What are the priorities for research of older people living in their own home, including those living with frailty? A systematic review and content analysis of studies reporting older people's priorities and unmet needs.

BACKGROUND: There is limited evidence regarding the needs of older people, including those living with frailty, to inform research priority setting. OBJECTIVES: This systematic review aimed to identify the range of research priorities of community-dwelling older people living in their own home, including those living with frailty. METHODS: Included studies were from economically developed countries and designed to identify the priorities for research or unmet needs of community-dwelling older people. Studies were excluded if they described priorities relating to specific health conditions. Medline, Embase, PsycInfo and CINAHL were searched (January 2010-June 2022), alongside grey literature. Study quality was assessed, but studies were not excluded on the basis of quality. A bespoke data extraction form was used and content analysis undertaken to synthesise findings. RESULTS: Seventy-five reports were included. Seven explicitly aimed to identify the priorities or unmet needs of frail older people; 68 did not specify frailty as a characteristic. Study designs varied, including priority setting exercises, surveys, interviews, focus groups and literature reviews. Identified priorities and unmet needs were organised into themes: prevention and management, improving health and care service provision, improving daily life, meeting carers' needs and planning ahead. DISCUSSION: Many priority areas were raised by older people, carers and health/care professionals, but few were identified explicitly by/for frail older people. An overarching need was identified for tailored, collaborative provision of care and support. CONCLUSION: Review findings provide a valuable resource for researchers and health/care staff wishing to focus their research or service provision on areas of importance for older people.

Development of the Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology: a qualitative synthesis of interventions in randomised controlled trials.

INTRODUCTION: Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology. METHOD: We developed our typology by qualitatively synthesising community-based complex interventions to sustain independence in older people, evaluated in randomised controlled trials (RCTs), in four stages: (i) systematically identifying relevant RCTs; (ii) extracting descriptions of interventions (including control) using the Template for Intervention Description and Replication; (iii) generating categories of key intervention features and (iv) grouping the interventions based on these categories. PROSPERO registration: CRD42019162195. RESULTS: Our search identified 129 RCTs involving 266 intervention arms. The Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology comprises 14 action components and 5 tailoring components. Action components include procedures for treating patients or otherwise intended to directly improve their outcomes; regular examples include formal homecare; physical exercise; health education; activities of daily living training; providing aids and adaptations and nutritional support. Tailoring components involve a process that may result in care planning, with multiple action components being planned, recommended or prescribed. Multifactorial action from care planning was the most common tailoring component. It involves individualised, multidomain assessment and management, as in comprehensive geriatric assessment. Sixty-three different intervention types (combinations) were identified. CONCLUSIONS: Our typology provides an empirical basis for service planning and evidence synthesis. We recommend better reporting about organisational aspects of interventions and usual care.

The role of the healthcare assistant on a stroke unit: A scoping review.

OBJECTIVE: This scoping review explores the role of a healthcare assistant on a stroke unit, potential barriers to role fulfilment and whether stroke-specific training could enhance rehabilitative practice. DATA SOURCES: Searches were conducted on CINAHL, MEDLINE and APA PsycInfo in May 2021 and repeated in September 2022. METHODS: This scoping review was guided by Arksey and O'Malley's framework. Article selection and data extraction were conducted by one researcher using a structured proforma. A narrative approach to data synthesis was undertaken following the research questions. RESULTS: From a combined total of 533 articles, sixty-six full-text articles were assessed for eligibility. Sixteen full articles were included in this review. A healthcare assistants' role was viewed as caring directly for patients - some individuals felt they contributed to rehabilitation during these tasks, and that they could be undervalued by multidisciplinary team members, patients and their families. The barriers identified to healthcare assistants' role fulfilment were lack of time, training and staffing shortages. Training was perceived to improve healthcare assistants' communication, confidence and knowledge but training needed to be flexible, ward based and accommodate staffing shortages. However, it is unclear whether training has any clinical benefit for patients. CONCLUSION: Healthcare assistants are well placed to enhance rehabilitative practice with patients; however, there are clear perceived barriers to this occurring. Future research should aim to define the role of healthcare assistants and explore whether further stroke-specific training could cause clinical benefits for patients.

