| 1. |
- Bergkvist, Max, 1976-
(author)
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Studies on Polarised Light Spectroscopy
- 2019
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Doctoral thesis (other academic/artistic)abstract
- This thesis project focuses on measurements of dermal microcirculation during vascular provocations with polarised light spectroscopy. This is done with a non-invasive method commercially available as Tissue viability imaging (TiVi) which measures concentration and oxygenation of red blood cells in the papillary dermis. Three studies were done with human subjects and one with an animal model, to validate and compare the TiVi technique with laser Doppler flowmetry, which is an established method of measuring dermal microcirculation.The TiVi consists of a digital camera with polarisation filters in front of the flash and lens, with software for analysis of the picture. When taking a picture with the TiVi, the polarised light that is reflected on the skin surface is absorbed by the second filter over the lens (which is perpendicular to the first filter) but a portion of light penetrates the surface of the skin and is scattered when it is reflected on tissue components. This makes the light depolarised, passes the second filter, and produces a picture for analysis. The red blood cell (RBC) has a distinct absorption pattern that differs between red and green colour compared to melanin and other components of tissue. This difference is used by the software that calculates differences in each picture element and produces a measure of output which is proportional to the concentration of red blood cells. The oxygenation of RBC can also be calculated, as there is a difference in absorption depending on oxygen state.The first paper takes up possible sources of error such as ambient light, and the angle and distance of the camera. The main experiment was to investigate how the local heating reaction is detected with TiVi compared to LDF.In the second paper arterial and venous stasis are examined in healthy subjects with TiVi.The Third paper is an animal study where skin flaps were raised on pigs, and the vascular pedicle is isolated to enable control of inflow and outflow of blood.The measurements were made during partial venous, total venous, and total arterial occlusion. The TiVi recorded changes in the concentration of RBC, oxygenation and heterogeneity and the results were compared with those of laser Doppler flowmetry.In the fourth paper oxygenation and deoxygenation of RBC: s was studied. Studies were made on the forearms of healthy subjects who were exposed to arterial and venous occlusion. Simultaneous measurements were made with TiVi and Enhanced perfusion and oxygen saturation or EPOS, which is a new device that combines laser Doppler flowmetry and diffuse reflectance spectroscopy in one probe.With TiVi, one can measure RBC concentration and oxygenation in the area of an entire picture or in one or multiple user defined regions of interest (ROI). Methods such as laser Doppler flowmetry makes single point measurements, which is a potential source of error both because of the heterogeneity of the microcirculation, and that the circulation be insufficient in the margins of the investigated area. TiVi has been able to measure venous stasis more accurately than laser Doppler flowmetry, and venous stasis is the more common reason for flaps to fail.The TiVi is an accurate way to measure the concentration of RBC and trends in oxygenation of the dermal microcirculation. It has interesting possible applications for microvascular and dermatological research, monitoring of flaps, and diagnosis of peripheral vascular disease. Future clinical studies are needed as well as development of the user interface.
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| 2. |
- Högstedt, Alexandra, 1993-
(author)
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Microvascular effects of insulin in the skin
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The microcirculation in the skin is essential for skin homeostasis. In instances of altered microvascular function, that may be the result of insulin resistance, tissue morbidity may ensue. The underlying mechanisms are however complex and not fully understood. By studying the physiological effects of insulin in the skin, the understanding of the complex interplay between glucose metabolism and skin microcirculation can be improved. The general aim of this thesis was to develop an experimental in vivo model to study metabolic and microvascular responses to insulin in the skin in healthy subjects. Microdialysis is a suiting technique as it allows for both local delivery of drugs and simultaneous monitoring of the local metabolic and vascular effects in the very same tissue compartment. The effects of local and systemic insulin provocation on skin blood flow and metabolism were investigated using microdialysis urea clearance and laser speckle contrast imaging (paper I). An insulin dependent increase in skin blood flow was observed, presumably induced through the nitric oxide pathway (paper II). Investigating the protein expression during an oral glucose provocation using proteomic approaches however indicates interactions with other pathways, such as the renin-angiotensin system and the kallikrein-kinin system (paper IV). Paper III also investigated methodological concerns regarding the sampling of insulin using microdialysis. This in vivo model can, in the future, be applied to assess the microvascular effects of insulin in the skin in different patient groups, including those with micro-vascular dysfunction due to, for instance, insulin resistance.
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| 3. |
- Shahin, Hady, 1989-
(author)
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Keratinocytes and Adipose-derived mesenchymal stem cells : The heir and the spare to regenerative cellular therapies for difficult-to-heal skin wounds
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Cell-based therapy is considered as Advanced Therapy Medicinal Product, (ATMP), which had increasingly stricter regulations in the last decade. The cells must be produced according to the ‘Guidelines on Good Manufacturing Practice (GMP) specific to Advanced Therapy Medicinal Products’, adopted by the European Medicines Agency (EMA). A fully compliant autologous keratinocyte-based ATMP certified for clinical use remains an unmet challenge in Europe. This necessitates the development of a comprehensive bio-production workflow to tackle key technical bottlenecks along this procedure. On the other hand, adipose-derived mesenchymal stem cells (AD-MSCs) hold promise as an effective alternative to primary keratinocytes in treating difficult-to-heal wounds, particularly for patients with extensive skin wounds. The overall aim of this thesis is to provide a bio-production workflow addressing the challenges associated with developing an autologous keratinocyte-based ATMP. Additionally, the thesis aims to elucidate the molecular and functional mechanisms that modulate the wound healing capabilities of keratinocytes and AD-MSCs. In papers I-III the bio-production procedure for an autologous keratinocyte-based ATMP to treat difficult-to-heal wounds was divided into 3 main stages; keratinocytes extraction, expansion, and transportation. Paper I validated the use of an animal-origin-free enzymatic workflow for the extraction of keratinocytes from the epidermis, compared to the classical workflow containing animal-derived products. Both workflows proved comparable in efficiency in terms of the final cell yield from skin samples, in addition to the purity and functionality of the keratinocytes following cultivation. This report confirms the feasibility of an entirely xeno-free workflow for acquiring GMP-compliant epidermal cells suitable for clinical application without altering key features of keratinocytes. Paper II evaluates an expansion approach for keratinocytes on three culture substrates (1) glass (2) conventional polystyrene (plastic) and (3) animal-derived collagen I ECM matrix. Keratinocytes cultured on glass showed better colonization and survival during the first 3 days of culture. Further molecular characterization revealed evidence of accelerated epidermal differentiation in keratinocytes cultured on glass. Henceforth, functional characterization revealed that glass enhanced the temporal angiogenic and migratory capabilities of keratinocytes. Our findings provided evidence that glass can be a promising substrate capable of supporting keratinocyte cultures, with enhanced wound repair characteristics favourable for transplantation applications. In paper III, we evaluated four candidate solutions for transporting keratinocytes in suspension at 4°C for 24h, namely (1) normal saline; (2) saline with 2.5% human serum albumin; (3) chemically defined, xenofree keratinocyte media; and (4) keratinocyte media with bovine pituitary extract. The tested conditions showed that 2.5% HSA preserved keratinocyte viability, colonization as well as phenotype. This study helped the research team to implement the use of human serum albumin as transportation solution for the proposed keratinocyte-ATMP approach. In paper IV, a direct co-culture model for human keratinocytes and AD-MSCs was proposed to investigate the ability of keratinocytes to enhance AD-MSCs’ differentiation toward the epidermal lineage. Furthermore, miRNA and protein content of human keratinocytes and AD-MSCs were analysed and bioinformatically analysed to identify possible regulations between differentially expressed miRNAs and proteins. This study predicted two potential miRNA-mediated gene regulations with strong implications in AD-MSCs-to-epidermal differentiation; the first was centred on epidermal growth factor (EGF) through miR-485-5p, miR-6765-5p and miR-4459. The second was the regulation of interleukin 1 alpha (IL-1α) by four isomers of miR-30-5p and miR-181a-5p. Paper V evaluates the regenerative potential of autologous AD-MSCs in-vivo using an excisional full-thickness porcine wound model. The data generated from miRNA and protein screening of AD-MSCs was re-analysed with a focus on possible regulations of AD-MCSs in wound healing. Our computational analyses predicted that miR-155 mediates multiple gene regulations of fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and vascular cell adhesion molecule 1. The predicted model was verified experimentally and revealed a positive regulation between miR-155 and the identified four factors. Each of these factors carries out key functions within the wound healing process including vascularization, inflammation, proliferation, and remodelling. In summary, the core of the work presented in this thesis provides a complete, in-vitro validated, and EMA-compliant bio-production procedure for autologous keratinocyte as an ATMP. We also presented novel miRNA-mediated epigenetic regulations in human keratinocytes and AD-MSCs. These models can serve as a valuable tool to develop novel hypotheses aiming to elucidate the biology of stem cell differentiation and wound healing.
