Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.

Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.

Abstract Background Cardiovascular disease (CVD) has an enormous impact on the lives and health of New Zealanders. There is substantial epidemiological evidence that supports identifying people at high risk of CVD and treating them with lifestyle and drug-based interventions. If fully implemented, this targeted high risk approach could reduce future CVD events by over 50%. Recent studies have shown that a formal CVD risk assessment to the systematically identify high risk patients is rarely done in routine New Zealand general practice and audits of CVD risk management have shown large evidence-practice gaps. The CVD risk prediction score recommended by New Zealand guidelines for identifying high CVD risk patients was derived from the US Framingham Heart Study using data collected between the 1960s and 1980s. This score has only modest prediction accuracy and there are particular concerns about it’s validity for New Zealand sub-populations such as high risk ethnic groups or people with diabetes. Aims The overall aims of this thesis were to investigate the potential of a computerised decision support system (CDSS) to improve the assessment and management of CVD risk in New Zealand general practice while simultaneously developing a sustainable cohort study that could be used for validating and improving CVD risk prediction scores and related research. Methods An environmental scan of the New Zealand health care setting’s readiness to support a CDSS was conducted .The epidemiological evidence was reviewed to assess the effect of decision support systems on the quality of health care and the types and functionality of systems most likely to be successful. This was followed by a focused systematic review of randomised trials evaluating the impact of CDSS on CVD risk assessment and management practices and patient CVD outcomes in primary care. A web-based CDSS (PREDICT) was collaboratively developed. This rules-based provider-initiated system with audit and feedback and referral functionalities was fully integrated with general practice electronic medical records in a number of primary health organisations (PHOs). The evidence-based content was derived from national CVD and diabetes guidelines. When clinicians used PREDICT at the time of a consultation, treatment recommendations tailored to the patient’s CVD and diabetes risk profile were delivered to support decision-making within seconds. Simultaneously, the patient’s CVD risk profiles were securely stored on a central server. With PHO permission, anonymised patient data were linked via encrypted patient National Health Index numbers to national death and hospitalisation data. Three analytical studies using these data are described in this thesis. The first evaluated changes in GP risk assessment practice following implementation of PREDICT; the second investigated patterns of use of the CDSS by GPs and practice nurses; and the third describes the emerging PREDICT cohort and a preliminary validation of risk prediction scores. Results Given the rapid development of organised primary care since the 1990’s, the high degree of general practice computerisation and the New Zealand policy (health, informatics, privacy) environment, the introduction of a CDSS into the primary care setting was deemed feasible. The evidence for the impact of CDSS in general has been moderately favourable in terms of improving desired practice. Of the randomised trials of CDSS for assessing or managing CVD risk, about two-thirds reported improvements in provider processes and two-fifths reported some improvements in intermediate patient outcomes. No adverse effects were reported. Since 2002, the PREDICT CDSS has been implemented progressively in PHOs within Northland and the three Auckland regional District Health Board catchments, covering a population of 1.5 million. A before-after audit conducted in three large PHOs showed that CVD risk documentation increased four fold after the implementation of PREDICT. To date, the PREDICT dataset includes around 63,000 risk assessments conducted on a cohort of over 48,000 people by over 1000 general practitioners and practice nurses. This cohort has been followed from baseline for a median of 2.12 years. During that time 2655 people died or were hospitalised with a CVD event. Analyses showed that the original Framingham risk score was reasonably well calibrated overall but underestimated risk in high risk ethnic groups. Discrimination was only modest (AUC 0.701). An adjusted Framingham score, recommended by the New Zealand Guideline Group (NZGG) overestimated 5-year event rates by around 4-7%, in effect lowering the threshold for drug therapy to about 10% 5-year predicted CVD risk. The NZGG adjusted score (AUC 0.676) was less discriminating than the Framingham score and over-adjusted for high risk ethnic groups. For the cohort aged 30-74 years, the NZGG-recommended CVD risk management strategy identified almost half of the population as eligible for lifestyle management +/- drug therapy and this group generated 82% of all CVD events. In contrast the original Framingham score classified less than one-third of the cohort as eligible for individualised management and this group generated 71% of the events that occurred during follow-up. Implications This research project has demonstrated that a CDSS tool can be successfully implemented on a large scale in New Zealand general practice. It has assisted practitioners to improve the assessment and management of CVD at the time of patient consultation. Simultaneously, PREDICT has cost-effectively generated one of the largest cohorts of Māori and non-Māori ever assembled in New Zealand. As the cohort grows, new CVD risk prediction scores will be able to be developed for many New Zealand sub-populations. It will also provide clinicians and policy makers with the information needed to determine the trade-offs between the resources required to manage increasing proportions of the populations and the likely impact of management on preventing CVD events.

