Patient and public involvement and engagement with underserved communities in dementia research: Reporting on a partnership to co-design a website for postdiagnostic dementia support.

INTRODUCTION: Despite the advancements in Patient and Public Involvement and Engagement (PPIE), the voices of traditionally underserved groups are still poorly reflected in dementia research. This study aimed to report on a PPIE partnership between academics and members of the public from underserved communities to co-design Forward with Dementia-Social Care, a resource and information website supporting people receiving a dementia diagnosis. METHODS: The PPIE partnership was set up in four stages: 1-identifying communities that have been under-represented from PPIE in dementia research; 2-recruiting PPIE partners from these communities; 3-supporting PPIE partners to become confident to undertake their research roles and 4-undertaking research co-design activities in an equitable fashion. RESULTS: To address under-representation from PPIE in dementia research we recruited seven PPIE partners from Black, Asian and other minority ethnic groups; lesbian, gay, bisexual, transgender, queer+ communities; remote/rural area; religious minorities and partners living with rare forms of dementia. The partners met regularly throughout the project to oversee new sections for the study website, refine existing content and promote the website within their communities. CONCLUSION: Strategies can be used to successfully recruit and involve PPIE partners from underserved communities in co-design activities. These include networking with community leaders, developing terms of reference, setting out 'rules of engagement', and investing adequate resources and time for accessible and equitable involvement. These efforts facilitate the co-design of research outputs that reflect the diversity and complexity of UK contemporary society. PATIENT OR PUBLIC CONTRIBUTION: This study received support from seven members of the public with lived experience of dementia from communities that have been traditionally underserved in dementia research. These seven members of the public undertook the role of partners in the study. They all equally contributed to the study design, recruitment of participants, development and revision of topic guides for the interviews and development of the website. Three of these partners were also co-authors of this paper. On top of the activities shared with the other partners, they contributed to write independently of the academic team the section in this paper titled 'Partners' experiences, benefits and challenges of the partnership'. Further, they provided input in other sections of the paper on a par with the other (academic) co-authors.

Determining capacity of people with dementia to take part in research: an electronic survey study of researcher confidence, competence and training needs.

BACKGROUND: Researchers are required to determine whether a person has capacity to consent to a research study before they are able to participate. The Mental Capacity Act and accompanying Code of Practice for England and Wales provide some guidance on this process, but researchers have identified that it can be difficult to determine capacity to consent when a person has complex cognitive or communication needs. This study aimed to understand the experiences and opinions of researchers who recruit people with dementia to research projects, to inform the future development of training resources. METHODS: A mixed method, cross-sectional, electronic survey was circulated via social media and research networks in England and Wales. The survey remained open for ten weeks and included open and closed questions exploring respondents' confidence in determining capacity in the context of recruiting people with dementia to consent, their views on training and support they have experienced and their suggestions for future training and support needs. RESULTS: 60 respondents completed the survey from across England and Wales. Although 75% of respondents had experience of determining capacity to consent with people with dementia to research, only 13% rated themselves as feeling 'very confident' in this. Qualitative content analysis of open responses led to the generation of six themes, explaining researchers' confidence, competence and future training needs in this area: (1) Researcher uncertainties, (2) Lack of time, (3) Balancing information complexity with accessibility, (4) Gatekeepers, (5) Existing enablers and (6) Envisioning future training. CONCLUSIONS: Researchers would benefit from specific training in undertaking conversations around consent with people with dementia. People with dementia may have fluctuating capacity, and despite support from caregivers, researchers have little practical guidance on methods of determining a person's ability to understand or appreciate the information they have provided during the consent process. Given the development of large complex trials within dementia research, there is an urgency to develop specific and practical guidance and training for researchers working with people with dementia and their families.

Prevalence and functional impact of social (pragmatic) communication disorders.

