Sjukvården lever med knappa resurser och investeringar i medicinsk teknik binder mycket kapital under en längre tid, vilket har ökat behovet av systematiska och noggranna utvärderingar av investeringarnas konsekvenser, både ekonomiska och icke-ekonomiska. Huvudsyftet med studien var att undersöka hur investeringsbedömningar inom sjukvården görs, och vilken roll ekonomiska utvärderingar har vid investeringsbeslut. Delsyftet var att utarbeta en investeringskalkyl och bedöma kostnadseffektiviteten för införandet av ett nytt undersökningsmetod för hjärtdiagnostik på Karolinska universitetssjukhuset i Huddinge (Cardiotom). Utgångspunkten i undersökningen finns i investeringsteori och hälsoekonomisk teori som därför presenteras i uppsatsen. En redogörelse av tidigare forskning både inom sjukvården och inom andra branscher ges, för att läsaren skulle kunna jämföra utfallet i den här studien med de andra studierna i ämnet. Som undersökningsmetod valde författarna att kombinera intervjuer med en enkätundersökning och på det sättet få en samlad bild av kalkyleringens betydelse och övrig problematik kring lönsamhetsbedömningen vid investeringar i medicinsk teknik. Resultatet av studien tyder bland annat på att investeringskalkyler spelar fortfarande ett begränsad roll vid investeringsbeslut, samt att dess betydelse kan komma att öka i samband med att kraven på kvantitativ utvärdering av samhällsekonomisk nytta ökar. Investeringsbedömningen av införandet av Cardiotom visar att investeringen är lönsam och utifrån kalkylens utfall, där hänsyn till patientnyttan också tagits med, borde genomföras.

Otitis media, which is an upper respiratory tract infection that affect the middle ear, is the second most common disease in childhood, outnumbered in prevalence only by the common cold. Diagnosis of middle ear inflammation is often performed in the primary healthcare where the normal procedure involves anamnesis and physical examination of the tympanic membranes (TM) of the patient, usually be means of otoscopy. The general aim of this thesis was to develop optical methods that enable quantification of TM characteristics associated with otitis media. Diffuse reflectance spectroscopy was applied to quantify TM erythema using previously suggested erythema detection algorithms. Healthy TM:s were significantly distinguished from TM:s with induced erythema (p < 0.01) and from TM:s in ears with mucous middle ear effusion (p < 0.05). A new technique for surface shape assessment based on an on-axis dual fibre array incorporated in an otoscope was developed and evaluated in ear models and on tympanic membranes from harvested temporal bones. The technique utilises the combined effects of source-detector fibre separation and fibre-to-sample distance on the detected light intensity. Optical phantoms, both polyacetal plastic solids and latex membranes, were utilised to demonstrate the ability of the surface shape assessment technique to differentiate between convex and concave surfaces – as a bulging tympanic membrane is typically associated with acute otitis media whereas a retracted eardrum is associated with otitis media with effusion. Monte Carlo simulations of the surface shape data were performed in order to validate the experimental results with a theoretical model that are consistent with light transport theory. Retracted and bulging tympanic membranes from harvested temporal bones could be separated with a single measurement, given that variations in measurement distance were accounted for and that measurement from normally positioned tympanic membranes were used for signal normalization. In conclusion, the studies implicate that for individual otitis diagnosis, the hyperaemic tympanic membrane was separated from the healthy by application of erythema indices using diffuse reflectance spectroscopy. Moreover, bulging and retracted positions of the tympanic membrane were separable by means of the source-detector intensity matrix. For further clinical studies it is reasonable to assume that data from both methods are needed for diagnosis.

Patch-based transdermal drug delivery offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections relating to issues such as patient acceptability and injection safety. However, conventional transdermal drug delivery is limited to therapeutics where the drug can diffuse across the skin barrier. By using miniaturized needles, a pathway into the human body can be established which allow transport of macromolecular drugs such as insulins or vaccines. These microneedles only penetrate the outermost skin layers, superficial enough not to reach the nerve receptors of the lower skin. Thus, microneedle insertions are perceived as painless. The thesis presents research in the field of microneedle-based drug delivery with the specific aim of investigating a microneedle-based transdermal patch concept. To enable controllable drug infusion and still maintain an unobtrusive and easy-to-use, patch-like design, the system includes a small active dispenser mechanism. The dispenser is based on a novel thermal actuator consisting of highly expandable microspheres. When actuated, the microspheres expand into a liquid reservoir and, subsequently, dispense stored liquid through outlet holes. The microneedles are fabricated in monocrystalline silicon by Deep Reactive Ion Etching. The needles are organized in arrays situated on a chip. To allow active delivery, the microneedles are hollow with the needle bore-opening located on the side of the needle. This way, the needle can have a sharp and well-defined needle tip. A sharp needle is a further requirement to achieve microneedle insertion into skin by hand. The thesis presents fabrication and evaluation of both the microneedle structure and the transdermal patch as such. Issues such as penetration reliability, liquid delivery into the skin and microneedle packaging are discussed. The microneedle patch was also tested and studied in vivo for insulin delivery. Results show that intradermal administration with microneedles give rise to similar insulin concentration as standard subcutaneous delivery with the same dose rate. / QC 20100623