In cellulo FRET-FLIM and single molecule tracking reveal the supra-molecular organization of the pyoverdine bio-synthetic enzymes in Pseudomonas aeruginosa.

The bio-synthesis of pyoverdine (PVD) in Pseudomonas aeruginosa involves multiple enzymatic steps including the action of non-ribosomal peptide synthetases (NRPSs). One hallmark of NRPS is their ability to make usage of non-proteinogenic amino-acids synthesized by co-expressed accessory enzymes. It is generally proposed that different enzymes of a secondary metabolic pathway assemble into large supra-molecular complexes. However, evidence for the assembly of sequential enzymes in the cellular context is sparse. Here, we used in cellulo single-molecule tracking and Förster resonance energy transfer measured by fluorescence lifetime microscopy (FRET-FLIM) to explore the spatial partitioning of the ornithine hydroxylase PvdA and its interactions with NRPS. We found PvdA was mostly diffusing bound to large complexes in the cytoplasm with a small exchangeable trapped fraction. FRET-FLIM clearly showed that PvdA is physically interacting with PvdJ, PvdI, PvdL, and PvdD, the four NRPS involved in the PVD pathway in Pseudomonas aeruginosa PAO1. The binding modes of PvdA were strikingly different according to the NRPS it is interacting with, suggesting that PvdA binding sites have co-evolved with the enzymatic active sites of NRPS. Our data provide evidence for strongly organized multi-enzymatic complexes responsible for the bio-synthesis of PVD and illustrate how binding sites have evolved to finely control the co-localization of sequential enzymes and promote metabolic pathway efficiency.

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53.

The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by 'high-risk' mucosal human papilloma viruses, including human cervical carcinoma and a growing number of head-and-neck cancers, p53 is degraded by the viral oncoprotein E6 (ref. 2). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4). Neither E6 nor E6AP are separately able to recruit p53 (refs 3, 5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus.

New horizons in evidence-based care for older people: individual participant data meta-analysis.

Evidence-based decisions on clinical and cost-effectiveness of interventions are ideally informed by meta-analyses of intervention trial data. However, when undertaken, such meta-analyses in ageing research have typically been conducted using standard methods whereby summary (aggregate) data are extracted from published trial reports. Although meta-analysis of aggregate data can provide useful insights into the average effect of interventions within a selected trial population, it has limitations regarding robust conclusions on which subgroups of people stand to gain the greatest benefit from an intervention or are at risk of experiencing harm. Future evidence synthesis using individual participant data from ageing research trials for meta-analysis could transform understanding of the effectiveness of interventions for older people, supporting evidence-based and sustainable commissioning. A major advantage of individual participant data meta-analysis (IPDMA) is that it enables examination of characteristics that predict treatment effects, such as frailty, disability, cognitive impairment, ethnicity, gender and other wider determinants of health. Key challenges of IPDMA relate to the complexity and resources needed for obtaining, managing and preparing datasets, requiring a meticulous approach involving experienced researchers, frequently with expertise in designing and analysing clinical trials. In anticipation of future IPDMA work in ageing research, we are establishing an international Ageing Research Trialists collective, to bring together trialists with a common focus on transforming care for older people as a shared ambition across nations.

An investigation into the optimal wear time criteria necessary to reliably estimate physical activity and sedentary behaviour from ActiGraph wGT3X+ accelerometer data in older care home residents.

BACKGROUND: Research protocols regarding the use of ActiGraph wGT3X+ accelerometers in care home residents are yet to be established. The purpose of this study was to identify the minimal wear time criteria required to achieve reliable estimates of physical activity (PA) and sedentary behaviour (SB) in older care home residents. METHODS: Ninety-four older adults from 14 care homes wore an ActiGraph wGT3X+ accelerometer on the right hip for 7 consecutive days. A pragmatic, staged approach was adopted in order to explore the effect of: monitoring day; minimum daily wear time and number of wear days on estimates of four outcomes derived from the accelerometer data: counts.day- 1, counts.minute- 1, PA time and SB time. RESULTS: Data from 91 participants (mean age: 84 ± 9 years, 34% male) was included in the analysis. No effect of monitoring day was observed. Lowering the daily wear time to ≥ 8 h (compared to ≥10 h) had no effect on the outcomes of interest. Four days of monitoring was sufficient to provide reliable estimates of all four outcomes. CONCLUSION: In this study, a minimum wear time criterion of ≥ 8 h on any 4 days was required to derive reliable estimates of PA and SB from ActiGraph wGT3X+ accelerometer data in older care home residents.