BACKGROUND: The aim of this study was to evaluate the Children's Communication Checklist-2 (CCC-2) for measuring social-pragmatic communication deficits and to ascertain their prevalence and functional impact in a community sample. METHODS: We used parent and teacher responses to the CCC-2 to approximate inclusion (poor social-pragmatic skills) and exclusion (poor structural language skills or autistic symptomatology) criteria for social (pragmatic) communication disorder (SPCD). We tested the prevalence of social-pragmatic deficits in a population-based sample of children (n = 386) aged 5-6 years old using CCC-2 algorithms. We also investigated the academic and behavioural profiles of children with broadly defined limitations in social-pragmatic competence on the CCC-2. RESULTS: Regardless of the diagnostic algorithm used, the resulting prevalence rates for social-pragmatic deficits indicated that very few children had isolated social-communication difficulties (0-1.3%). However, a larger proportion of children (range: 6.1-10.5%) had social-pragmatic skills outside the expected range alongside structural language difficulties and/or autism spectrum symptoms, and this profile was associated with a range of adverse academic and behavioural outcomes. CONCLUSIONS: A considerable proportion of children in the early years of primary school has social-pragmatic deficits that interfere with behaviour and scholastic activity; however, these rarely occur in isolation. Exclusionary criteria that include structural language may lead to underidentification of individuals with social-pragmatic deficits that may benefit from tailored support and intervention.

Mutualistic coupling of vocabulary and non-verbal reasoning in children with and without language disorder.

Mutualism is a developmental theory that posits positive reciprocal relationships between distinct cognitive abilities during development. It predicts that abilities such as language and reasoning will influence each other's rates of growth. This may explain why children with Language Disorders also tend to have lower than average non-verbal cognitive abilities, as poor language would limit the rate of growth of other cognitive skills. The current study tests whether language and non-verbal reasoning show mutualistic coupling in children with and without language disorder using three waves of data from a longitudinal cohort study that over-sampled children with poor language at school entry (N = 501, 7-13 years). Bivariate Latent Change Score models were used to determine whether early receptive vocabulary predicted change in non-verbal reasoning and vice-versa. Models that included mutualistic coupling parameters between vocabulary and non-verbal reasoning showed superior fit to models without these parameters, replicating previous findings. Specifically, children with higher initial language abilities showed greater growth in non-verbal ability and vice versa. Multi-group models suggested that coupling between language and non-verbal reasoning was equally strong in children with language disorder and those without. This indicates that language has downstream effects on other cognitive abilities, challenging the existence of selective language impairments. Future intervention studies should test whether improving language skills in children with language disorder has positive impacts on other cognitive abilities (and vice versa), and low non-verbal IQ should not be a barrier to accessing such intervention.

How effective are digital interventions in increasing flu vaccination among pregnant women? A systematic review and meta-analysis.

BACKGROUND: Flu can have serious consequences for pregnant woman and unborn babies. Vaccination provides safe and effective protection, yet uptake among pregnant women is below national targets. Digital interventions are effective at increasing adherence to health interventions. AIMS: This review aimed to establish whether digital interventions are effective at increasing rates of flu vaccination among pregnant women, and to determine the overall effect size. METHOD: Systematic searches identified digital intervention trials, aiming to increase rate of flu vaccination among pregnant women. Random-effects meta-analysis provided a combined effect size and examined which mode of digital interventions had the largest effects on flu vaccination. RESULTS: Ten studies were included in the review. The majority of digital interventions were more effective at increasing rates of flu vaccination (7-81.3% uptake) than usual care or non-digital interventions (7.3-47.1% uptake). When meta-analysed, digital interventions had a small, non-significant effect (odds ratio [OR] = 1.29, 95% confidence interval [CI]: 0.71, 2.31), P = 0.40. Text messages (OR = 1.25, 95% CI: 0.58, 2.67), P = 0.57 appeared less effective than other digital interventions (OR = 1.58, 95% CI: 1.02, 2.46), P = 0.04. CONCLUSIONS: Overall, there is a lack of high-quality studies reporting the effectiveness of digital interventions at increasing flu vaccination during pregnancy. Future interventions may benefit from using video or social media to communicate messages for maximum success in targeting an increase in rates of flu vaccination in pregnancy.

Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome.

Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, we present novel evidence of strong covariation between fungal and bacterial communities across the host phylogeny, indicative of recruitment by hosts for specific suites of microbes. Using co-occurrence networks, we demonstrate marked variation across host taxonomy in patterns of covariation between bacterial and fungal abundances. Host phylogeny drives differences in the overall richness of bacterial and fungal communities, but the effect of diet on richness was only evident in the mammalian gut microbiome. Sample type, tissue storage and DNA extraction method also affected bacterial and fungal community composition, and future studies would benefit from standardized approaches to sample processing. Collectively these data indicate fungal microbiomes may play a key role in host fitness and suggest an urgent need to study multiple agents of the animal microbiome to accurately determine the strength and ecological significance of host-microbe interactions.

