Assessing the short-term outcomes of a community-based intervention for overweight and obese children: The MEND 5-7 programme

Objective The aim of this study was to report outcomes of the UK service level delivery of MEND (Mind,Exercise,Nutrition...Do it!) 5-7, a multicomponent, community-based, healthy lifestyle intervention designed for overweight and obese children aged 5–7 years and their families. Design Repeated measures. Setting Community venues at 37 locations across the UK. Participants 440 overweight or obese children (42% boys; mean age 6.1 years; body mass index (BMI) z-score 2.86) and their parents/carers participated in the intervention. Intervention MEND 5-7 is a 10-week, family-based, child weight-management intervention consisting of weekly group sessions. It includes positive parenting, active play, nutrition education and behaviour change strategies. The intervention is designed to be scalable and delivered by a range of health and social care professionals. Primary and secondary outcome measures The primary outcome was BMI z-score. Secondary outcome measures included BMI, waist circumference, waist circumference z-score, children's psychological symptoms, parenting self-efficacy, physical activity and sedentary behaviours and the proportion of parents and children eating five or more portions of fruit and vegetables. Results 274 (62%) children were measured preintervention and post-intervention (baseline; 10-weeks). Post-intervention, mean BMI and waist circumference decreased by 0.5 kg/m2 and 0.9 cm, while z-scores decreased by 0.20 and 0.20, respectively (p<0.0001). Improvements were found in children's psychological symptoms (−1.6 units, p<0.0001), parent self-efficacy (p<0.0001), physical activity (+2.9 h/week, p<0.01), sedentary activities (−4.1 h/week, p<0.0001) and the proportion of parents and children eating five or more portions of fruit and vegetables per day (both p<0.0001). Attendance at the 10 sessions was 73% with a 70% retention rate. Conclusions Participation in the MEND 5-7 programme was associated with beneficial changes in physical, behavioural and psychological outcomes for children with complete sets of measurement data, when implemented in UK community settings under service level conditions. Further investigation is warranted to establish if these findings are replicable under controlled conditions

Σχεδιασμός και υλοποίηση υπολογιστικής μεθόδου για την ταξινόμηση πεπτιδίων με βάση τη βιοδραστηριότητά τους

