Design of a comprehensive modeling, characterization, rupture risk assessment and visualization pipeline for Abdominal Aortic Aneurysms

Abdominal aortic aneurysms (AAA) is a dilation of the abdominal aorta, typically within the infra-renal segment of the vessel that cause an expansion of at least 1.5 times the normal vessel diameter. It is becoming a leading cause of death in the United States and around the world, and consequentially, in 2009, the Society for Vascular Surgery (SVS) practice guidelines expressed the critical need to further investigate the factors associated with the risk of AAA rupture, along with potential treatment methods. For decades, the maximum diameter (Dmax) was introduced as the main parameter used to assess AAA behavior and its rupture risk. However, it has been shown that three main categories of parameters including geometrical indices, such as the maximum transverse diameter, biomechanical parameters, such as material properties, and historical clinical parameters, such as age, gender, hereditary history and life-style affect AAA and its rupture risk. Therefore, despite all efforts that have been undertaken to study the relationship among different parameters affecting AAA and its rupture, there are still limitations that require further investigation and modeling; the challenges associated with the traditional, clinical quality images represent one class of these limitations. The other limitation is the use of the homogenous hyper-elastic material property model to study the entire AAA, when, in fact, there is evidence that different degrees of degradation of the elastin and collagen network of the AAA wall lead to different regions of the AAA exhibiting different material properties, which, in turn, affect its biomechanical behavior and rupture. Moreover, the effects of all three main categories of parameters need to be considered simultaneously and collectively when studying the AAAs and their rupture, so once again, the field can further benefit from such studies. Therefore, in this work, we describe a comprehensive pipeline consisting of three main components to overcome some of these existing limitations. The first component of the proposed method focuses on the reconstruction and analysis of both synthetic and human subject-specific 3D models of AAA, accompanied by a full geometric parameter analysis and their effects on wall stress and peak wall stress. The second component investigates the effect of various biomechanical parameters, specifically the use of various homogeneous and heterogeneous material properties to model the behavior of the AAA wall. To this extent, we introduce two different patient-specific regional material property models to better mimic the physiological behavior of the AAA wall. Finally, the third component utilizes machine learning methods to develop a comprehensive predictive model that incorporates the effect of the geometrical, biomechanical and historical clinical data to predict the rupture severity of AAA in a patient-specific manner. This is the first comprehensive semi-automated method developed for the assessment of AAA. Our findings illustrate that using a regional material property model that mimics the realistic heterogeneity of the vessel’s wall leads to more reliable and accurate predictions of AAA severity and associated rupture risk. Additionally, our results indicate that using only Dmax as an indicator for the rupture risk is insufficient, while a combination of parameters from different sources along with PWS could serve as a more reliable rupture assessment. These methods can help better characterize the severity of AAAs, better predict their associated rupture risk, and, in turn, help clinicians with earlier, patient-customized diagnosis and patient-customized treatment planning approaches, such as stent grafting

The Economic Impact of Fluoroquinolone-related Adverse Reactions in Finland : Studies on Costs, Health Service Use and Mortality