Oceanographic features and limited dispersal shape the population genetic structure of the vase sponge Ircinia campana in the Greater Caribbean.

Understanding population genetic structure can help us to infer dispersal patterns, predict population resilience and design effective management strategies. For sessile species with limited dispersal, this is especially pertinent because genetic diversity and connectivity are key aspects of their resilience to environmental stressors. Here, we describe the population structure of Ircinia campana, a common Caribbean sponge subject to mass mortalities and disease. Microsatellites were used to genotype 440 individuals from 19 sites throughout the Greater Caribbean. We found strong genetic structure across the region, and significant isolation by distance across the Lesser Antilles, highlighting the influence of limited larval dispersal. We also observed spatial genetic structure patterns congruent with oceanography. This includes evidence of connectivity between sponges in the Florida Keys and the southeast coast of the United States (>700 km away) where the oceanographic environment is dominated by the strong Florida Current. Conversely, the population in southern Belize was strongly differentiated from all other sites, consistent with the presence of dispersal-limiting oceanographic features, including the Gulf of Honduras gyre. At smaller spatial scales (<100 km), sites showed heterogeneous patterns of low-level but significant genetic differentiation (chaotic genetic patchiness), indicative of temporal variability in recruitment or local selective pressures. Genetic diversity was similar across sites, but there was evidence of a genetic bottleneck at one site in Florida where past mass mortalities have occurred. These findings underscore the relationship between regional oceanography and weak larval dispersal in explaining population genetic patterns, and could inform conservation management of the species.

"She knows me best": a qualitative study of patient and caregiver views on the role of the primary care physician follow-up post-hospital discharge in individuals admitted with chronic obstructive pulmonary disease or congestive heart failure.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) are at high-risk of readmission after hospital discharge. There is conflicting evidence however on whether timely follow-up with a primary care provider reduces that risk. The objective of this study is to understand the perspectives of patients with COPD and CHF, and their caregivers, on the role of primary care provider follow-up after hospital discharge. METHODS: A qualitative study design with semi-structured interviews was conducted among patients or their family caregivers admitted with COPD or CHF who were enrolled in a randomized controlled study at three acute care hospitals in Ontario, Canada. Participants were interviewed between December 2017 to January 2019, the majority discharged from hospital at least 30 days prior to their interview. Interviews were analyzed independently by three authors using a deductive directed content analysis, with the fourth author cross-comparing themes. RESULTS: Interviews with 16 participants (eight patients and eight caregivers) revealed four main themes. First, participants valued visiting their primary care provider after discharge to build upon their longitudinal relationship. Second, primary care providers played a key role in coordinating care. Third, there were mixed views on the ideal time for follow-up, with many participants expressing a desire to delay follow-up to stabilize following their acute hospitalization. Fourth, the link between the post-discharge visit and preventing hospital readmissions was unclear to participants, who often self-triaged based on their symptoms when deciding on the need for emergency care. CONCLUSIONS: Patients and caregivers valued in-person follow-up with their primary care provider following discharge from hospital because of the trust established through pre-existing longitudinal relationships. Our results suggest policy makers should focus on improving rates of primary care provider attachment and systems supporting informational continuity.

Host genetics and geography influence microbiome composition in the sponge Ircinia campana.

Marine sponges are hosts to large, diverse communities of microorganisms. These microbiomes are distinct among sponge species and from seawater bacterial communities, indicating a key role of host identity in shaping its resident microbial community. However, the factors governing intraspecific microbiome variability are underexplored and may shed light on the evolutionary and ecological relationships between host and microbiome. Here, we examined the influence of genetic variation and geographic location on the composition of the Ircinia campana microbiome. We developed new microsatellite markers to genotype I. campana from two locations in the Florida Keys, USA, and characterized their microbiomes using V4 16S rRNA amplicon sequencing. We show that microbial community composition and diversity is influenced by host genotype, with more genetically similar sponges hosting more similar microbial communities. We also found that although I. campana was not genetically differentiated between sites, microbiome composition differed by location. Our results demonstrate that both host genetics and geography influence the composition of the sponge microbiome. Host genotypic influence on microbiome composition may be due to stable vertical transmission of the microbial community from parent to offspring, making microbiomes more similar by descent. Alternatively, sponge genotypic variation may reflect variation in functional traits that influence the acquisition of environmental microbes. This study reveals drivers of microbiome variation within and among locations, and shows the importance of intraspecific variability in mediating eco-evolutionary dynamics of host-associated microbiomes.

