are, however, late indicators of deranged hemodynamics pointing to a need for additional, more sensitive markers of circulatory compromise. In the beginning of the 20th century, the capillary refill (CR) time evolved as a possible, non-invasive adjunct to early prediction of the outcome in the critically ill. The manoeuvre entails application of blanching pressure on the skin of the finger pulp or sternum for 5 seconds. After release of the pressure, the observer estimates time in seconds for the skin to return to original colour. This time is hypothesized to reflect the dynamics of the microcirculation and its possible connection with hemodynamics. In the 1980s the “normal capillary refill time” was set to < 2 seconds and later extended to 3 seconds, without a clear scientific foundation. Naked-eye estimations of CR time met increasing scepticism in the 1990s due to subjectivity and poor prognostic value for shock or death. Several basic traits, such as age and sex, as well as ambient temperature, were also shown to independently influence the CR time. Various methods have evolved with the capability to measure CR time quantitatively, one of which is Polarisation Spectroscopy Imaging (PSI). PSI measures the Red Blood Cell (RBC) concentration in tissue (e.g. the skin) and can be used to measure CR time.Objectives: The purpose of this study was to establish basic characteristics for quantified CR (qCR), identify possible influencing factors in healthy subjects and to investigate how this relates to current practice. We also sought to identify technical demands for transfer of the technique into clinical studies. In paper I we analysed the (qCR) time characteristics at 5 different skin sites (forehead, sternum, volar forearm, finger pulp and dorsum finger). The objective of paper II was to investigate the inter- and intra-observer variability of naked eye CR assessments of different professions, nurses, doctors and secretaries (representing laymen). In paper III we observed the effect of low ambient temperature on the qCR time in different skin sites. In paper IV, we transferred the equipment from a laboratory to a clinical setting in the Emergency Department (ED) for application on potentially critically ill patients. In this study we evaluated the most important factors determining a reliable data collection and influencing the amount of data possible to analyse.Methods: qCR time was measured in a total of 38 volunteers and 10 patients in different skin sites (2-5 skin sites) at different ambient temperatures. PSI (TiVi 600 and 700, WheelsBridge AB, Linköping, Sweden) was used to determine the rapid temporal changes in RBC concentration in skin during the CR manoeuvre. Films using a range of the first measurements from paper I were shown for assessment to 48 observers working in the ED.Results: In paper I we could delineate qCR curves and suggest 2 possible equivalents to the naked-eye observed CR time which we named Time to Return to Baseline 1 (tRtB1) and Time to Peak (tpk). We demonstrated differences in qCR-curves depending on skin site and possibly due to skin temperature. In paper II we showed a poor inter- and intra-observer reproducibility in visually estimating the CR time regardless of profession (clinicians or laymen). Paper III demonstrated a rapid effect of ambient temperature on qCR time in peripheral skin sites such as finger pulp. The forehead, regarded as a more central skin site was the most temperature stable site and showed least variability in qCR time as determined using tRtB1. Paper IV, a study on patients in an ED setting, yielded assayable data in 80% of the measurements. We identified critical performance parameters to address in the further development of a more robust, easy-to-use device for future validation of the possible relevance of qCR in patient triage and monitoring.Conclusions: CR time can be quantified using PSI. Quantified CR time demonstrated a large variability between different skin sites, specifically, skin temperature was shown to be an important factor influencing qCR time, particularly at the fingertip. Naked-eye estimates of CR time were highly variable, both within and between observers. Agreement between quantified CR time and naked-eye estimates was poor. The prototypic PSI technique was feasible in a clinical setting and, with further improvements, clinical evaluation of qCR in relation to relevant patient outcomes will be possible.