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| 4. |
- Iredahl, Fredrik, 1988-
(author)
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Assessment of microvascular and metabolic responses in the skin
- 2016
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Doctoral thesis (other academic/artistic)abstract
- The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs.In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI.The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide.
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| 5. |
- Zdolsek, Markus, 1989-
(author)
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Volume effects of albumin infusion in humans
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Background: The use of colloids when treating a patient for hypovolemia has been debated throughout the years. During the last decade, albumin solutions have become the colloids of choice in both operating theatres and intensive care settings when crystalloid fluids are insufficient. The volume effects of albumin infusion are explored in this thesis. Methods: Recruitment of fluid from the interstitial fluid compartment to the plasma was estimated in healthy volunteers who received 3 ml/kg of albumin 20% infusion over 30 min. The same infusion protocol was applied to burn patients to study whether significant inflammation changes the volume effect of an albumin infusion. The influence of the infusion rate of albumin 20% on plasma volume (PV) was evaluated in a crossover fashion in healthy volunteers. Additionally, two concentrations, 5% and 20%, with equivalent amounts of albumin, were given to healthy volunteers in a crossover fashion to determine if a difference in volume effect occurred. The volume effects in terms of PV expansion and capillary leakage of albumin were calculated by mass balance and volume kinetics based on repeated blood samples. Results: There was a 10–20 min delay after completion of the albumin 20% infusion until maximum PV expansion was reached. Extravascular fluid was recruited at a ratio of 3.4 times the infused albumin 20%. Both healthy volunteers and burn patients had a 15% increase in PV. Capillary leakage of albumin occurred at a similar rate in both groups. Rapid infusion resulted in a longer intravascular half-life for albumin and a larger initial PV expansion over time without long-term negative compensation. Albumin 20% increased the PV to twice the infused volume in contrast to albumin 5%, which only increased the PV by two-thirds of the infused volume. Conclusion: Albumin infusions provide long-lasting PV expansion in both burn patients and healthy volunteers. Albumin 20% induces the recruitment of extravascular fluid, amounting to three times the infused fluid volume. A rapid infusion rate is beneficial, as it results in a larger initial PV expansion over time and a longer intravascular persistence of albumin. Further, albumin 20% provides a three times more potent PV expansion than albumin 5%. The infused fluid volume of an albumin solution depends more on the amount of albumin infused than the infused volume; albumin 20% could be preferred over other fluids for its dehydrating effect in the prevention of oedema.
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| 6. |
- Henricson, Joakim, 1977-
(author)
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Assessment of microvascular effects of vasoactive drugs : Methodological in vivo studies in humansbased on iontophoresis
- 2009
-
Doctoral thesis (other academic/artistic)abstract
- Cardiovascular disease is the leading cause of death in western societies and endothelial dysfunction is one of the earliest signs seen in the development of such conditions. Thedevelopment of prognostic tools to aid in the prediction of micro- and macrovascular diseasebased on assessment of vascular reactivity is therefore of paramount importance.Transdermal iontophoresis offers a quick, non-invasive and relatively straightforward way todeliver vasoactive substances in order to provoke a vascular response in man. When combined with either laser Doppler flowmetry (LDF) or tissue viability imaging (TiVi) for quantification of these responses the methodology offers a potentially powerful tool forvascular investigations. The technique has, however, not been established in clinical practice yet and is mostly used in experimental settings. The lack of consensus in what data analysistechnique to use, uncertainty concerning the actual drug dose applied, and the difficulties associated with the assessment of responses to vasoconstrictors may have contributed to thisfact. The aim of this thesis is therefore to address these issues and thus facilitate the use and improve the applicability of transdermal iontophoresis for assessment of cutaneous microvascular function.More specifically, a non-linear dose-response model (Emax-model) that is commonly used in in vitro investigations of vascular function was applied to the iontophoresis data. The resultsshow that the Emax-model accurately describes the cutaneous vascular responses totransdermally iontophoresed acetylcholine (ACh) and, sodium nitroprusside (SNP). The Emaxmodelgenerates variables that can be used for quantitative statistical analysis of data andenables a more powerful analysis compared to the methods presently used. It is furtherdemonstrated that the maximal dose effect and vascular responses vary between differentprotocols with the same total iontophoretic charge but with different current strengths anddurations. This finding implies that the assumption that the local drug dose is linearlyproportional to the iontophoretic charge (used for estimation of delivered drug dose to themicrovascular bed) may be inaccurate in in vivo investigations and that there is need for amore refined model.It is also demonstrated that in a vasoconstrictive setting (iontophoresis of noradrenaline andphenylephrine) TiVi is the favourable technique for measuring vascular responses as it issensitive enough to generate data that can be fitted to the Emax-model even without predilatationof the vessels.
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| 7. |
- Johansson, Joakim, 1973-
(author)
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Function of granulocytes after burns and trauma, associations with pulmonary vascular permeability, acute respiratory distress syndrome, and immunomodulation
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Background: Our innate immunesystem protects us from infections but, since its methods is not all specific for microorganisms, may also induce collateral damage.Severe physical injury often proved deadly throughout evolution. Such injuries may induce massive collateral damage. Nowadays we can initiate advanced critical care for affected patients and save them from imminent trauma-related death. We are therefore faced with the fact that the collateral damage from the immune system may pose a major threat to the patient, the pathophysiology of which is not amenable to direct medical treatment and which leaves us with only passive supportive measures.In this thesis we investigated the role of leucocytes under such circumstances.Our main aim was to understand better the role of leucocytes in the development of increased vascular permeability after burns and trauma.More specifically we investigated the impact of an injury on the function of leucocytes such as the dynamic change of certain cell-surface receptors on the leucocytes and in their numbers and immature forms. We wanted to find out if the increased pulmonary vascular permeability after a burn could be mediated through heparin binding protein (HBP) released from granuloctes, and whether HBP could be used as a biomarker for respiratory failure after trauma. We also wanted to confirm the possible role of histamine as a mediator of the systemic increase in vascular permeability after burns.Methods: The dynamic change of cell-surface receptors was measured by flow-acquired cytometer scanning (FACS) on blood samples taken after burns. The concentrations of HBP after a burn and mechanical trauma were analysed in plasma. Pulmonary vascular permeability after a burn was assessed using transpulmonary thermodilution. The histamine turnover after a burn was assessed with high performance liquid chromatography (HPLC) for concentrations of histamine and methylhistamine in urine.Results: We confirmed earlier investigations showing altered expression of receptors on leucocytes after a burn, receptors intimately associated with leucocyte functions (study I). In a pilot study of 10 patients we measured plasma concentrations of HBP and found them to be increased soon after a burn (study II). This finding was not confirmed in a larger, more extensive and specific study of 20 patients. We did, however, find an association between alterations in the number of leucocytes soon after a burn and pulmonary vascular permeability, indicating that they had a role in this process (study III).In another study of trauma (non burn) we found an association between the concentration of HBP in early plasma-samples after injury and the development of ARDS, indicating that granulocytes and HBP have a role in its aetiology (study IV).We found a small increase in urinary histamine and normal urinary methylhistamine concentrations but had anticipated a distinct increase followed by a decrease after reading the current papers on the subject. This indicates that the role of histamine as a mediator of increased vascular permeability after burns may have been exaggerated (study V).Conclusions: We conclude that leucocytes are affected by burns and trauma, and it is likely that they contribute to the development of respiratory failure and acute respiratory distress syndrome (ARDS). HBP is a candidate biomarker for the early detection of ARDS after trauma, and the white blood count (WBC) is a useful biomarker for the detection of decreased oxygenation soon after a burn.