Expansion and angiogenic potential of mesenchymal stem cells from patients with critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is a life- and limb-threatening condition affecting 1% to 10% of the population with peripheral arterial disease. Traditional revascularization options are not possible for up to 50% of CLI patients, in which case, the use of cellular therapies, such as bone marrow-derived mesenchymal stem cells (MSCs), hold great promise as an alternative revascularization therapy. However, no randomized, controlled phase 3 trials to date have demonstrated an improvement in limb salvage with cellular therapies. This may be due to poor cell quality (ie, inability to generate a sufficient number of angiogenic MSCs) or to the inadequate retention and viability of MSCs after delivery, or both. Because concerns remain about the expansion and angiogenic potential of autologous MSCs in the CLI population, the objective of this study was to examine the effect of our novel culture media supplement, pooled human platelet lysate (PL), in lieu of the standard fetal bovine serum (FBS), to improve the expansion potential of MSCs from CLI patients. We also characterized the in vitro angiogenic activity of MSCs from the tibia of amputated CLI limbs compared with MSCs from healthy donors. METHODS: MSCs were obtained from the tibia of four CLI patients (ISC) and four ISC patients with diabetes mellitus (ISC+DM) undergoing major amputation. Healthy MSCs were aspirated from the iliac crest of four young and healthy donors. MSCs were isolated and expanded in culture with PL or FBS. MSCs from passage 3 to 6 were used for phenotypic marker expression and for adipogenic and osteogenic differentiation and were tested for their in vitro angiogenic activity on human microdermal endothelial cells. In parallel MSCs were cultured to passage 11 for population-doubling calculations. RESULTS: MSCs from ISC and ISC+DM patients and from healthy patients exhibited appropriate expression of cell surface markers and differentiation capacity. Population doublings were significantly greater for PL-stimulated compared with FBS-stimulated MSCs in all groups. Biologically active amounts of angiogens were identified in the secretome of all MSCs without consistent trends among groups. PL expansion did not adversely affect the angiogenic activity of MSCs compared with FBS. The ISC and ISC+DM MSCs demonstrated angiogenic effects on endothelial cells similar to those of healthy and ISC MSCs. CONCLUSIONS: PL promotes the rapid expansion of MSCs from CLI and healthy persons. Importantly, MSCs expanded from CLI patients demonstrate the desired angiogenic activity compared with their healthy counterparts. We conclude that autologous MSCs from CLI patients can be sufficiently expanded with PL and be expected to deliver requisite angiogenic effects in vivo. We expect the improved expansion of ISC and ISC+DM with PL to be helpful in improving the successful delivery of autologous MSCs to patients with CLI.

A consensus introduction to serum replacements and serum-free media for cellular therapies.

The cell therapy industry is a fast-growing industry targeted toward a myriad of clinical indications. As the cell therapy industry matures and clinical trials hit their pivotal Phase 3 studies, there will be a significant need for scale-up, process validation, and critical raw material quality assurance. Part of the well discussed challenges of upscaling manufacturing processes there is a less discussed issue relating to the availability of raw materials in the needed quality and quantities. The FDA recently noted that over 80% of the 66 investigational new drug (IND) applications for mesenchymal stem cell (MSC) products analyzed described the use of FBS during manufacturing. Accumulated data from the past years show an acceleration in serum consumption by at least 10%-15% annually, which suggests that the global demand for serum may soon exceed the supply. Ongoing concerns of safety issues due to risks of various pathogen contaminations, as well as issues related to the aforementioned serum variability that can affect final product reproducibility, are strong motivators to search for serum substitutes or serum-free media. it is important to note that there are no accepted definitions for most of these terms which leads to misleading's and misunderstandings, where the same term might be defined differently by different vendors, manufacturer, and users. It is the drug developer's responsibility to clarify what the supplied labels mean and to identify the correct questions and audits to ensure quality. The paper reviews the available serum replacements, main components, basic strategies for replacement of serum and suggests definitions.

Extraction of maxillary canines: Esthetic perceptions of patient smiles among dental professionals and laypeople.