Σκοπός της παρούσας διδακτορικής διατριβής είναι η ανάπτυξη ενός ολοκληρωμένου συστήματος υποστήριξης της διάγνωσης (Decision Support System - DSS) με χρήση μεθόδων εξόρυξης δεδομένων για την ταξινόμηση επιχρισμάτων βιοψίας με λεπτή βελόνα (Fine Needle Aspiration - FNA). Δύο κατηγορίες επιλέχθηκαν για τα δείγματα FNA: καλοήθεια και κακοήθεια. Το σύστημα αυτό αποτελείται από τις ακόλουθες βαθμίδες: 1) συλλογής δεδομένων, 2) επιλογής δεδομένων, 3) εύρεσης κατάλληλων χαρακτηριστικών, 4) εφαρμογής ταξινόμησης με χρήση μεθόδων εξόρυξης δεδομένων. Επίσης, βασικός στόχος της παρούσας διδακτορικής διατριβής ήταν η βελτίωση της ορθής ταξινόμησης των ύποπτων επιχρισμάτων (suspicious), για τα οποία είναι γνωστή η αδυναμία της μεθόδου FNA να τα ταξινομήσει. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Για περιπτώσεις οι οποίες χαρακτηρίστηκαν ως μη κακοήθεις από την FNA, και για τις οποίες δεν είχαμε ιστολογικές επιβεβαιώσεις, το δείγμα προέκυψε από την συνεκτίμηση και άλλων κλινικών, εργαστηριακών και απεικονιστικών εξετάσεων. Στα πλαίσια της παρούσας διδακτορικής διατριβής συλλέχθηκαν εξετάσεις FNA θυρεοειδούς από το Εργαστήριο Παθολογοανατομίας του Α’ Τμήματος Παθολογίας της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών. Δεδομένου ότι το εν λόγω εργαστήριο λειτουργεί και σαν κέντρο αναφοράς, σημαντικός αριθμός των δειγμάτων εστάλησαν εκεί και από άλλα Εργαστήρια Παθολογοανατομίας για επανέλεγχο. Το αρχειακό υλικό ήταν πολύ καλά ταξινομημένο σε χρονολογική σειρά αλλά ήταν σε έντυπη μορφή. Αρχικά πραγματοποιήθηκε η ανάλυση απαιτήσεων για τη δομή και το σχεδιασμό της βάσης δεδομένων. Με βάση τα στοιχεία από την τεκμηριωμένη διάγνωση σχεδιάστηκε και αναπτύχθηκε προηγμένο σύστημα για την κωδικοποίηση και αρχικοποίηση των δεδομένων. Με τη βοήθεια του σχεδιασμού και ανάλυσης απαιτήσεων αναπτύχθηκε και υλοποιήθηκε η βάση δεδομένων στην οποία αποθηκεύτηκαν τα δεδομένα προς επεξεργασία. Παράλληλα, με το σχεδιασμό της βάσης έγινε και η προεργασία για το σχεδιασμό και την ανάλυση απαιτήσεων του γραφικού περιβάλλοντος εισαγωγής στοιχείων. Λαμβάνοντας υπόψη ότι το σύστημα θα μπορούσε να χρησιμοποιηθεί και πέρα από τα πλαίσια της παρούσας διδακτορικής διατριβής λήφθηκε μέριμνα ώστε να παρέχεται ένα φιλικό και ευέλικτο προς το χρήστη περιβάλλον. Σύμφωνα με τη μεθοδολογία προσέγγισης η οποία ακολουθήθηκε προηγήθηκε στατιστική ανάλυση των 9.102 συλλεχθέντων δειγμάτων FNA ως προς τα κυτταρολογικά χαρακτηριστικά τους και τις διαγνώσεις. Οι κυτταρολογικές διαγνώσεις των συγκεκριμένων δειγμάτων συσχετίστηκαν με τις ιστολογικές διαγνώσεις, στοχεύοντας στον υπολογισμό της πιθανής επίδρασης και συμβολής κάθε κυτταρολογικού χαρακτηριστικού σε μια ορθή ή ψευδή κυτταρολογική διάγνωση, έτσι ώστε να προσδιοριστούν οι πιθανές πηγές λανθασμένης διάγνωσης. Τα δείγματα τα οποία περιείχαν μόνο αίμα ή πολύ λίγα θυλακειώδη κύτταρα χωρίς κολλοειδές θεωρήθηκαν ανεπαρκή για τη διάγνωση. Οι βιοψίες εκτελέσθηκαν είτε στο Α’ τμήμα του Πανεπιστημίου Αθηνών (οι περισσότερες από τις περιπτώσεις με ψηλαφητούς όζους) είτε αλλού (κυρίως κάτω από την καθοδήγηση του κέντρου αναφοράς). Τα δείγματα επιστρωμένα σε πλακάκια, στάλθηκαν στο κέντρο αναφοράς από διάφορα νοσοκομεία, με διαφορετικά πρωτόκολλα σχετικά με τα κριτήρια εκτέλεσης βιοψίας FNA σε θυρεοειδή. Μετεγχειρητικές ιστολογικές επαληθεύσεις ήταν διαθέσιμες για 266 ασθενείς (κακοήθειες και μη). Το χαμηλό ποσοστό ιστολογικών επαληθεύσεων οφείλεται στην ετερογενή προέλευση των ασθενών και στην έλλειψη ολοκληρωμένης παρακολούθησης και επανελέγχου των ασθενών. Για την αξιολόγηση των δεδομένων χρησιμοποιήθηκαν περιγραφικά στατιστικά μεγέθη όπως, μέση τιμή, τυπική απόκλιση, ποσοστά, μέγιστο και ελάχιστο. Έγιναν επίσης και χ2 δοκιμές επιπέδου σημαντικότητας διαφόρων παραμέτρων για να ελεγχθεί η πιθανή συσχέτιση ή η ανεξαρτησία. Για τη συσχέτιση των κυτταρολογικών και των ιστολογικών διαγνώσεων και την αξιολόγηση των