Difficulties of Diagnosing Alzheimer's Disease: The Application of Clinical Decision Support Systems

Introduction: Alzheimer's disease is one of the most common causes of dementia, which gradually causes cognitive impairment. Diagnosis of Alzheimer's disease is a complicated process performed through several tests and examinations. Design and development of Clinical Decision Support System (CDSS) could be an appropriate approach for eliminating the existing difficulties of diagnosing Alzheimer's disease. Materials and Methods: This study reviews the current problems in the diagnosis of Alzheimer's disease with an approach to the application of CDSS. The study reviewed the articles published from 1990 to 2016. The articles were identified by searching electronic databases such as PubMed, Google Scholar, Science Direct. Considering the relevance of articles with the objectives of the study, 29 papers were selected. According to the performed investigations, various reasons cause difficulty in Alzheimer's diagnosis. Results: The complexity of diagnostic process and  the similarity of Alzheimer's disease with other causes of dementia are the most important of them. The results of studies about the application of CDSSs on Alzheimer's disease diagnosis indicated that the implementation of these systems could help to eliminate the existing difficulties in the diagnosis of Alzheimer's disease. Conclusion: Developing CDSSs based on diagnostic guidelines could be regarded as one of the possible approaches towards early and accurate diagnosis of Alzheimer's disease. Applying of computer-interpretable guideline (CIG) models such as GLIF, PROforma, Asbru, and EON can help to design CDSS with the capability of minimizing the burden of diagnostic problems with Alzheimer's disease

Human-AI Collaboration in Healthcare: A Review and Research Agenda

Advances in Artificial Intelligence (AI) have led to the rise of human-AI collaboration. In healthcare, such collaboration could mitigate the shortage of qualified healthcare workers, assist overworked medical professionals, and improve the quality of healthcare. However, many challenges remain, such as investigating biases in clinical decision-making, the lack of trust in AI and adoption issues. While there is a growing number of studies on the topic, they are in disparate fields, and we lack a summary understanding of this research. To address this issue, this study conducts a literature review to examine prior research, identify gaps, and propose future research directions. Our findings indicate that there are limited studies about the evolving and interactive collaboration process in healthcare, the complementarity of humans and AI, the adoption and perception of AI, and the long-term impact on individuals and healthcare organizations. Additionally, more theory-driven research is needed to inform the design, implementation, and use of collaborative AI for healthcare and to realize its benefits

Application of Mobile Health Services to Support Patient Self-Management of Chronic Conditions

