This diploma thesis deals with the topic concerning regulation of launching medical devices onto the market with regard to the analysis of key regulatory framework. The aim of the thesis is to find out if the legal framework really fulfils its de lege ferenda objectives. The purpose of this thesis is to confirm or disprove a hypothesis that the regulation of launching medical devices onto the market is sufficient and effective from the point of view of consumer protection and interests of other stakeholders. Secondary aim of this diploma thesis is to confirm or disprove a hypothesis that the harmonization of legal framework in the EU is appropriate and effective. These hypothesis are to a certain extent following up the verification of four essential goals that should be reached by the regulation. One of the key aims is assuring the safety of the products, enabling them to move freely in terms of the internal market of the EU and assuring that the consumer isn't misled when deciding about his optimal situation. Besides that the regulation shouldn't unnecessarily slow down the activities of businesses and inappropriately limit their innovation potential. The diploma thesis has a critical point of view concerning some aspects of this regulation and in the end the author suggests some proposals in order to improve the current practice.

Balanced Scorecard belongs to the most prominent managerial tools for performance measurement and strategy management. Aim of this thesis is to describe BSC with emphasis to small and medium enterprises using literature review. Additional supporting tools for strategy formulation are included as well. BSC is then proposed for implementation in privately owned small enterprise in the sector of medical devices. Based on the thorough analysis of the company and its environmental factors operational and strategical performance gaps are identified. Such gaps are then addressed by means of BSC including financial, customer, internal processes and learning and growth perspective. Despite some limitations inherent to SMEs in general introduction of BSC is feasible and could be of value to all company stakeholders.

Summary: Although the digital revolution has transformed many niches of human activity, healthcare sector and pharmaceutical drug development has been relatively slow in embracing emerging technologies to optimize health efficacy, especially in Nordic Countries. The topic is of more importance now owing to the present scenario of the corona virus (COVID-19)outbreak, which has caused unparalleled disruption in the conduct of clinical trials and presented challenges as well as opportunities for clinical trialists and data analysts. In this master thesis, the potential opportunity with virtual or digital clinical trials as viable options to enhance drug development efficiency is highlighted that offers diverse patients easier and attractive ways to participate in clinical trials. Special reference is made to wearable devices in clinical trial execution and generating real world data; its acquisition and processing in a virtual trial setting. Issues of patient safety, measurement reliability and validity, and data privacy & integrity are  reviewed, and considerations are put forward for mitigation of underlying regulatory andoperational barriers. The aim of this thesis is to assess the recent wearable technologies that generate Real World Data and to understand the potential of this data to transform Nordic healthcare industry. A systematic review of clinical trials involving wearable patient monitoring technique in North America, Nordic Countries and other European countries was conducted. Out of various innovative wearable technologies, Smartwatches are found to be the most common and it is also observed that these wearable technologies have been able to help in early detection and diagnosis of diseases and modify disease progression by real time monitoring of data and develop precision medicine. thus, it is concluded that Wearable Remote Patient Monitoring is a novel technique that has few barriers;but promises a big transformation in Nordic Countries as well as in entire healthcare industry.