Τα τελευταία χρόνια, η ανακάλυψη νέων θεραπειών κατά των λοιμώξεων έχει καταστεί επείγουσα εξαιτίας της ταχέως αυξανόμενης αντίστασης που εμφανίζεται έναντι στα συμβατικά αντιβιοτικά. Το γεγονός οτι τα περισσότερα δυνητικά αντιβιοτικά αποτυγχάνουν να σκοτώσουν παθογόνους οργανισμούς έχει αναπτύξει την ανάγκη σχεδιασμού νέων αντιμικροβιακών φορέων και η κλινική έρευνα πλέον επενδύει στην ταυτοποίηση νέων, μη συμβατικών θεραπειών κατά των μολύνσεων. Τα αντιμικροβιακά πεπτίδια (AMPs) έχουν κεντρίσει το ενδιαφέρον των ερευνητικών ομάδων ως νέα υποψήφια φάρμακα και χάρη στην ικανότητά τους να προστατεύουν το ξενιστή από ποικίλα παθογόνα βακτήρια είναι γνωστά και ως πεπτίδια άμυνας του ξενιστή. Πρόκειται για ολιγοπεπτίδια όπου ο αριθμός των αμινοξικών καταλοίπων τους κυμαίνεται συνήθως από πέντε ως εκατό και δρουν αποτελεσματικά έναντι ποικίλων στόχων, όπως είναι τα βακτήρια, οι ιοι, οι μύκητες και τα παράσιτα. Τα φυσικά αντιμικροβιακά πεπτίδια απαντώνται τόσο σε προκαρυωτικούς (π.χ. βακτήρια) όσο και σε ευκαρυωτικούς οργανισμούς (π.χ. πρωτόζωα, μύκητες, φυτά, έντομα και ζώα) και τα περισσότερα εμφανίζουν κατιονική και αμφιπαθητική ιδιότητα. Η αμφιπαθητικότητα τους τα καθιστά ιδανικά για το σχηματισμό διεπαφών και τους δίνει την ικανότητα διατάραξης της φυσικής ακεραιότητας της μικροβιακής μεμβράνης. Επιπλέον, οι ηλεκτροστατικές δυνάμεις μεταξύ της αρνητικά φορτισμένης βακτηριακής μεμβράνης και των κατιονικών αντιμικροβικακών πεπτιδίων, είναι ακόμα ένας καθοριστικός παράγοντας αυτής της αλληλεπίδρασης πεπτιδίου – μεμβράνης. Το ευρύ φάσμα των ιδιοτήτων που χαρακτηρίζουν τα αντιμικροβιακά πεπτίδια καθιστά τον in-silico σχεδιασμό νέων συνθετικών AMPs μια σοβαρή πρόκληση. Αρκετές δημόσιες βάσεις δεδομένων έχουν ηδη δημιουργηθεί με αποθηκευμένη πληροφορία για εκατοντάδες AMPs. Η ταυτοποίηση και ο χαρακτηρισμός των AMPs και των λειτουργικών τους τύπων έχει οδηγήσει σε πολλές μελέτες και ένας μεγάλος αριθμός μεθόδων έχει προταθεί για αυτόν τον σκοπό. Οι περισσότερες μέθοδοι έχουν εξάγει πληροφορία από την στοίχιση αλληλουχιών, ωστόσο, η αμινοξική σύνθεση δεν μπορεί να επεξηγήσει πάντα πλήρως τους μηχανισμούς αλληλεπίδρασης των AMPs. Πρόσφατα, η μηχανική εκμάθηση έχει συντελέσει στην ανάπτυξη διάφορων μεθόδων πρόβεψης, οι οποίες βασίζονται στα συνθετικά χαρακτηριστικά της αμινοξικής αλληλουχίας των AMPs. Σκοπός της παρούσας διπλωματικής εργασίας είναι η υλοποίηση μιας καινοτόμου υπολογιστικής μεθοδολογίας μηχανικής μάθησης που θα προσφέρει τη δυνατότητα χαρακτηρισμού των πεπτιδίων με βάση την αντιφλεγμονώδη ή/και την αντικαρκινική τους δράση. Το πρώτο βήμα ήταν η συλλογή πεπτιδίων από διάφορες κατηγορίες βιοδραστηριότητας, αντικαρκινική, αντιμικροβιακή, αντιβακτηριακή, αντιμυκητιακή, αντιϊική και εντομοκτόνα από τις υπάρχουσες βάσεις δεδομένων DRAMP και DAMPD, ως το θετικό δείγμα εκπαίδευσης. Παράλληλα, από τη Uniprot συλλέχθησαν πεπτίδια μήκους 10 ως 100 καταλοίπων με το κριτήριο να μην ανήκουν σε κάποια κατηγορία βιοδραστηριότητας, ως το αρνητικό δείγμα εκπαίδευσης. Η τεχνική της τυχαίας υπερδειγματοληψίας και υποδειγματοληψίας χρησιμοποιήθηκε για την αύξηση ή τη μείωση, αντίστοιχα, των δειγμάτων και το τελικό σύνολο πεπτιδίων διαμορφώθηκε σε 1491 πεπτίδια, 213 από κάθε μελετώμενη κατηγορία. Στη συνέχεια, υπολογίστηκε, για κάθε ένα πεπτίδιο, ένας αριθμός (44) από φυσικοχημικά και ακολουθιακά χαρακτηριστικά, τα οποία εχει αποδειχθεί να αποτελούν τα πιο αντιπροσωπευτικά στον χαρακτηρισμό των αντιμικροβιακών πεπτιδίων. Με αυτόν τον τρόπο δημιουργήθηκε το σύνολο δεδομένων εκπαίδευσης του μοντέλου πρόβλεψης. Το δεύτερο βήμα ήταν η εκτέλεση της EnsembleGASVR μεθοδολογίας ταξινόμησης, μιας υπολογιστικής μεθόδου που προτάθηκε στο παρελθόν για την πρόβλεψη ουδέτερων και παθογενών πολυμορφισμών κατηγοριοποιώντας τους Σημειακούς Μονονουκλεοτιδικούς Πολυμορφισμούς (SNPs) σε ουδέτερους και σε αυτούς που σχετίζονται με κάποια ασθένεια. Η εν λόγω μεθοδολογία συνδυάζει έναν ταξινομητή Support Vector Regression (SVR) και έναν Γενετικό Αλγόριθμο (GA). Επιπροθέτως, η μέθοδος αυτή έχει βελτιωθεί κατόπιν αντικατάστασης του γενετικού αλγόριθμου με έναν εξελικτικό multi-objective αλγόριθμο, σε μια προσπάθεια επίτευξης αυξημένης απόδοσης. Η μεθοδολογία αυτή έχει το πλεονέκτημα ότι χειρίζεται με πολύ αποδοτικό τρόπο τις ελλιπείς τιμές ενώ επίσης τα μοντέλα που εξάγονται από αυτήν παρέχουν και ένα βαθμό εμπιστοσύνης για κάθε πρόβλεψη τους. Επιπλέον κατασκευάστηκε και ένα δοκιμαστικό σύνολο δεδομένων, που εφαρμόστηκε ως είσοδος στο μοντέλο για την αξιολόγηση της απόδοσής του με βάση το αν προέβλεψε σωστά ή όχι την κατηγορία στην οποία ανήκει κάθε πεπτίδιο. Η εκτέλεση του αλγόριθμου επαναλήφθηκε πέντε φορές και ο μέσος όρος της