εργαστηριακών ευρημάτων, πέραν των περιγραφικών στατιστικών μεγεθών χρησιμοποιήθηκαν και υπολογισμοί της ευαισθησίας, της ειδικότητας, της συνολικής ακρίβειας, της αρνητικής και θετικής αξίας πρόβλεψης (negative and positive predictive value). Προκειμένου να καθοριστεί εάν μια κατηγορία ασθενειών συσχετίζεται ή όχι με συγκεκριμένες κυτταρολογικές παραμέτρους εφαρμόστηκε μέθοδος ελέγχου στατιστικής σημαντικότητας σε επίπεδο 5% (p < 0,05). Η διαδικασία ακολουθήθηκε για κάθε κατηγορία ασθενειών ή συνδυασμό τους και για κάθε παράμετρο των κυτταρολογικών και αρχιτεκτονικών στοιχείων της κυτταρολογικής διάγνωσης. Τα αποτελέσματα της στατιστικής ανάλυσης επέτρεψαν το διαχωρισμό των δεδομένων σε καλοήθη, κακοήθη, νεοπλασματικά, ύποπτα για κακοήθεια και οριακά με χαρακτηριστικά γνωρίσματα μεταξύ ενός καλοήθους και ενός νεοπλασματικού. Στην συνέχεια αναπτύχθηκε σύστημα υποστήριξης της διάγνωσης χρησιμοποιώντας εξειδικευμένες μεθόδους εξόρυξης δεδομένων. Το σύστημα αποτελείται από τέσσερις βαθμίδες. Η πρώτη βαθμίδα αυτού του συστήματος είναι το περιβάλλον Συλλογής Δεδομένων στην οποία τα δεδομένα αποθηκεύονται στη βάση δεδομένων. Η Δεύτερη Βαθμίδα αυτού του συστήματος αφορά στην Επιλογή Δεδομένων. Σύμφωνα με την καταγραφή των απαιτήσεων, την εισαγωγή και τη ψηφιοποίηση των στοιχείων, δημιουργήθηκαν 111 χαρακτηριστικά για κάθε ασθενή (record). Τα περισσότερα χαρακτηριστικά είχαν τιμές δυαδικού τύπου, αποτυπώνοντας την ύπαρξη ή μη του κάθε χαρακτηριστικού, ενώ κάποιες άλλες είχαν τιμές τύπων αριθμών ή αλφαριθμητικών χαρακτήρων. Από τα 111 χαρακτηριστικά επιλέχθηκαν 60 χαρακτηριστικά τα οποία περιγράφουν τη δομή των επιχρισμάτων ενώ δημιουργήθηκαν άλλα 7 χαρακτηριστικά τα οποία αφορούσαν στην ομαδοποίηση άλλων χαρακτηριστικών. Η Τρίτη Βαθμίδα του συστήματος αφορά στην εύρεση των Κατάλληλων Χαρακτηριστικών. Λόγω του αρχικά υψηλού αριθμού χαρακτηριστικών παραμέτρων (67 ανά περίπτωση), ήταν απαραίτητο να εξαλειφθούν οι χαρακτηριστικές παράμετροι που συσχετίζονταν γραμμικά ή δεν είχαν καμία διαγνωστική πληροφορία. H μέθοδος επιλογής χαρακτηριστικών εφαρμόστηκε πριν από την ταξινόμηση, με γνώμονα την ανεύρεση ενός υποσυνόλου των χαρακτηριστικών παραμέτρων που βελτιστοποιούν σε ακρίβεια τη διαδικασία ταξινόμησης. Εφαρμόστηκε η τεχνική επιπλέουσας πρόσθιας ακολουθιακά μεταβαλλόμενης επιλογής (SFFS). Ο αριθμός των δειγμάτων που χρησιμοποιήθηκαν είναι 2.036 (1.886 καλοήθειες και 150 κακοήθειες). Εξ αυτών, όλες οι κακοήθειες είναι ιστολογικά επιβεβαιωμένες. Επίσης, 140 καλοήθειες είναι ιστολογικά επιβεβαιωμένες με επάρκεια υλικού. Οι υπόλοιπες 1.726 καλοήθειες είναι επιβεβαιωμένες με συνεκτίμηση κλινικών, εργαστηριακών και απεικονιστικών ιατρικών εξετάσεων (υπέρηχοι κ.λπ.). Από τα 2.036 δείγματα, το 25% χρησιμοποιήθηκε για την επιλογή χαρακτηριστικών παραμέτρων, δηλαδή 37 περιπτώσεις κακοήθειας (Malignant) και 472 περιπτώσεις καλοήθειας (Non Malignant). Από την εφαρμογή της τεχνικής (SFFS) επιλέχθηκαν τελικά 12 χαρακτηριστικά ως βέλτιστα για την ταξινόμηση των δεδομένων FNA σε καλοήθη και κακοήθη. Η Τέταρτη βαθμίδα επεξεργασίας είναι η Εφαρμογής Ταξινόμησης με χρήση Μεθόδων Εξόρυξης Δεδομένων ή Ταξινομητής. Για το σκοπό αυτό, επιλέχθηκε να εφαρμοστεί μια πληθώρα αξιόπιστων, καλά επιβεβαιωμένων και σύγχρονων μεθόδων εξόρυξης δεδομένων. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Η ανεξάρτητη εφαρμογή τεσσάρων αξιόπιστων μεθόδων, Δέντρων Αποφάσεων (Decision Trees), Τεχνιτών Νευρωνικών Δικτύων (Artificial Neural Network), Μηχανών Στήριξης Διανυσμάτων (Support Vector Machine), και Κ - κοντινότερου γείτονα (k-NN), έδωσε αποτελέσματα συγκρίσιμα με αυτά της FNA μεθόδου. Περαιτέρω βελτίωση των αποτελεσμάτων επιτεύχθηκε με την εφαρμογή της μεθόδου πλειοψηφικού κανόνα (Majority Vote - CMV) συνδυάζοντας τα αποτελέσματα από την εφαρμογή των τριών καλύτερων αλγορίθμων, ήτοι των Νευρωνικών Δικτύων, Μηχανών Στήριξης Διανυσμάτων και Κ - κοντινότερου