Phosphorylation of Cardiac Sodium Channel at Ser571 Anticipates Manifestations of the Aging Myopathy.

Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated in the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na+ current (INaL) in cardiomyocytes, raising the possibility that INaL conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain-of-function, GoF) or ablated (loss-of-function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized INaL. At ~18 months (m) of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by INaL inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (~5 m) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca2+ transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (~24 m) WT myocytes, with respect to adult cells. In contrast, delayed Ca2+ transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated at old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na+ current modulates the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction.

Relationship between staff and quality of care in care homes: StaRQ mixed methods study.

Background: Quality of life and care varies between and within the care homes in which almost half a million older people live and over half a million direct care staff (registered nurses and care assistants) work. The reasons are complex, understudied and sometimes oversimplified, but staff and their work are a significant influence. Objective(s): To explore variations in the care home nursing and support workforce; how resident and relatives' needs in care homes are linked to care home staffing; how different staffing models impact on care quality, outcomes and costs; how workforce numbers, skill mix and stability meet residents' needs; the contributions of the care home workforce to enhancing quality of care; staff relationships as a platform for implementation by providers. Design: Mixed-method (QUAL-QUANT) parallel design with five work packages. WP1 - two evidence syntheses (one realist); WP2 - cross-sectional survey of routine staffing and rated quality from care home regulator; WP3 - analysis of longitudinal data from a corporate provider of staffing characteristics and quality indicators, including safety; WP4 - secondary analysis of care home regulator reports; WP5 - social network analysis of networks likely to influence quality innovation. We expressed our synthesised findings as a logic model. Setting: English care homes, with and without nursing, with various ownership structures, size and location, with varying quality ratings. Participants: Managers, residents, families and care home staff. Findings: Staffing's contribution to quality and personalised care requires: managerial and staff stability and consistency; sufficient staff to develop 'familial' relationships between staff and residents, and staff-staff reciprocity, 'knowing' residents, and skills and competence training beyond induction; supported, well-led staff seeing modelled behaviours from supervisors; autonomy to act. Outcome measures that capture the relationship between staffing and quality include: the extent to which resident needs and preferences are met and culturally appropriate; resident and family satisfaction; extent of residents living with purpose; safe care (including clinical outcomes); staff well-being and job satisfaction were important, but underacknowledged. Limitations: Many of our findings stem from self-reported and routine data with known biases - such as under reporting of adverse incidents; our analysis may reflect these biases. COVID-19 required adapting our original protocol to make it feasible. Consequently, the effects of the pandemic are reflected in our research methods and findings. Our findings are based on data from a single care home operator and so may not be generalised to the wider population of care homes. Conclusions: Innovative and multiple methods and theory can successfully highlight the nuanced relationship between staffing and quality in care homes. Modifiable characteristics such as visible philosophies of care and high-quality training, reinforced by behavioural and relational role modelling by leaders can make the difference when sufficient amounts of consistent staff are employed. Greater staffing capacity alone is unlikely to enhance quality in a cost-effective manner. Social network analysis can help identify the right people to aid adoption and spread of quality and innovation. Future research should focus on richer, iterative, evaluative testing and development of our logic model using theoretically and empirically defensible - rather than available - inputs and outcomes. Study registration: This study is registered as PROSPERO CRD42021241066 and Research Registry registration: 1062. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/144/29) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 8. See the NIHR Funding and Awards website for further award information.

This study was about the relationship between staffing and quality in care homes. Almost half a million older people live in care homes in England. Why quality of care and quality of life for residents vary so much between and within homes is unknown, but staff and the ways they work are likely to be important. Researching staffing and quality is difficult: quality means different things to different people and a lot of things shape how quality feels to residents, families and staff. In the past, researchers have oversimplified the problem to study it and may have missed important influences. We took a more complex view. In five interlinked work packages, we collected and analysed: (1) research journal articles; (2) national data from different care homes; (3) data from a large care organisation to look at what it is about staffing that influences quality; (4) reports and ratings of homes from the Care Quality Commission; and (5) we looked at the networks between staff in homes that shape how quality improvement techniques might spread. We used theories about how our findings might be linked to plan for this data collection and analysis. The results were combined into something called a 'logic model' ­ a diagram and explanation that make it easier for managers, researchers and people interested in care homes to see how staffing influences quality. Staffing considerations that might improve quality include: not swapping managers too much; having sufficient and consistent staff for family-like relationships in homes and putting residents' needs first; supporting staff and giving them freedom to act; and key staff leading by example. Research examining care home quality should capture those aspects that mean the most to residents, their families and staff.