ακρίβειας πρόβλεψης υπολογίστηκε 66.77 ενώ η διακύμανση υπολογίστηκε 31.07. Απώτερος σκοπός είναι η βελτίωση της απόδοσης και τελικά η εφαρμογή των εκπαιδευμένων μοντέλων σε ένα αυξημένο σύνολο από αχαρακτήριστα πεπτίδια που περιλαμβάνονται σε φυτικούς οργανισμούς έτσι ώστε να προταθούν καινούρια πεπτίδια και φυτά που μπορούν να χρησιμοποιηθούν για την καταπολέμηση των φλεγμονών αλλά και την πρόληψη κατά του καρκίνου.In recent years, the discovery of new infection therapeutics has become an urgent due to the rapidly increasing infection resistance toward conventional antibiotics. The fact that most potential antibiotics fail to kill pathogens has grown the need to design new antimicrobial agents and the clinical research is now invested into identification of new, non-conventional anti-infective therapies. Antimicrobial peptides (AMPs) have captured the research attention as novel drug candidates and they are also known as host defense peptides because they can protect the host from various pathogenic bacteria. They are oligopeptides with a varying number of amino acids, five to one hundred, and they are effective towards a wide variety of targets, such as bacteria, viruses, fungi and parasites. Natural AMPs can be found in both prokaryotes (e.g., bacteria) and eukaryotes (e.g., protozoan, fungi, plants, insects, and animals) most of which are cationic and amphipathic. This amphipathicity gives them the ability to disrupt the physical integrity of the microbial membrane. Moreover, the electrostatic forces between the negatively charged bacterial surface and the cationic AMPs is another determinant for this interaction between peptides and microbial membrane. The design of novel synthetic AMPs, in-silico, has turned to be a serious challenge because of the broad spectrum of properties that characterize AMPs. Public databases have been already developed and store useful information for hundreds of natural AMPs. Identifying and characterizing AMPs and their functional types has led to many studies and a number of methods have been proposed. Most of them have extracted information from sequence alignment, however, the amino acid composition cannot fully explain the interaction mechanisms of AMPs. Recently, various predictors using machine learning have been developed, based on the compositional characteristics of AMPs amino acid sequences. In this study, a novel computational methodology has been implemented which will offer the ability to characterize the peptides depending on their anti-inflammatory and/or anticancer bioactivity. The first step was the collection of antimicrobial, anticancer, antibacterial, antifungal, antiviral and insecticidal AMPs from DRAMP and DAMPD databases, as the positive sample. Peptides that do not appear to present any bioactivity were collected from Uniprot, as the negative sample. The technique of boosting and random oversampling increased the number of the samples and the final peptide amount was 1491; 213 from each studied category. A number of physicochemical and sequential features (44), which have been proved to be the most indicative for characterizing the antimicrobial peptides, was calculated for each peptide and constituted the final training dataset. The second step was the execution of EnsembleGASVR classification methodology; a computational framework that was proposed in the past for predicting neutral and pathogenic polymorphism variations by classifying missense SNPs (Single Nucleotide Polymorphism) to neutral and disease associated. This methodology facilitates a two-step algorithm, which combines a Support Vector Regression (SVR) classifier with a Genetic Algorithm. Additionally, the method was further improved after replacing the Genetic Algorithm, in its second step, with an evolutionary multi-objective framework, in an attempt to achieve higher performance. The advantage of this method is the effective handling of missing values and the produced models provide a confidence score on every prediction. The training dataset was used to train the aforementioned algorithm. Finally, the quality of the method was evaluated after applying the trained models on a test dataset which predicted the category of the bioactivity that a peptide could belong to. The algorithm was executed five times and the mean of accuracy was calculated to 66.77, while the variance was calculated to 31.07. The ultimate purpose of this algorithm is to apply the best trained models on a superset of uncharacterized peptides, which are met in plant organisms, in order to propose new peptides and plants that can be used in the cancer prevention and the fight against inflammation

