The 7 Habits of Highly Effective Implementation of eHealth Enabled Integrated Care

Introduction: ‘E-health enabled integrated care’ (eHEIC) has high potential to improve quality of care, widen access and increase efficiency. Experts and scholars increasingly report about difficulties of sustainable eHEIC implementation. These reports indicate in particular ‘human factors’ often being underestimated, in particular relating to changes in interdisciplinary collaboration and the role of physicians. More insight in determinants and interventions impacting these human factors is required to facilitate effective eHEIC implementation. Method: To identify relevant determinants and interventions, a mixed methods approach was undertaken. Two systematic literature reviews were performed to scrutinize current knowledge and experience related to the constructs of medical leadership and interdisciplinary collaboration during eHEIC implementation. Results from these reviews were compared and synthesized with the thematic analysed transcripts of 84 interviews with groups and individuals across Europe, preceded with 13 scoping interviews with topic experts. All interviews were held during structured site visits at 11 different deployment sites of the 3 ‘trail-blazing’ European eHEIC projects: BeyondSilos, CareWell and SmartCare. Furthermore, preparatory to all site visits, an online survey was (n = 159) held among the interviewees and their interdisciplinary teams. Results: Results provide insights in determinants and interventions that impact implementation, specifically relating the role of physicians. Identified determinants are categorized in 7 ‘habits and conditions’ characterizing effective eHEIC implementation: (1) Optimising work process impact, (2) (Re)defining and spanning interdisciplinary boundaries; (3) Knowledge sharing and mutual adaptability; (4) Creating and supporting reflective collaborations; (5) Hardwiring a climate of equality and trust; (6) Supporting laws, regulations and rules and (7) Leading for transformation. Identified interventions focus on: attitude, communication, engagement, knowledge, leadership/champions, relationships, shared mental model, tasks roles and responsibilities and training. Furthermore, this study revealed 6 domains relating the role of physicians engaged in eHEIC implementation, including: competencies in guiding new work-processes and associated socio-emotional issues; medical leadership; virtual physician-patient relationship and change management. Interviews and surveys showed that physicians are to be regarded as most critical in eHEIC implementation, impacting several determinants and influencing other professionals. Furthermore, interviewees often stated that physicians should be champions and/or coordinators in leading this implementation. Discussion & Practical Implications: While process redesign and IT use related issues regarding eHEIC have been studied extensively; it is the impact of these innovations on human factors between individual and groups of actors that makes a difference. This study emphasises the multi-faceted and complex characteristics of effective eHEIC implementation programs. Based on the current literature and a pan-European field study on such factors in eHEIC projects the identified topics provide guidance when preparing various disciplines and professionals. Also, this study indicates towards new fields in education of healthcare workforces, in particular physicians. Limitations & Further Study: Generalizability of our results must be reflected, as eHEIC implementation should be tailored to couleur locale. Although to date this study breaks new ground, it touches only on few aspects of eHEIC related change management. Further work, including wider variety of nations, regions and modes of integrated care, must be done to create omnipotent eHEIC implementation tool-kits

Do social cues in instructional videos affect attention allocation, perceived cognitive load, and learning outcomes under different visual complexity conditions?

Background:There are only few guidelines on how instructional videos should be designed to optimize learning. Recently, the effects of social cues on attention allocation and learning in instructional videos have been investigated. Due to inconsistent results, it has been suggested that the visual complexity of a video influences the effect of social cues on learning.Objectives:Therefore, this study compared the effects of social cues (i.e., gaze & gesture) in low and high visual complexity videos on attention, perceived cognitive load,and learning outcomes.Methods:Participants (N=71) were allocated to a social cue or no social cue condition and watched both a low and a high visual complexity video. After each video, participants completed a knowledge test.Results and Conclusions: Results showed that participants looked faster at referenced information and had higher learning outcomes in the low visual complexity condition. Social cues did not affect any of the dependent variables, except when including prior knowledge in the analysis: In this exploratory analysis, the inclusion of gaze and gesture cues in the videos did lead to better learning outcomes.Takeaways: Our results show that the visual complexity of instructional videos and prior knowledge are important to take into account in future research on attention and learning from instructional videos