Fluoroquinolones are a group of broad-spectrum antibacterial agents that are widely used and indicated for the treatment of genitourinary, respiratory, gastrointestinal, skin, and soft tissue infections. In Finland, fluoroquinolones comprise 5% of all systemic antimicrobial prescriptions. Fluoroquinolones are generally well tolerated and their common adverse reactions, such as nausea and headache, are mostly mild and resolve quickly. However, fluoroquinolones are also associated with more serious adverse reactions, including tendon injuries, Clostridioides difficile infections, and aortic ruptures, which can result in long-term impairment to patients and high healthcare costs. The aim of this study was to estimate the economic impact of fluoroquinolone-related adverse reactions in Finland. A systematic literature review (study I) was conducted to identify health service use and subsequent costs associated with ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin -related adverse events. A retrospective observational cost of illness study (study II) was conducted to assess costs and health service use associated with tendon injuries after fluoroquinolone use in Finland during 2002-2012 with data from the Finnish Pharmaceutical Insurance Pool's pharmaceutical injury claims. Regression models were used to analyze the impact of patient characteristics on hospital days, as well as the relationship between patient characteristics and tendon ruptures. In study III, a cost of illness decision tree model was built to predict costs and mortality associated with serious adverse drug reactions. Severe Clostridioides difficile infections, severe cutaneous adverse reactions, tendon ruptures, aortic ruptures and liver injuries were included as serious adverse drug reactions in the model. In study I, 19 observational studies, including five case-control studies, fulfilled the inclusion criteria. Length of hospital stay associated with adverse events varied between <5 and 45 days. Clostridioides difficile infections were the adverse event type associated with the longest stays in hospital. The estimated cost of an adverse event treatment episode ranged between 140 € and 18,252 €. In study II, fifty-one percent of the claimants were hospitalized due to tendon injuries, with an average duration of 21 days and an average cost of 9,915 € per hospital episode. Hospital days and direct costs increased with the severity of the injury. Concurrent use of oral glucocorticoids and increasing age were associated with a higher likelihood of tendon ruptures. In study III, a total of 1,831,537 fluoroquinolone prescriptions were filled between 2008 and 2019 in Finland. Severe Clostridioides difficile infections were the most frequent, fatal, and costly serious adverse reactions associated with the use of fluoroquinolones. Because of the wide clinical use of fluoroquinolones, in particular serious fluoroquinolone-related adverse reactions can have substantial economic implications, in addition to imposing potential long-term disability for patients. Accordingly, the risks and benefits of fluoroquinolones should be weighed carefully in antibiotic prescription policies, and additional measures should be developed to prevent and reduce health service use and costs associated with fluoroquinolone-related adverse reactions.Fluorokinolonit ovat laajakirjoisia mikrobilääkkeitä, joiden käyttöaiheita ovat virtsatie-, hengitystie-, suolisto-, iho- sekä pehmytkudosinfektiot. Kaikista määrätyistä mikrobilääkkeistä fluorokinolonien osuus on noin 5 %. Vaikka useimmat fluorokinoloneihin liitetyt haittavaikutukset, kuten pahoinvointi ja päänsärky, ovat lieviä ja ohimeneviä, niiden käyttö on myös yhdistetty vakaviin haittavaikutuksiin, kuten jännevaurioihin, Clostridioides difficile -infektioihin sekä aortan repeämiin. Haittavaikutusten hoito vaatii usein sairauslomaa sekä terveyspalvelujen käyttöä, joista kertyy sekä potilaalle että yhteiskunnalle merkittäviä kustannuksia. Tämän tutkimuksen tavoite oli arvioida fluorokinolonien aiheuttamien haittavaikutusten taloudellisia seurauksia. Järjestelmällisessä kirjallisuuskatsauksessa (tutkimus I) kartoitettiin siprofloksasiinin, levofloksasiinin, moksifloksasiinin, norfloksasiinin ja ofloksasiinin käytöstä aiheutuneiden haittatapahtumien hoitoon liittyvää terveyspalveluiden käyttöä sekä kustannuksia. Retrospektiivisessa havainnoivassa tutkimuksessa (tutkimus II) arvioitiin fluorokinolonien käytöstä aiheutuneiden jännevaurioiden kustannuksia ja terveyspalveluiden käyttöä Suomessa vuosina 2002–2012. Tutkimuksessa analysoitiin taustamuuttujien vaikutusta sairaalapäivien määrään sekä jännevaurion ilmenemiseen regressiomalleilla, minkä lisäksi toteutettiin useita alaryhmäanalyyseja. Kolmannessa tutkimuksessa rakennettiin päätöspuumalli, jonka avulla arvioitiin fluorokinolonien käyttöön liitettyjen vakavien haittavaikutusten kustannuksia ja kuolleisuutta. Malliin sisältyivät vakavat Clostridioides difficile -infektiot, vakavat ihoreaktiot, jännerepeämät, aortan repeämät sekä vakavat maksahaitat. Mallin pohjana toimi Suomessa kirjoitettujen fluorokinolonireseptien määrä. Kirjallisuushaussa fluorokinolonien haittoja käsittelevistä julkaisuista 19 täytti sisäänottokriteerit (tutkimus I). Kaikki tutkimukset olivat tutkimusasetelmaltaan havainnoivia, ja niistä viisi oli kontrolloituja. Haittatapahtumiin liittyvän sairaalahoidon kesto vaihteli 5 ja 45 päivän välillä, joista pisimmät liittyivät Clostridioides difficile -infektioihin. Haittatapahtuman arvioidut kustannukset vaihtelivat 140 eurosta ja 18 252 euroon. Tutkimuksessa II fluorokinolonihoitoon liittyvän jännevaurion sairaalajakson kustannukset olivat keskimäärin 9 915 €. Sairaalapäivät ja suorat kustannukset lisääntyivät vamman vakavuuden myötä. Samanaikainen kortisonilääkitys sekä ikääntyminen ennustivat suurempaa jännerepeämän todennäköisyyttä. Tutkimuksessa III havaittiin, että vakaviin Clostridium difficile-infektioihin liittyivät suurimmat kustannukset sen lisäksi, että ne olivat kaikkien yleisimpiä ja eniten kuolemaan johtavia fluorokinolonien käyttöön liittyviä vakavia haittavaikutuksia. Fluorokinoloneja käytetään laajasti ja niiden vakavilla haittavaikutuksilla näyttäisi olevan merkittäviä taloudellisia seurauksia sen lisäksi, että ne voivat aiheuttaa potilaille pitkäaikaisia vammoja. Fluorokinolonien määräämisen yhteydessä tulisi hyödyt ja haitat punnita erityisen tarkasti, jotta haitoista johtuvaa terveyspalveluiden käyttöä sekä kustannuksia voitaisiin ehkäistä

