Interventions for preventing falls and fall-related fractures in community-dwelling older adults: A systematic review and network meta-analysis.

OBJECTIVE To compare the effectiveness of single, multiple, and multifactorial interventions to prevent falls and fall-related fractures in community-dwelling older persons. METHODS MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) evaluating the effectiveness of fall prevention interventions in community-dwelling adults aged ≥65 years, from inception until February 27, 2019. Two large RCTs (published in 2020 after the search closed) were included in post hoc analyses. Pairwise meta-analysis and network meta-analysis (NMA) were conducted. RESULTS NMA including 192 studies revealed that the following single interventions, compared with usual care, were associated with reductions in number of fallers: exercise (risk ratio [RR] 0.83; 95% confidence interval [CI] 0.77-0.89) and quality improvement strategies (e.g., patient education) (RR 0.90; 95% CI 0.83-0.98). Exercise as a single intervention was associated with a reduction in falls rate (RR 0.79; 95% CI 0.73-0.86). Common components of multiple interventions significantly associated with a reduction in number of fallers and falls rate were exercise, assistive technology, environmental assessment and modifications, quality improvement strategies, and basic falls risk assessment (e.g., medication review). Multifactorial interventions were associated with a reduction in falls rate (RR 0.87; 95% CI 0.80-0.95), but not with a reduction in number of fallers (RR 0.95; 95% CI 0.89-1.01). The following single interventions, compared with usual care, were associated with reductions in number of fall-related fractures: basic falls risk assessment (RR 0.60; 95% CI 0.39-0.94) and exercise (RR 0.62; 95% CI 0.42-0.90). CONCLUSIONS In keeping with Tricco et al. (2017), several single and multiple fall prevention interventions are associated with fewer falls. In addition to Tricco, we observe a benefit at the NMA-level of some single interventions on preventing fall-related fractures

Self-management interventions for adults living with obesity to improve patient-relevant outcomes : An evidence map

To conduct an evidence map on self-management interventions and patient-relevant outcomes for adults living with overweight/obesity. Following Arksey and O'Malley methodology, we searched in five electronical databases including randomized controlled trials (RCTs) on SMIs for overweight/obesity. We used the terms "self-management", "adult" and "obesity" for content. Two independent reviewers assessed eligible references; one reviewer extracted data, a second checked accuracy. We identified 497 RCTs (58% US, 20% Europe) including 99,741 (median 112, range 11-5145) adults living with overweight/obesity. Most research evaluated clinical outcomes (617, 55%) and behaviors adherence (255, 23%). Empowerment skills, quality of life and satisfaction were less targeted (8%, 7%, 0.2%, respectively). The most frequent techniques included sharing information (858, 99%), goal setting (619, 72%) and self-monitoring training (614, 71%), provided face-to-face (386, 45%) or in combination with remote techniques (256, 30%). Emotional management, social support and shared-decision were less frequent (18%, 26%, 4%). Socio-economic status, minorities or health literacy were seldom reported. There is a need of widening the scope of research by focusing on outcomes important to patients, assessing emotional/social/share-decision support, exploring remote techniques and including vulnerable populations

Using a Taxonomy to Systematically Identify and Describe Self-Management Interventions Components in Randomized Trials for COPD

Self-management interventions (SMIs) may improve outcomes in Chronic Obstructive Pulmonary Disease (COPD). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study systematically describes intervention components and characteristics in randomized controlled trials (RCTs) related to COPD self-management using the COMPAR-EU taxonomy as a framework, identifying components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Overall, 235 RCTs published between 2010 and 2018, from a systematic review were coded using the taxonomy, which includes 132 components across four domains: intervention characteristics, expected patient (or caregiver) self-management behaviours, patient relevant outcomes, and target population characteristics. Risk of bias was also assessed. Interventions mainly focused on physical activity (67.4%), and condition-specific behaviours like breathing exercise (63.5%), self-monitoring (50.8%), and medication use (33.9%). Support techniques like education and skills-training, self-monitoring, and goal setting (over 35% of the RCTs) were mostly used for this. Emotional-based techniques, problem-solving, and shared decision-making were less frequently reported (less than 15% of the studies). Numerous SMIs components were insufficiently incorporated into the design of COPD SMIs or insufficiently reported. Characteristics like mode of delivery, intensity, location, and providers involved were often not described. Only 8% of the interventions were tailored to the target population's characteristics. Outcomes that are considered important by patients were hardly taken into account. There is still a lot to improve in both the design and description of SMIs for COPD. Using a framework such as the COMPAR-EU SMI taxonomy may contribute to better reporting and to better informing of replication efforts. In addition, prospective use of the taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective SMIs in COPD