γείτονα. Η τροποποιημένη μέθοδος τεχνητών αυτοάνοσων συστημάτων (Artificial Immune Systems – AIS) χρησιμοποιήθηκε για πρώτη φορά στην ταξινόμηση και παρουσίασε ιδιαίτερα βελτιωμένα αποτελέσματα στην ταξινόμηση των επιχρισμάτων τα οποία χαρακτηρίζονται ύποπτα (suspicious) από τους ειδικούς και αποτελούν το αδύναμο σημείο της μεθόδου FNA. Αυτές οι περιπτώσεις υπόνοιας αποτελούν ένα πολύ δύσκολο κομμάτι για τη διάκριση μεταξύ των καλοηθειών και των κακοηθειών, ακόμα και για τους πλέον ειδικούς. Επειδή όλα τα περιστατικά που χαρακτηρίζονται από την βιοψία FNA ως υπόνοιες αντιμετωπίζονται κλινικά σαν κακοήθειες, η εφαρμογή των αλγοριθμικών μεθόδων βελτιώνει αισθητά τη διαχείριση αυτών των περιπτώσεων μειώνοντας τον αριθμό των άσκοπων χειρουργικών επεμβάσεων θυρεοειδεκτομών. / The Aim of present thesis is the development of an integrated system for supporting diagnosis (Decision Support System - DSS) using for categorizing FNA biopsy smears. Two categories were selected for the FNA smears: malignant and nonmalignant. The system is constituted by the following stages of 1) data collection, 2) data selection 3) choice of suitable clinical and cytological features, 4) application of data mining method for the categorization of FNA biopsy smears. Furthermore a fundamental objective of the doctoral thesis was the improvement of suspect smears (suspicious) categorization, for the latter FNA Biopsy has a known restriction. The system had been trained and checked in relation to the sample that histologic evaluation existed (ground truth). For smears that characterized as nonmalignant by FNA and histological data we’re not available, complementary clinical, laboratory and imaging evaluations took into account in order to create the sample. Τhe smears that were available in this thesis, were collected from FNA biopsies in Pathologoanatomy Laboratory, A’ Pathology Department, Medical School of Athens University. Given that the above referred laboratory is a reference center, an important number of FNA smears were sent to it from other laboratories for cross check. The examination files were sorted in chronological order, but there were in paper forms. The requirements for the formation and the design of database system were collected. Based on the material of the diagnosis an improved system was designed and developed for data initialization and coding. The database was developed based on the design and analysis of requirements; in this database data were stored for further investigation. Analysis of the graphical user interface design was performed in parallel to the database design. Taking into account that the system might be used after the completion of thesis, the graphical user interface was designed in order to be user friendly and flexible environment. According to the methodological approach that was followed, the various cytological characteristic of 9102 FNA smears aspired among 2000-2004 was analyzed statistically. The cytological reports cross correlated with histological diagnoses, aiming to calculate the effect or contribution of each cytological characteristic to a false or true cytological diagnosis and to find the possible sources of erroneous diagnosis. The smears that have blood or a few follicular cells without colloid were characterized as insufficient for further diagnosis. The aspiration was performed either in Α’ department of Athens University (most of the cases with palpable nodules) or elsewhere (mainly under guidance of the reference center). The acquired smears being send to the reference center from various hospitals with different protocols concerning criteria to perform a thyroid FNA. Histological reports were available for 266 patients. The small number of histological verifications was due to the heterogeneity and the lack of patients files. For evaluating of data, descriptive statistic values were used like