Additive manufacturing (AM) has enabled the possibility for the hospitals to become their own implant producers developing implants that are tailored to patient’s anatomy. Despite the enormous potential of custom-made implants there are challenges that complicate the implementation of them into clinical practice. The aim of this research is to (1) identify the main driving forces and barriers for the delivery of custom-made implants; (2) explore staff stakeholder views and practices related to the implementation of AM in surgery for the development of custom-made implants; (3) formulate recommendations on how to cope with the implementation challenges. The research method was an explorative qualitative study consisted of a literature review on the challenges of custom-made implants in clinical applications coupled with the collection and inductive analysis of empirical data. The empirical study was based on ten semi-structured interviews conducted among both domestic and international hospital managers medical doctors and research engineers. The consolidated framework for implementation research (CFIR) was utilized for data collection. Using the five domains of CFIR, the following results were obtained: (1) Characteristics of individuals: Most research participants indicated a positive attitude towards the innovation expressing self-efficacy to its use; (2) Intervention characteristics: Custom-made implants were perceived to have a relative advantage in surgical practice due to their high degree of observability and geometrical adaptability providing increased surgical quality, perfect patient fit and better understanding of pathologies. However, high implementation costs, low degree of trialability and high degree of complexity in the development process were regarded as drawbacks of the innovation; (3) Outer setting: the regulatory uncertainty and lack of reimbursement limit the accessibility of custom-made implants to low income populations; (4) Inner setting: scarcity of resources, staff resistance to change, insufficient management support, communication difficulties, limited access to educational materials and training opportunities as well as lack of time and innovative capacity were regarded by the majority of participants as implementation barriers; (5) Process: central for the success of implementation is the need for a coherent implementation plan and evaluation process as well as the engagement of key stakeholders such as hospital managers, payers, regulatory and implementation advisors. This dissertation proffers a deeper understanding of the implementation issues related to custom-made implants and offers preliminary recommendations on how to cope with implementation impediments through the use of Rogers diffusion of innovation coupled with concepts from the field of organizational change and innovation management including Clayton’s disruptive innovation.

Global rise in life expectancy has resulted in an increased demand for affordable healthcare and monitoring services. The advent of miniature and low–power sensor technologies coupled with the emergence of the Internet–of–Things has paved the way towards affordable health monitoring tools in wearable platforms. However, ensuring power–efficient operation, data accuracy and user comfort are critical for such wearable systems. This thesis focuses on the development of accurate and computationally efficient algorithms and low–cost, unobtrusive devices with potential predictive capability for monitoring mobility and cardiac health in a wearable platform. A three–stage complementary filter–based approach is developed to realize a computationally efficient method to estimate sensor orientation in real–time. A gradient descent–based approach is used to estimate the gyroscope integration drift, which is subsequently subtracted from the integrated gyroscope data to get the sensor orientation. This predominantly gyroscope–based orientation estimation approach is least affected by external acceleration and magnetic disturbances. A two–stage complementary filter–based efficient sensor fusion algorithm is developed for real–time monitoring of lower–limb joints that estimates the IMU inclinations in the first stage and uses a gradient descent–based approach in the second stage to estimate the joint angles. The proposed method estimates joint angles primarily from the gyroscope measurements without incorporating the magnetic field measurement, rendering the estimated angles least affected by any external acceleration and insensitive to magnetic disturbances. An IMU–based simple, low–cost and computationally efficient gait–analyzer is developed to track the course of an individual's gait health in a continuous fashion. Continuous monitoring of gait patterns can potentially enable detecting musculoskeletal or neurodegenerative diseases at the early onset. The proposed gait analyzer identifies an anomalous gait with moderate to high accuracy by evaluating the gait features with respect to the baseline clusters corresponding to an individual’s healthy peer group. The adoption of a computationally efficient signal