Επιχειρησιακή στρατηγική για ένα ηλεκτρονικό σύστημα κλινικής διάγνωσης γενετικών συνδρόμων
| dc.contributor.advisor | Πολλάλης, Ιωάννης | |
| dc.contributor.author | Ντούζγου, Σοφία | |
| dc.date.accessioned | 2017-07-21T08:03:13Z | |
| dc.date.available | 2017-07-21T08:03:13Z | |
| dc.date.issued | 2013 | |
| dc.identifier.uri | https://dione.lib.unipi.gr/xmlui/handle/unipi/9817 | |
| dc.description.abstract | Το 2007, το έργο DYSCERNE χρηματοδοτήθηκε από τον Εκτελεστικό Οργανισμό Δημόσιας Υγείας της Ευρωπαϊκής Ένωσης (EU DG Sanco), ως πιλοτικό πρόγραμμα που αποσκοπεί στη δημιουργία ενός δικτύου εμπειρογνωμοσύνης για τις σπάνιες παθήσεις με δυσμορφίες. Στο πλαίσιο του έργου DYSCERNE συστάθηκε ένα δυσμορφολογικό σύστημα διάγνωσης (DDS) με στόχο τη διευκόλυνση ιατρών από όλη την Ευρωπαϊκή Ένωση να υποβάλουν ηλεκτρονικά περιστατικά προς διάγνωση, μέσω της χρήσης μιάς ασφαλούς διασύνδεσης βασισμένης στο διαδίκτυο που φιλοξενείται σε καθορισμένα σημεία πρόσβασης (κόμβοι υποβολής), σε 26 διαφορετικές ευρωπαϊκές χώρες. Στη παρούσα εργασία περιγράφεται ο σχεδιασμός καθώς και τα αποτελέσματα της εν λόγω υπηρεσίας για 200 περιστατικά τα οποία υποβλήθηκαν στο σύστημα διαδοχικά, μεταξύ Ιανουαρίου 2010-Ιανουαρίου 2012. Κάθε υπόθεση εξετάστηκε, κατά μέσο όρο, από 5 σχολιαστές εμπειρογνώμονες. Προτάθηκαν, ανά περίπτωση, 3 πιθανές διαγνώσεις, κατά μέσο όρο. Στο 22,5% των περιπτώσεων, επιτεύχθηκε συναίνεση των σχολιαστών εμπειρογνωμόνων σχετικά με την κλινική διάγνωση. Προτάθηκαν γενετικές εξετάσεις στο 70,5% των περιπτώσεων, ενώ οι εμπειρογνώμονες εισηγήθηκαν περαιτέρω διαγνωστικές έρευνες, εργαστηριακές και απεικονιστικές, στο 35,5% και το 26% των περιπτώσεων, αντίστοιχα. Στο 23,5% των περιπτώσεων, προτάθηκαν περαιτέρω γνωμοδοτήσεις ειδικών. Σαράντα - τρεις περιπτώσεις υποβλήθηκαν με προσωρινή διάγνωση, η οποία επιβεβαιώθηκε από τους σχολιαστές μόνο στο 26% των περιπτώσεων. Συνολικά, για τη διάγνωση των 200 περιπτώσεων, ελήφθησαν υπόψη στην διαφορική διάγνωση 181 πολύ ή εξαιρετικά σπάνια γενετικά σύνδρομα. Σε 2 περιπτώσεις, οι σχολιαστές υποστήριξαν ότι οι διαπιστώσεις αντιπροσώπευαν νέο σύνδρομο/κλινική οντότητα και σε ένα από αυτά ανακαλύφθηκε στη συνέχεια η υποκείμενη γενετική αιτία. Άλλα οφέλη του συστήματος είναι η δυνατότητα να κατευθύνονταi τα περιστατικά σε συγκεκριμένα κέντρα για τις διαγνωστικές δοκιμές ή η συμμετοχή σε ερευνητικά και εκπαιδευτικά προγράμματα. | el |
| dc.format.extent | 52 | el |
| dc.language.iso | el | el |
| dc.publisher | Πανεπιστήμιο Πειραιώς | el |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Διεθνές | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
| dc.title | Επιχειρησιακή στρατηγική για ένα ηλεκτρονικό σύστημα κλινικής διάγνωσης γενετικών συνδρόμων | el |
| dc.title.alternative | Strategic management of a web-based system for the clinical diagnosis of rare genεtic syndromes | el |
| dc.type | Master Thesis | el |
| dc.contributor.department | Σχολή Οικονομικών, Επιχειρηματικών και Διεθνών Σπουδών. Τμήμα Οικονομικής Επιστήμης | el |
| dc.description.abstractEN | In 2007, the DYSCERNE project was funded by the European Commission Public Health Executive Agency (EU DG Sanco) as a pilot project aimed at setting up a network of expertise for rare dysmorphic disorders. As part of the DYSCERNE project a Dysmorphology Diagnostic System (DDS) was set up to enable clinicians throughout the EU to submit cases electronically for diagnosis using a secure, web-based interface, hosted at specified access points (Submitting nodes), in 26 different European countries. We report the outcome of this service for 200 cases submitted consecutively between January 2010-January 2012. Each case was reviewed by an average of 5 expert reviewers. An average of 3 possible syndromic diagnoses were suggested per case. In 22.5% of cases, a consensus clinical diagnosis was reached. Genetic testing was suggested in 70.5% of cases while further laboratory investigations and diagnostic imaging were recommended in 35.5% and 26% of the cases, respectively. Further specialist opinions were suggested in In 23.5% of the cases. Forty-three cases were submitted with a provisional diagnosis but these were confirmed by the reviewers in only 26%. Overall, a total of 181 very rare or extremely rare genetic syndromes were considered in the differential diagnosis of the 200 cases. In 2 cases the reviewers suggested that the findings represented a new syndrome and in one of these the underlying genetic cause was subsequently identified. Other benefits of the submission process included the possibility of directing case submitters to specific centres for diagnostic testing or participation in research and educational benefit derived for both case submitters and reviewers. With the wide availability of internet access, databases have become an integral aspect of practice in clinical genetics and dysmorphology. Available resources to date include, among others, the Online Mendelian Inheritance in Man (OMIM, Johns Hopkins University, Baltimore, MD, USA) and