Patient specific insights into thoracic aortic disease:Exploring male-female differences

There are clear differences between males and females with thoracic aortic aneurysms (TAA). For starters, thoracic aortic aneurysm (TAA) between is known to have a higher incidence in males. Furthermore, females seem to present with thoracic aortic aneurysm at an older age. However, little is known about possible differences between male and female TAA patients in presentation, management and outcomes. Worse outcomes in females after thoracic aortic dissection and elective thoracic aortic surgery have been reported, which lead to uncertainties about optimal timing of preventive thoracic aortic surgery in male and female patients. The mechanisms underlying these male-female differences in outcome remain unclear. As a result, there has been debate about the appropriateness of the use of absolute aortic diameter for the timing of surgery. Currently, sex and body size are not taken into account when timing preventive aortic surgery. However, male-female specific cut-off values for maximal aortic diameter might be helpful. Furthermore, the risk of aortic dissection causes stress and anxiety in TAA patients, which could impact quality of life. The effect of TAA on quality of life might be different in males and females, since male-female differences in emotional functioning, coping strategies and stress (i.e. anxiety/depression) are well known to exist in the general population. Moreover, limited information is available on the safety of daily activities, such as exercise and sports participation in both male and female patients with thoracic aortic disease. All these male-female differences have largely been neglected in patients with heart disease in general and aortic disease in particular. Therefore, research in all these aspects of aortic disease is essential. This thesis is part of the ‘Size Matters’ project, funded by ZonMW, aims to identify male-female differences and other patient specific insights into thoracic aortic aneurysm diagnosis, treatment and outcomes. More accurate identification of patients at risk for thoracic aortic dissection allows for better timing of intervention, and will hopefully contribute to better survival, as well as stress reduction and better quality of life

Patient specific insights into thoracic aortic disease:Exploring male-female differences

There are clear differences between males and females with thoracic aortic aneurysms (TAA). For starters, thoracic aortic aneurysm (TAA) between is known to have a higher incidence in males. Furthermore, females seem to present with thoracic aortic aneurysm at an older age. However, little is known about possible differences between male and female TAA patients in presentation, management and outcomes. Worse outcomes in females after thoracic aortic dissection and elective thoracic aortic surgery have been reported, which lead to uncertainties about optimal timing of preventive thoracic aortic surgery in male and female patients. The mechanisms underlying these male-female differences in outcome remain unclear. As a result, there has been debate about the appropriateness of the use of absolute aortic diameter for the timing of surgery. Currently, sex and body size are not taken into account when timing preventive aortic surgery. However, male-female specific cut-off values for maximal aortic diameter might be helpful. Furthermore, the risk of aortic dissection causes stress and anxiety in TAA patients, which could impact quality of life. The effect of TAA on quality of life might be different in males and females, since male-female differences in emotional functioning, coping strategies and stress (i.e. anxiety/depression) are well known to exist in the general population. Moreover, limited information is available on the safety of daily activities, such as exercise and sports participation in both male and female patients with thoracic aortic disease. All these male-female differences have largely been neglected in patients with heart disease in general and aortic disease in particular. Therefore, research in all these aspects of aortic disease is essential. This thesis is part of the ‘Size Matters’ project, funded by ZonMW, aims to identify male-female differences and other patient specific insights into thoracic aortic aneurysm diagnosis, treatment and outcomes. More accurate identification of patients at risk for thoracic aortic dissection allows for better timing of intervention, and will hopefully contribute to better survival, as well as stress reduction and better quality of life