Accidents related to medical devices are a worldwide problem and result in many deaths each year. It affects patients, relatives, health care workers and society. Due to the complexity of intensive care units (ICUs), such accidents lead to particularly serious consequences. The aim of this thesis was to identify patient safety aspects at ICUs in public and private hospitals in Bangladesh, in order to provide a basis for improving the quality of performance of devices as well as personnel, care and cost effectiveness. The objectives were to a)      compare the conditions of medical devices at ICUs in private and public hospitals, b)      increase understanding of errors, risks and accidents related to medical devices, c)      study reporting systems and communication between staff at ICUs and d)      find ways to minimize hazards related to medical equipment to ensure effective and safe use of devices. Data was collected through interviews during field visits to six hospitals in Dhaka, Bangladesh. Interviews were held with the chiefs of the ICUs, physicians, nurses and technicians. It was noticed that the admission fees to the public hospitals were lower and had more limited resources. Differences between public and private hospitals could be seen in the aspects of finance, the existence of a Biomedical Engineering Department, maintenance and calibration of medical equipment, further education of staff, working environment and infection control. The reporting systems for adverse events and communication about patients’ conditions between coworkers were weak at all hospitals. The procurement process was lengthy at all hospitals. Access to disposable items was limited at several hospitals. The lower admission fee at the government hospitals results in the patients of these hospitals often having a lower income and status, thus less inclined to be critical of the received care. A number of suggestions have been proposed in order to improve the work in the ICU. These include a)      following up rules made by the authorities to ensure they are implemented at each hospital, b)      increasing documentation of malfunctioning devices and adverse events, c)      nurses and physicians taking part in the procurement process, d)      establishing a Biomedical Engineering Department at all hospitals, e)      organizing workshops for health care workers, f)       developing biomedical products adapted for multiple time use and with less need for calibration, g)      providing more education for health care workers in infection control, management of specific devices, solutions to common technical problems, patient safety and user safety, for example using Information and Communication Technology tools (audio and audiovisual material) and discussion platforms as well as h)      constructing an internet forum for consultation on the abovementioned subjects for technicians. / Olyckor relaterade till medicinteknisk utrustning är ett globalt problem som leder till många dödsfall varje år. Det påverkar patienter, anhöriga, sjukvårdspersonal och samhället. Den komplexa miljön på intensivvårdsavdelningar gör att olyckorna leder till allvarliga konsekvenser. Uppsatsen syftade till att identifiera patientsäkerhetsaspekter på intensivvårdsavdelningar i Bangladesh för att skapa en grund för prestandaförbättring, både gällande utrustning och gällande personal. Det ska också öka vård- och konstandseffektiviteten. Målet uppnåddes genom att a)      jämföra användandemiljön för medicinteknisk utrustning på intensivvårdsavdelningar på statliga och privata sjukhus, b)      öka förståelsen för fel, risker och olyckor relaterade till medicinteknisk utrustning, c)      studera rapporteringssystem samt kommunikation mellan personal på intensivvårdsavdelningar och d)      hitta sätt att minimera faror relaterade till medicinteknisk utrustning för att försäkra en effektiv och säker användning av utrustningen. Data samlades in genom intervjuer under en fältstudie på sex sjukhus i Dhaka, Bangladesh. Intervjuer hölls med cheferna på intensivvårdsavdelningarna, läkare, sjuksköterskor och tekniker. Det upptäcktes att patientavgiften på de statliga sjukhusen var lägre och resurserna var mer begränsade. Skillnader mellan statliga och privata sjukhus kunde ses inom ekonomiska resurser, förekomsten av medicintekniskavdelning, underhåll och kalibrering av medicinteknisk utrustning, vidareutbildning av personal, arbetsmiljö och infektionskontroll. Rapporteringssystemen för olyckor samt kommunikationen om patienters tillstånd mellan medarbetare var bristfällig på alla sjukhus. Upphandlingsprocesserna av ny medicintekniskutrustning var lång på alla sjukhus. Tillgången på engångsartiklar var begränsad på flera utav sjukhusen. Den lägre avgiften på de statliga sjukhusen resulterar i att patienterna på dessa sjukhus ofta har lägre inkomst samt status i samhället och är därför mindre benägna att vara kritiska till den mottagna vården. Ett antal ändringar föreslogs för att