Background: Chronic conditions are the leading cause of ill-health, disability and premature death, adding huge health and socioeconomic burden to the healthcare system. Although mobile health (mHealth) services have the potential to provide patients with a timely, ubiquitous, and cost-effective means to access healthcare services, to date, much remains to be revealed for their application in chronic condition management. Aim: This doctoral project aims to comprehensively understand the application of mHealth services to support patient self-management of chronic conditions. This aim is achieved through four objectives: (1) to synthesise research evidence about health outcomes of applying mHealth services to support patient self-management of chronic conditions and the essential components to achieve these outcomes, (2) to determine the mechanism for applying mHealth services to support patient self-management of chronic conditions, (3) to explore critical factors and how these factors influence patients\u27 intention to continuously use mHealth services, and (4) to apply the above findings to guide the design of a prototype mHealth service. Methods: To increase the generalisability of the findings, three chronic conditions that could benefit from mHealth services were purposively studied to address the research objectives within the feasibility of available study sites and resources at different stages of the project. First, two literature review studies were conducted to achieve Objective 1. One was a systematic review to investigate health outcomes of mHealth services to support patient self-management of one chronic condition, unhealthy alcohol use, and the essential components to achieve these outcomes. The other was a rapid review on using behavioural theory to guide the design of mHealth services that support patient self-management of another chronic condition, hypertension. Second, two field studies were conducted to achieve Objectives 2 and 3, respectively. One was an interview study that explored patients\u27 perceptions of a mHealth service to support their self-management of hypertension in China. The other was a questionnaire survey study conducted on the same site that explored critical factors influencing patients\u27 intention to continuously use the mHealth service. Third, a clinician-led, experience-based co-design approach was implemented to apply the above-mentioned learning experience to the development practice of a mHealth service that supports patient self-management of obesity before elective surgery in Australia, achieving Objective 4. Results: Literature reviews identify five structural components - context, theory, content, delivery mode, and implementation procedure - which are essential for mHealth services to achieve three health outcomes - behavioural, physiological, and cognitive outcomes. Inductive synthesis of the interview findings lead to a 6A framework that summarises the mechanisms for mHealth services: access, assessment, assistance, awareness, ability, and activation. Mobile health services provide patients with easy access to health assessment and healthcare assistance to increase their self-management awareness and ability, thereby activating their self-management behaviours. Questionnaire survey study finds that patients\u27 intention to continuously use mHealth services can be influenced by the information quality, system quality and service quality by influencing their perceived usefulness and satisfaction with the mHealth services. Guided by Social Cognitive Theory, the developed prototype mHealth service provide patients with functions of automatic push notifications, online resources, goal setting and monitoring, and interactive health-related exchanges that encourage their physical activity, healthy eating, psychological preparation, and a positive outlook for elective surgery. The patients\u27 requirements in two focus group discussions enabled the research team to improve the mHealth service design. Conclusion: Mobile health services guided by behavioural theories can provide patients with easy access to health assessment and healthcare assistance to increase their self-management awareness and ability, thereby activating their self-management behaviours. The effort for designing mHealth services needs to be placed on crafting content (to improve information quality), developing useful functions and selecting a proper delivery mode (to improve system quality), and establishing effective implementation procedures (to improve service quality). These will ensure patients\u27 perceived usefulness and satisfaction with mHealth services, increase their intention to continuously use such services, thus supporting long-term patient self-management of chronic conditions. As demonstrated by the design case, the findings of this PhD project can be generalised to guide the design of other mHealth services that aim to support patient self-management of chronic conditions