Computational fluid dynamics indicators to improve cardiovascular pathologies

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.Postprint (published version

Diseases of the Chest, Breast, Heart and Vessels 2019-2022

This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology

Promoting shared decision-making in the surgical realm:From the surgeons’ preferred treatment for patients to the patients’ preferred treatment for surgery

To improve the quality of healthcare. Equality between doctor and patients is becoming increasingly important. In our modern society, the ethical principle that patients have the right to be better involved in the decision-making process regarding their health issues gets more recognition, while at the same time an increasing number of treatment options has become available. The aim of this thesis was to explore the current level of shared decision-making (SDM) and risk communication in the out-patient clinic, and to improve this level by developing and implementing SDM and risk communication tools. An essential step in the process of SDM, is the communication about the possible treatment options with their pros and cons. Because visual presentation of information may increase patient comprehension, a web-based, publicly available (www.mapping.nu) application that provides graphical representation of numerical benefits and risk of surgical treatment options was developed. Besides the MAPPING app we developed various decision support tools (DSTs). DSTs were developed for four vascular disorders, i.e., patients with an abdominal aortic aneurysm (AAA), carotid artery disease (CAD), intermittent claudication (IC) and varicose veins (VV). The various support tools included patient decision aids, consultation cards, and decision cards. Besides the usual content of DAs, the DAs we developed contain 3D-animations of each of the treatment options to better explain and illustrate what these treatments involve. The patients go through the decision aid prior to the decision-making consultation in order to enter this conversation as well prepared as possible.The OVIDIUS trial showed that the introduction of decision support tools improves the degree of shared decision-making, the knowledge about treatment options and that patients opt less often for invasive treatments. In addition, it was seen that the online decision aid was most effective for patients and that the shared decision-making training was the most effective for clinicians

Promoting shared decision-making in the surgical realm:From the surgeons’ preferred treatment for patients to the patients’ preferred treatment for surgery

To improve the quality of healthcare. Equality between doctor and patients is becoming increasingly important. In our modern society, the ethical principle that patients have the right to be better involved in the decision-making process regarding their health issues gets more recognition, while at the same time an increasing number of treatment options has become available. The aim of this thesis was to explore the current level of shared decision-making (SDM) and risk communication in the out-patient clinic, and to improve this level by developing and implementing SDM and risk communication tools. An essential step in the process of SDM, is the communication about the possible treatment options with their pros and cons. Because visual presentation of information may increase patient comprehension, a web-based, publicly available (www.mapping.nu) application that provides graphical representation of numerical benefits and risk of surgical treatment options was developed. Besides the MAPPING app we developed various decision support tools (DSTs). DSTs were developed for four vascular disorders, i.e., patients with an abdominal aortic aneurysm (AAA), carotid artery disease (CAD), intermittent claudication (IC) and varicose veins (VV). The various support tools included patient decision aids, consultation cards, and decision cards. Besides the usual content of DAs, the DAs we developed contain 3D-animations of each of the treatment options to better explain and illustrate what these treatments involve. The patients go through the decision aid prior to the decision-making consultation in order to enter this conversation as well prepared as possible.The OVIDIUS trial showed that the introduction of decision support tools improves the degree of shared decision-making, the knowledge about treatment options and that patients opt less often for invasive treatments. In addition, it was seen that the online decision aid was most effective for patients and that the shared decision-making training was the most effective for clinicians