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| 8. |
- Karlsson, Matilda, 1981-
(author)
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Studying the healing and long-term outcomes of two partial thickness wound models using different wound dressings
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background: Safe and effective wound dressing treatments are important for proper wound healing. Such procedures therefore need to be evidence-based regarding the most important outcome measures such as healing time, less discomfort for the patient, duration of hospital care and, importantly, less scarring. As the relation between longer healing times and more severe scarring is known, it is important to find dressing treatments that reduces such complications by providing fast and proper wound healing. In this thesis, four established wound dressing treatments (hydrofibre covered with film; porcine xenografts and polyurethane foam, with and without silver), were evaluated for two types of acute, partial thickness wounds: split thickness skin graft (STSG) donor sites and partial thickness burn wounds in two randomised, controlled clinical trials (RCT) with longterm scar follow ups. The relations between factors thought to influence wound healing and scarring as sex, infection, wound extent and depth, healing time and skin grafting were also investigated in these two wound models.Methods: Data from these trials were collected on sex, infection rates, wound depth and extent, need of skin grafting, healing times and scarring frequency together with demographic data. Scars were evaluated at 8 years in Study II and III and at 6 and 12 months after injury in Study V.Results: Two dressing treatments; hydrofibre covered with film and porcine xenografts gave significantly faster healing of the STSG donor sites than the standard of care (SOC) dressing, the polyurethane foam. The hydrofibre was thereafter implemented as the new SOC at the department. The long-term scar follow up showed that the hydrofibre group was most satisfied with their donor site scar, providing further evidence for the implementation of this dressing strategy. From the observer’s perspective no differences were found between these treatment groups. For partial thickness burns the treatment with a silvercontaining foam dressing showed significantly shorter healing time, whereas for the scars, no difference between dressing groups could be detected. A number of factors were identified that affected healing time: for donor sites only male sex was associated with shorter healing time. Sex was also the only factor that influenced donor site scarring, where female patients, both subjectively and objectively, were rated with higher scores (worse outcome). For partial thickness burns a larger extent of the burn wound, presence of deep dermal burns, and the need of skin grafting, all had a negative impact on both healing time and final scar. The final scar was also significantly affected by longer wound healing times and infection.Conclusion: The results suggest that the use of hydrofibre dressings covered with film on donor sites resulted in positive short-term and long-term outcomes. Regarding partial thickness burns, silver foam dressing resulted in faster healing but as for the final scar, no difference could be seen. Several factors were associated with longer healing times and more severe scarring such as: female sex, larger burns, deep dermal burns, skin grafting, and infection. Longer healing times were related to more severe scarring.
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| 9. |
- Nilsson, Andreas, 1974-
(author)
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Patient-controlled sedation in procedural care
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The need for procedural sedation is extensive and on the increase in numbers of patients. Minor treatments or diagnostic procedures are being performed with inadequate sedation or even without any sedatives or analgesics. Also, sedation techniques that support advanced, high-quality, in-patient care procedures representing easy performance and rapid recovery are requested for increased effectiveness. In this doctoral thesis, patient-controlled sedation (PCS) using propofol and alfentanil for surgical and diagnostic procedures was studied. The overall aim was to study aspects of safety, procedural feasibility and patients’ experiences. The main hypothesis was that PCS using only propofol is a safe and effective method for the induction and maintenance of moderate procedural sedation. The studies included were prospective, interventional, and in some cases, randomized and double-blinded.Data on cardiopulmonary changes, level of conscious sedation (bispectral index and Observer’s assessment of alertness/sedation [OAA/S]), pain, discomfort, anxiety, nausea (visual analogue scales), interventions performed by nurse anaesthetists, surgeons’ evaluation of feasibility, procedure characteristics, recovery (Aldrete score) and pharmacokinetic simulation of concentrations of drugs at the effect site supported the analysis and comparison between PCS and anaesthetist-controlled sedation and propofol PCS with or without alfentanil.PCS can be adjusted to cover a broad range of areas where sedation is needed, which, in this thesis, included burn care, gynaecological out-patient surgery and endoscopic procedures for the diagnosis and treatment of diseases in the bile ducts (endoscopic retrograde cholangiopancreatography [ERCP]). PCS for burn wound treatment demands the addition of alfentanil, but still seems to be safe. PCS was preferred by the patients instead of anaesthetist-controlled sedation. The addition of alfentanil to PCS as an adjunct to gynaecological surgical procedures also using local anaesthesia increases the surgeon’s access to the patients, but impairs safety. Apnoea and other such conditions requiring interventions to restore respiratory function were seen in patients receiving both alfentanil and propofol for PCS. Patients’ experiencing perioperative pain and anxiety did not explain the effect-site concentrations of drugs. Different gynaecological procedures and patients’ weights seemed to best explain the concentrations. For discomfort and pain during the endoscopic procedure (ERCP), propofol PCS performs almost the same as anaesthetist-performed sedation. Overall, as part of the pre-operative procedures, PCS does not seem to be time-consuming. In respect to the perioperative perspective, PCS supports rapid recovery with a low incidence of tiredness, pain, and post-operative nausea and vomiting (PONV).The data suggest that PCS further needs to be adapted to the patient, the specific procedure and the circumstances of sedation for optimal benefit and enhanced safety.