There is a large need for accurate methods detecting cardiovascular diseases, since they are one of the leading causes of mortality in the world, accounting for 29.3% of all deaths. Due to the complexity of the cardiovascular system, it is very challenging to develop methods for quantification of its function in order to diagnose, prevent and treat cardiovascular diseases. Ultrasound is a technique allowing for inexpensive, noninvasive imaging, but requires an experienced echocardiographer. Nowadays, methods like Tissue Doppler imaging (TDI) and Speckle tracking imaging (STI), measuring motion and deformation in the myocardium and the vessel walls, are getting more common in routine clinical practice, but without a proper visualization of the data provided by these methods, they are time-consuming and difficult to interpret. Thus, the general aim of this thesis was to develop novel ultrasound-based methods for accurate quantification and easily interpretable visualization of cardiovascular function. Five methods based on TDI and STI were developed in the present studies. The first study comprised development of a method for generation of bull’s-eye plots providing a color-coded two-dimensional visualization of myocardial longitudinal velocities. The second study proposed the state diagram of the heart as a new circular visualization tool for cardiac mechanics, including segmental color-coding of cardiac time intervals. The third study included development of a method describing the rotation pattern of the left ventricle by calculating rotation axes at different levels of the left ventricle throughout the cardiac cycle. In the fourth study, deformation data from the artery wall were tested as input to wave intensity analysis providing information of the ventricular – arterial interaction. The fifth study included an in-silico feasibility study to test the assessment of both radial and longitudinal strain in a kinematic model of the carotid artery. The studies showed promising results indicating that the methods have potential for the detection of different cardiovascular diseases and are feasible for use in the clinical setting. However, further development of the methods and both quantitative comparison of user dependency, accuracy and ease of use with other established methods evaluating cardiovascular function, as well as additional testing of the clinical potential in larger study populations, are needed. / QC 20100727

Uppsatsens syfte är att undersöka vilka ekonomiska effekter införandet av distansuppföljning för ICD-patienter har ur ett samhällsperspektiv. Delsyftet är att identifiera ekonomiska argument och kvalitativa aspekter för och emot införandet av tjänsten distansuppföljning. Författarna har kommit fram till ett antal slutsatser. Att införa distansuppföljning som uppföljningsmetod för ICD-patienter istället för konventionella återbesök på sjukhus innebär stora kostnadsbesparingar. Nettonuvärdet uppgår till drygt 268 miljoner kronor efter femton år. Vid tidsperiodens slut erhålls en kostnadsbesparing på cirka 35,6 procent. De ekonomiska fördelarna överstiger kostnaderna redan efter ett år, och hela investeringskostnaden återfås efter sju år. Kvalitativa argument som talar för distansuppföljning är tidsbesparingar, förenklad uppföljning, bättre övervakning och att patienterna upplever en större trygghet.

Hasomed GmbH, a German company in the Field of medicine technology, intends to introduce a gait analysis system on the market. The system includes an inertial sensor which collects data used for generating movement patterns of the feet. This thesis describes the development and evaluation of a new version of the sensor, aimed at minimizing costs, maximizing performance and facilitating production. Algorithms used in the gait analysis system are sensitive to noise. Noise sources and precautions taken in order to minimize noise levels are described and discussed. By minimizing the physical size of analogue electronics blocks, static noise and occasional high frequency components were substantially reduced. New features including internal temperature sensors, firmware update via serial interface, self-test functions and a wireless link were implemented. Additional improvements are e.g. lower power consumption and an extension of the interface from 2 to 256 (theoretical limit) attached devices. By reducing the number of included components and PCB (Printed Circuit Board) layers, together with use of components that do not require advanced soldering techniques, easier and cheaper production was obtained. Research and development presented in this thesis resulted in a sensor with overall good performance and new features.