INTRODUCTION: Maxillary canines are generally considered important both cosmetically and functionally. Most claims on the importance of maxillary canines, however, have been based on expert opinions and clinician-based studies. There are no scientific studies in the literature reporting on their cosmetic importance or how laypeople perceive a smile treated by maxillary canine extractions. Our objective was to investigate whether there is any difference in the perceptions of patients' smiles treated by extracting either maxillary canines or first premolars, as judged by orthodontists, dentists, and laypeople. METHODS: This retrospective study included 24 participants who had unilateral or bilateral extraction of maxillary permanent canines and fixed appliances in the maxillary and mandibular arches to comprehensively correct the malocclusion, selected from orthodontic patients treated at Chesterfield Royal Hospital NHS trust in the United Kingdom over the last 20 years. The control group of patients had extraction of maxillary first premolars followed by fixed appliances and finished to an extremely high standard judged by the requirement that they had been submitted for the Membership in Orthodontics examination. The finished Peer Assessment Rating scores for this group were less than 5. The end-of-treatment frontal extraoral smiling and frontal intraoral views were presented for both groups. The photographs were blinded for extraction choice and standardized for size and brightness using computer software (Adobe Photoshop CC version 14.0; Adobe Systems, San Jose, Calif). The work file was converted to an editable pdf file and e-mailed to the assessors. The assessor panel consisted of 30 members (10 orthodontists, 10 dentists, and 10 laypeople), who were purposely selected. The measures were rated on a 10-point Likert scale. RESULTS: The attractiveness ratings were not statistically significantly different between the canine extraction and premolar extraction groups, with a mean difference of 0.33 (SD, 0.29) points. A 1-way repeated-measures analysis of variance to test the difference in scores among the laypeople, orthodontists, and dentists (n = 30) showed no statistically significant difference (Wilks lambda = 0.835; P = 0.138), and the Bonferroni test indicated that no pair-wise difference was statistically significant. CONCLUSIONS: No statistically significant difference was found in the smile attractiveness between canine extraction and premolar extraction patients as assessed by general dentists, laypeople, and orthodontists. Further high-quality studies are required to evaluate the effect of canine extraction and premolar substitution on functional occlusion.

Differential coloring reveals that plastids do not form networks for exchanging macromolecules.

Stroma-filled tubules named stromules are sporadic extensions of plastids. Earlier, photobleaching was used to demonstrate fluorescent protein diffusion between already interconnected plastids and formed the basis for suggesting that all plastids are able to form networks for exchanging macromolecules. However, a critical appraisal of literature shows that this conjecture is not supported by unequivocal experimental evidence. Here, using photoconvertible mEosFP, we created color differences between similar organelles that enabled us to distinguish clearly between organelle fusion and nonfusion events. Individual plastids, despite conveying a strong impression of interactivity and fusion, maintained well-defined boundaries and did not exchange fluorescent proteins. Moreover, the high pleomorphy of etioplasts from dark-grown seedlings, leucoplasts from roots, and assorted plastids in the accumulation and replication of chloroplasts5 (arc5), arc6, and phosphoglucomutase1 mutants of Arabidopsis thaliana suggested that a single plastid unit might be easily mistaken for interconnected plastids. Our observations provide succinct evidence to refute the long-standing dogma of interplastid connectivity. The ability to create and maintain a large number of unique biochemical factories in the form of singular plastids might be a key feature underlying the versatility of green plants as it provides increased internal diversity for them to combat a wide range of environmental fluctuations and stresses.

Multiple repair sequences in everyday conversations involving people with Parkinson's disease.

BACKGROUND: Features of dysarthria associated with Parkinson's disease (PD), such as low volume, variable rate of speech and increased pauses, impact speaker intelligibility. Those affected report restricted interactional participation, although this area is under explored. AIMS: To examine naturally occurring instances of problems with intelligibility that resulted in multiple attempts at repair in order to consider repair initiation strategies that might restrict or enhance participation. METHODS & PROCEDURES: Thirteen people with PD (PwPD) video-recorded over 10 h of informal conversation data in their home setting involving familiar conversation partners (CPs). Using a conversation analytic (CA) approach, and drawing on an existing typology of repair initiators (RIs) for everyday talk-in-interaction and their relative power to locate a turn's repairable element, the design and ordering of RIs used by CPs was addressed, alongside their local consequences. OUTCOMES & RESULTS: CPs tended to increase the specificity of their RIs in line with the existing typology, progressing from open class forms (e.g. 'mm?') to more specific forms (e.g. questions/partial repeats). Repeated open class repair initiators (OCRIs) were used where PD speakers' self-repair attempts provided limited information. Sometimes, however, specificity was increased too soon, before enough syntactic knowledge was gleaned, which resulted in an extended repair sequence. Where one OCRI followed another, the second always took a different form: lexically or in terms of prosodic/non-verbal features. RI forms not described in the existing typology were also identified, such as 'prompts to modify speech' (e.g. 'Speak louder') and repeating/rephrasing the original first pair part (e.g. question), and their effectiveness examined. CONCLUSIONS & IMPLICATIONS: First steps are presented towards the design of a communication intervention promoting the efficient resolution of repair to moderate social withdrawal and increase participation for this client group. Future research will need to explore the feasibility and acceptability of such a resource.