mean, standard deviation, percentage, maximum and minimum. In addition to that χ2 tests of significance were performed in order to check possible correlation or independence. For correlating cytological and histological diagnosis and evaluating laboratory findings, apart from the descriptive statistic parameters also calculated sensitivity, specificity, total accuracy, negative predictive value and positive predictive value. Method of statistical significance in the level of 5% (p < 0,05) was applied in order to specify if a disease was correlated to a cytological parameter. Those checks were performed for each disease category in correlation to any cytological parameter. Statistical analysis divided the smears into nonmalignant, malignant, neoplasms, suspicious for malignancy and borderline. A diagnosis support system was implemented using data mining methods. The system is consisted of four stages. The First stage of the system is the Data Collection environment, which stores the data to the database. The Second stage of this system concerns the Selection of Data. User requirements concluded that 111 characteristics are needed to describe each patient (record). Most of them have binary values, presenting existence and not existence, other have alphanumeric and number values. Among them 60 were selected and 7 more are produced from grouping other characteristics. The final analysis reveals that 67 characteristics of the smears are capable for describing the structure of smears in general. The Third stage of system concerns the Selection of Best Characteristics. Due to the high number of attributes (67 per case), it was essential to eliminate the characteristics that are connected linearly or do not bring diagnostics information. The choice of characteristics applied before the classification, having the aim of discovering a subset of characteristics that optimizes the process of classification. The technique of Sequential Float Forward Search (SFFS) was applied. The number of patients that used was 2,036 (1886 non malignancies and 150 malignancies). Among them all malignancies were histologically confirmed. In addition to that 140 no malignancies were histologically confirmed in correlation to evaluation of clinics, laboratorial and medical image actions (ultrasounds etc.). Among 2.036 smears the 25% used for characteristics selection, 37 smears of Malignant and smears of Non Malignant. The Sequential Float Forward Search (SFFS) Technique, choose the best 12 elements that they reveal high performance to FNA data categorization. The Fourth stage is the Application of Classification using Data Mining Methods or in other words data mining method. For this aim a set of reliable, well confirmed but also modern methods applied. In addition to that the system was trained and was checked using the sample with histological verifications (ground truth). The independent application of four reliable methods, Decision Trees, Artificial Neural Network, Support Vector Machine, and k-NN, resulting to comparable outcomes concerning those of FNA. However, further improvement was achieved with the application of Majority (Majority Vote - CMV) using of previous results of three algorithms Artificial Neural Network, Support Vector Machine, and k-NN. The modified Artificial Immune System (AIS) was applied for first time. AIS presents particularly improved results for the categorization of smears, which are characterised “suspicious” by the experts and is a known weakness of FNA method. These cases constitute a very difficult part for the discrimination among non-malignant and malignant, even for a specialist. Since all these cases are faced clinically using FNA as malignancies, the application of an improved algorithmic method improves accordingly the management of these cases by decreasing the number of useless surgical thyroid operations.