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| 10. |
- Parenmark, Fredric, 1974-
(author)
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Premature Discharge from Intensive Care with Special Reference to Night-Time Discharge and Capacity Transfers
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Objectives Intensive care is an expensive and limited resource, and when a demand supply mismatch between available beds and influx of patients occurs, one temporary measure is to discharge a patient to make room for the new admission. Sometimes the patient is discharged sooner from its original ICU than ideal; i.e., a so-called ‘premature discharge’. This could be either to a different ward within the same hospital if the patient is deemed well enough to cope with a lower level of care, or to another intensive care unit if critical care is still to be provided. Data from the Swedish intensive care register (SIR) showed that there was a high incidence and increased mortality of patients discharged at night. There were also differences in mortalities between patients that were transferred from one ICU to another. I have analysed the mortality associated with different types of ICU-to-ICU transfers and control groups and examined a national quality improvement project regarding discharges at night to see if mortality, incidence, or discharge culture could change. Methods All three studies are conducted with data from the Swedish intensive care register and vital status was ascertained by linking SIR to the Swedish population register. Study I consisted of two parts: mortality, and incidence of night-time discharge. The quality improvement project in Study I was analysed in a before and after approach with local improvement projects at different ICUs. In Studies II and III, transfers were grouped by the attending intensivist according to SIR guidelines into one of three defined categories: capacity transfer, clinical transfer, or repatriation. The groups were compared to each other in Study II, and capacity transfers were matched to a control group that remained in the ICU in Study III. Multilevel logistic regression was used, and all studies contained some statistics using individual ICUs as a random factor. Life sustaining treatment limitations were included in Studies II and III. Results In Study I, there was a decrease in night-time discharges during the study period. The incidence fell from 7.0% in 2006 to 4.9% in 2015. Alongside this, the mortality associated with night-time discharge was reduced, the odds ratio fell from 1.20 to 1.06 with a loss of significance. All this coincided in time with the national improvement project. Study II showed that 14.8% of all discharges from a Swedish ICU ended with transfer to another ICU, and that an increased mortality rate was associated with ICU-to-ICU transfers during periods of demand–supply mismatch. Capacity transfers were 15.8% of all transfers accounting for roughly 2.0% of ICU survivors. One in four capacity transferred patient died within 30 days of discharge, compared to one in seven for transfers due to clinical reasons. The third study showed that capacity transfer was associated with an average risk increase in 30-day mortality of 4.7%, and a 180-day mortality of 4.9% compared to non-transferred patients when analysed using a potential outcomes framework. Conclusion The studies concludes that patients experiencing a capacity transfer are exposed to increased mortality risk, both when compared to other types of inter hospital ICU-to-ICU transfers as well as when compared to patients that were not transferred. The increased risk appeared to be unrelated to patient characteristics and illness severity as well as many additional factors measured in the referring ICU. The studies also suggest that a suboptimal outcome after premature discharge at night can be changed and that a national project to adjust outcome and incidence can be undertaken with positive results.
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| 11. |
- Thorfinn, Johan, 1970-
(author)
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Studies on sitting pressure and buttock microcirculation : aiming at developing an alarm in the prevention of pressure ulcers in patients with spinal cord injuries
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Pressure ulcers in patients with spinal cord injuries are a major problem, the prevalence in this group being reported as high as 20 – 30 percent. Most pressure ulcers develop around the pelvic girdle, and the key-contributing factor in the development of pressure ulcers is ischaemia due to longstanding pressure. Loss of mobility and lack of sensation below the level of injury are prominent risk factors for the development of pressure ulcers. Although many factors are known to contribute to pressure ulcer development, the exact aetiology is not completely clear. Prevention is suggested as the best way to deal with the problem. The studies in this thesis investigate some aspects of the physiology of sitting in patients with spinal cord injuries and healthy controls, aiming at developing a pressure ulcer alarm device to aid in the prevention of pressure ulcers. Methods used are laser Doppler perfusion imaging (LDPI) for measurement of superficial skin blood flow, as well microdialysis and a microelectrode (Licox®) to measure direct and indirect signs of ischaemia. In addition sitting pressures are mapped. The main findings are that patients with spinal cord injuries have almost four-fold mean maximum sitting pressures 43 and 49 N/cm2, left and right buttock) compared with healthy controls 12 and 13 N/cm2, left and right buttock). In the subcutaneous fat in healthy individuals, the tissue oxygen pressure decreases significantly during 30 minutes of sitting on a wheel chair cushion 13,7 mmHg) compared with 30 minutes of sitting on a hard surface 19,8 mmHg) implying that the tissues deep in the skin are exposed to a reduction in blood supply. This is also confirmed by a decrease in extracellular glucose during sitting for 30 minutes on a hard surface 1,8 mmol/L) and on a wheel chair cushion 1,7 mmol/L). The post-sitting reactive hyperaemia is dependent on duration of sitting in both patients and healthy subjects. It seems to be attenuated in patients in the sitting position but intensified while lying prone. Furthermore, four repeated loadings on a hard surface 15 minutes of sitting followed by five minutes of rest) without allowing the tissues to return to resting perfusion results in a significantly increasing reactive hyperaemia for each loading in healthy subjects, suggesting that it is important to unload the buttock skin completely before the next sitting period starts. This thesis also describes the construction of an alarm device that measures surface interface pressures during sitting continuously in eight predefined points, to alert the user by an audible signal after a given period of time when the pressure has reached a dangerously high level. It is concluded that the reactive hyperaemia that is observed in the buttock skin after sitting, as well as the reduction in glucose and oxygen in adipose tissue during sitting, are due to a reduction in blood supply relative or absolute ischaemia) caused by a compression of the vasculature by the ischial tuberosities. These findings imply a multilayer aetiology in pressure ulcer development. The altered hyperaemic reaction in patients with spinal cord injuries after sitting is possibly related to alterations in sympathetic activity due to the cord lesion. Lastly, the alarm device is supposed to be an aid to pressure ulcer prevention in patients with spinal cord injuries who lack normal sensory feedback.
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| 12. |
- Berkius, Johan, 1960-
(author)
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Intensive care in chronic obstructive pulmonary disease : treatment with non-invasive ventilation and long-term outcome
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. When we began this project our knowledge about the outcome of COPD patients admitted to the ICU in Sweden was scarce.Aims: To investigate the characteristics, survival and health-related quality of life (HRQL) of COPD patients admitted to Swedish ICUs. To investigate how ICU personnel decide whether to use invasive or non-invasive ventilatory treatment (NIV) of the newly admitted COPD patient in need of ventilatory support. To investigate outcome according to mode of ventilation.Material and methods: Detailed data, including HRQL during recovery, from COPD patients admitted to ICUs that participated in the Swedish intensive care registry were analysed. A questionnaire was distributed to personnel in 6 of the participating ICUs in order to define factors deemed important in making the choice between invasive and non-invasive ventilation immediately after admission. The answers were analysed.Results: The proportion of COPD patients admitted to Swedish ICUs in need of ventilatory support is 1.3-1.6 % of all admissions. The patients are around 70 years-old and are severely ill on admission, with high respiratory rates and most have life-threatening disturbances in their acid-base balance and blood gases. There are more women than men. The short- and long-term mortality is high despite intensive care treatment. The majority of patients are treated with NIV. The length of stay on the ICU is shorter when NIV is used. The choice between NIV and invasive ventilation in these patients may be irrational. It is guided by current guidelines, but other non-patient-related factors seem to influence this decision. NIV seems to be preferable to invasive ventilation at admission, not only according to short-term benefits but also to long-term survival. Failure of NIV followed by invasive ventilation does not have a poorer prognosis than directly employing invasive ventilation. The health-related quality of life of COPD patients after treatment on Swedish ICUs is lower than in the general population. However it does not decline between 6 and 24 months after ICU discharge. After 24 months the HRQL is quite similar to that of COPD patients not treated on the ICU.Conclusions: COPD patients in need of ventilatory support admitted to Swedish ICUs are severely ill on admission, and their short- and long-term mortality is high despite ICU care and ventilatory treatment. Non-invasive ventilation should be the first line treatment on admission. NIV has short- and long-term benefits compared to invasive ventilation, without increasing mortality risk in case of failure. After discharge from the ICU and recovery, the HRQL of COPD patients is lower than in the general population, but comparable to COPD patients not treated on the ICU.