analysis technique renders the analyzer suitable for systems with limited processing capabilities. A flexible dry capacitive electrode and a wireless ECG monitoring system with automatic anomaly detection capability are developed. The flexible capacitive electrode reduces motion artifacts and enables sensing bio–potential over a dielectric material such as cotton cloth. The virtual ground of the electrode allows for obtaining single–lead ECG using two electrodes only. ECG measurements obtained over different types of textile materials and in presence of body movements show comparable performance to other reported ECG monitoring systems. An algorithm is developed separately as a potential extension of the software to realize automatic identification of Atrial Fibrillation from short single–lead ECGs. The association between human gait and cardiac activities is studied. The gait is measured using wearable IMUs and the cardiac activity is measured with a single–lead handheld ECG monitor. Some key cardiac parameters, such as heart rate and heart rate variability and physical parameters, such as age and BMI show good association with gait asymmetry and gait variation. These associations between gait and heart can be useful in realizing low–cost in–home personal monitoring tool for early detecting CVD–related changes in gait features before the CVD symptoms are manifested. / Thesis / Doctor of Philosophy (PhD) / Wearable health monitoring systems can be a viable solution to meet the increased demand for affordable healthcare and monitoring services. However, such systems need to be energy–efficient, accurate and ergonomic to enable long–term monitoring of health reliably while preserving user comfort. In this thesis, we develop efficient algorithms to obtain real–time estimates of on–body sensors' orientation, gait parameters such as stride length, and gait velocity and lower–limb joint angles. Furthermore, we develop a simple, low–cost and computationally efficient gait–analyzer using miniature and low–power inertial motion units to track the health of human gait in a continuous fashion. In addition, we design flexible, dry capacitive electrodes and use them to develop a portable single–lead electrocardiogram (ECG) device. The flexible design ensures better conformity of the electrode to the skin, resulting in better signal quality. The capacitive nature allows for obtaining ECG signals over insulating materials such as cloth, thereby potentially enabling a comfortable means of long–term cardiac health monitoring at home. Besides, we implement an automatic anomaly detection algorithm that detects Atrial Fibrillation with good accuracy from short single–lead ECGs. Finally, we investigate the association between gait and cardiac activities. We observe that some important cardiac signs, such as heart rate and heart rate variability and physical parameters, such as age and BMI show good association with gait asymmetry and gait variation.

<p>The rapid expansion of consumer Internet-of-Things (IoT) technology across various application domains has made it one of the most sought-after and swiftly evolving technologies. IoT devices offer numerous benefits, such as enhanced security, convenience, and cost reduction. However, as these devices need access to sensitive aspects of human life to function effectively, their abuse can lead to significant financial, psychological, and physical harm. While previous studies have examined the vulnerabilities of IoT devices, insufficient research has delved into the impact and mitigation of threats to users' privacy and safety. This dissertation addresses the challenge of protecting user safety and privacy against threats posed by IoT device vulnerabilities. We first introduce a novel IWMD architecture, which serves as the last line of defense against unsafe operations of Implantable and Wearable Medical Devices (IWMDs). We demonstrate the architecture's effectiveness through a prototype artificial pancreas. Subsequent chapters emphasize the safety and privacy of smart home device users. First, we propose a unique device activity-based categorization and learning approach for network traffic analysis. Utilizing this technology, we present a new smart home security framework and a device type identification mechanism to enhance transparency and access control in smart home device communication. Lastly, we propose a novel traffic shaping technique that hinders adversaries from discerning user activities through traffic analysis. Experiments conducted on commercially available IoT devices confirm that our solutions effectively address these issues with minimal overhead.</p>