Development of sequential oligopeptide carries for diagnostics and vaccine candidates against avian influenza virus

The entry of influenza virus into susceptible cells is mediated by the viral hemagglutinin (HA) glycoprotein which constitutes the major surface antigen against which neutralizing antibodies are directed. The receptor binding preference of influenza viruses correlates with the animal species from which the viruses are isolated. Human isolates preferentially bind to the terminal sialic acid of glycoprotein and glycolipid receptors with a2,6 linkages to galactose (SAa2,6Gal) whereas avian isolates prefer a2,3 linkages (SAa2,3Gal). Aiming to contribute in the development of an influenza vaccine several SOCT cell epitope conjugates were synthesized and tested for their immunogenicity in mice after challenge infection with influenza virus. The influenza hemagglutinin CD8 Τ cell epitopes were predicted by computational methods and were then coupled on the SOC₄-I carrier in two copies in order to improve their immunogenicity. The desired macromolecules of branched architecture were obtained either by using the step by step Boc/Bzl solid phase peptide synthesis or by the chemoselective ligation approach through oxime bond formation between the appropriately modified for this purpose peptide fragments. Mice immune response to these SOC-T cell epitope conjugates was not adequate to induce protective immunity against influenza infection. Moreover, this work also aims to contribute in the development of highly specific and sensitive biological assays for the diagnosis and discrimination between avian and human influenza viruses. To this end, we synthesized four glycopeptide analogs mimicking the hemagglutinin receptor. Their synthesis was achieved via a chemoselective ligation approach which generates an oxime bond between the Νε- aminooxyacetylated- SOC₄-I oligopeptide carrier and the carbonyl group at the reducing end of different sialosaccharides. Conformational studies by circular dichroism spectroscopy (CD) revealed no significant influence of the sugar moiety to the well defined secondary structure of the SOC₄-I oligopeptide carrier though confirming the initial design of the SOCn molecules and broadening their applications. The resulted glycopeptide conjugates were used for the development of an ELISA binding assay with influenza pseudoviruses. Preliminary results suggest the usefulness of those glycopeptide conjugates to the diagnosis of influenza infections as well as to receptor specificity studies of different influenza virus isolates.Η είσοδος του ιού γρίπης στα κύτταρα διαμεσολαβείτε από την ιική γλυκοπρωτεΐνη αιμοσυγκολλητίνη (HA) που συνιστά το κύριο επιφανειακό αντιγόνο έναντι του οποίου κατευθύνονται τα εξουδετερωτικά αντισώματα. Η προτίμηση ιών γρίπης για πρόσδεση στον υποδοχέα σχετίζεται με το είδος από το οποίο οι ιοί αυτοί απομονώνονται. Οι ανθρωπινοί ιοί προσδένονται επιλεκτικά στο τελικό σιαλικό οξύ γλυκοπρωτεϊνών και γλυκολιπιδίων όπου αυτό συνδέεται μέσω α2,6 γλυκοζιτικού δεσμού με γαλακτόζη ενώ οι ιοί των πτηνών προτιμούν α2,3 γλυκοζιτικούς δεσμούς. Με στόχο τη συνεισφορά στην ανάπτυξη εμβολίου έναντι της γρίπης συντέθηκαν συμπλέγματα SOC-CD8 Τ κυτταρικών επίτοπων και ελέγχθηκαν ως προς την ανοσογονικότητά τους σε ποντίκια μετά από πρόκληση μόλυνσης με ιό γρίπης. Οι Τ επίτοποι της αιμοσυγκολητίνης Η5 του ιού της γρίπης που προβλέφθηκαν με υπολογιστικές μεθόδους προσδέθηκαν στον ολιγοπεπτιδικό φορέα SOC₄-I σε δυο αντίγραφα με σκοπό την ενίσχυση της ανοσογονικότητάς τους. Τα επιθυμητά μακρομόρια διακλαδισμένης αρχιτεκτονικής ελήφθησαν είτε με βήμα-προς-βήμα πεπτιδική σύνθεση σε στερεή φάση (Boc/Bzl στρατηγική) είτε μέσω χημειοεκλεκτικής πρόσδεσης σε μια αντίδραση σχηματισμού δεσμού οξίμης μεταξύ κατάλληλα τροποποιημένων πεπτιδικών τμημάτων. Η ανοσολογική απόκριση που προκάλεσε σε ποντίκια η ανοσοποίηση με αυτά τα SOC-συμπλέγματα δεν ήταν ικανοποιητική ώστε να επάγουν προστατευτική ανοσία έναντι της γρίπης. Επιπλέον, με στόχο τη συμβολή στην ανάπτυξη εξειδικευμένων και ευαίσθητων βιολογικών δοκιμασιών για τη διάγνωση και διάκριση μεταξύ ιών γρίπης ανθρώπων και πτηνών συντέθηκαν γλυκοπεπτιδικά ανάλογα ως μιμητικά του υποδοχέα της αιμοσυγκολλητίνης στο ξενιστικό κύτταρο. Η σύνθεση αυτών των αναλόγων επετεύχθη μέσω αντίδρασης χημειοεκλεκτικής πρόσδεσης που οδηγεί στη δημιουργία δεσμού όξιμης μεταξύ του Νε-αμινοοξυακετυλιωμένου φορέα SOC₄-I και της καρβονυλικής ομάδας στο αναγωγικό άκρο διαφόρων σιαλοσακχαριτών. Διαμορφωτικές μελέτες με φασματοσκοπία κυκλικού διχρωϊσμού απέδειξαν ότι η πρόσδεση σακχάρων δεν επηρεάζει την κανονική δευτεροταγή δομή του φορέα SOC₄-I επιβεβαιώνοντας έτσι τον αρχικό σχεδιασμό αυτής της κατηγορίας μορίων-φορέων και διευρύνοντας τις εφαρμογές τους. Τα γλυκοπεπτιδικά μοντέλα του υποδοχέα χρησιμοποιούνται στην ανάπτυξη μιας μεθοδολογίας ELISA για την ανίχνευση και τη μελέτη εξειδίκευσης για υποδοχέα ιών γρίπης τεχνική που αναμένεται να συμβάλλει ουσιαστικά προς την κατεύθυνση νέων διαγνωστικών εργαλείων του ιού της γρίπης των πτηνών