The purpose of the study was to describe the effects of an EMR on patient management in selected HIV clinics in Johannesburg. A quantitative, descriptive, cross-sectional study was undertaken in four HIV clinics in Johannesburg. The subjects (N=44) were the healthcare workers selected by stratified random sampling. Consent was requested from each subject and from the clinics in Johannesburg. Data was collected using structured questionnaires. Median age of subjects was 36, 82% were female. 86% had tertiary qualifications. 55% were clinicians. 52% had 2-3 years work experience. 80% had computer experience, 86% had over one year EMR experience. 90% used the EMR daily, 93% preferred EMR to paper. 93% had EMR training, 17% used EMR to capture clinical data. 87% perceived EMR to have more benefits; most felt doctor-patient relationship was not interfered with. 89% were satisfied with the EMR’s overall performance. The effects of EMR benefit HIV patient management. / Health Studies / MA (Public Health)

Made available in DSpace on 2015-03-13T17:08:40Z (GMT). No. of bitstreams: 1 ClenubioFS.pdf: 1330843 bytes, checksum: f44365144a87dbadb85a95129360dfdc (MD5) Previous issue date: 2006-10-09 / The northern coast of Rio Grande do Norte State (RN) shows areas of Potiguar basin with high activity in petroleum industry. With the goal of avoiding and reducing the accident risks with oil it is necessary to understand the natural vulnerability, mapping natural resources and monitoring the oil spill. The use of computational tools for environmental monitoring makes possible better analyses and decisions in political management of environmental preservation. This work shows a methodology for monitoring of environment impacts, with purpose of avoiding and preserving the sensible areas in oil contact. That methodology consists in developing and embedding an integrated computational system. Such system is composed by a Spatial Decision Support System (SDSS). The SDSS shows a computational infrastructure composed by Web System of Geo-Environmental and Geographic Information - SWIGG , the System of Environmental Sensibility Maps for Oil Spill AutoMSA , and the Basic System of Environmental Hydrodynamic ( SisBAHIA a System of Modeling and Numerical Simulating SMNS). In a scenario of oil spill occurred coastwise of Rio Grande do Norte State s northern coast, the integration of such systems will give support to decision agents for managing of environmental impacts. Such support is supplied through a system of supporting to spatial decisions / O litoral norte do Estado do Rio Grande do Norte (RN) apresenta ?reas da bacia Potiguar com intensa atividade da ind?stria petrol?fera. Com a finalidade de prevenir e minimizar os riscos de acidentes com ?leo, faz-se necess?rio compreender a vulnerabilidade natural, mapear os recursos naturais e monitorar os derrames de ?leo. O uso de ferramentas computacionais para o monitoramento ambiental, possibilita uma melhor an?lise e tomada de decis?o no planejamento de pol?ticas de conserva??o ambiental. A presente disserta??o apresenta uma metodologia de trabalho para o monitoramento de impactos ambientais, com o prop?sito de avaliar e proteger as regi?es sens?veis ao contato do ?leo. A metodologia consiste em desenvolver e implantar um sistema integrado, constituindo um Sistema de Apoio ? Decis?o Espacial (SADE). O SADE apresenta uma infra-estrutura computacional composta pelo SWIGG (Sistema Web de Informa??es Geogr?ficas e Geoambientais), o AutoMSA (Automatizador de Mapas de Sensibilidade Ambiental para derramamentos de ?leo) e o Sistema BAse de HIdrodin?mica Ambiental (SisBAHIA um Sistema de Modelagem e Simula??o Num?rica - SMSN). Num cen?rio de derramamento de ?leo ocorrido pr?ximo ?s ?reas costeiras do litoral norte do Estado do RN a integra??o destes sistemas disponibilizar? aos agentes respons?veis pelo gerenciamento dos danos ambientais, um sistema de suporte a tomada de decis?o espacial

Project control is essential to ensure that the investment on a project is providing the intended benefits and is valuable to the customers. Previous methods offer project performance monitoring and forecasting tools, but they lack accuracy and the associated techniques omit the project financial risk (any unplanned event that has an impact on schedule and budget); the main factor of project failure. Poor project execution, and particularly failure to control and accurately forecast the project performance, may lead to increased costs, upset customers and eventually loss of market share. These gaps have been filled in this study by the development of novel models that use statistical analysis of the previous project performance, including risk evaluation techniques. The proposed models succeeded in providing remarkably improved forecasts in three project dimensions: duration, cost and resources. The robustness of the models has been verified by testing them on real projects. The results show superiority in terms of accuracy and easy application compared to any existing method, proving that the risk inclusion provides improvement compared to previous studies. The most important features of the models are: risk-based adjustment of the forecasted values, periodic and completion forecasts, statistical processing and holistic approach. The greatest advancements have been made in the cost forecast, for which the risk adjustment inclusion is examined for the first time. The resources (man-hours) forecast is another pioneer element of the proposed models. All the above provide a complete image of the project status and paint the picture of future performance. The models results are fed in a Decision Support System, which highlights the overperforming and underperforming areas of the project. This confirms the proposition that the model results can be used to initiate restorative action. The contribution of this study to the project management field is easy-to-use and accurate models, which include the financial risk and facilitate the project manager’s decisions and actions. Anticipation of the project performance, by considering the risk, can result to significant time and cost savings, crucial for project success.