förbättra arbetet på intensivvårdsavdelningarna. Dessa inkluderar att a)      följa upp de av myndigheterna satta reglerna för att försäkra att de är implementerade på varje sjukhus, b)      öka dokumentationen av icke fungerande utrustning tillika olyckor, c)      sjuksköterskor och läkare skall delta i upphandlingsprocesserna, d)      starta medicintekniska avdelningar på alla sjukhus, e)      organisera workshops för vårdpersonal, f)       utveckla medicintekniska produkter som är anpassade för att användas flera gånger och som behöver kalibreras mer sällan, g)      ge mer utbildning till sjukvårdspersonal om infektionskontroll, hantering av specifika maskiner, lösningar till vanligt förekommande tekniska problem, patientsäkerhet och användarsäkerhet till exempel genom att använda information- och kommunikationsteknik-verktyg (audio och audiovisuellt material) och diskussionsplattformar samt h)      konstruera ett internetforum där tekniker kan få konsultation angående ovannämnda ämnen. / To develop patient safety system to improve the safety and quality of patient care at the Intensive Care Units

There is no doubt Medical Devices have a crucial role in hospital processes such as surgeries and therapeutic procedures. Medical devices available in hospitals are of two types; reusable and non-resalable medical devices. Reusable medical devices are washed and sterilized after each use. The process of sterilizing medical devices is performed in the sterilization department. Each medical device travels through a cycle each time it is utilized. It is explicit that any part of the sterilization cycle that delays the process can cause serious problems for hospitals’ performance. The washing step of the sterilization process has been a bottleneck in the system. Thus, optimization approaches can be highly advantageous to improve this bottleneck. The data of the medical devices are usually unknown prior to the scheduling process since the finishing time of the surgeries are not known in advance. Thus, there is no information available on the ready time of medical devices to be sterilized. Due to this factor, to develop applicable solutions, it is critical to consider this problem as an online problem and develop online scheduling methods. In this thesis, we take advantage of mathematical programming and heuristic algorithms to solve both the offline and online settings of the problem. We model the washing step of the sterilization cycle as a scheduling problem. Batch scheduling and bin packing, two well-known optimization approaches, are used for this purpose. Medical devices are batched together first and then scheduled on machines to reduce the total washing time of all medical devices. First, a mathematical model for the offline problem is provided and tested to solve the problem. Then a series of heuristic algorithms are developed using the batch scheduling approach for solving both offline and online problems. Moreover, a special case with divisible job sizes and equal release dates is studied. It was proved that for the strongly divisible sequence the First Fit Increasing algorithm finds the optimal solution, also for the weakly divisible sequence a Dynamic Programming algorithm is developed. Finally, we couple optimization with simulation to test the impact of the optimization of the washing step on the entire sterilization system. Moreover, since the next step of the sterilization cycle, the sterilization step, is very similar to the washing step, we also implement the developed heuristics in this step to evaluate its performance and improve it further. The results show that as long as the washing step is optimized it does not differ which algorithm is used in the sterilization step, thus, the optimization of this step is not necessary.

Orientador: Aldo Eloizo Job / Resumo: As vantagens do uso de dispositivos ópticos na área das ciências da vida são amplamente exploradas, especialmente para o diagnóstico médico e protocolos de tratamento em uma prática de cuidados de saúde. Além disso, alguns pesquisadores têm atraído muita atenção ao desenvolvimento de materiais biocompatíveis e vestíveis para melhorar a segurança de dispositivos médicos, bem como para estabelecer novos procedimentos para monitorar a resposta de terapia e diagnóstico clínico. O presente trabalho tem como objetivo desenvolver uma membrana biocompatível-luminescente não invasiva para reduzir os erros mais comuns relatados em fototerapia convencional de luz azul para icterícia neonatal. Dentre estes erros destacam-se: intensidade de irradiância que chega ao recém-nascido bem como seu posicionamento frente a fonte de radiação e qualidade das lâmpadas dos aparelhos fototerápicos. Neste contexto, a membrana foi confeccionada como um filme de sensor de luz azul, fluorescente e colorimétrico a partir de polímeros: poli [2-metoxi, 5-(2'etilhexyloxy)-pfenilenovileno (MEH-PPV) em uma matriz de borracha natural. Para tal, as membranas de borracha natural (BN) foram