Risk factors for manifestations of frailty in hospitalized older adults: A qualitative study.

AIMS: To explore the experiences of older people and ward staff to identify modifiable factors (risk factors) which have the potential to reduce development or exacerbation of manifestations of frailty during hospitalization. To develop a theoretical framework of modifiable risk factors. DESIGN: Qualitative descriptive study. METHODS: Qualitative interviews with recently discharged older people (n = 18) and focus groups with ward staff (n = 22) were undertaken between July and October 2019. Data were analysed using directed content analysis. RESULTS: Themes identified related to attitude to risk, communication and, loss of routine, stimulation and confidence. Using findings from this study and previously identified literature, we developed a theoretical framework including 67 modifiable risk factors. Risk factors are grouped by patient risk factor domains (pain, medication, nutritional/fluid intake, mobility, elimination, infection, additional patient risk factors) and linked care management sub-domains (including risk factors relating to the ward environment, process of care, ward culture or broader organizational set up). Many of the additional 36 risk factors identified by this study were related to care management sub-domains. CONCLUSION: A co-ordinated approach is needed to address modifiable risk factors which lead to the development or exacerbation of manifestations of frailty in hospitalized older people. Risk assessment and management practices should not be duplicative and, should recognize and address modifiable risk factors which occur at the ward and organizational level. IMPACT: Some older people leave hospital more dependent than when they come in and this is, in part, due to the environment and process of care and not just the severity of their presenting illness. Many of the risk factors identified need to be addressed at an organizational rather than individual level. Findings will inform a programme of research to develop and test a novel system of care aimed at preventing loss of independence in hospitalized older people.

Inter-rater reliability of care home staff's proxy judgements with residents' assessments of their own health-related quality of life: an analysis of the PATCH trial EQ-5D data.

OBJECTIVES: to compare care staff proxies with care home residents' self-assessment of their health-related quality of life (HRQoL). METHODS: we assessed the degree of inter-rater reliability between residents and care staff proxies for the EQ-5D-5L index, domains and EQ Visual Analogue Scale at baseline, 3 months and 6 months, collected as part of the PATCH trial. We calculated kappa scores. Interpreted as <0 no agreement, 0-0.2 slight, 0.21-0.60 fair to moderate and >0.6 substantial to almost perfect agreement. Qualitative interviews with care staff and researchers explored the challenges of completing these questions. RESULTS: over 50% of the HRQoL data from residents was missing at baseline compared with a 100% completion rate by care staff proxies. A fair-to-moderate level of agreement was found for the EQ-5D-5L index. A higher level of agreement was achieved for the EQ-5D-5L domains of mobility and pain. Resident 'non-completers' were more likely to: be older, have stayed a longer duration in the care home, have lower Barthel Index and Physical Activity and Mobility in Residential Care (PAM-RC) scores, a greater number of co-morbidities and have joined the trial through consultee agreement. Interviews with staff and researchers indicated that it was easier to rate residents' mobility levels than other domains, but in general it was difficult to obtain data from residents or to make an accurate proxy judgement for those with dementia. CONCLUSIONS: whilst assessing HRQoL by care staff proxy completion provides a more complete dataset, uncertainty remains as to how representative these values are for different groups of residents within care homes.

An intervention to increase physical activity in care home residents: results of a cluster-randomised, controlled feasibility trial (the REACH trial).