Estudo de caso : EduAVC : metodologia de concepção e avaliação de aplicativo mHealth

Tese (Doutorado) — Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências Da Saúde, 2022.O AVE - Acidente Vascular Encefálico, ocorre quando um vaso sanguíneo no cérebro é rompido ou bloqueado, interrompendo o fluxo sanguíneo e o oxigênio cerebral, sendo a 2ª principal causa de morte no mundo. Em virtude da popularização e acessibilidade dos celulares no Brasil, sugerimos que é possível desenvolver aplicativos inovadores para educação em AVE. O objetivo desse estudo, foi elaborar uma metodologia de concepção e avaliação de aplicativo, identificando e apresentando as percepções sobre aprendizado e uso do app EduAVC. Sobre a metodologia, trata-se de uma pesquisa de natureza aplicada, de abordagem qualitativa, com objetivo descritivo conforme orientam os autores Maria Cecília de Souza Minayo e John W. Creswell, em que optamos pela modalidade estudo de caso, assim como orienta Robert Yin. Consistiu no desenvolvimento do aplicativo EduAVC para sistemas Android, em língua portuguesa, para as lojas Google Play. O app possuí informações cientificas, vídeos animados e ilustrações sobre a doença, sendo uma tecnologia para aplicativo do tipo mHealth. A partir das referências e inspirações dos instrumentos MAUQ, PSSUQ e SUS, criamos um instrumento personalizado, objetivando coletar as percepções dos participantes da pesquisa, em relação aos 37 itens, em 4 seções, que visavam mensurar o aprendizado, facilidade de uso, organização das informações e utilidade do aplicativo, sendo uma pesquisa aprovada pelo comitê de Ética em Pesquisa (CEP) em Ciências da Saúde, da Universidade de Brasília, com CAAE - Certificado de Apresentação de Apreciação Ética número: 40507820.4.0000.0030. Nos resultados, observamos a predominância de usuários “Muito satisfeitos” e “Satisfeitos” com o app EduAVC, e percepções que indicaram uma maioria de usuários que possuem pós graduação, tendo presenciado um AVE na família. Nas conclusões, indicamos que o aplicativo registrou aceitabilidade de uso pelos participantes e alguma eficácia na educação sobre a doença, podendo ser uma tecnologia adequada para o aprendizado e autocuidado em AVE no Brasil, e em países emergentes.Coordenação de Aperfeiçoamento do Pessoal de Ensino Superior (CAPES).Stroke occurs when a blood vessel in the brain is ruptured or blocked, interrupting blood flow and cerebral oxygen, being the 2nd leading cause of death in the world. Due to the popularization and accessibility of cell phones in Brazil, we suggest that it is possible to develop innovative applications for stroke education. The objective of this study was to develop a methodology for app design and evaluation, identifying and presenting perceptions about learning and using the EduAVC app. Regarding the methodology, this is an applied research, with a qualitative approach, with a descriptive objective as guided by the authors Maria Cecília de Souza Minayo and John W. Creswell, in which we opted for the case study modality, as guided by Robert Yin. It consisted in the development of the EduAVC application for Android systems, in Portuguese, for Google Play stores. The app has scientific information, animated videos and illustrations about the disease, being a technology for an mHealth application. From the references and inspirations of the MAUQ, PSSUQ and SUS instruments, we created a personalized instrument to collect the perceptions of the research participants, in relation to the 37 items, in 4 sections, which measured learning, ease of use, organization of information and usefulness of the application, being a research approved by the Research Ethics Committee in Health Sciences, University of Brasília, with Certificate of Presentation of Ethical Appreciation number: 40507820.4.0000.0030. In the results, we observed the predominance of “Very satisfied” and “Satisfied” users with the EduAVC app, and perceptions that indicated a majority of users who have postgraduate degrees, having witnessed a stroke in the family. In the conclusions, we indicate that the application registered acceptability of use by the participants and effectiveness in education about the disease, being able to be an appropriate technology for learning and self-care in stroke in Brazil, and in emerging countries