Phase-contrast magnetic resonance imaging (PC-MRI) is a powerful tool for measuring blood flow and has a wide range of cardiovascular applications. Simulation of PC-MRI from numerical flow data would be useful for addressing the data quality of PC-MRI measurements and to study and understand different artifacts. It would also make it possible to optimize imaging parameters prior to the PC-MRI measurements and to evaluate different methods for measuring wall shear stress. Based on previous studies a PC-MRI simulation tool was developed. An Eulerian-Lagrangian approach was used to solve the problem. Computational fluid dynamics (CFD) data calculated on a fix structured mesh (Eulerian point of view) were used as input. From the CFD data spin particle trajectories were computed. The magnetization of the spin particle is then evaluated as the particle travels along its trajectory (Lagrangian point of view). The simulated PC-MRI data were evaluated by comparison with PC-MRI measurements on an in vitro phantom. Results indicate that the PC-MRI simulation tool functions well. However, further development is required to include some of the artifacts. Decreasing the computation time will make more accurate and powerful simulations possible. Several suggestions for improvements are presented in this report.

Image registration is the process of aligning two images such that their mutual features overlap. This is of great importance in several medical applications. In 2008 a novel method for simultaneous T1, T2 and proton density quantification was suggested. The method is in the field of quantitative Magnetic Resonance Imaging or qMRI. In qMRI parameters are quantified by a pixel-to-pixel fit of the image intensity as a function of different MR scanner settings. The quantification depends on several volumes of different intensities to be aligned. If a patient moves during the data aquisition the datasets will not be aligned and the results are degraded due to this. Since the quantification takes several minutes there is a considerable risk of patient movements. In this master thesis three image registration methods are presented and a comparison in robustness and speed was made. The phase based algorithm was suited for this problem and limited to finding rigid motion. The other two registration algorithms, originating from the Statistical Parametrical Mapping, SPM, package, were used as references. The result shows that the pixel-to-pixel fit is greatly improved in the datasets with found motion. In the comparison between the different methods the phase based algorithm turned out to be both the fastest and the most robust method.

En stor del av befolkningen har en hörselnedsättning men långt ifrån alla som skulle kunna dra nytta av hörselhjälpmedel söker vård i tid. Det finns ett behov av att kunna göra ett snabbt och enkelt screening-test hemifrån och i flera andra europeiska länder har det för det ändamålet tagits fram telefon- och Internetbaserade hörseltest av tresiffertyp.  Dessa tester spelar upp tre inlästa siffror samtidigt som ett störande brus-ljud och en adaptiv metod används för att automatiskt uppskatta testpersonens genomsnittliga, uppfattbara signal-brus-förhållande. Studier har visat att förmågan att urskilja tal i brus försämras för personer med hörselnedsättning och att den absoluta uppspelningsvolymen inte spelar väsentlig roll så länge ljudet är klart hörbart.  Ett svenskt talmaterial för ett sådant test har tagits fram inom EU-projektet HearCom. Syftet med examensarbetet var att implementera och validera en funktionell och prisvärd lösning i samarbete med en aktör inom telekommunikationsbranschen.  Efter en upphandlingsprocess valdes ett Linux-baserat system med den öppna telefonserver-programvaran Asterisk. En normalstudie genomfördes där resultaten pekar på att det utvecklade testet är jämförbart med liknande test i andra länder. Telefontestet jämfördes även med en befintlig Internetversion och båda testerna utvärderades med avseende på användbarhet. Vissa förbättringsåtgärder har föreslagits för testerna.  Rapporten tar också upp förutsättningar för en relevant gränssättning av testerna samt de återstående stegen till en färdig talsvarstjänst som allmänheten kan ha nytta av.

MobileMe is a recently developed system for monitoring and recording physiological variables. It is wireless, and can therefore be suitable for field research, for example when measuring motion sickness symptoms. The aim of this thesis was to conclude whether the MobileMe recording system was valid for research studies. A validation study, consisting of two parts and including 10 subjects, was performed. The first part was a laboratory study, where data from MobileMe and a reference equipment were compared. A field study was also performed, onboard a combat boat, to determine the equipment’s validity in uncontrolled environments. Furthermore, the field study included an investigation of motion sickness symptoms, and provided data for evaluation of motion sickness rating scales. Statistical results from the laboratory study, and results from evaluation of data from the field study, showed that MobileMe was valid in both controlled and uncontrolled environments.