The presence of antibodies recognizing a peptide derived from the second conserved region of HIV-1 gp120 correlates with non-progressive HIV infection

The C-terminus of the second conserved region of HIV-1 gp120 represents a functionally important domain, as it encompasses amino acids directly involved in the binding to the CD4 receptor and in post-receptor binding events. Previous studies have suggested that antibodies with specific affinity to a 23 amino acids-long NTM polypeptide, derived from this HIV-1 gp120 domain, may be involved in the control of HIV disease progression. In the current work, we searched for NTM-recognizing antibodies in specific cohorts of HIV-1 infected individuals, including long-term non-progressors (LTNP) and progressors. For this purpose, we employed a previously defined bioinformatics criterion for design of an NTM peptide mimetic to select an octapeptide, NTMs (FTDNAKTI), which is more suitable for use in a solid-state enzyme-linked immunosorbent assay (ELISA). Our results show that NTMs-reactive antibodies are significantly more prevalent (p LT 0.01) in LTNP as compared to progressors and healthy control subjects, indicating their association with non-progressive infection. The presence of antibodies recognizing the second conserved region of the HIV-1 gp120 derived peptide, NTMs, in LTNP sera suggest that these antibodies could be of considerable interest for development of anti-HIV immune-based therapies and vaccines

Medication review interventions to reduce hospital readmissions in older people.