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| 13. |
- Bäckström, Denise, 1976-
(author)
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Injury mortality in Sweden; changes over time and the effect of age and injury mechanism
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Background: Injuries are one of the most common causes of death in the world. Varying types of injuries dominate in different parts of the world, which also have separate influences mortality. In Scandinavia blunt injuries dominates and the majority of those who die do so pre hospital. Over time different injury pattern may vary and by analyzing this we can assess when, where and how preventive work can be reinforced. The aim of this thesis was to study injury epidemiology in Sweden and assess the contribution of different injury patters on mortality. Method: We used the Swedish cause of death and the national patient registries which have a complete national coverage. ICISS was calculated (based on ICD-10) in the in hospital population. We have chosen to do this investigation with a broad perspective using the term injury, which includes trauma but also other diagnoses like suffocation and drowning. Results: During the study period (1999-2012) the number of deaths because of injury was 1213, 25 388, and 18 332 among children, working age and elderly, respectively. Mortality declined in the children and in the working age but inclined in the elderly. Mortality increased with each age group except between the ages of 15–25 and 26–35 years. One thousand two hundred sixty four (97%) of those who died because of penetrating trauma (sharp objects and firearms) were killed by intentional trauma (assault and intentional self-harm). One thousand and seventeen (83%) of the children died prehospital. In the working age 22 211 (80%) of 25 388 died pre hospital. Nine thousand six hundred and eighteen (53%) of 18 332 of the elderly died prehospital. During 2001- 2011 the risk adjusted in hospital mortality decreased in traffic and assault but not in fall related injuries. Discussion: Largely, the anticipated injury mortality picture was found, with blunt injuries (traffic accidents) dominating in the working age and falls in elderly. Further a significant portion of the deaths occurred pre hospital. The intentional injuries are dominated by intentional selfharm. The decrease in child injury mortality is notable as Sweden already has one of the lowest incidences in child injury mortality in the world. The decrease in injury mortality in the working age also implies that preventive work has had an effect. The incline in injury mortality in elderly on the other hand needs to be further studied. Areas of particular importance for future preventive work is the incline in injury mortality in elderly and intentional injuries among children.
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| 14. |
- Klaff, Rami, 1971-
(author)
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Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
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Doctoral thesis (other academic/artistic)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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| 15. |
- Mirdell, Robin, 1989-
(author)
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Blood Flow Dynamics in Burns
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Objectives:Burns of intermediate thickness are hard to evaluate clinically. This often leads to unnecessary delays of up to 14 days before a surgical decision can be made. To counter this, several objective methods have been developed to determine the healing potential of the wound. Over the years, measurement of perfusion has proven to be the most successful method for evaluation of healing potential. Laser Doppler imaging (LDI) is currently the most used method and can determine surgical need 2 days after injury with an accuracy >90%. There are however emerging techniques like laser speckle contrast imaging (LSCI), which also measure perfusion. LSCI have several advantages over LDI and is easier to use. LSCI can also investigate aspects of the microcirculation, previously not possible with LDI. The aim of this thesis was to investigate LSCI’s ability to evaluate surgical need in burns of indeterminate partial-thickness. The first objective was to investigate the dynamics of perfusion the first 14 days after injury. The purpose was to find the optimal time-window for perfusion measurements. The next goal was to determine the accuracy of different perfusion cut-offs. In this second study, the benefit of a subsequent measurement was also investigated. After this, interobserver variation between different profession groups was studied. Both the agreement of perfusion measurements and observer assessments were evaluated. Finally, cardiac vasomotion in combination with perfusion (pulsatility) was investigated as a method to determine surgical need <48 hours after injury. Methods:Perfusion was measured in a total of 77 patients at the Department of Plastic Surgery, Hand Surgery and Burns at Linköping University Hospital, Sweden. Most of these patients were children and the most common type of burn was scalds. A laser speckle contrast imager (PeriCam PSI System, Perimed AB, Järfälla, Sweden) was used to measure perfusion. Results: In the first paper we showed a clear relation between perfusion dynamics and the healing potential of the wound. The changes in perfusion were largest the first 5 days after injury, why this time interval was selected for subsequent papers. Perfusion measurements done day 3-4 after injury could predict surgical need with a sensitivity of 100% (95% CI: 83.9-100%) and a specificity of 90.4% (95% CI: 83.8-94.9%). If two measurements were used, <24 hours and 3-4 days after injury, the accuracy was 100%. Furthermore, we found that different observers could consistently predict perfusion, while there was a large variation in their clinical assessments. This was not improved by extensive burn experience. Finally, pulsatility could be used to predict surgical need the same day as the injury occurred with a sensitivity of 100% (95% CI: 88.1-100%) and a specificity of 98.8% (95% CI: 95.7- 99.9%). Conclusions: LSCI is a promising method for evaluation of burns and provides several benefits over LDI. The surgical need of burns can be determined mere hours after injury when pulsatility is measured. However, the benefits of early scald diagnostics in children with LSCI need to be evaluated in a prospective study before the method is ready for routine clinical use.
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| 16. |
- Samuelsson, Anders, 1960-
(author)
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Effects of burns and vasoactive drugs on human skin : Clinical and Experimental studies using microdialysis
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function.Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling.Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis.We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries.In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (Emax) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model.We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.
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| 17. |
- Steinvall, Ingrid
(author)
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Organ dysfunction among patients with major burns
- 2011
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Doctoral thesis (other academic/artistic)abstract
- The number of patients who are admitted for in-hospital care in Sweden because of burns is about 12/100,000, and only a small proportion of these have larger burns. Among them, and particularly among those who die in hospital, a condition referred to as “organ dysfunction” is common and an important factor in morbidity and mortality. The fact that the time of the initial event is known, and the magnitude of the insult is quantifiable, makes the burned patient ideal to be studied. In this doctoral thesis organ dysfunction and mortality were studied in a descriptive, prospective, exploratory study (no interventions or control groups) in patients admitted consecutively to a national burn centre in Sweden.The respiratory dysfunction that is seen after burns was found to be equally often the result of acute respiratory distress syndrome and inhalation injury. We found little support for the idea that this early dysfunction is caused by pneumonia, ventilator-induced lung injury, or sepsis. Acute kidney injury (AKI) was also common, and mortality was associated with severity. Importantly, renal dysfunction recovered among the patients who survived. Pulmonary dysfunction and systemic inflammatory response syndrome developed before the onset of AKI. Sepsis was a possible aggravating factor for AKI in 48% of 31 patients; but we could find no support for the idea that late AKI was mainly associated with sepsis. We found that older age (over 60 years), greater TBSA%, and respiratory dysfunction were associated with increased mortality, but there was no association between the overall mortality and sex. We also found that early transient liver dysfunction was common, and recorded early hepatic “hyper”- function among many young adults. Persistent low values indicating severe liver dysfunction were found among patients who eventually died.We conclude from this investigation that overall organ dysfunction is an early and common phenomenon among patients with severe burns. Our data suggest that the prognosis of organ dysfunction among these patients is good, and function recovers among most survivors. Multiple organ failure was, however, the main cause of death. The findings of the early onset in respiratory dysfunction and a delay in signs of sepsis are congruous with the gutlymphatic hypothesis for the development of organ dysfunction, and the idea of the lung as an inflammatory engine for its progression. We think that the early onset favours a syndrome in which organ dysfunction is induced by an inflammatory process mediated by the effect of the burn rather than being secondary to sepsis.Our data further suggest that clinical strategies to improve burn care further should be focused on early interventions, interesting examples of which include: selective decontamination of the gastrointestinal tract to prevent translocation of gut-derived toxic and inflammatory factors; optimisation of fluid replacement during the first 8 hours after injury by goal-directed resuscitation; and possible improvement in the fluid treatment given before admission.
