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Patient-reported experiences and outcomes of virtual care during COVID-19: a systematic review
Abstract Introduction The onset of COVID-19 has caused an international upheaval of traditional in-person approaches to care delivery. Rapid system-level transitions to virtual care provision restrict the ability of healthcare professionals to evaluate care quality from the patient's perspective. This poses challenges to ensuring that patient-centered care is upheld within virtual environments. To address this, the study’s objective was to review how virtual care has impacted patient experiences and outcomes during COVID-19, through the use of patient-reported experience and outcome measures (PREMs and PROMs), respectively. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to evaluate patient responsiveness to virtual care during COVID-19. Using an exhaustive search strategy, relevant peer-reviewed articles published between January 2020 and 2022 were pulled from MEDLINE, CINAHL, EMBASE, and PsychInfo databases. Study quality was independently assessed by two reviewers using the Mixed Methods Appraisal Tool. A patient partner was consulted throughout the study to provide feedback and co-conduct the review. Results After removing duplicates, 6048 articles underwent title and abstract review, from which 644 studies were included in the full-text review stage. Following this, 102 articles were included in the study. Studies were published in 20 different countries, were predominantly cross-sectional, and reported on the delivery of virtual care in specialized adult outpatient settings. This review identified 29 validated PREMs and 43 PROMs. Several advantages to virtual care were identified, with patients citing greater convenience, (such as saving travel time and cost, less waiting experienced to see care providers) and increased protection from viral spread. Some studies also reported challenges patients and caregivers faced with virtual care, including feeling rushed during the virtual care appointment, lack of physical contact or examination presenting barriers, difficulty with communicating symptoms, and technology issues. Conclusion This review provides supportive evidence of virtual care experiences during the COVID-19 pandemic from patient and caregiver perspectives. This research provides a comprehensive overview of what patient-reported measures can be used to record virtual care quality amid and following the pandemic. Further research into healthcare professionals’ perspectives would offer a supportive lens toward a strong person-centered healthcare system.
Supporting physical activity for mobility in older adults with mobility limitations (SuPA Mobility): study protocol for a randomized controlled trial
Abstract Background Limited mobility in older adults consistently predicts both morbidity and mortality. As individuals age, the rates of mobility disability increase from 1.0% in people aged 15–24 to 20.6% in adults over 65 years of age. Physical activity can effectively improve mobility in older adults, yet many older adults do not engage in sufficient physical activity. Evidence shows that increasing physical activity by 50 min of moderate intensity physical activity in sedentary older adults with mobility limitations can improve mobility and reduce the incidence of mobility disability. To maximize the healthy life span of older adults, it is necessary to find effective and efficient interventions that can be delivered widely to prevent mobility limitations, increase physical activity participation, and improve quality of life in older adults. We propose a randomized controlled trial to assess the effect of a physical activity health coaching intervention on mobility in older adults with mobility limitations. Methods This randomized controlled trial among 290 (145 per group) community-dwelling older adults with mobility limitations, aged 70–89 years old, will compare the effect of a physical activity health coaching intervention versus a general healthy aging education program on mobility, as assessed with the Short Physical Performance Battery. The physical activity health coaching intervention will be delivered by exercise individuals who are trained in Brief Action Planning. The coaches will use evidence-based behavior change techniques including goal-setting, action planning, self-monitoring, and feedback to improve participation in physical activity by a known dose of 50 min per week. There will be a total of 9 health coaching or education sessions delivered over 26 weeks with a subsequent 26-week follow-up period, wherein both groups will receive the same duration and frequency of study visits and activities. Discussion The consequences of limited mobility pose a significant burden on the quality of life of older adults. Our trial is novel in that it investigates implementing a dose of physical activity that is known to improve mobility in older adults utilizing a health coaching intervention. Trial registration ClinicalTrials.gov Protocol Registration System: NCT05978336; registered on 28 July 2023.
A novel approach to risk exposure and epigenetics—the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health
Abstract Background Each mother–child dyad represents a unique combination of genetic and environmental factors. This constellation of variables impacts the expression of countless genes. Numerous studies have uncovered changes in DNA methylation (DNAm), a form of epigenetic regulation, in offspring related to maternal risk factors. How these changes work together to link maternal-child risks to childhood cardiometabolic and neurocognitive traits remains unknown. This question is a key research priority as such traits predispose to future non-communicable diseases (NCDs). We propose viewing risk and the genome through a multidimensional lens to identify common DNAm patterns shared among diverse risk profiles. Methods We identified multifactorial Maternal Risk Profiles (MRPs) generated from population-based data (n = 15,454, Avon Longitudinal Study of Parents and Children (ALSPAC)). Using cord blood HumanMethylation450 BeadChip data, we identified genome-wide patterns of DNAm that co-vary with these MRPs. We tested the prospective relation of these DNAm patterns (n = 914) to future outcomes using decision tree analysis. We then tested the reproducibility of these patterns in (1) DNAm data at age 7 and 17 years within the same cohort (n = 973 and 974, respectively) and (2) cord DNAm in an independent cohort, the Generation R Study (n = 686). Results We identified twenty MRP-related DNAm patterns at birth in ALSPAC. Four were prospectively related to cardiometabolic and/or neurocognitive childhood outcomes. These patterns were replicated in DNAm data from blood collected at later ages. Three of these patterns were externally validated in cord DNAm data in Generation R. Compared to previous literature, DNAm patterns exhibited novel spatial distribution across the genome that intersects with chromatin functional and tissue-specific signatures. Conclusions To our knowledge, we are the first to leverage multifactorial population-wide data to detect patterns of variability in DNAm. This context-based approach decreases biases stemming from overreliance on specific samples or variables. We discovered molecular patterns demonstrating prospective and replicable relations to complex traits. Moreover, results suggest that patterns harbour a genome-wide organisation specific to chromatin regulation and target tissues. These preliminary findings warrant further investigation to better reflect the reality of human context in molecular studies of NCDs. Graphical Abstract
Let There be Morphine: Structural Insights into Functional and Evolutionary Relationships of Morphine Biosynthesis in Opium Poppy
Benzylisoquinoline alkaloids are a large and diverse class of plant specialized metabolites known for their pharmaceutical properties, including the tumor suppressant noscapine, vasodilator papaverine, antimicrobial sanguinarine, and the important analgesics codeine, morphine, and their semisynthetic derivatives. The latter group of analgesics are known as morphinan alkaloids or opiates and are produced solely in select members of the genus Papaver, most importantly Papaver somniferum commonly known as opium poppy. This thesis highlights the use of structural biology in multidisciplinary approaches to understand the biosynthesis of morphinan alkaloids in opium poppy and related species. Dehydroreticuline reductase and codeinone reductase are closely related enzymes from the aldo-keto reductase superfamily catalyzing the second and second-last steps, respectively, in morphine biosynthesis in opium poppy. The elucidation of the crystal structure of codeinone reductase reveals novel structural features allowing for the in-depth analysis of substrate binding and catalysis leading to the engineering of substrate specificity. This structure also provides the means for the homology modeling of dehydroreticuline reductase giving insight into its novel catalytic mechanism. Transcriptomic analysis of representative Papaver species reveals putative morphinan biosynthetic enzyme orthologues and the ubiquitous distribution of dehydroreticuline reductase and codeinone reductase, among other morphinan biosynthetic enzymes. Structural analysis and functional/kinetic characterization of aldo-keto reductases demonstrates the ubiquitous conservation of dehydroreticuline reductase and codeinone reductase activity in the genus Papaver. These results challenge the current evolutionary narrative of morphinan biosynthesis suggesting:  a more ancient neofunctionalization of early enzymatic steps of morphinan biosynthesis than previously believed and  that morphinan biosynthesis evolved via the patchwork evolutionary model. Enzymatic latency and ligand binding affinity both provide a platform for the neofunctionalization of novel enzymatic activities. The alkaloid binding capabilities of pathogenesis related 10 proteins provides a means to understand the neofunctionalization of the morphine biosynthetic enzymes thebaine synthase and neopinone isomerase, alongside a biological role in alkaloid storage for abundant non-catalytic pathogenesis related 10 proteins. Their binding to alkaloids is predicted to promote the formation of protein-alkaloid aggregates based on binding-induced conformational changes observed through X-ray crystallography and dramatic changes in sucrose gradient fractionation.