Le transport fluvial de conteneurs constitue une activité économique importante qui suscite un intérêt grandissant de la part de scientifiques. Considéré comme durable et économique, le transport par barge a été identifié comme étant une alternative compétitive pour le transport de marchandises, en complément des modes traditionnels de transport, routier et ferroviaire. Néanmoins, les travaux de recherche en rapport avec la planification et le management du transport par barge, en particulier dans le contexte du transport intermodal, sont encore peu abondants. Le but de cette thèse est d’apporter une contribution dans ce domaine, par la proposition de modèles et de méthodes de planification et gestion avancées, dans le cadre d’un système d’aide à la décision pour le transport de conteneurs par barge développé pour accompagner les opérateurs de transport. La méthodologie proposée fait appel à des concepts et principes de gestion du revenu, des ressources et des services de transport pour la conception de plans de services réguliers avec horaires, au niveau tactique. Les opérateurs de transport peuvent ainsi offrir des plans de transport avec des services plus flexibles pour leurs clients, tout en assurant un meilleur niveau de fiabilité. Plus de demandes de transport pourront ainsi être satisfaites, avec globalement une plus grande satisfaction des chargeurs. Une originalité importante proposée par notre approche est l’utilisation de principes et techniques de gestion du revenu (segmentation du marché, classes tarifaires...) aussi bien au niveau opérationnel de la modélisation qu’au niveau tactique. Les problèmes d’optimisation sont formalisés sous forme de modèles de programmation linéaire mixte en nombres entiers (PLNE), implémentés et testés sous différentes configurations de réseaux de transport et différents scénarios de demandes, et ce pour chaque niveau de décision. Au niveau tactique, une nouvelle approche de résolution, combinant la recherche adaptative à voisinage large (ALNS) et la recherche taboue, est proposée pour résoudre des problèmes PLNE de grande taille. Une plateforme de simulation, qui intègre les niveaux tactique et opérationnel de prise de décision, est proposée pour la validation du système d’aide à la décision sous différentes configurations : différentes topologies du réseau physique, différents paramètres pour la gestion du revenu, différents degrés de précision caractérisant les prévisions de demande. Pour l’analyse des résultats numériques ainsi obtenus, plusieurs types d’indicateurs de performance sont proposés et utilisés. / Barge transportation is an important research topic that started to draw increasing scientific attention in the recent decade. Considered as sustainable, environment-friendly and economical, barge transportation has been identified as a competitive alternative for freight transportation, complementing the traditional road and rail modes. However, contributions related to barge transportation, especially in the context of intermodal transportation, are still scarce. The objective of this thesis is to contribute to fill this gap by proposing a reactive decision support system for freight intermodal barge transportation from the perspective of the carriers. The proposed system incorporates resource and revenue management concepts and principles to build the optimal set of scheduled services plans at the tactical level. Carriers may thus benefit from transportation plans offering increased flexibility and reliability. They could thus serve more demands and better satisfy customers. One novelty of the approach is the application of revenue management considerations (e.g., market segmentation and price differentiation) at both operational and tactical planning levels. The optimization problems are mathematically formalized and mixed integer linear programming (MILP) models are proposed, implemented and tested against various network settings and demand scenarios, for each decision level. At the tactical level, a new solution approach, combining adaptive large neighborhood search (ALNS) and Tabu search is designed to solve large scale MILP problems. An integrated simulation framework, including the tactical and the operational levels jointly, is proposed to validate the decision support system in different settings, in terms of physical network topology, revenue management parameters and accuracy degree of demand forecasts. To analyze the numerical results corresponding to the solutions of the optimization problems, several categories of performance indicators are proposed and used.