The medical device industry has seen rapid growth in recent years, and the increasing valuations has caught the attention of investors. Although their growth has outpaced many indices, medical device companies’ reliance on capital to finance research, patents, and clinical testing to reach pre-market approval makes due-diligence and the investment research process especially complex. Investors frequently rely on intuition when making investment decisions and it would therefore be particularly valuable if there was a way to accurately predict future returns. Although stock return prediction and market anomalies are a frequently debated topic among finance researchers, unlike other studies which look at whole markets this study looks at a particular subset of companies. This study looks at 63 recently listed medical device companies in the US market to analyze the predictability of future shareholder returns. The metrics analyzed are some of the most common quantitative metrics used by investors. A multiple linear regression model is used to determine if the metrics can predict future total returns, and abnormal returns. An interview was conducted with an industry investment expert to get more insight in the sector and to evaluate the chosen metrics. This study also examines the same data set during two eras; predictability before and after the financial crisis in 2009, to see if predictability is constant over time. The findings show that free cash flow yield is the only statistically significant variable in the model. This implies that if a recently listed medical device company has a negative free cash flow yield for one year, it will have a positive return the following year. From the analysis on the two eras, before and after 2009, predictability is found to be lower after the financial crisis. / Den medicintekniska industrin har sett snabb tillväxt de senaste åren och de ökande värderingarna har lockat investerarnas intresse. Även om deras tillväxt har överträffat många index, innebär medicintekniska företags beroende av kapital för att finansiera forskning, patent och kliniska tester för att nå godkännande före marknaden en särskilt komplicerad besiktnings- och analyseringsprocess. Investerare förlitar sig ofta på intuition när de fattar investeringsbeslut och det skulle därför vara synnerligen värdefullt om det fanns ett sätt att noggrant förutsäga framtida avkastning. Även om aktieavkastnings förutsägbarhet och marknadsavvikelser är ett ofta diskuterat ämne bland finansforskare, undersöker denna studie en viss undergrupp av företag till skillnad från andra studier som undersöker hela marknader. Denna studie analyserar 63 nyligen börsnoterade medicintekniska företag på den amerikanska marknaden för att analysera förutsägbarheten av framtida aktieägaravkastning. Mätvärdena som analyseras är några av de vanligaste kvantitativa mätvärdena som används av investerare. En multipellinjär regressionsmodell används för att avgöra om måtten kan förutsäga framtida totalavkastning och abnorm avkastning. En intervju genomfördes med en expert på investeringar inom denna sektor för att få mer insikt och för att utvärdera de valda variablerna. Denna studie undersöker också samma datauppsättning under två epoker; förutsägbarhet före och efter finanskrisen 2009, för att se om förutsägbarheten är konstant över tid. Resultaten visar att fri kassaflödesavkastning är den enda statistiskt signifikanta variabeln i modellen. Detta innebär att om ett nyligen börsnoterat medicintekniskt företag har en negativ avkastning på fritt kassaflöde under ett år, kommer det att ha en positiv aktieavkastning året därpå. Från analysen av de två epokerna, före och efter 2009, visar sig förutsägbarheten vara lägre efter finanskrisen.

Medical devices, such as catheters and heart valves, are an important part of patient care. However, blood-contacting devices can activate the blood coagulation cascade to produce factor (f) Xa, the clotting enzyme that induces thrombin generation. By activating platelets and converting soluble fibrinogen to fibrin, thrombin leads to blood clot formation. Blood clots that form on medical devices create problems because they may foul the device and/or serve as a nidus for infection. In addition, clots can break off from the device, travel through the circulation and lodge in distant organs; a process known as embolization. This is particularly problematic with central venous catheters because clots that form on them can break off and lodge in pulmonary arteries, thereby producing a pulmonary embolism. Similarly, clots that form on heart valves can break off and lodge in cerebral arteries, thereby producing a stroke. Therefore, anticoagulants, blood thinning drugs, are frequently used to prevent clotting on medical devices. Conventional anticoagulants, such as heparin and warfarin, target multiple clotting factors. Heparin binds to antithrombin in plasma and accelerates the rate at which it inhibits fXa, thrombin and many other clotting enzymes. Warfarin, which is a vitamin K antagonist, attenuates thrombin generation by interfering with the synthesis of the vitamin K-dependent clotting factors, which include fX and prothrombin, the precursor of thrombin. In contrast to heparin and warfarin, more recent anticoagulants inhibit only a single clotting enzyme. For example, fondaparinux, a synthetic heparin fragment, only inhibits fXa and dabigatran, an oral thrombin inhibitor, only targets thrombin. Although effective for many indications, fondaparinux was less effective than heparin for preventing clotting on catheters in patients undergoing heart