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| 18. |
- Wilhelms, Susanne, 1985-
(author)
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The epidemiology of severe sepsis in Sweden : Methodological aspects on the use of ICD coding in national registries
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Severe sepsis is characterized by acute organ dysfunction caused by an infection. Despite advanced treatment with antibiotics and organ support the mortality remains high. The epidemiological research on severe sepsis has expanded over the years but has led to conflicting results. In this thesis, we present evidence that some of these conflicting results may be explained by inappropriate methods used in epidemiological studies on severe sepsis. The definition of severe sepsis relies on consensus criteria including a number of clinical signs, parameters and laboratory findings. To facilitate large nation-wide studies on the incidence of severe sepsis in already existing administrative datasets, several investigators have attempted to mirror the clinical criteria by using combinations of the International Classification of Diseases (ICD) codes for infection and organ dysfunction. In paper I of this thesis, however, we found that three different ICD code abstraction strategies applied on the same dataset (the Swedish National Patient Register) generated three almost separate cohorts of patients. Furthermore, in paper II, where we followed intensive care unit (ICU)-treated patients with severe sepsis according to clinical consensus criteria to discharge, we observed that most patients did not meet any ICD code abstraction strategies for severe sepsis when reviewing their ICD codes registered at discharge from the hospital. In conclusion, the ICD code abstraction strategies previously used in the epidemiological research on sepsis seem to be inaccurate in the Swedish setting. Sepsis may also result in poor long-term outcomes, and contribute to an increased risk of late mortality. However, the actual causes of late mortality in sepsis remain unclear. In paper III, we investigated causes of death over 1 year after treatment of sepsis in the ICU. In this study, a matched control group consisting of ICU-treated patients without sepsis was included. The most common causes of late mortality in both the sepsis group and the control group were heart diseases and cancer. The sepsis group, however, had a significantly increased incidence of infectious-related deaths compared with the control group, even over 1 year after the initial ICU event.
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| 19. |
- Bäckman, Carl G
(author)
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The photo-diary and follow-up appointment on the ICU: Giving back the time to patients and relatives. : A descriptive and interventional study
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Background: Patients on the ICU often spend a great deal of their time either unconscious or heavily sedated. When they return from the zone between life and death they are often in a state of confusion where dreams and delusions are intertwined with reality and it is not always easy to distinguish them apart. These experiences could lead to psychological problems and post-traumatic stress disorder (PTSD). Recovery may be improved by filling in the significant memory gaps and explaining what really happened during the “chaotic” time on the ICU. The provision of a diary describing the patients’ stay in ICU on a day to day basis and a follow-up meeting (together named the ICU-diary concept), may help the whole family to understand.Aim: The principal aim of this thesis was to see if the ICU-diary concept was of help to patients and relatives in the recovery after critical illness. A further aim was to look for precipitants in the ICU of PTSD.Material and Methods: ICU patients in a handful of European countries and their relatives have been studied. The studies have been single and multi-centred and we have used descriptive observational, randomised controlled and cohort study designs, including matched case-control designs. Quantitative methods have been used with questionnaires and structured interviews using established instruments (i.e Post-traumatic stress syndrome screening-14, Post-traumatic diagnostic scale, ICU memory tool, Short Form-36, Pearlin-Schooler Mastery Scale, Hopelessness scale) as the principal means of data collection.Results: The ICU-diary concept was seen to be a positive and useful aid in helping patients and their relatives understand the events that took place during the time on the ICU. It also decreased the risk for PTSD among patients and relatives. Patients that were supported with the ICU-diary concept perceived a better health-related quality of life even 3 years after the ICU stay. We did not find any definite improvement by the ICU-diary concept in mastery and hope. Variations in how the patients were cared for in the ICU had a significant effect on the development of PTSD. The implementation of an ICU diary, for instance, was associated with a lower frequency of PTSD.Conclusions: The ICU-diary concept was found helpful by patients and their relatives. It was associated with a reduction in new onset PTSD and improved health-related quality of life. The results are encouraging and suggest that an ICU diary may represent an important first step to help patients and relatives come to terms with their experiences during critical illness.ISBN 978-
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| 20. |
- Cirillo, Marco Domenico, et al.
(author)
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Time-Independent Prediction of Burn Depth using Deep Convolutional Neural Networks
- 2019
-
In: Journal of Burn Care & Research. - : Oxford University Press. - 1559-047X .- 1559-0488. ; 40:6, s. 857-863
-
Journal article (peer-reviewed)abstract
- We present in this paper the application of deep convolutional neural networks, which are a state-of-the-art artificial intelligence (AI) approach in machine learning, for automated time-independent prediction of burn depth. Colour images of four types of burn depth injured in first few days, including normal skin and background, acquired by a TiVi camera were trained and tested with four pre-trained deep convolutional neural networks: VGG-16, GoogleNet, ResNet-50, and ResNet-101. In the end, the best 10-fold cross-validation results obtained from ResNet- 101 with an average, minimum, and maximum accuracy are 81.66%, 72.06% and 88.06%, respectively; and the average accuracy, sensitivity and specificity for the four different types of burn depth are 90.54%, 74.35% and 94.25%, respectively. The accuracy was compared to the clinical diagnosis obtained after the wound had healed. Hence, application of AI is very promising for prediction of burn depth and therefore can be a useful tool to help in guiding clinical decision and initial treatment of burn wounds.
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| 21. |
- Droog Tesselaar, Erik, 1977-
(author)
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Assessment of microvascular function by use of transdermal iontophoresis : methodological aspects
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Assessment of the microcirculation is of major importance in understanding the physiology of the vasculature and in assessing te vascular effects of pathological conditions such as diabetes, hypertension and sepsis. Transdermal iontophoresis can be used to non‐invasively introduce vasoactive drugs into the skin. The response to these drugs of the local cutaneous microvasculature can be measured by laser Doppler flowmetry methods. Although these techniques have been used together for over two decades, there are still important methodological issues to be resolved. This work is aimed at optimizing transdermal iontophoresis as a tool for microvascular assessment by focusing on the main methdological issues: non‐specific vasodilatation, drug delivery protocols and analysis of blood flow data.Non‐specific vasodilatation, an increase blood flow during iontophoresis of non‐vasoactive compounds, is an important problem as it interferes with the response to the administered drug. By investigating this effect in healthy volunteers, we found that the extent of the non‐specific response differs between the positive and negative electrode and that it is dependent on the voltage over the skin andon the ionic strength of the vehicle in which the drug is dissolved. We also found that the extent of the non‐specific response could be reduced by applying local anesthetics and by pre‐treatment with antihistamine drugs. These results suggest that non‐specific effects could be mediated by depolarization or hyperpolarisation of cells, triggering neural and histamine related mechanisms that finally lead to vasodilatation of the local microvasculature.To prevent non‐specific effects from occurring during the experiments, our results show that the current strength and the total electric charge during iontophoresis should be limited to 0.02 mA and12 mC, respectively. Furthermore, drug solutions at physiological ionic strengths should be used. Under these conditions, adequate responses to the most commonly used drugs, acetylcholine (ACh) and sodium nitroprusside (SNP), are obtained while no significant non‐specific vasodilatation occurs.The results of our investigations show that blood responses to ACh and SNP applied by a single iontophoretic pulse can well be escribed by conventional dose‐response models, which enables a more powerful analysis and comparison between drugs or possibly patient groups as compared with conventional aalysis methods. Finally, we have incorporated drug transport and physiological response to the local drug concentration during iontophoresis of vasoactve drugs into a single model. Validation of this model using measured responses to ACh and SNP shows that the commonly used assumption that the local drug concentration during iontophoresis is linearly proportional to the electric charge may not be valid.