BACKGROUND: Care home (CH) residents are mainly inactive, leading to increased dependency and low mood. Strategies to improve activity are required. DESIGN AND SETTING: Cluster randomised controlled feasibility trial with embedded process and health economic evaluations. Twelve residential CHs in Yorkshire, United Kingdom, were randomised to the MoveMore intervention plus usual care (UC) (n = 5) or UC only (n = 7). PARTICIPANTS: Permanent residents aged ≥65 years. INTERVENTION: MoveMore: a whole home intervention involving all CH staff designed to encourage and support increase in movement of residents. OBJECTIVES AND MEASUREMENTS: Feasibility objectives relating to recruitment, intervention delivery, data collection and follow-up and safety concerns informed the feasibility of progression to a definitive trial. Data collection at baseline, 3, 6 and 9 months included: participants' physical function and mobility, perceived health, mood, quality of life, cognitive impairment questionnaires; accelerometry; safety data; intervention implementation. RESULTS: 300 residents were screened; 153 were registered (62 MoveMore; 91 UC). Average cluster size: MoveMore: 12.4 CHs; UC: 13.0 CHs. There were no CH/resident withdrawals. Forty (26.1%) participants were unavailable for follow-up: 28 died (12 MoveMore; 16 UC); 12 moved from the CH. Staff informant/proxy data collection for participants was >80%; data collection from participants was <75%; at 9 months, 65.6% of residents provided valid accelerometer data; two CHs fully, two partially and one failed to implement the intervention. There were no safety concerns. CONCLUSIONS: Recruiting CHs and residents was feasible. Intervention implementation and data collection methods need refinement before a definitive trial. There were no safety concerns.

Information provision for stroke survivors and their carers.