obtidas utilizando o látex, extraído das árvores Hevea brasiliensis (clone RRIM 600), por casting, com posterior tratamento térmico em estufa. Em seguida, também por casting, a solução de MEH-PPV/BN, razão igual a 4000, foi depositada na membrana BN para fazer uma camada fina de material luminescente. A membrana de MEH-PPV/BN fo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The advantages of optical devices in the life sciences are widely exploited, especially for medical diagnosis and treatment protocols in a health care practice. In addition, some researchers have attracted much attention to development flexible and biocompatible materials to improve security of medical devices, as well as to establish new procedures for monitoring therapy response and clinical diagnosis. The present paper aims to develop a new noninvasive biocompatible-luminescent membrane to reduce the most common user errors with conventional blue-light phototherapy of neonatal jaundice. The membrane was design based on a polymer-based fluorescent and colorimetric blue-light sensor film. This material was based on poly[2-methoxy,5-(2'etilhexyloxy)-p-fenilenovileno (MEH-PPV) in a natural rubber matrix. Natural rubber membranes (BN) were obtained using latex from Hevea brasiliensis trees (clone RRIM 600) by casting, with the time and temperature of thermal treatment fixed on 65°C for 10h. Then, also by casting, MEH-PPV/NR solution, ratio equal to 4000, was deposited on NR membrane for make thin-layer of luminescent material. The MEH-PPV/NR membrane was submitted to the same conditions used for neonatal hyperbilirubinemia treatment (Blue light phototherapy, 40 µW/m2 /nm, 460nm). The proprieties of membranes were characterized by optical (UV-Vis, PL) and infrared (FTIR) spectroscopy confocal microscopy (MC), scanning electron microscopy (SEM) and atomic force microscopy (AFM) a... (Complete abstract click electronic access below) / Doutor

Growing populations and especially the growing proportion of elderly in the developing countries in South Asia pose an increasingly higher pressure on the health care systems in these countries. For example, in Bangladesh, a part of the pressure is currently eased by the unofficial health care workers called village doctors but with the cost of wrong diagnoses and unnecessary medications leading to excess use of e.g. antibiotics. In order to help to produce a correct diagnosis and in planning the follow-up or preventive measures to improve the general health of the population, medical technology could be brought to the village doctors. Even though medical equipments are already been imported from developed countries to developing countries it has not notably improved the situation. This project has been conducted to unravel factors that affect bringing new medical technology to low resource settings, and to find outthe specific needs that countries with large rural populations but low income status have with medical technology. The purpose of this study is to investigate what demands should be placed on basic monitoring medical devices to ensure highly accurate and reliable readings, similar to those in Europe, but also an affordable product that meets the specific needs of rural health care in low income countries such as Bangladesh. This study also aims to find out what is the current need in therural areas of Bangladesh. The goal on the long run is to contribute to the development of safe and efficient medical devices that would increase the accessibility and quality of healthcare especially for the people living in the rural areas. The research questions were approached by first defining the current situation and the currenly known barriers in bringing two cost efficient medical devices for monitoring purposes to the Bangladeshi-market, and to define which requirements they should fulfil for the needs of the public health care. Secondly, European legislation was examined to research how the goal could be reached in practice. The methodology chosen for this project is qualitative methodology based on literature research and standard open-ended interviews. In addition, sensor-development work was done at KTH to study the properties of the sensors and the electric circuits. The results of this project show that, currently, medical technology is not used in large parts in South Asia such as in the rural areas of Bangladesh, but that there is a need and potential market for new devices that has not been researched before. Medical companies are aware of this, but the technology has not been developed yet to meet the local conditions. The results of this report suggest the following areas to be researched when developing new medical technology for rural areas in Bangladesh: technical requirements from an internationally acknowledged regulation (e.g. the EU regulation 2017/745 and ISO standards), reusability, robustness, user friendliness, post market surveillance, monitoring of performance and maintenance work. / Världens