the European resource for information on rare disorders, Orphanet (Institut National de la Santé et de la Recherche medicale, Paris, France). However, dysmorphologists prefer specialised databases, such as the Winter–Baraitser Dysmorphology Database from the London Medical Databases and POSSUM, Pictures of Standard Syndromes and Undiagnosed Malformations, for their content. In particular, the reference images of the conditions and syndromes within these databases often trigger diagnostic insights to prompt diagnosis. The diagnostic value of these resources has proven significant in clinical-genetic discussion groups and dysmorphology education. This study proves that it is possible for expert reviewers to make a clinical genetic diagnosis on the basis of web-organised, representative, consented, clinical photographs of patients and short clinical summaries. The percentage of cases in which diagnoses were suggested by the DDS was 22.5%. Dysmorphologists have long recognised the value of peer review of their cases as an adjunct to making a diagnosis for patients and their families with rare genetic conditions. This is the first study that formally describes the clinical diagnostic rate of a dysmorphology discussion group and the types of diagnosis suggested. The rarity of these diseases highlights why a consensus expert opinion is so valuable. In an attempt to test whether there was any correlation between the level of expertee of the submitting node and the likelihood of the panel giving a diagnosis, we designated all of the submitting nodes as either established (E) or developing (D) in the limited number of cases with laboratory feedback (Table 4). The odds ratio calculated in this way shows that if the case was submitted from an established node, the DYSCERNE diagnosis was 7.714 times more likely to be positive rather than if the case was submitted from a developing node. This work was funded as a research study and, of course, if the DDS were to be employed in clinical practice then costs would be incurred. On average, cases where a consensus opinion was reached were reviewed by five reviewers, and based on practice in our own center we would estimate that 10–15 min of reviewer time was spent on each case. While collating results, the diagnosis suggested at the top was the one in which most experts agreed, and if three or more experts agreed on a single diagnosis this was considered as a strong evidence for the diagnosis. Further reviewers were senior clinicians paid at consultant level. Costs would vary depending on the typical salary for the country involved but are estimated at 16 Euros per case per reviewer for reviewer time, given the typical review panel of five experts. Added to this would be the costs for hosting of the website (7 Euros per case if utilised to full capacity) and for the clinical coordinator collating reports (40 Euros per case if salaried). An estimated cost per case might therefore be 127 Euros. Even if this is an underestimate of the time taken, it compares very favourably to an average genetic test of 500 Euros for a single gene or 1500 Euros for a ‘panel’ test or exome using NextGeneration sequencing. Of course clinical diagnoses would need to be confirmed, but targeted testing would probably be cheaper than organising a whole battery of tests with no specific diagnosis in mind. In addition, some suggested clinical diagnoses would not be detected or would be difficult to detect on routine genetic testing, for example, teratogenic syndromes or some mosaic disorders. The marked differences in the provision of genetic services between countries have obvious consequences for access to diagnosis. In some countries, diagnostic genetic testing is partly or wholly provided from commercial, private settings. The DDS is currently available to a number of professionals and to their patients in many countries with staffing shortages in clinical genetics or where access to more modern genetic diagnostic technologies is not available or is limited by a significant economic burden on the family. Thus, it is particularly relevant for low/middle income or developing countries. The DDS system was particularly helpful for professionals working in isolation or in developing countries. To access the system, a professional needs to be granted a site licence, however, the number of which remains limited at this point in time. The DECR provided at the end of the evaluation of each case is a document sent to the submitting node electronically, with immediate benefits for the patient and the family. The DDS has an impact on the management of the patient, with advice about clinically relevant genetic or other investigations, imaging studies, recommendations for further specialised opinions, screening and, in some cases, treatment. Most importantly, in the cases of consensus clinical diagnosis, a recurrence risk was given that aided genetic counselling of the individual or the family. In some cases where a specific diagnosis could