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| 22. |
- Engerström, Lars
(author)
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The significance of risk adjustment for the assessment of results in intensive care. : An analysis of risk adjustment models used in Swedish intensive care.
- 2018
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Doctoral thesis (other academic/artistic)abstract
- To study the development of mortality in intensive care over time or compare different departments, you need some kind of risk adjustment to make analysis meaningful since patient survival varies with severity of the disease. With the aid of a risk adjustment model, expected mortality can be calculated. The actual mortality rate observed can then be compared to the expected mortality rate, giving a risk-adjusted mortality.In-hospital mortality is commonly used when calculating riskadjusted mortality following intensive care, but in-hospital mortality is affected by the duration of care and transfer between units. Time-fixed measurements such as 30-day mortality are less affected by this and are a more objective measure, but the intensive care models that are available are not adapted for this measure. Furthermore, how length of follow-up affects risk adjusted mortality has not been studied. The degree and pattern of loss of physiological data that exists and how this affects performance of the model has not been properly studied. General intensive care models perform poorly for cardiothoracic intensive care where admission is often planned, where cardiovascular physiology is more affected by extra corporeal circulation and where the reasons for admission are usually not the same.The model used in Sweden for adult general intensive care patients is the Simplified Acute Physiology Score 3 (SAPS3). SAPS3 recalibrations were made for in-hospital mortality and 30-, 90- and 180-day mortality. Missing data were simulated, and the resulting performance compared to performance in datasets with originally missing data.We conclude that SAPS3 works equally well using 30-day mortality as in-hospital mortality.The performance with both 90- and 180-day mortality as outcome was also good. It was found that the model was stable when validated in other patients than it was recalibrated with.We conclude that the amount of data missing in the SIR has a limited effect on model performance, probably because of active data selection based on the patient's status and reason for admission.A model for cardiothoracic intensive care based on variables available on arrival at Swedish cardiothoracic intensive care units was developed and found to perform well.
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| 23. |
- Farnebo, Simon, 1972-
(author)
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On microvascular blood flow assessment with the new microdialysis urea clearance technique
- 2010
-
Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to develop and evaluate a new way of monitoring blood flow with microdialysis. A thin catheter consisting of a semipermeable membrane is implanted in the tissue being studied. The catheter is perfused by a solution that closely resembles interstitial fluid, and small water-soluble substances are allowed to diffuse passively through the pores of the membrane with the aim at reaching equilibrium with the surrounding tissue. The minimally invasive character of microdialysis, and its ability to sample from the organ being studied, make microdialysis attractive in most research settings as well as for clinical surveillance. It has, however, become increasingly evident that microdialysis under conditions of non-equilibrium - for example, fluctuating regional blood flow, will alter the results gained. We have therefore aimed to explore the possibilities of developing a new marker of blood flow that will yield information about changes in blood flow that occur in the area of the microdialysis catheter itself.We hypothesised that the changes in the diffusion of exogenous urea could be used as markers of changes in tissue blood flow. The theoretical basis for this approach is that the mass transfer of urea will increase across the dialysis membrane secondary to increased blood flow. As removal of urea from the vicinity of the dialysis membrane increases with increased blood flow, the concentration gradient of urea between the perfusate and tissue will also increase. This in turn will result in a greater loss of urea from the perfusate. The changes noted in retrieval of urea from dialysate by the system are therefore thought to be inversely related to changes in blood flow. We tested our hypothesis in two species of animal (rat and pig) and in man, and in three organ systems (muscle, liver, and skin), and present four papers that indicate that the urea clearance technique provides reliable and reproducible results. The technique was evaluated against conventional metabolic markers (lactate and glucose), the ethanol clearance technique (microdialysis), laser Doppler perfusion imaging (LDPI), and polarisation light spectroscopy (TiVi).We present evidence that the urea clearance technique can be used to assess blood flow in the organs studied reliably and reproducibly with microdialysis. The microdialysis technique is minimally invasive and safe for the recipient, and catheters can easily be implanted during operation to monitor organs at risk. Urea is easily analysed as a standard assay among other “basic” metabolic markers (in a standard microdialysis kit) and has favourable characteristics with a standardised measurement system that is routinely used for monitoring metabolites in the clinic. The technique is also effective when used at lower perfusate flow rates (<1 μl/minute), which is advantageous as the recovery of metabolic markers increases at low perfusate flow rates.
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| 24. |
- Grossmann, Benjamin
(author)
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Procedural sedation : Aspects on methods, safety and effectiveness
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background: Safety and effectiveness are fundamental principles within the healthcare sector to provide quality of care and health improvement for patients. By ensuring that care is provided based on evidence-based knowledge, risks and complications can be minimised and the use of scarce resources optimised. An increasing demand for diagnostic and therapeutic procedures challenges the traditional methods for sedation regarding safety and effectiveness. It is desirable that the fundamental principles are improved when refining existing or developing new sedation methods. In this doctoral thesis, safety and effectiveness were evaluated for adult patient-controlled sedation (PCS) using propofol during two endoscopic procedures: endoscopic retrograde cholangiopancreaticography (ERCP) and flexible bronchoscopy (FB); and different doses of rectal racemic ketamine for paediatric (< 4 years) burn wound care.Methods: Data on vital functions, sedation level, safety interventions, procedure feasibility, patient-reported outcome and experience measures, and recovery, from three clinical randomised controlled trials were collected. Costs of sedation for the endoscopic procedures were compiled in a cost-analysis study.Results: PCS with propofol and bedside anaesthetic personnel was shown to be a safe and effective alternative method of sedation during ERCP and FB compared with intravenous sedation with midazolam. The PCS method gives stable cardiorespiratory conditions with few adverse events and interventions, with a low risk of oversedation. PCS offers similar (FB) or better (ERCP) procedure feasibility and patient satisfaction during the procedures than midazolam. Recovery after PCS is quick, minimises the risk for prolonged hospitalisation and is thereby a potential cost-saving sedation method. The optimal dose of rectal racemic ketamine, 6 mg/kg with the addition of 0.5 mg/kg midazolam during severely painful procedures, gives minimal risk for outbreaks of pain, offers stable vital signs conditions and allows rapid recovery without affecting procedure feasibility.Conclusions: The sedation method can be adjusted to type of procedure and patient population. PCS with propofol offers an alternative and reliable method for adult sedation during endoscopic procedures, whereas rectal racemic ketamine combined with midazolam provides good conditions for burn care dressing procedures in young children.
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| 25. |
- Kildal, Morten
(author)
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Perceived Physical and Psychological Outcome After Severe Burn Injury
- 2003
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Doctoral thesis (other academic/artistic)abstract
- There is very little data on physical and psychological long-term outcome after severe burn injury. The aim of the present thesis was to improve current instruments for assessment of these issues, to assess long-term outcome in a cohort of patients with burn injuries, and to explore the contribution of the individual factors of personality and coping on perceived outcome.Patients treated at the Burn Unit, Uppsala University Hospital, between 1980 and 1995 were included on a consecutive basis if they were 18 years of age or older at follow-up, had burn injuries of ten percent or more, or hospitalization times of seven days or more. A total of 350 patients fulfilled these inclusion criteria.A factor analytic approach was used to derive a 40-item instrument called the Burn Specific Health Scale-Brief (BSHS-B), resulting in nine well-defined domains. Most burn patients reported a very good perceived outcome but a subgroup reported problems years after injury. On a group level most problems were related to Heat Sensitivity, Work and Body Image. The depth of injury, gender, marital status and living conditions were all related to outcome. Neurotic personality traits were related to perceived health, and were not confined only to psychological aspects of life but also included physical aspects. A 33-item burn-specific coping scale, the Coping with Burns Questionnaire (CBQ), with six clearly separated domains with acceptable internal consistencies was developed. Coping strategies were strongly related to outcome in the subgroup of patients reporting most problems in perceived health, and coping contributed more to psychosocial than physical health. Avoidant coping and Emotional support seeking had independent effects on outcome.The observation that Neuroticism and Avoidant coping strategies are related to bad outcome after severe burn injury indicates that patients with such characteristics should be given special attention during rehabilitation.