Ontology driven clinical decision support for early diagnostic recommendations

Diagnostic error is a significant problem in medicine and a major cause of concern for patients and clinicians and is associated with moderate to severe harm to patients. Diagnostic errors are a primary cause of clinical negligence and can result in malpractice claims. Cognitive errors caused by biases such as premature closure and confirmation bias have been identified as major cause of diagnostic error. Researchers have identified several strategies to reduce diagnostic error arising from cognitive factors. This includes considering alternatives, reducing reliance on memory, providing access to clear and well-organized information. Clinical Decision Support Systems (CDSSs) have been shown to reduce diagnostic errors. Clinical guidelines improve consistency of care and can potentially improve healthcare efficiency. They can alert clinicians to diagnostic tests and procedures that have the greatest evidence and provide the greatest benefit. Clinical guidelines can be used to streamline clinical decision making and provide the knowledge base for guideline based CDSSs and clinical alert systems. Clinical guidelines can potentially improve diagnostic decision making by improving information gathering. Argumentation is an emerging area for dealing with unstructured evidence in domains such as healthcare that are characterized by uncertainty. The knowledge needed to support decision making is expressed in the form of arguments. Argumentation has certain advantages over other decision support reasoning methods. This includes the ability to function with incomplete information, the ability to capture domain knowledge in an easy manner, using non-monotonic logic to support defeasible reasoning and providing recommendations in a manner that can be easily explained to clinicians. Argumentation is therefore a suitable method for generating early diagnostic recommendations. Argumentation-based CDSSs have been developed in a wide variety of clinical domains. However, the impact of an argumentation-based diagnostic Clinical Decision Support System (CDSS) has not been evaluated yet. The first part of this thesis evaluates the impact of guideline recommendations and an argumentation-based diagnostic CDSS on clinician information gathering and diagnostic decision making. In addition, the impact of guideline recommendations on management decision making was evaluated. The study found that argumentation is a viable method for generating diagnostic recommendations that can potentially help reduce diagnostic error. The study showed that guideline recommendations do have a positive impact on information gathering of optometrists and can potentially help optometrists in asking the right questions and performing tests as per current standards of care. Guideline recommendations were found to have a positive impact on management decision making. The CDSS is dependent on quality of data that is entered into the system. Faulty interpretation of data can lead the clinician to enter wrong data and cause the CDSS to provide wrong recommendations. Current generation argumentation-based CDSSs and other diagnostic decision support systems have problems with semantic interoperability that prevents them from using data from the web. The clinician and CDSS is limited to information collected during a clinical encounter and cannot access information on the web that could be relevant to a patient. This is due to the distributed nature of medical information and lack of semantic interoperability between healthcare systems. Current argumentation-based decision support applications require specialized tools for modelling and execution and this prevents widespread use and adoption of these tools especially when these tools require additional training and licensing arrangements. Semantic web and linked data technologies have been developed to overcome problems with semantic interoperability on the web. Ontology-based diagnostic CDSS applications have been developed using semantic web technology to overcome problems with semantic interoperability of healthcare data in decision support applications. However, these models have problems with expressiveness, requiring specialized software and algorithms for generating diagnostic recommendations. The second part of this thesis describes the development of an argumentation-based ontology driven diagnostic model and CDSS that can execute this model to generate ranked diagnostic recommendations. This novel model called the Disease-Symptom Model combines strengths of argumentation with strengths of semantic web technology. The model allows the domain expert to model arguments favouring and negating a diagnosis using OWL/RDF language. The model uses a simple weighting scheme that represents the degree of support of each argument within the model. The model uses SPARQL to sum weights and produce a ranked diagnostic recommendation. The model can provide justifications for each recommendation in a manner that clinicians can easily understand. CDSS prototypes that can execute this ontology model to generate diagnostic recommendations were developed. The decision support prototypes demonstrated the ability to use a wide variety of data and access remote data sources using linked data technologies to generate recommendations. The thesis was able to demonstrate the development of an argumentation-based ontology driven diagnostic decision support model and decision support system that can integrate information from a variety of sources to generate diagnostic recommendations. This decision support application was developed without the use of specialized software and tools for modelling and execution, while using a simple modelling method. The third part of this thesis details evaluation of the Disease-Symptom model across all stages of a clinical encounter by comparing the performance of the model with clinicians. The evaluation showed that the Disease-Symptom Model can provide a ranked diagnostic recommendation in early stages of the clinical encounter that is comparable to clinicians. The diagnostic performance can be improved in the early stages using linked data technologies to incorporate more information into the decision making. With limited information, depending on the type of case, the performance of the Disease-Symptom Model will vary. As more information is collected during the clinical encounter the decision support application can provide recommendations that is comparable to clinicians recruited for the study. The evaluation showed that even with a simple weighting and summation method used in the Disease- Symptom Model the diagnostic ranking was comparable to dentists. With limited information in the early stages of the clinical encounter the Disease-Symptom Model was able to provide an accurately ranked diagnostic recommendation validating the model and methods used in this thesis