OBJECTIVE To assess the efficacy of medication review as an isolated intervention and with several co-interventions for preventing hospital readmissions in older adults. METHODS Ovid MEDLINE, Embase, The Cochrane Central Register of Controlled Trials and CINAHL were searched for randomized controlled trials evaluating the effectiveness of medication review interventions with or without co-interventions to prevent hospital readmissions in hospitalized or recently discharged adults aged ≥65, until September 13, 2019. Included outcomes were "at least one all-cause hospital readmission within 30 days and at any time after discharge from the index admission." RESULTS Twenty-five studies met the inclusion criteria. Of these, 11 studies (7,318 participants) contributed to the network meta-analysis (NMA) on all-cause hospital readmission within 30 days. Medication review in combination with (a) medication reconciliation and patient education (risk ratio (RR) 0.45; 95% confidence interval (CI) 0.26-0.80) and (b) medication reconciliation, patient education, professional education and transitional care (RR 0.64; 95% CI 0.49-0.84) were associated with a lower risk of all-cause hospital readmission compared to usual care. Medication review in isolation did not significantly influence hospital readmissions (RR 1.06; 95% CI 0.45-2.51). The NMA on all-cause hospital readmission at any time included 24 studies (11,677 participants). Medication review combined with medication reconciliation, patient education, professional education and transitional care resulted in a reduction of hospital readmissions (RR 0.82; 95% CI 0.74-0.91) compared to usual care. The quality of the studies included in this systematic review raised some concerns, mainly regarding allocation concealment, blinding and contamination. CONCLUSION Medication review in combination with medication reconciliation, patient education, professional education and transitional care, was associated with a lower risk of hospital readmissions compared to usual care. An effect of medication review without co-interventions was not demonstrated. Trials of higher quality are needed in this field

Correction: Do reporting guidelines have an impact? Empirical assessment of changes in reporting before and after the PRISMA extension statement for network meta-analysis

Medicine, Faculty ofOther UBCNon UBCReviewedFacult

Do reporting guidelines have an impact? Empirical assessment of changes in reporting before and after the PRISMA extension statement for network meta-analysis

Background The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for network meta-analysis (NMA) published in 2015 promotes comprehensive reporting in published systematic reviews with NMA. PRISMA-NMA includes 32 items: 27 core items as indicated in the 2009 PRISMA Statement and five items specific to the reporting of NMAs. Although NMA reporting is improving, it is unclear whether PRISMA-NMA has accelerated this improvement. We aimed to investigate the impact of PRISMA-NMA and highlight key items that require attention and improvement. Methods We updated our previous collection of NMAs with articles published between April 2015 and July 2018. We assessed the completeness of reporting for each NMA, including main manuscript and online supplements, using the PRISMA-NMA checklist. The PRISMA-NMA checklist originally includes 32 total items (i.e. a 32-point scale original PRISMA-NMA score). We also prepared a modified version of the PRISMA-NMA checklist with 49 items to evaluate separately at a more granular level all multiple-content items (i.e. a 49-point scale modified PRISMA-NMA score). We compared average reporting scores of articles published until and after 2015. Results In the 1144 included NMAs the mean modified PRISMA-NMA score was 32.1 (95% CI 31.8–32.4) of a possible 49-excellence-score. For 1-year increase, the mean modified score increased by 0.96 (95% CI 0.32 to 1.59) for 389 NMAs published until 2015 and by 0.53 (95% CI 0.02 to 1.04) for 755 NMAs published after 2015. The mean modified PRISMA-NMA score for NMAs published after 2015 was higher by 0.81 (95% CI 0.23 to 1.39) compared to before 2015 when adjusting for journal impact factor, type of review, funding, and treatment category. Description of summary effect sizes to be used, presentation of individual study data, sources of funding for the systematic review, and role of funders dropped in frequency after 2015 by 6–16%. Conclusions NMAs published after 2015 more frequently reported the five items associated with NMA compared to those published until 2015. However, improvement in reporting after 2015 is compatible with that observed on a yearly basis until 2015, and hence, it could not be attributed solely to the publication of the PRISMA-NMA.Medicine, Faculty ofOther UBCNon UBCReviewedFacult