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| 26. |
- Larsen, Robert, 1980-
(author)
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Risk-Adjustment for Swedish In-Hospital Trauma Mortality using International Classification of disease Injury Severity Score (ICISS) : issues with description and methods
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- IntroductionDifferent methods have been used to describe the epidemiology of trauma with varying results. Crude mortality outcome data differ significantly from risk-adjusted information. A previous standard method for risk-adjustment in trauma was the Injury Severity Score (ISS), although it has several shortcomings. In this thesis I examine Swedish injury statistics from an epidemiological perspective using crude and risk-adjusted mortality, and to adjust for injury I used the International Classification of disease Injury Severity Score (ICISS). The groups of most lethal injuries (fall, traffic, and assault) were examined separately using an ICISS mortality prediction model that focused particularly on the effects on the prediction of mortality by adding coexisting conditions (comorbidity) to it. Differences in mortality between the sexes and changes over time were tested separately.Material and MethodsData from all patients with ICD-10 based diagnoses of injury (ICD-10: V01 to Y36) in the Swedish National Patient Registry and Cause of Death Registry were collected from 1999 to 2012 and used for assessment of mortality and comorbidity. A subgroup (patients in hospital) from 2001-2011 were selected as the study group. Their injuries were in the subgroups of falls, traffic, and assaults, and are the focus of this thesis. Mortality within 30 days of injury was used as the endpoint. The severity of injury was adjusted for using the ICISS, which was first described by Osler et al. The model was also adjusted for age, sex, and comorbidities.ResultsThe study group comprised 815 846 patients (of whom 17 721 died). There was a decrease over time in injuries caused by falls and traffic (coefficient -4.71, p=0.047 and coefficient -5.37, p<0.001), whereas there was no change in assault-related injuries/100 000 inhabitants. The risk-adjusted 30-day mortality showed a decrease in injuries related to traffic and assault (OR 0.95, p<0.001 and OR 0.93, p=0.022) whereas for falls it remained unchanged. There was also a risk-adjusted survival benefit for women, which increased with increasing age. Adjusting for comorbidities made the prediction of 30-day mortality by the ICISS model better (accuracy, calibration, and discrimination). However, most of this effect was found to be the result of the other characteristics of the fall related injury group (they were older, and had more coexisting conditions).ConclusionDuring a 10-year period, there has been a significant overall decrease in crude as well as risk-adjusted mortality for these three injury groups combined. Within these groups there is a clear, risk-adjusted, female survival advantage. The ICISS model for the prediction of mortality improves when comorbidities are added, but this effect is minor and seen mainly among the injuries caused by falls, where comorbidity is significant. The ICISS method was a valuable adjunct in the investigation of data on Swedish mortality after injury that has been gathered from health care registry data.
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| 27. |
- Orwelius, Lotti, 1956-
(author)
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Health related quality of life in adult former intensive care unit patients
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Background: Patients treated in an intensive care unit (ICU) are seriously ill, have a high co‐morbidity, morbidity and mortality. ICUs are resource – demanding as they consume significant hospital resources for a minority of patients. The development of new medical procedures for critical care patients has over the years led to survival of larger numbers with more complex illnesses and extensive injuries. Improved survival rates lead to needs for outcome measures other than survival. The present study examines health‐related quality of life (HRQoL) and factors assumed to be important for the long term HRQoL for former ICU patients.Methods: This is a multicenter cohort study of 980 adult patients admitted to one of three mixed medical‐surgical ICUs in Southern Sweden, during 2000 to 2004. The patients were studied at four different occasions after their critical illness: 6, 12, 24, and 36 months after discharge from the ICU and hospital. HRQoL was assessed by the EuroQol 5‐Dimensions (EQ‐5D) and Medical Outcome Short Form (SF‐36), sleep disturbances by the Basic Nordic Sleep questionnaire (BNSQ), and pre‐existing diseases was collected by self‐reported disease diagnosis. Data from a large public health survey (n=6093) of the county population were used as reference group.Results: Compared with the age and sex adjusted general reference group the patients who had been in the ICU had significantly lower scores on EQ‐5D and in SF‐ 36 all eight dimensions. This was seen both for the general ICU patients as well as for the multiple trauma patients. Significant improvement over time was seen only in single and separate dimensions for the general ICU group, and for the multiple trauma group. Long term effects of ICU care on sleep patterns were found minor as 70 % reported an unchanged sleep pattern and only 9% reported worse sleep after the IC period. Pre‐existing diseases were found to be the factor that had the largest influence on HRQoL in both the short‐ and long term perspective for the general ICU patients as well as for the multiple trauma patients. It was also found to have negative impact on sleep. IC ‐related factors showed only a minor influence on HRQoL or sleep patterns after the ICU stay.Conclusions: This multicenter study shows that pre‐existing diseases influence the HRQoL short‐ and long‐term after IC, and it must be accounted for when HRQoL and outcome after IC are studied. Approximately, 50% of the decline in HRQoL for the ICU patients could be explained by pre‐existing diseases. Future research needs to focus on the remaining factors of importance for the total HRQoL impairment for these patients.
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- Pompermaier, Laura, 1975-
(author)
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Outcome of burn care : the mortality perspective
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Background: Despite the improvements in burn care during the last decades, burns remain catastrophic for the patients and a challenge for the care-givers. The early outcome of burn care is to assess its quality and to improve it, but the crucial outcome is mortality, which is the main focus of this thesis. In particular, I address questions about mortality that have arisen from working with burned patients and that can have clinical consequences: the impact of pre- existing medical conditions; long-term survival; the causes of unexpected deaths; and the possible differences between sexes in the provision of resources.Patients with burns share the fact that the time of their injury is known, its severity can be quantified from the size of the burn, and the care is relatively standardised. The analysis of outcome among burned patients treated at a single burn centre may therefore be of general value to others who treat burns.Methods: We retrospectively analysed data that had been collected prospectively (the burn unit database) from patients with burns admitted consecutively to a national burn centre in Sweden during the last 25 years.Results: Age and percentage of total body surface area burned (TBSA %) affected the in- hospital mortality, whereas pre-existing medical conditions did not influence the prediction of outcome (Paper I). After discharge, both age and the presence of full thickness burns reduced the long-term survival, whereas the extent of the burn (TBSA %) did not (Paper II). Most patients with moderate burns who die in hospital despite a good prognosis, die for reasons other than the burn (Paper III). Previously, it has been shown that sex is not an independent factor for mortality during burn care; in this thesis we show that the sex of the patients did not affect the number of medical interventions given either (Paper IV).Conclusion: The addition of “coexisting condition” to a mortality model based on age and size of burn does not improve its predictive value; rather, the factor “age” is sufficient to adjust for comorbidity in the assessment of a burn and its outcome (Paper I).If patients with burns survive, the long-term prognosis is good. The effect of age is the one that governs survival, whereas the effect of the extent of the burn ends when the patient is discharged (Paper II).The in-hospital mortality during burn care is low, but some patients die for reasons other than the actual burn (Paper III).In a centre where the mortality is independent of the sex of the patient, the provision of medical interventions is also equal between men and women (Paper IV).
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