växande befolkning och speciellt den ökande andelen äldre i utvecklingsländerna utgör ett allt större tryck på hälsovårdssystemen i dessa länder. Till exempel i Bangladesh tas en del av trycket hand om av de inofficiella vårdpersonal, så kallade by-läkare. Eftersom en by-läkare oftast inte är utbildad inom medicin blir felaktiga diagnoser och onödiga läkemedel allt vanligare. Detta kan i sin tur leda till överdriven användning av till exempel antibiotika. För att bidra till mer effektiva och pålitliga diagnoser samt att underlätta planeringen av uppföljning eller förebyggande åtgärder för att förbättra allmänhälsan skulle medicinsk teknik kunna användas mer av by-läkarna. Trots att medicinsk utrustning redan har importerats från västländer till utvecklingsländer har det inte förbättrat situationen avsevärt. Det här examensarbetet har genomförts för att hitta olika faktorer som påverkar hur medicinsk teknik kan implementeras i låga resursinställningar samt för att ta reda på de specifika behov som länder med stora populationer men låg inkomst har med att använda medicinsk teknik. Syftet med denna studie är att undersöka vilka krav bör ställas på grundläggande övervakningsmedicintekniska produkter som används i rurala omständigheter för att säkerställa pålitliga och säkra resultat som i Europa. Samtidigt borde denna produkt uppfylla även de specifika behoven hos landsbygdshälsovården i låginkomstländer som Bangladesh. På lång sikt är målet att bidra till utvecklingen av medicinsk utrustning av hög kvalitet som skulle öka tillgängligheten och kvaliteten på vården särskilt för de som bor i landsbygden i låginkomstländer. Först definierades de viktigaste hindren för två kostnadseffektiva medicintekniska produkter som skulle användas i övervakningssyfte att komma till den bangladeshiska marknaden. De krav som produkterna borde uppfylla för att möta folkhälsovårdens behov definierades. EU-lagstiftningen analyserades och hur målet skulle kunna nås i praktiken undersöktes. Metoden som valdes för detta projekt är kvalitativ metodik. Därmed är resultaten baserad på litteraturforskning och öppna intervjuer. Även sensorutvecklingsarbete utfördes vid KTH för att studera egenskaperna hos sensorerna och el-kretsarna. Resultaten som hittades i detta projekt visar att ny medicinsk teknik används inte tillräckligt i stora områden i Södra Asien som till exempel i Bangladesh. Det finns en potentiell marknad men detta har inte undersökts tidigare. Resultaten antyder att de följande områdena som borde undersökas när ny medicinsk teknologi utvecklas till denna marknaden är: tekniska krav från en internationellt erkänd lagstiftning (till exempel EU:s medicinsktekniska direktivet 2017/745 samt ISO standarder), återanvändbarhet, robusthet, användarvänlighet, reglerad ”post-market”-uppföljning, samt underhållsarbete.

<p>The untethered transfer of energy and scalability of magnetic actuators enables functionality to an otherwise passive system. For example, wireless magnetic actuation can turn static 2D and 3D cell cultures into a more physiologically-relevant dynamic environment while limiting contamination. Moreover, indwelling catheters and implantable sensors are typically stationary devices that are notorious for their short lifespan when implanting into the body due to immune responses. Magnetic microactuators may be used for wireless actuation for in situ removal of biological materials accumulated on chronically implanted devices. In this dissertation, I will demonstrate examples of novel biomedical microdevices enabled by magnetic actuation for added functional benefits. First, I will describe a soft polymer magnetic actuator that can facilitate the study of a physiologically relevant cell culturing system. By cyclically stretching an extracellular matrix protein in a 3D cell culture, this system can elucidate the process by which breast cancer cells respond to a dynamic environment in the lungs. The fibrillar fibronectin suspended across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that has not yet been recapitulated in vitro until now. Our results demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases. As a second application, I will demonstrate the use of magnetic microactuators to remove biofouling on an implantable biosensor in order to prolong its functionality. The results of our work suggest that the motion of the actuator on the sensor surface can maintain biosensor signal integrity and prevents the downstream effects of the foreign body response. Additionally, I will present the design and proof of concept testing of a novel aspiration thrombectomy catheter meant to improve the engagement between the catheter and the blood clot being removed. Preliminary results demonstrate the added benefit of incorporating a microstructure in the inner diameter of the catheter meant to increase the retraction force aspiration catheters have when retrieving corked emboli at the catheter tip. </p> <p><br></p>