Self-Management Interventions for Adults Living with Type II Diabetes to Improve Patient-Important Outcomes : An Evidence Map

Self-management interventions (SMIs) may be promising in the treatment of Diabetes Mellitus Type 2 (T2DM). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study summarizes intervention components and characteristics in randomized controlled trials (RCTs) related to T2DM using a taxonomy for SMIs as a framework and identifies components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Following evidence mapping methodology, we searched MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO from 2010 to 2018 for randomized controlled trials (RCTs) on SMIs for T2DM. We used the terms 'self-management', 'adult' and 'T2DM' for content. For data extraction, we used an online platform based on the taxonomy for SMIs. Two independent reviewers assessed eligible references; one reviewer extracted data, and a second checked accuracy. We identified 665 RCTs for SMIs (34% US, 21% Europe) including 164,437 (median 123, range 10-14,559) adults with T2DM. SMIs highly differed in design and content, and characteristics such as mode of delivery, intensity, location and providers involved were poorly described. The majority of interventions aimed to improve clinical outcomes like HbA1c (83%), weight (53%), lipid profile (45%) or blood pressure (42%); 27% (also) targeted quality of life. Improved knowledge, health literacy, patient activation or satisfaction with care were hardly used as outcomes (<16%). SMIs most often used education (98%), self-monitoring (56%), goal-setting (48%) and skills training (42%) to improve outcomes. Management of emotions (17%) and shared decision-making (5%) were almost never mentioned. Although diabetes is highly prevalent in some minority groups, in only 13% of the SMIs, these groups were included. Our findings highlight the large heterogeneity that exists in the design of SMIs for T2DM and the way studies are reported, making accurate comparisons of their relative effectiveness challenging. In addition, SMIs pay limited attention to outcomes other than clinical, despite the importance attached to these outcomes by patients. More standardized and streamlined research is needed to better understand the effectiveness and cost-effectiveness of SMIs of T2DM and benefit patient care

Talking the same language on patient empowerment

Context: The literature on self-management interventions (SMIs) is growing exponentially, but it is characterized by heterogeneous reporting that limits comparability across studies and interventions. Building an SMI taxonomy is the first step towards creating a common language for stakeholders to drive research in this area and promote patient self-management and empowerment. Objective: To develop and validate the content of a comprehensive taxonomy of SMIs for long-term conditions that will help identify key characteristics and facilitate design, reporting and comparisons of SMIs. Methods: We employed a mixed-methods approach incorporating a literature review, an iterative consultation process and mapping of key domains, concepts and elements to develop an initial SMI taxonomy that was subsequently reviewed in a two-round online Delphi survey with a purposive sample of international experts. Results: The final SMI taxonomy has 132 components classified into four domains: intervention characteristics, expected patient/caregiver self-management behaviours, outcomes for measuring SMIs and target population characteristics. The two-round Delphi exercise involving 27 international experts demonstrated overall high agreement with the proposed items, with a mean score (on a scale of 1-9) per component of 8.0 (range 6.1-8.8) in round 1 and 8.1 (range 7.0-8.9) in round 2. Conclusions: The SMI taxonomy contributes to building a common framework for the patient self-management field and can help implement and improve patient empowerment and facilitate comparative effectiveness research of SMIs. Patient or public contribution. Patients’ representatives contributed as experts in the Delphi process and as partners of the consortium.</p