BACKGROUND: A stroke is a sudden loss of brain function caused by lack of blood supply. Stroke can lead to death or physical and cognitive impairment and can have long lasting psychological and social implications. Research shows that stroke survivors and their families are dissatisfied with the information provided and have a poor understanding of stroke and associated issues. OBJECTIVES: The primary objective is to assess the effects of active or passive information provision for stroke survivors (people with a clinical diagnosis of stroke or transient ischaemic attack (TIA)) or their identified carers. The primary outcomes are knowledge about stroke and stroke services, and anxiety. SEARCH METHODS: We updated our searches of the Cochrane Stroke Group Specialised Register on 28 September 2020 and for the following databases to May/June 2019: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5) and the Cochrane Database of Systematic Reviews (CDSR; 2019, Issue 5) in the Cochrane Library (searched 31 May 2019), MEDLINE Ovid (searched 2005 to May week 4, 2019), Embase Ovid (searched 2005 to 29 May 2019), CINAHL EBSCO (searched 2005 to 6 June 2019), and five others. We searched seven study registers and checked reference lists of reviews. SELECTION CRITERIA: Randomised trials involving stroke survivors, their identified carers or both, where an information intervention was compared with standard care, or where information and another therapy were compared with the other therapy alone, or where the comparison was between active and passive information provision without other differences in treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. We categorised interventions as either active information provision or passive information provision: active information provision included active participation with subsequent opportunities for clarification and reinforcement; passive information provision provided no systematic follow-up or reinforcement procedure. We stratified analyses by this categorisation. We used GRADE methods to assess the overall certainty of the evidence. MAIN RESULTS: We have added 12 new studies in this update. This review now includes 33 studies involving 5255 stroke-survivor and 3134 carer participants. Twenty-two trials evaluated active information provision interventions and 11 trials evaluated passive information provision interventions. Most trials were at high risk of bias due to lack of blinding of participants, personnel, and outcome assessors where outcomes were self-reported. Fewer than half of studies were at low risk of bias regarding random sequence generation, concealment of allocation, incomplete outcome data or selective reporting. The following estimates have low certainty, based on the quality of evidence, unless stated otherwise. Accounting for certainty and size of effect, analyses suggested that for stroke survivors, active information provision may improve stroke-related knowledge (standardised mean difference (SMD) 0.41, 95% confidence interval (CI) 0.17 to 0.65; 3 studies, 275 participants), may reduce cases of anxiety and depression slightly (anxiety risk ratio (RR) 0.85, 95% CI 0.68 to 1.06; 5 studies, 1132 participants; depression RR 0.83, 95% CI 0.68 to 1.01; 6 studies, 1315 participants), may reduce Hospital Anxiety and Depression Scale (HADS) anxiety score slightly, (mean difference (MD) -0.73, 95% CI -1.10 to -0.36; 6 studies, 1171 participants), probably reduces HADS depression score slightly (MD (rescaled from SMD) -0.8, 95% CI -1.27 to -0.34; 8 studies, 1405 participants; moderate-certainty evidence), and may improve each domain of the World Health Organization Quality of Life assessment short-form (WHOQOL-BREF) (physical, MD 11.5, 95% CI 7.81 to 15.27; psychological, MD 11.8, 95% CI 7.29 to 16.29; social, MD 5.8, 95% CI 0.84 to 10.84; environment, MD 7.0, 95% CI 3.00 to 10.94; 1 study, 60 participants). No studies evaluated positive mental well-being. For carers, active information provision may reduce HADS anxiety and depression scores slightly (MD for anxiety -0.40, 95% CI -1.51 to 0.70; 3 studies, 921 participants; MD for depression -0.30, 95% CI -1.53 to 0.92; 3 studies, 924 participants), may result in little to no difference in positive mental well-being assessed with Bradley's well-being questionnaire (MD -0.18, 95% CI -1.34 to 0.98; 1 study, 91 participants) and may result in little to no difference in quality of life assessed with a 0 to 100 visual analogue scale (MD 1.22, 95% CI -7.65 to 10.09; 1 study, 91 participants). The evidence is very uncertain (very low certainty) for the effects of active information provision on carers' stroke-related knowledge, and cases of anxiety and depression. For stroke survivors, passive information provision may slightly increase HADS anxiety and depression scores (MD for anxiety 0.67, 95% CI -0.37 to 1.71; MD for depression 0.39, 95% CI -0.61 to 1.38; 3 studies, 227 participants) and the evidence is very uncertain for the effects on stroke-related knowledge, quality of life, and cases of anxiety and depression. For carers, the evidence is very uncertain for the effects of passive information provision on stroke-related knowledge, and HADS anxiety and depression scores. No studies of passive information provision measured carer quality of life, or stroke-survivor or carer positive mental well-being. AUTHORS' CONCLUSIONS: Active information provision may improve stroke-survivor knowledge and quality of life, and may reduce anxiety and depression. However, the reductions in anxiety and depression scores were small and may not be important. In contrast, providing information passively may slightly worsen stroke-survivor anxiety and depression scores, although again the importance of this is unclear. Evidence relating to carers and to other outcomes of passive information provision is generally very uncertain. Although the best way to provide information is still unclear, the evidence is better for strategies that actively involve stroke survivors and carers and include planned follow-up for clarification and reinforcement.

Benchtop holdup assay for quantitative affinity-based analysis of sequence determinants of protein-motif interactions.

Many protein-protein interactions are mediated by short linear peptide motifs binding to cognate proteins or protein domains. Such interactions often display affinities in the mid-micromolar range that are challenging to quantify accurately, especially when the motifs harbor single-point mutations. Here, we present a manual benchtop assay for determining affinities of weak interactions between a purified protein and a peptide array representing mutants of a target motif. The assay is based on the "holdup" principle, a chromatographic approach allowing sensitive detection of weak interactions at equilibrium and accurate estimation of their binding free energy. We tested two alternative setups using, as a readout, either capillary electrophoresis or fluorescence. Using this approach, we studied the amino acid sequence determinants of the interactions between HPV16 E6 viral oncoprotein and single-point mutants of its prototypical target LXXLL motif from the E3 ubiquitin ligase E6AP. Comparing SPOT peptide array and holdup approaches revealed a good agreement for most interactions except the weakest ones, which were only detected by holdup assay. In addition, the strongest interactions were validated by Surface-Plasmon Resonance. The manual holdup procedure proposed here can be readily adapted for accurate evaluation of a wide variety of protein-motif interactions displaying low to medium affinities.

A posture and mobility training package for care home staff: results of a cluster randomised controlled feasibility trial (the PATCH trial).

BACKGROUND: provision of care for care home residents with complex needs is challenging. Physiotherapy and activity interventions can improve well-being but are often time-limited and resource intensive. A sustainable approach is to enhance the confidence and skills of staff who provide care. This trial assessed the feasibility of undertaking a definitive evaluation of a posture and mobility training programme for care staff. DESIGN AND SETTING: a cluster randomised controlled feasibility trial with embedded process evaluation. Ten care homes in Yorkshire, United Kingdom, were randomised (1:1) to the skilful care training package (SCTP) or usual care (UC). PARTICIPANTS: residents who were not independently mobile. INTERVENTION: SCTP-delivered by physiotherapists to care staff. OBJECTIVES AND MEASUREMENTS: key objectives informed progression to a definitive trial. Recruitment, retention and intervention uptake were monitored. Data, collected by a blinded researcher, included pain, posture, mobility, hospitalisations and falls. This informed data collection feasibility and participant safety. RESULTS: a total of 348 residents were screened; 146 were registered (71 UC, 75 SCTP). Forty two were lost by 6 months, largely due to deaths. While data collection from proxy informants was good (>95% expected data), attrition meant that data completion rates did not meet target. Data collection from residents was poor due to high levels of dementia. Intervention uptake was variable-staff attendance at all sessions ranged from 12.5 to 65.8%. There were no safety concerns. CONCLUSION: care home and resident recruitment are feasible, but refinement of data collection approaches and intervention delivery are needed for this trial and care home research more widely.

Factors influencing sedentary behaviours after stroke: findings from qualitative observations and interviews with stroke survivors and their caregivers.

BACKGROUND: Stroke survivors are more sedentary than healthy, age-matched controls, independent of functional capacity. Interventions are needed to encourage a reduction in overall sedentary time, and regular breaks in prolonged periods of sedentary behaviour. This study captured the views and experiences of stroke survivors and their caregivers related to sedentary behaviour after stroke, to inform the development of an intervention to reduce sedentary behaviour. METHODS: Mixed-methods qualitative study. Non-participant observations were completed in two stroke services, inclusive of inpatient and community settings in the United Kingdom. Semi-structured interviews were conducted with stroke survivors and their caregivers (if available) at six- or nine-months post-stroke. Underpinned by the capability, opportunity and motivation (COM-B) model of behaviour change, observational data (132 h) were analysed thematically and interview data (n = 31 stroke survivors, n = 12 caregivers) were analysed using the Framework approach. RESULTS: Observation participants differed in functional ability whereas stroke survivor interviewees were all ambulant. Six themes related to sedentary behaviour after stroke were generated: (1) sedentary behaviour levels and patterns after stroke; (2) the physical and social environment in the stroke service and in the home; (3) standing and movement capability after stroke; (4) emotion and motivation after stroke; (5) caregivers' influence on, and role in influencing stroke survivors' sedentary behaviour; and (6) intervening to reduce sedentary behaviour after stroke. Capability, opportunity and motivation were influenced by the impact of the stroke and caregivers' inclination to support sedentary behaviour reduction. Stroke survivors reported being more sedentary than they were pre-stroke due to impaired balance and co-ordination, increased fatigue, and reduced confidence in mobilising. Caregivers inclination to support stroke survivors to reduce sedentary behaviour depended on factors including their willingness to withdraw from the caregiver role, and their perception of whether the stroke survivor would act on their encouragement. CONCLUSIONS: Many stroke survivors indicate being open to reducing sedentary behaviour, with appropriate support from stroke service staff and caregivers. The findings from this study have contributed to an intervention development process using the Behaviour Change Wheel (BCW) approach to develop strategies to reduce sedentary behaviour after stroke.

Evaluation of an Extended Stroke Rehabilitation Service (EXTRAS): A Randomized Controlled Trial and Economic Analysis.

Background and Purpose- There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined. Methods- EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat. Results- Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, -0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: -£311 (-$450 [95% CI, -£3292 to £2787; -$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95% CI, 0.01 to 0.12]). At current conventional thresholds of willingness to pay (£20 000 [$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective. Conclusions- EXTRAS did not significantly improve stroke survivors' performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care. Clinical Trial Registration- URL: www.isrctn.com. Unique identifier: ISRCTN45203373.

Supporting carers of stroke survivors to reduce carer burden: development of the Preparing is Caring intervention using Intervention Mapping.

BACKGROUND: Burden is well documented among carers of stroke survivors, yet current evidence is insufficient to determine if any strategies reduce this negative outcome. Existing interventions for carers of stroke survivors typically involve supporting carers according to their individual needs through face-to-face interactions and provision of information including workbooks or educational guides. To date, no interventions have been developed using a method which systematically incorporates evidence, behaviour change theories, and stakeholder involvement to change the behaviours of carers and relevant individuals who support carers. This study aimed to develop a programme plan for a theory and evidence-based intervention to reduce burden in carers of stroke survivors. METHODS: Informed by evidence from two systematic reviews and 33 qualitative interviews, the first four stages of Intervention Mapping were used to guide the intervention development process: 1) needs assessment; 2) identifying outcomes and objectives; 3) selecting theoretical methods and practical applications; and 4) creating a programme plan. Structured and facilitated involvement from stakeholders, including carers, researchers, and professionals from health and community services was integral to the intervention development process. Stakeholders helped to prioritise the focus of the intervention, develop the goals, outcomes and objectives for the programme, and generate and refine intervention ideas. RESULTS: Stakeholders prioritised the need for carers to feel prepared before and during the transition from hospital to home as key to reducing burden. The proposed intervention 'Preparing is Caring' targets this need and involves providing and signposting carers to relevant information and support for practical and emotional needs. This is to be delivered before, during, and immediately after the stroke survivor's transition from hospital to home by a person taking on a single point of contact role. It is comprised of multiple theory-based components including: training packages for information and support providers working with carers and wider staff teams, plus elements to support carers to feel prepared. CONCLUSIONS: We have developed a comprehensive programme plan for a multiple-component, theory and evidence informed behaviour change intervention aimed at preparing carers before and during the transition from hospital to home. Future work is required to refine, implement and evaluate the Preparing is Caring intervention.

How do stroke survivors with communication difficulties manage life after stroke in the first year? A qualitative study.

BACKGROUND: Interest in how stroke survivors might be better supported to manage life after stroke has grown rapidly in recent years, with a particular emphasis on enabling 'self-management'. Post-stroke communication difficulties may pose a unique barrier to longer term adaptation and adjustment. It is important to understand how stroke survivors with communication difficulties manage life after stroke and what support may be needed to facilitate this process. AIMS: To explore how stroke survivors with communication difficulties manage life after stroke in the first year. METHODS & PROCEDURES: A cross-sectional qualitative study involving in-depth semi-structured interviews with stroke survivors with communication difficulties (aphasia, dysarthria or apraxia of speech) and/or their family members at single time points during the first year post-stroke. A total of 21 participants (14 stroke survivors and seven family members) took part in interviews for the study. Interview data were analysed using thematic analysis. OUTCOME & RESULTS: A total of six themes were identified: (1) strategies to manage changes to communication; (2) testing communication outside of the home; (3) balancing support and independence; (4) hope for recovery; (5) obtaining support from healthcare professionals; and (6) adapting activities and keeping busy. Stroke survivors with communication difficulties and their family members undertook significant work (practical, relational, emotional) to manage their condition. Adaptation and adjustment was often facilitated by 'doing'; testing out which activities could be managed independently and which required additional support. Some stroke survivors and their family members demonstrated considerable resourcefulness and creativity in developing strategies to manage their communication difficulties. Despite the work undertaken, many expressed a lack of confidence in their ability and feelings of powerlessness and abandonment at the point of discharge from community services. CONCLUSIONS & IMPLICATIONS: Stroke survivors and their family members develop personally meaningful and context-specific strategies to adjust to and manage life after stroke. Future interventions should recognize, support and build upon the active work already undertaken by stroke survivors with communication difficulties and their families. Further support before and around the point of discharge from community services may be needed to help build confidence and skills to manage in the longer term. The benefit of a supported self-management approach for stroke survivors with communication difficulties should be further investigated.