interventions and dabigatran was less effective than warfarin for preventing strokes in patients with mechanical heart valves. The failure of these new anticoagulants highlights the need for a better understanding into the drivers of clotting on medical devices. Therefore, the overall purpose of this thesis is to gain this understanding so that more rational approaches to its prevention can be identified. In the classical model of blood coagulation, clotting is triggered via two distinct pathways; the tissue factor (TF) pathway or extrinsic pathway and the contact pathway or intrinsic pathway; pathways which are initiated by fVIIa and fXIIa, respectively. The mechanism by which medical devices initiate clotting is uncertain. Platelet and complement activation and microparticle formation have been implicated, which would drive clotting via the TF pathway. Alternatively, medical devices can bind and activate fXII, thereby initiating the contact pathway. We hypothesized that medical devices trigger clotting via the contact pathway and induce the local generation of fXa and thrombin in concentrations that exceed the capacity of fondaparinux and dabigatran to inhibit them. To test this hypothesis, we used catheters as a prototypical medical device and we used a combination of in vitro and rabbit models. Several lines of evidence indicate that catheters initiate clotting via the contact pathway. First, catheter segments shortened the clotting time of human plasma, and this activity was attenuated in fXII- or fXI-deficient plasma, which are key components of the contact pathway, but not in fVII-deficient plasma, which is the critical component of the extrinsic pathway. Second, corn trypsin inhibitor (CTI), a potent and specific inhibitor of fXIIa, attenuates catheter thrombosis. Third, selective knockdown of fXII or fXI with antisense oligonucleotides attenuated catheter-induced thrombosis in rabbits, whereas knockdown of fVII had no effect. Therefore, these results revealed the importance of the contact pathway in device-associated thrombosis, and identified CTI or fXII or fXI knockdown as novel strategies for preventing this problem. Focusing on fXIIa as the root cause of medical device associated clotting, we coated catheters with CTI using a polyethylene glycol (PEG) spacer. In addition to unmodified catheters, other controls included catheters coated with albumin via a PEG spacer or catheters coated with PEG alone. Compared with unmodified catheters or with the other controls, CTI-coated catheters attenuated clotting in buffer or plasma systems and were resistant to occlusion in rabbits. These findings support the concept that catheter-induced clotting is driven via the contact pathway and identify CTI coating as a viable strategy for its prevention. We next set out to test the hypothesis that fondaparinux and dabigatran, which inhibit fXa and thrombin, respectively, are less effective than heparin, which inhibits multiple clotting enzymes. Fondaparinux and dabigatran were less effective than heparin at preventing catheter induced clotting and thrombin generation, respectively. Likewise, in a rabbit model of catheter thrombosis, fondaparinux was less effective than heparin and dabigatran was only effective when administered at doses that yielded plasma dabigatran levels similar to those found at peak in human given the drug; at trough levels, dabigatran was no better than placebo. Finally, we also showed synergy between heparin and either fondaparinux or dabigatran. Thus, when co-administered to rabbits in doses that on their own had no effect, the combination of fondaparinux or dabigatran plus heparin extended the time to catheter thrombosis. These findings support the hypothesis that when catheters trigger clotting via the contact pathway, fXa and thrombin are generated in concentrations that overwhelm the capacity of fondaparinux or dabigatran to inhibit them. Furthermore, the synergy between heparin and fondaparinux or dabigatran has clinical implications because it explains why supplemental heparin attenuated the risk of catheter thrombosis in patients treated with fondaparinux who underwent cardiac procedures and it identifies the potential role of supplemental heparin in dabigatran-treated patients who require such interventions. In summary, we have shown that catheters trigger clotting via the contact pathway and have identified CTI coating or fXII or fXI knockdown as viable strategies for prevention of this problem. In addition, for prevention of catheter thrombosis, we also have shown that heparin, which inhibits multiple coagulation enzymes, is more effective than fondaparinux or dabigatran, which only inhibit fXa or thrombin, respectively; findings consistent with the clinical observations. Moreover, the synergy that we observed between fondaparinux or dabigatran and heparin identifies supplemental heparin as strategy for preventing catheter thrombosis in patients receiving these drugs. Taken together, these studies provide insight into the mechanisms of catheter thrombosis and potential strategies for its prevention. / Thesis / Doctor of Philosophy (PhD)