Prediction and Monitoring of Progression of Alzheimer’s Disease : Multivariable approaches for decision support

Alzheimerin tauti, yksi yleisimmistä muistisairauksista, on hitaasti etenevä aivoja rappeuttava tauti, jolle ei ole vielä parantavaa hoitoa. Tietyt lääkkeet ja elämäntapainterventiot voivat kuitenkin hidastaa taudin etenemistä ja lievittää sen oireita, mikä parantaa potilaiden elämänlaatua ja terveydenhuollon kustannusvaikuttavuutta. Alzheimerin taudin varhainen diagnostiikka on erittäin tärkeää, koska erilaiset interventiot pitäisi aloittaa jo taudin varhaisessa vaiheessa, jotta niillä saataisiin aikaan paras mahdollinen vaikutus. Taudin varhainen diagnostiikka on kuitenkin haastavaa, koska muutokset aivoissa alkavat vuosia tai vuosikymmeniä ennen ensimmäisten oireiden ilmaantumista. Lisäksi viime vuosien tutkimus on tuottanut tietoa suuresta määrästä erilaisia testejä ja biomarkkereita, jotka voivat vaikuttaa taudin diagnoosiin ja prognoosiin. Tiedon suuri määrä saattaa aiheuttaa informaatioähkyä kliinikoille vaikeuttaen heidän päätöksentekoaan. Datalähtöiset analytiikka- ja visualisointimenetelmät voivat auttaa suuren ja heterogeenisen tietomäärän tulkinnassa ja hyödyntämisessä. Ne voivat siten tukea kliinikkoa hänen päätöksenteossaan. Lisäksi nämä menetelmät voivat auttaa tunnistamaan sopivia potilaita kliinisiin lääketutkimuksiin, joiden tavoitteena on kehittää Alzheimerin taudin etenemistä hidastavia lääkkeitä. Tämän väitöskirjan tavoitteena oli kehittää datalähtöisiä menetelmiä Alzheimerin taudin etenemisen ennustamiseen ja seurantaan taudin eri vaiheisiin alkaen normaalista kognitiosta ja edeten kuolemaan. Mallien kehittämisessä hyödynnettiin kognitiivisten ja neuropsykologisten testien tuloksia, magneettikuvantamista (MRI), selkäydinnestenäytteitä, ja genetiikkaa (apolipoproteiini E). Väitöskirja koostuu neljästä alkuperäisestä tutkimuksesta, jotka on julkaistu kansainvälisissä tieteellisissä lehdissä. Ensimmäinen osatutkimus keskittyi Alzheimerin taudin varhaiseen vaiheeseen. Tutkimuksessa käytettiin ohjattua koneoppimisen menetelmää Disease State Index (DSI, taudin tilan indeksi) ennustamaan, kenellä subjektiivisesti koettu kognition heikkeneminen etenee taudin vakavampaan vaiheeseen eli lievään kognition heikentymiseen (mild cognitive impairment, MCI) tai dementiaan. Tutkimuksen aineisto koostui 647 henkilöstä kolmesta eurooppalaisesta muisti- klinikkakohortista. Kun yhdistettiin useita eri muuttujia DSI-menetelmällä, ROC- käyrän (engl. Receiver Operating Characteristic curve) alle jäävä pinta-ala (AUC) oli 0.81 ja tasapainotettu tarkkuus oli 74%. Negatiivinen ennustearvo oli korkea (93%) ja positiivinen ennustearvo oli matala (38%). Kun DSI-malli validoitiin erillisellä testikohortilla, mallin AUC huononi 11%. Lisäanalyysit osoittivat, että useat erot kohorttien välillä voivat selittää suorituskyvyn alenemista. Toinen osatutkimus keskittyi taudin myöhäisempään vaiheeseen. DSI-menetelmällä analysoitiin pitkittäistä dataa, joka koostui 273 henkilön MCI-kohortista. Kohortti hankittiin Alzheimer’s Disease and Neuroimaging (ADNI 1) tietokannasta. DSI-arvojen muutokset ajan kuluessa olivat erilaiset niillä, joiden tauti eteni Alzheimerin taudin dementiaksi, ja niillä, joilla tauti pysyi MCI-vaiheessa. Lisäksi huomattiin, että stabiilina pysynyt MCI-ryhmä koostui kahdesta aliryhmästä: ensimmäisessä ryhmässä DSI-arvot pysyivät vakaina ja toisessa ryhmässä DSI-arvot kohosivat. Tämä indikoi, että toisessa ryhmässä tauti saattaa edetä dementiaksi tulevaisuudessa. Näiden analyysien lisäksi DSI:in oleellisesti liittyvä Disease State Fingerprint (DSF, taudin tilan sormenjälki) -visualisointimenetelmä laajennettiin pitkittäiselle datalle. Kolmas osatutkimus ennusti hippokampuksen surkastumista 24 kuukauden ai- kana lähtötilanteen mittausten perusteella. Tutkimuskohortti koostui henkilöistä, joilla oli normaali kognitio, MCI tai Alzheimerin taudin dementia, ja se hankittiin ADNI 1 (n=530) ja Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing (AIBL, n=176) tutkimuksista. Useita eri datatyyppejä sisältävät mallit ennustivat hippokampuksen surkastumista tarkemmin kuin pelkistä MRI-muuttujista koostuvat mallit. Kuitenkin molemmat mallit aliarvioivat todellista surkastumista erityisesti suuremmilla surkastumisnopeuksilla, aliarviointi oli suurempaa pelkästään MRI-muuttujiin perustuvilla malleilla. Kun ennustettiin kaksiluokkaista vastemuuttujaa, eli nopea vs. hidas surkastuminen, mallien tarkkuus oli 79-87%. MRI-mallien suorituskyky oli hyvä, kun testauksessa käytettiin erillistä AIBL-aineistoa. Viimeinen osatutkimus keskittyi Alzheimerin taudin viimeisimpiin vaiheisiin. Siinä tutkittiin, mitkä tautiin liittyvät tekijät ovat yhteydessä kuolleisuuteen potilailla, joilla oli Alzheimerin taudin dementia. Aineisto koostui 616 henkilöstä Amsterdam Dementia Cohort -aineistosta. Iällä ja sukupuolella vakioidun Coxin suhteellisen vaaran mallin mukaan vanhempi ikä, miessukupuoli, huonommat pisteet kognitiivisessa toimintakyvyssä, ja aivojen kuoriosien ja mediaalisen ohimolohkon surkastuminen olivat yhteydessä kuolleisuuteen. Optimaalinen muuttujien yhdistelmä sisälsi iän, sukupuolen, tulokset kahdesta kognitiivisesta testistä (digit span backward, Trail Ma- king Test A), mediaalisen ohimolohkon surkastumisen ja selkäydinnestenäytteestä mitatun kohdasta 181 (treoniini) fosforyloidun tau-proteiinin määrän. Yhteenvetona todetaan, että datalähtöisillä menetelmillä voidaan ennustaa ja seu- rata Alzheimerin taudin etenemistä varhaisesta vaiheesta myöhäiseen vaiheeseen. Yhdistämällä useita eri datatyyppejä saadaan parempia tuloksia kuin käyttämällä vain yhtä datatyyppiä. Tulokset