'Smart' BLE wearables for digital contact tracing in care homes during the COVID-19 pandemic-a process evaluation of the CONTACT feasibility study.

BACKGROUND: Rapid and mass transmission of the SARS-CoV-2 virus amongst vulnerable people led to devastating effects from COVID-19 in care homes. The CONTACT intervention introduced Bluetooth Low Energy 'smart' wearable devices (BLE wearables) as a basis for automated contact tracing in, and feedback on infection risks and patterns to, care homes to try and improve infection prevention and control (IPC). We planned a cluster randomised controlled trial (RCT) of CONTACT. To be feasible, homes had to adopt CONTACT's technology and new ways of working. This paper reports on the process evaluation conducted alongside CONTACT's feasibility study and explains why it lacked the feasibility and acceptability for a definitive RCT. METHODS: This mixed method process evaluation used Normalisation Process Theory (NPT) qualitative (interviews, field notes, study case report forms and documents, and observation) and quantitative (survey instruments, counts of activity) data to plan, implement, and analyse the mechanisms, effects, and contextual factors that shaped the feasibility and acceptability of the CONTACT intervention. RESULTS: Thirteen themes within four core NPT constructs explained CONTACT's lack of feasibility. Coherence: the home's varied in the scale and extent of commitment and understanding of the technology and study procedures. Leadership credibility was important but compromised by competing priorities. Management and direct care staff saw CONTACT differently. Work to promote (cognitive participation) and enact (collective action) CONTACT was burdensome and failed to be prioritised over competing COVID-19-related demands on time and scarce human and cognitive resources. Ultimately, staff appraisal of the value of CONTACT-generated information and study procedures (reflexivity) was that any utility for IPC was insufficient to outweigh the perceived burden and complexity involved. CONCLUSIONS: Despite implementation failure, dismissing BLE wearables' potential for contact tracing is premature. In non-pandemic conditions, with more time, better co-design and integration of theory-driven implementation strategies tailored to care homes' unique contexts, researchers could enhance normalisation in readiness for future pandemic challenges. TRIAL REGISTRATION: ISRCTN registration: 11,204,126 registered 17/02/2021.

Time-Temperature-Transformation (TTT) Diagram of Battery-Grade Li-Garnet Electrolytes for Low-Temperature Sustainable Synthesis.

Efficient and affordable synthesis of Li+ functional ceramics is crucial for the scalable production of solid electrolytes for batteries. Li-garnet Li7 La3 Zr2 O12-d (LLZO), especially its cubic phase (cLLZO), attracts attention due to its high Li+ conductivity and wide electrochemical stability window. However, high sintering temperatures raise concerns about the cathode interface stability, production costs, and energy consumption for scalable manufacture. We show an alternative "sinter-free" route to stabilize cLLZO as films at half of its sinter temperature. Specifically, we establish a time-temperature-transformation (TTT) diagram which captures the amorphous-to-crystalline LLZO transformation based on crystallization enthalpy analysis and confirm stabilization of thin-film cLLZO at record low temperatures of 500 °C. Our findings pave the way for low-temperature processing via TTT diagrams, which can be used for battery cell design targeting reduced carbon footprints in manufacturing.

Variations in measurement of interprofessional core competencies: a systematic review of self-report instruments in undergraduate health professions education.

Educating health care professionals for working in interprofessional teams is a key preparation for roles in modern healthcare. Interprofessional teams require members who are competent in their roles. Self-assessment instruments measuring interprofessional competence (IPC) are widely used in educational preparation, but their ability to accurately and reliably measure competence is unknown. We conducted a systematic review to identify variations in the characteristics and use of self-report instruments measuring IPC. Following a systematic search of electronic databases and after applying eligibility criteria, 38 articles were included that describe 8 IPC self-report instruments. A large variation was found in the extent of coverage of IPC core competencies as articulated by the Interprofessional Education Collaborative. Each instrument's strength of evidence, psychometric performance and uses varied. Rather than measuring competency as "behaviours", they measured indirect proxies for competence, such as attitudes towards core interprofessional competencies. Educators and researchers should identify the most appropriate and highest-performing IPC instruments according to the context in which they will be used.Systematic review registration: Open Science Framework (https://archive.org/details/osf-registrations-vrfjn-v1).

Evaluating the performance of wearable devices for contact tracing in care home environments.

COVID-19 has had a devastating impact worldwide, including in care homes where there have been substantial numbers of cases among a very vulnerable population. A key mechanism for managing exposure to the virus and targeting interventions is contact tracing. Unfortunately, environments such as care homes that were most catastrophically impacted by COVID-19 are also those least amenable to traditional contact tracing. A promising alternative to recall and smartphone-based contact tracing approaches is the use of discrete wearable devices that exploit Bluetooth Low Energy (BLE) and Long-Range Wide Area Network (LoRaWAN) technologies. However, the real-world performance of these devices in the context of contact tracing is uncertain. A series of experiments were conducted to evaluate the performance of a wearables system that is based on BLE and LoRaWAN technologies. In each experiment, the number of successful contacts was recorded and the physical distance between two contacts was compared to a calculated distance using the Received Signal Strength Indication (RSSI) to determine the precision, error rate, and duration of proximity. The overall average system contact detection success rate was measured as 75.5%; when wearables were used as per the manufacturer's guidelines the contact detection success rate increased to 81.5%, but when obstructed by everyday objects such as clothing or inside a bag the contact detection success rate was only 64.2%. The calculated distance using RSSI was close to the physical distance in the absence of obstacles. However, in the presence of typical obstacles found in care home settings, the reliability of detection decreased, and the calculated distance usually appeared far from the actual contact point. The results suggest that under real-world conditions there may be a large proportion of contacts that are underestimated or undetected.

The effects of computerised decision support systems on nursing and allied health professional performance and patient outcomes: a systematic review and user contextualisation.

Background: Computerised decision support systems (CDSS) are widely used by nurses and allied health professionals but their effect on clinical performance and patient outcomes is uncertain. Objectives: Evaluate the effects of clinical decision support systems use on nurses', midwives' and allied health professionals' performance and patient outcomes and sense-check the results with developers and users. Eligibility criteria: Comparative studies (randomised controlled trials (RCTs), non-randomised trials, controlled before-and-after (CBA) studies, interrupted time series (ITS) and repeated measures studies comparing) of CDSS versus usual care from nurses, midwives or other allied health professionals. Information sources: Nineteen bibliographic databases searched October 2019 and February 2021. Risk of bias: Assessed using structured risk of bias guidelines; almost all included studies were at high risk of bias. Synthesis of results: Heterogeneity between interventions and outcomes necessitated narrative synthesis and grouping by: similarity in focus or CDSS-type, targeted health professionals, patient group, outcomes reported and study design. Included studies: Of 36,106 initial records, 262 studies were assessed for eligibility, with 35 included: 28 RCTs (80%), 3 CBA studies (8.6%), 3 ITS (8.6%) and 1 non-randomised trial, a total of 1318 health professionals and 67,595 patient participants. Few studies were multi-site and most focused on decision-making by nurses (71%) or paramedics (5.7%). Standalone, computer-based CDSS featured in 88.7% of the studies; only 8.6% of the studies involved 'smart' mobile or handheld technology. Care processes - including adherence to guidance - were positively influenced in 47% of the measures adopted. For example, nurses' adherence to hand disinfection guidance, insulin dosing, on-time blood sampling, and documenting care were improved if they used CDSS. Patient care outcomes were statistically - if not always clinically - significantly improved in 40.7% of indicators. For example, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity, and accurate triaging were features of professionals using CDSS compared to those who were not. Evidence limitations: Allied health professionals (AHPs) were underrepresented compared to nurses; systems, studies and outcomes were heterogeneous, preventing statistical aggregation; very wide confidence intervals around effects meant clinical significance was questionable; decision and implementation theory that would have helped interpret effects - including null effects - was largely absent; economic data were scant and diverse, preventing estimation of overall cost-effectiveness. Interpretation: CDSS can positively influence selected aspects of nurses', midwives' and AHPs' performance and care outcomes. Comparative research is generally of low quality and outcomes wide ranging and heterogeneous. After more than a decade of synthesised research into CDSS in healthcare professions other than medicine, the effect on processes and outcomes remains uncertain. Higher-quality, theoretically informed, evaluative research that addresses the economics of CDSS development and implementation is still required. Future work: Developing nursing CDSS and primary research evaluation. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in Health and Social Care Delivery Research; 2023. See the NIHR Journals Library website for further project information. Registration: PROSPERO [number: CRD42019147773].