Corrigendum: Accessing care services after sexual violence: A systematic review exploring experiences of women in South Africa.

No abstract available.

A Novel Dehydrated Human Umbilical Cord Particulate Medical Device: Matrix Characterization, Performance, and Biocompatibility for the Management of Acute and Chronic Wounds.

Chronic wounds present a significant socioeconomic burden forecasted to increase in prevalence and cost. Minimally manipulated human placental tissues have been increasingly employed and proven to be advantageous in the treatment of chronic wounds, showing improved clinical outcomes and cost-effectiveness. However, technological advances have been constrained by minimal manipulation and homologous use criteria. This study focuses on the characterization of a novel dehydrated human umbilical cord particulate (dHUCP) medical device, which offers a unique allogeneic technological advancement and the first human birth tissue device for wound management. Characterization analyses illustrated a complex extracellular matrix composition conserved in the dHUCP device compared to native umbilical cord, with abundant collagens and glycosaminoglycans imbibing an intricate porous scaffold. Dermal fibroblasts readily attached to the intact scaffold of the dHUCP device. Furthermore, the dHUCP device elicited a significant paracrine proliferative response in dermal fibroblasts, in contrast to fibrillar collagen, a prevalent wound device. Biocompatibility testing in a porcine full-thickness wound model showed resorption of the dHUCP device and normal granulation tissue maturation during healing. The dHUCP device is a promising advancement in wound management biomaterials, offering a unique combination of structural complexity adept for challenging wound topographies and a microenvironment supportive of tissue regeneration.

Reflections on co-production: Developing a dementia research funding application with a diverse lived experience group.

Introduction and Background to Study: Published work on dementia research co-production focuses on developing health and social care interventions. Less is written about practicalities and experiences of co-producing dementia research funding applications. UK public contributors are typically from white middle class populations. Widening involvement is essential for co-produced research that meaningfully addresses health inequalities. We provide an example of a diverse lived experience group co-producing a dementia research funding application. An NIHR Dementia Career Development award funded PPIE work to develop a broad research idea. A culturally diverse lived experience group consisted of one person living with dementia, four carers and one former carer. Virtual group sessions drew on each person's unique experiences and expertise. Two co-leads collaborated closely with the researcher. Methods: We reflected on our experiences of diversity and inclusion within the group, based on a coproduced set of questions to guide reflection. Written records of reflections were captured and refined by the group. Results: We structured reflections into three overarching categories: Diversity and inclusion, Benefits to group members and Challenges. The group felt empowered, heard, and like equals in the process. Members valued diversity and mutual learning within the group. Involvement of co-leads was seen as democratic and inclusive. Some members felt Equality, Diversity and Inclusion (EDI) discussions were challenging. Discussion and Conclusions: We share valuable lessons learned in the process, including suggestions for facilitating EDI discussions, building in funding for time and travel to support relationship building, and ensuring PPIE remuneration processes are accessible and streamlined.

Access to personalised dementia care planning in primary care: a mixed methods evaluation of the PriDem intervention.