Attendance, Weight Loss, and Participation in a Behavioural Diabetes Prevention Programme

Background: Weight loss in diabetes prevention programmes has been shown to be associated with participants’ age, socio-economic status, and ethnicity. However, little is known about how these differences relate to attendance and whether such differences can be mediated by other potentially modifiable factors. Differential effectiveness across these factors may exacerbate health inequalities. Method: Prospective analysis of participant data collected by one provider of the standardised national NHS diabetes prevention programme in England. Mediation analysis was performed via a structural equation model to examine whether the number of attended sessions mediated the associations of age, socio-economic status, and ethnicity with follow-up weight. The group-level factor of number of attended sessions was examined using multiple linear regression as a benchmark; multilevel linear regression using three levels (venue, coach, and group); and fixed effects regression to account for venue-specific and coach-specific characteristics. Results: The associations of age, socio-economic status, and ethnicity with follow-up weight were all mediated by the number of attended sessions. Group size was associated with attendance in an inverted ‘U’ shape, and the number of days between referral and group start was negatively associated with attendance. Time of day, day of the week, and the number of past groups led by the coach were not associated with attendance. Conclusion: Most of the differences in weight loss initially attributed to socio-demographic factors are mediated by the attendance of the diabetes prevention programme. Therefore, targeted efforts to improve uptake and adherence to such programmes may help alleviate inequalities

Is BMI alone a sufficient outcome to evaluate interventions for child obesity?

BACKGROUND: BMI is often used to evaluate the effectiveness of childhood obesity interventions, but such interventions may have additional benefits independent of effects on adiposity. We investigated whether benefits to health outcomes following the Mind, Exercise, Nutrition…Do It! (MEND) childhood obesity intervention were independent of or associated with changes in zBMI. METHODS: A total of 79 obese children were measured at baseline; 71 and 42 participants were followed-up at 6 and 12 months respectively, and split into four groups depending on magnitude of change in zBMI. Differences between groups for waist circumference, cardiovascular fitness, physical and sedentary activities, and self-esteem were investigated. RESULTS: Apart from waist circumference and its z-score, there were no differences or trends across zBMI subgroups for any outcome. Independent of the degree of zBMI change, benefits in several parameters were observed in children participating in this obesity intervention. CONCLUSION: We concluded that isolating a single parameter like zBMI change and neglecting other important outcomes is restrictive and may undermine the evaluation of childhood obesity intervention effectiveness

Attendance, Weight Loss, and Participation in a Behavioural Diabetes Prevention Programme

Background Weight loss in diabetes prevention programmes has been shown to be associated with participants’ age, socio-economic status, and ethnicity. However, little is known about how these differences relate to attendance and whether such differences can be mediated by other potentially modifiable factors. Differential effectiveness across these factors may exacerbate health inequalities. Method Prospective analysis of participant data collected by one provider of the standardised national NHS diabetes prevention programme in England. Mediation analysis was performed via a structural equation model to examine whether the number of attended sessions mediated the associations of age, socio-economic status, and ethnicity with follow-up weight. The group-level factor of number of attended sessions was examined using multiple linear regression as a benchmark; multilevel linear regression using three levels (venue, coach, and group); and fixed effects regression to account for venue-specific and coach-specific characteristics. Results The associations of age, socio-economic status, and ethnicity with follow-up weight were all mediated by the number of attended sessions. Group size was associated with attendance in an inverted ‘U’ shape, and the number of days between referral and group start was negatively associated with attendance. Time of day, day of the week, and the number of past groups led by the coach were not associated with attendance. Conclusion Most of the differences in weight loss initially attributed to socio-demographic factors are mediated by the attendance of the diabetes prevention programme. Therefore, targeted efforts to improve uptake and adherence to such programmes may help alleviate inequalities

Long-Term Outcomes following the MEND 7-13 Child Weight Management Program.

