Machine Learning and Information Theory Measures in financial solvency prediction

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Εφαρμοσμένες Μαθηματικές Επιστήμες

Η Σχολική και Συναισθηματική Επάρκεια των Παιδιών με Δυσλεξία

Η παρούσα έρευνα έχει ως στόχο την διερεύνηση της Ψυχοκοινωνικής Προσαρμογής, και συγκεκριμένα των διαστάσεων της Σχολικής και Συναισθηματικής Επάρκειας σε παιδιά με δυσλεξία, συγκριτικά με τους τυπικά αναπτυσσόμενους συνομηλίκους τους. Επιπλέον, επιδιώχθηκε η διερεύνηση των διαφυλικών διαφορών στις διαστάσεις αυτές, καθώς και η σχέση μεταξύ της Σχολικής και Συναισθηματικής Επάρκειας. Το δείγμα αποτελούταν συνολικά από 135 παιδιά που φοιτούσαν στην Πέμπτη και Έκτη τάξη του Δημοτικού σχολείου. Από το σύνολο των 135 παιδιών τα 26 αποτελούσαν το δείγμα παιδιών με δυσλεξία, ενώ τα υπόλοιπα 109 αποτελούσαν το γενικό δείγμα τυπικής ανάπτυξης. Όσον αφορά την κατανομή του δείγματος ως προς το Φύλο αποτελούταν από 69 αγόρια και 57 κορίτσια. Τα εργαλεία που χρησιμοποιήθηκαν ήταν το ερωτηματολόγιο αυτοαναφοράς από το «Τεστ Ψυχοκοινωνικής Προσαρμογής των Χατζηχρήστου, Πολυχρόνη, Μπεζεβέγκη και Μυλωνά (2008), καθώς και ένα αυτοσχέδιο ερωτηματολόγιο που χρησιμοποιήθηκε για τη συλλογή των απαραίτητων δημογραφικών δεδομένων. Τα αποτελέσματα που προέκυψαν επιβεβαιώνουν την ύπαρξη διαφοροποιήσεων μεταξύ των παιδιών με και χωρίς δυσλεξία ως προς τους παράγοντες της Σχολικής και Συναισθηματικής Επάρκειας, με εξαίρεση την μεταβλητή της Διαχείρισης Συναισθημάτων και του Αυτοελέγχου. Ως προς τη μεταβλητή του Φύλου, παρατηρήθηκαν διαφοροποιήσεις στις υπό μελέτη διαστάσεις, με το κάθε φύλο να εναρμονίζεται με τα χαρακτηριστικά που προκύπτουν από τα κοινωνικά στερεότυπα για το κάθε φύλο. Τέλος, όσον αφορά τη σχέση μεταξύ Σχολικής και Συναισθηματικής Επάρκειας σημειώθηκε συνάφεια με θετική κατεύθυνση.The present study aims to examine Social and Psychological Adjustment, and more specifically the dimensions of Academic and Emotional Capacity in children with dyslexia in comparison with their typically developing peers. Additionally, we pursued the examination of gender differences in regards to those dimensions, as well as the relationship between Academic Emotional Capacity themselves. The sample was comprised of 135 children attending the fifth and sixth grade of grade school. From the total of 135, 26 children comprised the sample of children with dyslexia, while the remaining 109 were part of the typical development sample. As far as gender distribution is concerned, 69 children were male and 57 were female. The tools that were utilized were the self-administered questionnaire from "Social and Psychological Adjustment Test" of Chatzichristou, Polychroni, Bezevekis, and Milonas (2008), alongside a custom questionnaire that was used for the collection of the necessary demographic information. The study results confirm the existence of differentiation between children with dyslexia and those without, in terms of the factors of Academic and Emotional Capacity, with the exception of the Emotion Regulation and Self-control variable. As for the Gender variable, we noted differences in the dimensions under examination, with each gender adhering to characteristics that stem from social stereotypes for said gender. Last, in terms of the relationship between Academic and Emotional Capacity themselves, a positive correlation was noted

Clinical implementation of preemptive pharmacogenomics in psychiatryResearch in context

Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II\ue2\u80\u93IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56\uc2\ub76 [SEM 4\uc2\ub75] vs 68\uc2\ub73 [4\uc2\ub75]; rank-based treatment difference \ue2\u88\u9211\uc2\ub77, 95% CI \ue2\u88\u9224\uc2\ub73 to 0\uc2\ub796; p=0\uc2\ub70698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals