Acute Care Physical and Occupational Therapy Early Intervention Pathway After Transcatheter Aortic Valve Replacement: A Retrospective Study

Purpose: Transcatheter aortic valve replacement (tAVR) has emerged as a less-invasive alternative to traditional surgical aortic valve replacement. The purpose of this study was to examine the effect of a novel clinical pathway with an emphasis on early physical therapy and occupational therapy on patients undergoing tAVR in the acute care setting. Methods: A retrospective study was conducted involving 189 patients who underwent tAVR. The control group (n = 74) included patients who underwent tAVR prior to the implementation of the pathway. The intervention group (n = 115) included patients who underwent tAVR following the implementation of the pathway. Inpatient length of stay and discharge disposition were measured. Results: No differences in demographics or clinical variables were found; for example, mean age was 79.5 ± 11.2 years, with 57% male in the control group versus 81.6 ± 8.4 years and 59% male in the intervention group. Length of stay was significantly lower in the intervention group (control 6.9 ± 5.4 days, intervention 4.8 ± 5.4 days,P = .009) and significantly shorter length of stay postprocedure (control 4.8 ± 2.9 days, intervention 3.5 ± 4.0, P= .015). The incidence of the patient\u27s discharge disposition to home increased from 77% of patients in the control group to 86% of patients in the intervention group but was not statistically significant (P = .118). Conclusions: A clinical pathway specific to patients post-tAVR provided early mobility, targeted education, individualized functional goals, and discharge disposition recommendations. Patients in the intervention group experienced reduced hospital length of stay

A systematic review of process evaluations for psychosocial interventions designed to improve the wellbeing and quality of life of community-dwelling people with dementia and their carers

Background: Psychosocial interventions improve the wellbeing and quality of life of People Living with Dementia (PLWD) and their family carers; but due to their complexity it can be challenging to identify mechanisms of action. We reviewed process evaluations that have sought to elucidate how these interventions work, to inform their implementation. Method: We systematically reviewed process evaluations of studies evaluating psychosocial interventions for PLWD in their own home and/or their family carers. We rated study quality using the Mixed Methods Appraisal Tool (MMAT). We described, with reference to Medical Research Council (2015) process evaluation guidance, how implementation, mechanisms of impact and contextual factors were investigated; and describe commonalities in the mechanisms of action identified across studies. Results: 24 included studies evaluated the processes of 22 interventions. These studies collectively applied five frameworks; almost all frameworks’ advised evaluations were theory-based and used mixed-methods analyses, but only 5/24 evaluation designs were informed by the intervention theory and 8/24 used mixed methods. 8/24 evaluations considered contextual factors in their design, though 20/24 cited contextual factors in findings. Interventions were more successful where PLWD were motivated and aware of potential benefits, and when carers could support engagement and were themselves supported by the intervention. How the intervention aligned with participants’ current needs and stage of dementia were key influencing factors. Conclusion: Knowing how interventions can influence change for community-dwelling people with dementia and their family carers will improve translation of trial findings into practice. Robust, theory-driven process evaluations can enable this

Pre-implementation planning for a new personalised, dementia post-diagnostic support intervention: exploring the perspective of professional stakeholders

Background: Onlya third of people with dementia receive both a diagnosis and post-diagnostic support.A new eight session, manualised, modular post-diagnostic support system (NIDUS (New Interventions for Independence in Dementia Study) –family), delivered remotely by non-clinical facilitators is the first scalable intervention to improve personalised goal attainment for people living with dementia.If widely translated into practice it could significantly improve care quality. Aims: We aimed to explore system-readiness for a scalable, personalised post-diagnostic support intervention. Methods: We conducted semi-structured interviews with professionals from dementia care services; the Consolidated Framework for Implementation Research (CFIR) guided interviews and their thematic analysis. Results: From 2022-23,we interviewed a purposive sample of 21 professionals from seven English NHS, health and social care services. We identified three themes: 1.Potential value of a personalised intervention:interviewees perceived the capacity for choice, supporting person-centred care and delivery by non-clinical facilitators as relative advantages over existing resources. 2. Compatibility and deliverability with existing systems:the NIDUS-family intervention model was perceived as compatible with service goals and clients’ needs, but current service infrastructures, financing and commissioning briefs constraining resources to those at greatest need as barriers to providing universal,post-diagnostic care. 3.Fit with current workforce skills:The intervention model aligned well with staff development plans and national policy to upskill support workers. Conclusion: Translating evidence for scalable and effective post-diagnostic care into practice will support national policies to widen access to support, but require a greater focus on prevention in commissioning briefs and resource planning

High-level transgene expression by homologous recombination-mediated gene transfer

Gene transfer and expression in eukaryotes is often limited by a number of stably maintained gene copies and by epigenetic silencing effects. Silencing may be limited by the use of epigenetic regulatory sequences such as matrix attachment regions (MAR). Here, we show that successive transfections of MAR-containing vectors allow a synergistic increase of transgene expression. This finding is partly explained by an increased entry into the cell nuclei and genomic integration of the DNA, an effect that requires both the MAR element and iterative transfections. Fluorescence in situ hybridization analysis often showed single integration events, indicating that DNAs introduced in successive transfections could recombine. High expression was also linked to the cell division cycle, so that nuclear transport of the DNA occurs when homologous recombination is most active. Use of cells deficient in either non-homologous end-joining or homologous recombination suggested that efficient integration and expression may require homologous recombination-based genomic integration of MAR-containing plasmids and the lack of epigenetic silencing events associated with tandem gene copies. We conclude that MAR elements may promote homologous recombination, and that cells and vectors can be engineered to take advantage of this property to mediate highly efficient gene transfer and expression

A Cytochrome b561 with Ferric Reductase Activity from the Parasitic Blood Fluke, Schistosoma japonicum

Parasites acquire their food from their hosts, either by feeding directly on tissues of the host, or by competing for ingested food. Adult schistosomes live within the vasculature of humans and rely on the blood cells and plasma they ingest and dissolved solutes they derive across their body surface, the tegument, for their nutrition. Schistosomes require host trace elements, notably iron, which is used as a co-factor in many biological reactions. Iron is especially important for schistosomes, for it has a significant role in egg formation and embryogenesis. In human tissues, iron predominates in the trivalent (ferric) form; however, it is the divalent (ferrous) form that is used as an essential co-factor for multiple biomolecules and enzymes. In order to be acquired from the host environment, the valency of iron must be modified to render it suitable for transport across the parasite membrane. This paper describes the molecular characterisation of a schistosome molecule that is crucial for bringing about this change in iron. Schistosoma japonicum Cytb561 is the first ferric reductase characterised in any parasitic helminth and emphasises the importance of iron, and other divalent cations, in these organisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A process evaluation of the new interventions for independence in dementia study family stream (NIDUS-Family)

The New Interventions for independence in Dementia Study (NIDUS)-Family is an effective Alzheimer’s Society funded manualised psychosocial intervention supporting people living with dementia and their family carers to attain goals they set towards living as independently and as well as possible at home for longer. The aim of this thesis was to conduct a process evaluation embedded into the intervention-arm population of the NIDUS-Family randomised controlled trial (RCT) to understand the causal pathways through which the intervention influenced change.A systematic review of process evaluation methodology for this population informed the design of the NIDUS-Family process evaluation. The Medical Research Council (MRC) Guidance (Moore et al, 2015) recommendations and a theory-driven convergent mixed-method design were applied. Research questions interrogated the theoretical principles and hypothesised causal assumptions to understand how NIDUS-Family influenced goal attainment and wellbeing in practice through identifying core implementation, mechanisms of impact and contextual factors.Overall, findings indicated participants positively experienced the NIDUS-Family intervention, describing it as being transformative, supportive, and having a positive impact on their wellbeing and dyadic relationship. Attrition, reach, adherence, delivery, and fidelity data demonstrated NIDUS-Family was delivered as intended against the protocol to its target audience. Core implementation factors were delivery from the facilitator of the NIDUS-Family approaches, strategies, and values. For dyads, mechanisms of impact were building a respectful, trusting, and impartial relationship with their facilitator which aided the development of meaningful goals and/or actions in which they could work through the modules towards finding manageable solutions. Core contextual factors impacting intervention implementation and mechanisms were dyadic participation and knowledge of dementia.These findings will directly inform the NIDUS-Family implementation study in helping adapt and translate the intervention into practice and widen the knowledge of process evaluation design to ensure more robust applications of frameworks and methods to enable more generalisable outcomes.</p