Background: In the current study, we report outcomes 2.4 years from baseline in a random subsample of overweight and obese children who attended MEND 7-13 programs delivered in UK community settings under service level conditions. Methods: The study employed an uncontrolled pre-follow-up design. A total of 165 children were measured. Outcomes included anthropometry, parental perception of emotional distress, body esteem, and self-esteem. Results: Overall, there were significant improvements in all outcomes apart from BMI z-score. In boys, BMI z-score, waist circumference z-score, and psychometrics all improved. In girls, there were no statistically significant differences at 2.4 years, except for body esteem. Conclusions: In real-world settings, the MEND intervention, when delivered by nonspecialists, may result in modest, yet positive, long-term outcomes. Subsequent research should focus on improving the outcome effect size, providing effective behavior change maintenance strategies, and further investigating the reasons behind the observed gender differences

Addressing childhood obesity in low-income, ethnically diverse families: outcomes and peer effects of MEND 7–13 when delivered at scale in US communities

Objectives: Implementation of a large-scale, child weight management program in underserved communities provided an important opportunity to evaluate its effectiveness under service level conditions. Methods: MEND 7–13 is a community-based, multicomponent, childhood obesity intervention designed to improve dietary, physical activity and sedentary behaviors. It comprises twice weekly sessions for 10 consecutive weeks (total of 35 contact hours) and is delivered to groups of children and their accompanying parents/caregivers. The current evaluation used an uncontrolled, repeated measures design. 4,324 children attended 415 MEND 7–13 programs in seven USA states, of which 2,738 (63%) had complete data for change in zBMI. The intervention targeted underserved families (70% with an income <$40,000 per year; 85.6% Hispanic or African American). Changes in anthropometric, fitness and psychological outcomes were evaluated. A longitudinal multivariate imputation model was used to impute missing data. Peer effects analysis was conducted using the instrumental variables approach and group fixed effects. Results: Mean changes in BMI, and zBMI at 10 weeks were -0.42 kg/m2 (95%CI: -0.49, -0.35) and -0.06 (95%CI: -0.08, -0.04) respectively. Benefits were observed for all other study outcomes. Mean peer reduction in zBMI was associated with a reduction in participant zBMI in the instrumental variables model (B=0.78, p=0.04, 95%CI: 0.03, 1.53). Mean program attendance and retention were 70.8% and 84.7% respectively. Conclusion: Similar to recently published efficacy trial results, implementing MEND 7–13 under service level conditions was associated with short-term improvements in anthropometric, fitness and psychological indices in a large sample of underserved overweight and obese children. A peer effect was quantified showing that benefits for an individual child were enhanced if peers in the same group also performed well. To our knowledge, this is the first study to show positive peer effects associated with participation in a childhood obesity intervention

Psychosocial Interventions in the Treatment of Severe Adolescent Obesity: The SHINE Programme

Purpose: Psychosocial Interventions (PSI) are characterised by three phases: 1) an initial in-depth assessment, 2) an intensive multifaceted intervention to stem a condition, and 3) an extensive maintenance programme. PSIs are often used for treatment of mental health conditions, however applicability in the treatment of adolescent obesity is unknown. This paper sought to evaluate the service-level outcomes of a PSI for young people (aged 10-17) with severe obesity. Methods: A retrospective evaluation of participants attending the SHINE programme between 2011-2016 (n = 435; Age: 13.1±2.1 years, Male: 51%, White: 87.4%, BMI: 33.5±7.5 kg/m2, BMI SDS: 3.1±0.5 units). Anthropometric measurements (BMI and WC) were collected at baseline, 3-, 6-, 9-, and 12-months. Psychosocial measures (anxiety, depression, and self-esteem) were collected at baseline and 3 months. Participant retention was also assessed. Results: After 3 months, 95% of participants remained with a mean BMI SDS reduction of 0.19 units (95% CI: 0.17, 0.21). Anxiety, depression, and self-esteem improved by 50%, 54% and 38% respectively. BMI SDS reductions of 0.29, 0.35 and 0.41 were found at 6-, 9-, and 12- months. Fifty-four percent of participants chose to attend the final intervention phase. A higher baseline BMI SDS and a greater reduction in BMI SDS predicted final intervention phase attendance. Conclusion: The SHINE PSI demonstrated positive mean reductions in all measurements across all time points. In contrast to other community-based weight management services, these results suggest the utility of, and further exploration of, PSIs in the treatment of severe adolescent obesity