<p>Wearable devices and their ubiquitous use and deployment across multiple areas of health provide key insights in patient and individual status via big data through sensor capture at key parts of the individual’s body. While small and low cost, their limitations rest in their computational and battery capacity. One key use of wearables has been in individual activity capture. For accelerometer and gyroscope data, oscillatory patterns exist between daily activities that users may perform. By leveraging spatial and temporal learning via CNN and LSTM layers to capture both the intra and inter-oscillatory patterns that appear during these activities, we deployed data sparsification via autoencoders to extract the key topological properties from the data and transmit via BLE that compressed data to a central device for later decoding and analysis. Several autoencoder designs were developed to determine the principles of system design that compared encoding overhead on the sensor device with signal reconstruction accuracy. By leveraging asymmetric autoencoder design, we were able to offshore much of the computational and power cost of signal reconstruction from the wearable to the central devices, while still providing robust reconstruction accuracy at several compression efficiencies. Via our high-precision Bluetooth voltmeter, the integrated sparsified data transmission configuration was tested for all quantization and compression efficiencies, generating lower power consumption to the setup without data sparsification for all autoencoder configurations. </p> <p><br></p> <p>Human activity recognition (HAR) is a key facet of lifestyle and health monitoring. Effective HAR classification mechanisms and tools can provide healthcare professionals, patients, and individuals key insights into activity levels and behaviors without the intrusive use of human or camera observation. We leverage both spatial and temporal learning mechanisms via CNN and LSTM integrated architectures to derive an optimal classification architecture that provides robust classification performance for raw activity inputs and determine that a LSTMCNN utilizing a stacked-bidirectional LSTM layer provides superior classification performance to the CNNLSTM (also utilizing a stacked-bidirectional LSTM) at all input widths. All inertial data classification frameworks are based off sensor data drawn from wearable devices placed at key sections of the body. With the limitation of wearable devices being a lack of computational and battery power, data compression techniques to limit the quantity of transmitted data and reduce the on-board power consumption have been employed. While this compression methodology has been shown to reduce overall device power consumption, this comes at a cost of more-or-less information loss in the reconstructed signals. By employing an asymmetric autoencoder design and training the LSTMCNN classifier with the reconstructed inputs, we minimized the classification performance degradation due to the wearable signal reconstruction error The classifier is further trained on the autoencoder for several input widths and with quantized and unquantized models. The performance for the classifier trained on reconstructed data ranged between 93.0\% and 86.5\% accuracy dependent on input width and autoencoder quantization, showing promising potential of deep learning with wearable sparsification. </p>

Acute congestive heart failure is a leading cause of morbidity and mortality. Patients often undergo repeated hospitalizations with an annual cost in excess of $32B dollars. Early detection of impending acute congestion allows for pharmaceutical interdiction that prevents hospitalization, improves outcomes, and reduces healthcare spending. A subcutaneous implantable monitoring device that detects impending acute congestive heart failure by using heart sounds may provide a valuable tool that can be used to titrate heart failure medications to prevent acute heart failure requiring hospitalization. The device may be used to measure changes in the intervals between the R-wave and S1 and S2 heart sounds, and to detect evolving S3 and S4 heart sounds consistent with volume overload. The amplitudes of S1 and S3 heart sounds change as heart failure patients' symptoms worsen. Designing a non-invasive, external device, capable of recording heart sounds and EKGs in patients undergoing pharmaceutical regression of acute congestive heart failure in a hospital setting may give important insight into the nature of heart sound and EKG changes that occur in patients during progression of acute heart failure while they lead their day-to-day lives. This thesis details the design of a portable, non-invasive device, worn externally on the left-pectoral muscle, capable of continuously recording human EKG signals and heart sounds (through custom MEMS accelerometer technology) over a period of two days. Hardware testing for the scope of this thesis exclusively involved healthy volunteers.