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| 29. |
- Tordön, Rikard, Doktorand, 1969-
(författare)
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Health, Experienced Support and School Performance among Children in Out-of-home care
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Children in out-of-home care (OHC) have higher risks for developing poorer health and school achievement, being subjected to more abuse experiences, as well as negative long-term outcomes related to occupational performance, socioeconomic status, addiction, and criminality. Research related to OHC children is fragmented and the effects of interventions are under-studied.This thesis aimed to explore health, abuse, support, and preconditions for school among children in OHC and to assess changes after an intervention targeting foster children’s school performance.Paper I compared OHC pupils in last year high school to non-OHC peers in a national survey with 5 839 pupils. The study showed that risks of abuse and poor mental health are evident for adolescents in out-of-home care. Also, results indicated a lower disclosure rate of sexual abuse, particularly to police or social services.Paper II compared OHC pupils to peers in birth parent care by analyzing responses in four consecutive year surveys in a regional sample comprising 23 798 pupils in 8th-year compulsory and 2nd-year high school. Responses from the 311 pupils in OHC showed poorer outcomes than did birth-parent care peers in perceived satisfaction with social life and relations, trust to other persons in different relations, abuse experiences online, and sense of security in the school and at home. These results also applied when compared to a subset of pupils living with a single birth parent.Paper III analyzed prospective test and questionnaire data of intelligence, adaptive behavior, mathematics, literacy skills, and psychosocial wellbeing from 856 children in foster care. Results revealed poorer preconditions for school performance of between 0.5 and 1.0 standard deviations below age-standardized norms. The analysis also provided results regarding different intelligence domains, where working memory showed the lowest scores while perceptual functioning were close to norms. Boys generally scored poorer than girls except in mathematics.Paper IV explored the effects of a school-based intervention, Skolfam, on a subset of Paper III cohort (n= 475). Results showed improved skills in higher-order cognitive executive functions such as reading comprehension, sentence chains, mathematics, and intelligence. For less complex cognitive functions, affective functioning or psychosocial symptoms, no improvements were seen, except for reduced hyperactivity.Conclusion: The studies confirm that children in OHC have poorer mental health, are less satisfied with social life, have more adverse experiences both online and in real life and have poorer preconditions for school performance than do non-OHC peers. Importantly, Skolfam intervention can partially enhance preconditions for school performance. Further studies on longitudinal risk, with a design to identify specific protective factors, development of school-related competencies and ways to support OHC children in school are needed.
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| 30. |
- Westerberg, Johanna, 1971-
(författare)
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Middle ear cholesteatoma : Surgical outcome and aspects of the innate immunity
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cholesteatomas are bone destructive expansions of keratinizing squamous epithelium in the middle ear and temporal bone. Today, surgery is the only treatment. There are several controversies regarding cholesteatomas, including the definition, the pathogenesis and the surgical method. Intense efforts have been made searching for a comprehension of the cholesteatoma process at a cellular and molecular level. Recurrent infections and inflammation seem to be contributing factors for the cholesteatomas to expand. The innate immunity, essential to keep a healthy middle ear environment and to protect the middle ear from intruding pathogens, is therefore a matter of interest.In this thesis, results are presented from a cohort of cholesteatoma surgeries in Östergötland from a 16-year period. A group of patients also filled in a questionnaire to assess changes in health-related quality of life (HRQoL) after surgery. According to the findings in this thesis, the residual and recurrence frequencies are low, and the hearing and HRQoL are improved in the majority of cases.This thesis also presents an investigation of the innate immunity in ears with acquired cholesteatoma, in comparison with healthy controls. The expression of mRNA of toll-like receptors 2 and 4, participants of the Janus kinase/signal transducer and activator of transcription pathway, and nitric oxide synthases in middle ear mucosa, were investigated with quantitative polymerase chain reaction. An investigation of nitric oxide (NO) in the middle ear, with chemiluminescence measurements, is also presented.A derangement of the innate immune system is seen in ears with cholesteatoma, which supports the idea that the innate immunity participates in the cholesteatoma process, though the underlying mechanisms are still unclear. The suggestion of NO production in the middle ear sheds light on NOs possible participation in the healthy middle ear environment.
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