OBJECTIVES: Provision of personalised care planning is a national priority for people with dementia. Research suggests a lack of quality and consistency of care plans and reviews. The PriDem model of care was developed to deliver feasible and acceptable primary care-based postdiagnostic dementia care. We aimed to increase the adoption of personalised care planning for people with dementia, exploring implementation facilitators and barriers. DESIGN: Mixed-method feasibility and implementation study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: A medical records audit collected data on 179 community-dwelling people with dementia preintervention, and 215 during the intervention year. The qualitative study recruited 26 health and social care professionals, 14 people with dementia and 16 carers linked to participating practices. INTERVENTION: Clinical dementia leads (CDL) delivered a 12-month, systems-level intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to people with dementia and their carers. PRIMARY AND SECONDARY OUTCOME MEASURES: Adoption of personalised care planning was assessed through a preintervention and postintervention audit of medical records. Implementation barriers and facilitators were explored through semistructured qualitative interviews and non-participant observation, analysed using codebook thematic analysis informed by Normalisation Process Theory. RESULTS: The proportion of personalised care plans increased from 37.4% (95% CI 30.3% to 44.5%) preintervention to 64.7% (95% CI 58.3% to 71.0%) in the intervention year. Qualitative findings suggest that the flexible nature of the PriDem intervention enabled staff to overcome contextual barriers through harnessing the skills of the wider multidisciplinary team, delivering increasingly holistic care to patients. CONCLUSIONS: Meaningful personalised care planning can be achieved through a team-based approach. Although improved guidelines for care planning are required, commissioners should consider the benefits of a CDL-led approach. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Evaluating a model of best practice in primary care led post-diagnostic dementia care: feasibility and acceptability findings from the PriDem study.

OBJECTIVES: To evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures. DESIGN: A non-randomised, mixed methods, feasibility study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: We aimed to recruit 80 people with dementia (PWD) and 66 carers INTERVENTION: Clinical Dementia Leads delivered a 12-month intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to PWD and carers. OUTCOMES: Recruitment and retention rates were measured. A mixed methods process evaluation evaluated feasibility and acceptability of the intervention and study procedures. Using electronic care records, researchers extracted service use data and undertook a dementia care plan audit, preintervention and postintervention, assessing feasibility of measuring the primary implementation outcome: adoption of personalised care planning by participating general practices. Participants completed quality of life, and service use measures at baseline, 4 and 9 months. RESULTS: 60 PWD (75% of recruitment target) and 51 carers (77% of recruitment target) were recruited from seven general practices across four PCNs. Retention rate at 9 months was 70.0% of PWD and 76.5% of carers. The recruitment approach showed potential for including under-represented groups within dementia. Despite implementation challenges, the intervention was feasible and acceptable, and showed early signs of sustainability. Study procedures were feasible and accessible, although researcher capacity was crucial. Participants needed time and support to engage with the study. Care plan audit procedures were feasible and acceptable. CONCLUSIONS: The PriDem model is an acceptable and feasible intervention. A definitive study is warranted to fully inform dementia care policy and personalised dementia care planning guidance. Successful strategies to support inclusion of PWD and their carers in future research were developed. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Human platelet lysate stimulates high-passage and senescent human multipotent mesenchymal stromal cell growth and rejuvenation in vitro.

BACKGROUND AIMS: Multipotent mesenchymal stromal cells (MSCs) are clinically useful because of their immunomodulatory and regenerative properties, but MSC therapies are limited by the loss of self-renewal and cell plasticity associated with ex vivo expansion culture and, on transplantation, increased immunogenicity from xenogen exposure during culture. Recently, pooled human platelet lysate (hPL) has been used as a culture supplement to promote MSC growth; however, the effects of hPL on MSCs after fetal bovine serum (FBS) exposure remain unknown. METHODS: MSCs were cultured in medium containing FBS or hPL for up to 16 passages, and cell size, doubling time and immunophenotype were determined. MSC senescence was assessed by means of a fluorometric assay for endogenous ß-galactosidase expression. MSCs cultured with FBS for different numbers of passages were switched to hPL conditions to evaluate the ability of hPL to "rescue" the proliferative capacity of MSCs. RESULTS: hPL culture resulted in more rapid cell proliferation at earlier passages (passage 5 or earlier) than remove FBS; by day 4, hPL (5%) yielded an MSC doubling time of 1.28 days compared with 1.52 days in 16% FBS. MSCs cultured first in FBS and switched to hPL proliferated more and demonstrated less ß-galactosidase production and smaller cell sizes than remove MSCs continuously propagated in FBS. CONCLUSIONS: hPL enables rapid expansion of MSCs without adversely affecting immunophenotype. hPL culture of aged and senescent MSCs demonstrated cellular rejuvenation, reflected by decreased doubling time and smaller cell size. These results suggest that expansion of MSCs in hPL after FBS exposure can enhance cell phenotype and proliferative capacity.