not be offered, the submitting clinician was at least directed to a group of disorders. A total of 23 different groups of disorders were differentially diagnosed in these cases. We think that assigning a condition to one of these groups is clinically relevant, as it might prove useful in the future for the families with a tentative diagnosis as laboratory diagnostic capabilities increase. The contribution of the DDS to arriving at a diagnosis compares favourably to the types of genetic testing, such as chromosomal microarray analysis (aCGH). The diagnostic yield of aCGH was identified as 8.5% according to a recent study of >2000 postnatal cases. Of note, most cases accepted onto the DDS had negative or nonclinically relevant aCGH results. Though the use of aCGH as an initial screening test is becoming a standard clinical practice, our findings reinforce the fact that the DDS serves as a further tool in the diagnostic armamentarium for the specific group of dysmorphic patients in which standard laboratory investigations have given normal results, as it may lead to the suggestion of a clinical diagnosis that was previously not considered and thus allow the targeting of further specific diagnostic testing. However, we accept that clinical diagnoses are not always confirmed on testing and that any clinical diagnosis suggested in an individual case also needs to be considered in the context of molecular findings to arrive at the correct diagnosis on which management and counselling decisions are based. We believe that platforms such as the DDS will have a place even in the era of NextGeneration Sequencing. This technology is still not widely available and there are several congenital dysmorphic conditions that are caused by environmental, multifactorial or epigenetic causes not diagnosed by this method. As it has always been the case in health services, a clinical insight often directs targeted testing and might save the cost of a whole-genome sequencing technique. Moreover, as laboratory diagnosis of rare dysmorphic syndromes improves, the attention of the clinical geneticist will shift to the clinical management of these patients that can be facilitated by systems such as the DDS. This type of approach could be a future model for regional genetic services as has already been tested in central Italy. It might be of value, particularly, where an urgent opinion is needed to facilitate the management of a newborn patient or to determine recurrence risk in a pregnant member of the family. There are significant limitations to be considered regarding wider implementation of the DDS. DYSCERNE is a clinical genetic service that provides expert clinical opinions. Follow-up of the suggested diagnoses, decisions regarding genetic testing and the management of the patient/family are left to the judgement of the submitting clinician. This current study was not specifically designed to explore the results of the suggested genetic tests, as the decisions to undertake such tests and their availability were out of our control. In an effort to seek more objective feedback, we approached 40 randomly selected submitting clinicians to ask them what actions they took upon receiving the DYSCERNE diagnosis, and this provided some limited feedback on the genetic-testing results. Sustainability is the main issue, as currently the coordinator and the expert reviewers participate free of charge. The case submission forms require careful completion by submitting clinicians, and gatekeeping is a time-consuming process. Only a finite number of cases can be reviewed at any point in time. In some case, particularly those with fewer dysmorphic features, there was no response or low response from reviewers. Despite these limitations, these results demonstrate that the DDS system is a digital clinical genetic service that can improve accessibility and delivery of high-quality diagnostic services and fullfil individual needs for diagnosis as identified by user groups. In the era of genomic medicine, the integration of the trained intuition of dysmorphology and NextGeneration sequencing would be very productive in research and clinical translation. | el |
| dc.corporate.name | ΤΕΙ Πειραιά | el |
| dc.contributor.master | Οικονομικά και Διοίκηση της Υγείας | el |
| dc.subject.keyword | Δυσμορφολογία | el |
| dc.subject.keyword | Σύνδρομο | el |
| dc.subject.keyword | Υπηρεσίες κλινικής γενετικής | el |
| dc.subject.keyword | Γενετικές δοκιμές | el |
| dc.subject.keyword | Διαδίκτυο (Internet) | el |
| dc.subject.keyword | Dysmorphology | el |
| dc.subject.keyword | Syndrome | el |
| dc.subject.keyword | Clinical genetics | el |
| dc.subject.keyword | Service | el |
| dc.subject.keyword | Genetic testing | el |
| dc.subject.keyword | Digital | el |
| dc.subject.keyword | Network | el |
| dc.subject.keyword | Expertise | el |
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Τμήμα Οικονομικής Επιστήμης
Department of Economics
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