Quantifying domain-ligand affinities and specificities by high-throughput holdup assay.

Many protein interactions are mediated by small linear motifs interacting specifically with defined families of globular domains. Quantifying the specificity of a motif requires measuring and comparing its binding affinities to all its putative target domains. To this end, we developed the high-throughput holdup assay, a chromatographic approach that can measure up to 1,000 domain-motif equilibrium binding affinities per day. After benchmarking the approach on 210 PDZ-peptide pairs with known affinities, we determined the affinities of two viral PDZ-binding motifs derived from human papillomavirus E6 oncoproteins for 209 PDZ domains covering 79% of the human 'PDZome'. We obtained sharply sequence-dependent binding profiles that quantitatively describe the PDZome recognition specificity of each motif. This approach, applicable to many categories of domain-ligand interactions, has wide potential for quantifying the specificities of interactomes.

Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units.

OBJECTIVE: To identify why the National Clinical Guideline recommendation of 45 minutes of each appropriate therapy daily is not met in many English stroke units. DESIGN: Mixed-methods case-study evaluation, including modified process mapping, non-participant observations of service organisation and therapy delivery, documentary analysis and semi-structured interviews. SETTING: Eight stroke units in four English regions. SUBJECTS: Seventy-seven patients with stroke, 53 carers and 197 stroke unit staff were observed; 49 patients, 50 carers and 131 staff participants were interviewed. RESULTS: Over 1000 hours of non-participant observations and 433 patient-specific therapy observations were undertaken. The most significant factor influencing amount and frequency of therapy provided was the time therapists routinely spent, individually and collectively, in information exchange. Patient factors, including fatigue and tolerance influenced therapists' decisions about frequency and intensity, typically resulting in adaptation of therapy rather than no provision. Limited use of individual patient therapy timetables was evident. Therapist staffing levels were associated with differences in therapy provision but were not the main determinant of intensity and frequency. Few therapists demonstrated understanding of the evidence underpinning recommendations for increased therapy frequency and intensity. Units delivering more therapy had undertaken patient-focused reorganisation of therapists' working practices, enabling them to provide therapy consistent with guideline recommendations. CONCLUSION: Time spent in information exchange impacted on therapy provision in stroke units. Reorganisation of therapists' work improved alignment with guidelines.

The PiTSTOP study: a feasibility cluster randomized trial of delirium prevention in care homes for older people.

BACKGROUND AND OBJECTIVES: delirium is a distressing but potentially preventable condition common in older people in long-term care. It is associated with increased morbidity, mortality, functional decline, hospitalization and significant healthcare costs. Multicomponent interventions, addressing delirium risk factors, have been shown to reduce delirium by one-third in hospitals. It is not known whether this approach is also effective in long-term care. In previous work, we designed a bespoke delirium prevention intervention, called 'Stop Delirium!' In preparation for a definitive trial of Stop Delirium, we sought to address key aspects of trial design for the particular circumstances of care homes. DESIGN: a cluster randomized feasibility study with an embedded process evaluation. SETTING AND PARTICIPANTS: residents of 14 care homes for older people in one metropolitan district in the UK. INTERVENTION: Stop Delirium!: a 16-month-enhanced educational package to support care home staff to address key delirium risk factors. Control homes received usual care. MEASUREMENTS: we collected data to determine the following: recruitment and attrition; delirium rates and variability between homes; feasibility of measuring delirium, resource use, quality of life, hospital admissions and falls; and intervention implementation and adherence. RESULTS: two-thirds (215) of eligible care home residents were recruited. One-month delirium prevalence was 4.0% in intervention and 7.1% in control homes. Proposed outcome measurements were feasible, although our approach appeared to underestimate delirium. Health economic evaluation was feasible using routinely collected data. CONCLUSION: a definitive trial of delirium prevention in long-term care is needed but will require some further design modifications and pilot work.