| 1. |
- Bergkvist, Max, 1976-
(författare)
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Studies on Polarised Light Spectroscopy
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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. |
- Iredahl, Fredrik, 1988-
(författare)
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Assessment of microvascular and metabolic responses in the skin
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 3. |
- Karlsson, Matilda, 1981-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 4. |
- Bäckström, Denise, 1976-
(författare)
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Injury mortality in Sweden; changes over time and the effect of age and injury mechanism
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 5. |
- Klaff, Rami, 1971-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 6. |
- Mirdell, Robin, 1989-
(författare)
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Blood Flow Dynamics in Burns
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 7. |
- Wilhelms, Susanne, 1985-
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 8. |
- Cirillo, Marco Domenico, et al.
(författare)
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Time-Independent Prediction of Burn Depth using Deep Convolutional Neural Networks
- 2019
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Ingår i: Journal of Burn Care & Research. - : Oxford University Press. - 1559-047X .- 1559-0488. ; 40:6, s. 857-863
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Engerström, Lars
(författare)
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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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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 10. |
- Grossmann, Benjamin
(författare)
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Procedural sedation : Aspects on methods, safety and effectiveness
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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