Structure of the Cytoplasmic Loop between Putative Helices II and III of the Mannitol Permease of Escherichia coli: A Tryptophan and 5-Fluorotryptophan Spectroscopy Study

In this work, four single tryptophan (Trp) mutants of the dimeric mannitol transporter of Escherichia coli, EIImtl, are characterized using Trp and 5-fluoroTrp (5-FTrp) fluorescence spectroscopy. The four positions, 97, 114, 126, and 133, are located in a region shown by recent studies to be involved in the mannitol translocation process. To spectroscopically distinguish between the Trp positions in each subunit of dimeric EIImtl, 5-FTrp was biosynthetically incorporated because of its much simpler photophysics compared to those of Trp. The steady-state and time-resolved fluorescence methodologies used point out that all four positions are in structured environments, both in the absence and in the presence of a saturating concentration of mannitol. The fluorescence decay of all 5-FTrp-containing mutants was highly homogeneous, suggesting similar microenvironments for both probes per dimer. However, Stern-Volmer quenching experiments using potassium iodide indicate different solvent accessibilities for the two probes at positions 97 and 133. A 5 Å two-dimensional (2D) projection map of the membrane-embedded IICmtl dimer showing 2-fold symmetry is available. The results of this work are in better agreement with a 7 Å projection map from a single 2D crystal on which no symmetry was imposed.

Stability of neuropsychological test performance in older adults serving as normative controls for a study on postoperative cognitive dysfunction

OBJECTIVE: Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test-retest reliability. RESULTS: All tests had moderate to excellent test-retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation. Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014)

Rational Reprogramming of Fungal Polyketide First Ring Cyclization

Resorcylic acid lactones (RAL) and dihydroxyphenylacetic acid lactones (DAL) represent important pharmacophores with heat shock response and immune system modulatory activities. The biosynthesis of these fungal polyketides involves a pair of collaborating iterative polyketide synthases (iPKSs): a highly reducing iPKS (hrPKS) whose product is further elaborated by a nonreducing iPKS (nrPKS) to yield a 1,3-benzenediol moiety bridged by a macrolactone. Biosynthesis of unreduced polyketides requires the sequestration and programmed cyclization of highly reactive poly-β-ketoacyl intermediates to channel these uncommitted, pluripotent substrates towards defined subsets of the polyketide structural space. Catalyzed by product template (PT) domains of the fungal nrPKSs and discrete aromatase/cyclase enzymes in bacteria, regiospecific first-ring aldol cyclizations result in characteristically different polyketide folding modes. However, a few fungal polyketides, including the DAL dehydrocurvularin, derive from a folding event that is analogous to the bacterial folding mode. The structural basis of such a drastic difference in the way a PT domain acts has not been investigated until now. We report here that the fungal versus the bacterial folding mode difference is portable upon creating hybrid enzymes, and structurally characterize the resulting unnatural products. Using structure-guided active site engineering, we unravel structural contributions to regiospecific aldol condensations, and show that reshaping the cyclization chamber of a PT domain by only three selected point mutations is sufficient to reprogram the dehydrocurvularin nrPKS to produce polyketides with a fungal fold. Such rational control of first ring cyclizations will facilitate efforts towards the engineered biosynthesis of novel chemical diversity from natural unreduced polyketides

A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer

CRUK programme grant C587/A16354 and a research grant from Affitech AS.The study was supported by Cancer Research UK (CRUK) programme grant C587/A16354 and a research grant from Affitech AS

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation

AIMS: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1β, in patients with COVID-19, myocardial injury, and heightened inflammation. METHODS AND RESULTS: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg ( CONCLUSION: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28