Der Einsatz numerischer Simulationen zur Bearbeitung klinischer Fragestellungen ist eine innovative Vorgehensweise. Im Rahmen der vorliegenden Arbeit wurde eine Methode zur Auswertung von Ergebnissen einer Finite-Elemente-Analyse zum Stentgraftverhalten konzipiert, implementiert und im Rahmen einer deutschlandweiten Benutzerstudie getestet. Für einen Vergleich unterschiedlicher Stentgraftkonfigurationen im Kontext mit dem patientenspezifischen Gefäß wurden Stentgraftbewertungsgrößen eingeführt. Hierzu gehören die Fixierungskraft und der Kontaktstatus zwischen Stentringen und Blutgefäßbestandteilen. Für eine Bereitstellung der Ergebnisgrößen im gefäßmedizinischen Arbeitsumfeld wurde eine graphische Mensch-Maschine-Schnittstelle entwickelt. Diese ermöglicht eine quantitative und qualitative Auswertung von Stentgraftbewertungsgrößen. Hierfür wurden Module zur automatisierten Auswertung von Fixierungskräften sowie zur 2D- und 3D- Ergebnisvisualisierung implementiert. Im Rahmen der Benutzerstudie wurde die Anwendung der entwickelten Methode für die Ermittlung des Einsatzpotenzials numerischer Simulationen zur Unterstützung der Stentgraftauswahl demonstriert. Im Ergebnis wurde als wesentliches Einsatzpotenzial die Festlegung eines Mindestmaßes an Überdimensionierung, die Optimierung der Schenkellänge sowie der Ver- gleich unterschiedlicher Stentgraftdesigns ermittelt. Weiterhin konnten grundlegende Anforderungen an ein System zur Generierung und Bewertung von Stentgraftkonfigurationen im klinischen Alltag definiert werden. Zu den wesentlichen Funktionen, die der Implanteur für einen Vergleich von Stentgrafts benötigt, zählen eine Übersichtskarte zu farbkodiertem Migrationsrisiko pro Stentgraft und Landungszone, die Visualisierung des Abdichtungszustandes der Stentkomponenten sowie die Darstellung von Stentgraft- und Gefäßdeformationen im 3D-Modell.

Text in English / In recent years, there have been tremendous advances in information technology, robotics, communication technology, nanotechnology, and artificial intelligence, resulting in the merging of physical, digital, and biological worlds that have come to be known as the "fourth industrial revolution”. In this context, the present study engages such technology in the green economy and to tackle the techno-economic environmental impact assessments challenges associated with floating solar system applications in the agricultural sector of South Africa. In response, this exploratory study aimed to examine the development of a Geographical Information System (GIS)-based support platform for Environmental Impact Assessment (EIA) and due-diligence analyses for future planned agricultural floating solar systems, especially with the goal to address the vast differences between the environmental impacts for land-based and water-based photovoltaic energy systems. A research gap was identified in the planning processes for implementing floating solar systems in South Africa’s agricultural sector. This inspired the development of a novel GIS-based modelling tool to assist with floating solar system type energy infrastructure planning in the renewable energy discourse. In this context, there are significant challenges and future research avenues for technical and environmental performance modelling in the new sustainable energy transformation. The present dissertation and geographical research ventured into the conceptualisation, designing and development of a software GIS-based decision support tool to assist environmental impact practitioners, project owners and landscape architects to perform environmental scoping and environmental due-diligence analysis for planned floating solar systems in the local agricultural sector. In terms of the aims and objectives of the research, this project aims at the design and development of a dedicated GIS toolset to determine the environmental feasibility around the use of floating solar systems in agricultural applications in South Africa. In this context, the research objectives of this study included the use of computational modelling and simulation techniques to theoretically determine the energy yield predictions and computing environmental impacts/offsets for future planned agricultural floating solar systems in South Africa. The toolset succeeded in determining these aspects in applications where floating solar systems would substitute Eskom grid power. The study succeeded in developing a digital GIS-based computer simulation model for floating solar systems capable of (a) predicting the anticipated energy yield, (b) calculating the environmental offsets achieved by substituting coal-fired generation by floating solar panels, (c) determining the environmental impact and land-use preservation benefits of any floating solar system, and (d) relating these metrics to water-energy-land-food (WELF) nexus parameters suitable for user project viability analysis and decision support. The research project has demonstrated how the proposed GIS toolset supports the body of geographical knowledge in the fields of Energy and Environmental Geography. The new toolset, called EIAcloudGIS, was developed to assist in solving challenges around energy and environmental sustainability analysis when planning new floating solar installations on farms in South Africa. Experiments conducted during the research showed how the geographical study in general, and the toolset in particular, succeeded in solving a real-world problem. Through the formulation and development of GIS-based computer simulation models embedded into GIS layers, this new tool practically supports the National Environmental Management Act (NEMA Act No. 107 of 1998), and in particular, associated EIA processes. The tool also simplifies and semi-automates certain aspects of environmental impact analysis processes for newly envisioned and planned floating solar installations in South Africa. / Geography / M.Sc. (Geography)