korostavat myös, että datalähtöiset menetelmät on tärkeä arvioida erillisellä aineistolla, jota ei ole käytetty menetelmien kehittämiseen. Lisäksi näiden menetelmien käyttöönotto eri ympäristöissä tai maissa saattaa vaatia potilaan tutkimusmenetelmien ja diagnoosikriteereiden harmonisointia.Alzheimer’s disease (AD), the most common form of dementia, is a slowly progressing neurodegenerative disease, which cannot be cured yet. However, certain medications and lifestyle interventions can delay progression of the disease and its symptoms, thereby positively influencing both quality of life of patients as well as cost- effectiveness of healthcare. Early diagnosis of AD is important because such interventions should be started already at an early phase of the disease to have the best effect. However, early diagnosis is challenging because pathological changes in the brain occur years before the clinical symptoms become visible. In addition, the re- search during the past years has produced information from a large number of different tests and biomarkers that can potentially contribute to diagnosis and prognosis of AD. This excessive amount of data can cause information overload for clinicians, thus hampering the clinicians’ decision making. Data-driven analysis and visualization methods may help with interpretation and utilization of large amounts of heterogeneous patient data and support the clinicians’ decision-making process. Furthermore, the methods may aid in identifying suitable patients for clinical drug trials. The aim of the work described in this thesis was to develop and validate data- driven methods for predicting and monitoring progression of Alzheimer’s disease at the different phases of the disease spectrum, starting from normal cognition and ending to death, using data from neuropsychological and cognitive tests, magnetic resonance imaging (MRI), cerebrospinal fluid samples (CSF), comorbidities, and genetics (apolipoprotein E). The thesis consists of four original studies published as international journal articles. The first study focused on the early phase of AD. A supervised machine learning method called Disease State Index (DSI) was utilized to predict who of the individuals with subjective cognitive decline (SCD) will progress to a more severe condition, i.e., mild cognitive impairment (MCI) or dementia. The study population included 647 subjects from three different memory clinic-based cohorts in Europe. When all data modalities were combined, the area under the receiver operating characteristic curve (AUC) was 0.81 and balanced accuracy was 74%. Negative predictive value was high (93%), whereas positive predictive value was low (38%). Performance of the DSI method in terms of AUC decreased by 11% when validated with an in- dependent test set. Additional analyses suggested that several differences between the cohorts may explain the decrease in the performance. The second study focused on a more advanced disease stage. The DSI method was applied to longitudinal data collected from an MCI cohort of 273 subjects obtained from the Alzheimer’s Disease and Neuroimaging (ADNI 1) study. Longitudinal profiles of the DSI values differed between the subjects progressing to dementia due to AD and subjects remaining as MCI. In addition, two subgroups were found in the group remaining as MCI: one group with stable DSI values over time and another group with increasing DSI values, suggesting the latter group may progress to dementia due to AD in the future. This study also extended the Disease State Fingerprint (DSF) data visualization method for longitudinal data. The third study predicted hippocampal atrophy over 24 months using baseline data and penalized linear regression. The cohorts consisted of subjects with normal cognition, MCI, and dementia due to AD and were obtained from the ADNI 1 (n=530) and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing (AIBL, n=176) studies. The models including different data modalities per- formed better than the models including only MRI features. However, both models underestimated the real change at higher atrophy rate levels, the MRI-only models showing a greater underestimation. When predicting dichotomized outcome, i.e., fast vs. slow atrophy, the models obtained a prediction accuracy of 79-87%. The MRI-only models performed well when evaluated with an independent validation cohort (AIBL). The last study focused on the latest phase of AD by identifying which disease- related determinants are associated with mortality in patients with dementia due to AD. The cohort included 616 patients from the Amsterdam Dementia Cohort. Age- and sex-adjusted Cox proportional hazards models revealed that older age, male sex, and worse scores on cognitive functioning, as well as more severe medial temporal lobe and global cortical atrophy were associated with an increased risk of mortality. An optimal combination of variables comprised age, sex, performance on digit span backward test and Trail Making Test A, medial temporal lobe atrophy, and tau phosphorylated at threonine 181 in CSF. In conclusion, data-driven methods can be used for predicting and monitoring progression of AD from the mildest stages to the more advanced stages. Combining information from several data modalities provides better prediction performance than individual data modalities alone. The results also highlight the importance of the validation of the methods with independent validation cohorts. Introduction of these methods to different environments and countries may require harmonization of patient examination methods and diagnostic criteria

Front-Line Physicians' Satisfaction with Information Systems in Hospitals

Day-to-day operations management in hospital units is difficult due to continuously varying situations, several actors involved and a vast number of information systems in use. The aim of this study was to describe front-line physicians' satisfaction with existing information systems needed to support the day-to-day operations management in hospitals. A cross-sectional survey was used and data chosen with stratified random sampling were collected in nine hospitals. Data were analyzed with descriptive and inferential statistical methods. The response rate was 65 % (n = 111). The physicians reported that information systems support their decision making to some extent, but they do not improve access to information nor are they tailored for physicians. The respondents also reported that they need to use several information systems to support decision making and that they would prefer one information system to access important information. Improved information access would better support physicians' decision making and has the potential to improve the quality of decisions and speed up the decision making process.Peer reviewe

Disease state index and disease state fingerprint: supervised learning applied to clinical decision support in Alzheimer’s disease

Due to scientific and technological advancements, investigations in modern medicine are producing more measurement data than ever before. Since a large amount of information exists, and it is also being produced at ever-increasing rates, no single person can digest all current knowledge of diseases. Data collected from large patient cohorts may contain valuable knowledge of diseases, which could be useful to clinicians when making diagnoses or choosing treatments. Making use of the large volumes of data in clinical decision-making requires ancillary help from information technologies, but such systems have not yet become widely available. This thesis addresses the challenge by proposing a computer-based decision support method that is suited to clinical use.This thesis presents the Disease State Index (DSI), a supervised machine learning method intended for the analysis of patient data. The DSI comprehensively compares patient data with previously diagnosed cases with or without a disease. Based on this comparison, the method provides an estimate of the state of disease progression in the patient. Interpreting the DSI is made possible by its visual counterpart, the Disease State Fingerprint (DSF), which allows domain experts to gain a comprehensive view of patient data and the state of the disease at a quick glance. In the design and development of these methods, both performance and applicability in clinical use were taken into account equally.Alzheimer’s disease (AD) is a slowly progressing neurodegenerative disease and one of the largest social and economic burdens in the world today, and it will continue to be so in the future. Studies with large patient cohorts have significantly improved our knowledge of AD during the last decade. This information should be made extensively available at memory clinics to maximize the benefits for diagnostics and treatment of the disease. The DSI and DSF methods proposed in this thesis were studied in the early diagnosis of AD and as a measure of disease progression in six original publications. The methods themselves and their implementation within a clinical decision support system, the PredictAD tool, were quantitatively evaluated with regard to their performance and potential benefits in clinical use. The results show that the methods and clinical decision support tool based on these methods can be used to follow disease progression objectively and provide earlier diagnoses of AD. These, in turn, could improve treatment efficacy due to earlier interventions and make drug trials more efficient by allowing better patient selection