Computerised decision support systems (CDSS) are software or computer-based technologies providing advice to professionals making clinical decisions ­ for example, which patients to treat first in emergency departments. CDSS improve some doctors' decisions and patients' outcomes, but we don't know if they improve nurses', midwives' and therapists' or other staff decisions and patient outcomes. Research into, and health professionals' use of, technology ­ for example, in video consultations ­ has grown since the last relevant systematic review in 2009. We systematically searched electronic databases for research measuring how well nurses, midwifes and other therapists/staff followed CDSS advice, how CDSS influence their decisions, how safe CDSS are, and their financial costs and benefits. We interviewed CDSS users and developers and some patient representatives from a general practice to help understand our findings. Of 35 relevant studies ­ from 36,106 initially found ­ most (71%) focused on nurses. Just over half (57%) involved hospital-based staff, and three-quarters (75%) were from richer countries like the USA or the UK. Research quality had not noticeably improved since 2009 and all studies were at risk of potentially misleading readers. CDSS improved care in just under half (47%) of professional behaviours, such as following hand-disinfection guidance, working out insulin doses, and sampling blood on time. Patient care ­ judged using outcomes like falls, pressure ulcers, diabetes control and triage accuracy ­ was better in 41% of the care measured. There wasn't enough evidence to judge CDSS safety or the financial costs and benefits of systems. CDSS can improve some nursing and therapist decisions and some patient outcomes. Studies mostly measure different behaviours and outcomes, making comparing them hard. Theories explaining or predicting how decision support systems might work are not used enough when designing, implementing or evaluating CDSS. More research into the financial costs and benefits of CDSS and higher-quality evidence of their effects are still needed. Whether decision support for nurses, midwives and other therapists reliably improves decision-making remains uncertain.

Experimental and Computational Study of the Orientation Dependence of Single-Crystal Ruthenium Nanowire Stability.

Single-crystal nanowires are of broad interest for applications in nanotechnology. However, such wires are subject to both the Rayleigh-Plateau instability and an ovulation process that are expected to lead to their break up into particle arrays. Single crystal Ru nanowires were fabricated with axes lying along different crystallographic orientations. Wires bound by equilibrium facets along their length did not break up through either a Rayleigh-Plateau or ovulation process, while wires with other orientations broke up through a combination of both. Mechanistic insight is provided using a level-set simulation that accounts for strongly anisotropic surface energies, providing a framework for design of morphologically stable nanostructures.

Reducing delayed transfer of care in older people: A qualitative study of barriers and facilitators to shorter hospital stays.

INTRODUCTION: Growing numbers of older patients occupy hospital beds despite being 'medically fit' for discharge. These Delayed Transfers of Care amplify inefficiencies in care and can cause harm. Delayed transfer because of family or patient choice is common; yet, research on patient and family perspectives is scarce. To identify barriers to, and facilitators of, shorter hospital stays, we sought to understand older people's and caregivers' thoughts and feelings about the benefits and harms of being in hospital and the decisions made at discharge. METHODS: A multimethod qualitative study was carried out. Content analysis was carried out of older people's experiences of health or care services submitted to the Care Opinion online website, followed by telephone and video interviews with older people and family members of older people experiencing a hospital stay in the previous 12 months. RESULTS: Online accounts provide insight into how care was organized for older people in the hospital, including deficiencies in care organization, the discharge process and communication, as well as how care was experienced by older people and family members. Interview-generated themes included shared meanings of hospitalization and discharge experiences and the context of discharge decisions including failure in communication systems, unwarranted variation and lack of confidence in care and lack of preparation for ongoing care. CONCLUSION: Poor quality and availability of information, and poor communication, inhibit effective transfer of care. Communication is fundamental to patient-centred care and even more important in discharge models characterized by limited assessments and quicker discharge. Interventions at the service level and targeted patient information about what to expect in discharge assessments and after discharge could help to address poor communication and support for improving discharge of older people from hospital. PATIENT OR PUBLIC CONTRIBUTION: The Frailty Oversight Group, a small group of older people providing oversight of the Community Aging Research 75+ study, provided feedback on the research topic and level of interest, the draft data collection tools and the feasibility of collecting data with older people during the COVID-19 pandemic. The group also reviewed preliminary findings and provided feedback on our interpretation.

Development of a core outcome set for the evaluation of interventions to prevent COVID-19 in care homes (COS-COVID-PCARE Study).

BACKGROUND: People living in care homes have experienced devastating impact from COVID-19. As interventions to prevent the transmission of COVID-19 are developed and evaluated, there is an urgent need for researchers to agree on the outcomes used when evaluating their effectiveness. Having an agreed set of outcomes that are used in all relevant trials can ensure that study results can be compared. OBJECTIVE: The aim of the study was to develop a core outcome set (COS) for trials assessing the effectiveness of pharmacological and non-pharmacological interventions for preventing COVID-19 infection and transmission in care homes. METHODS: The study used established COS methodology. A list of candidate outcomes was identified by reviewing registered trials to evaluate interventions to prevent COVID-19 in care homes. Seventy key stakeholders participated in a Delphi survey, rating the candidate outcomes on a nine-point scale over two rounds, with the opportunity to propose additional outcomes. Stakeholders included care home representatives (n = 19), healthcare professionals (n = 20), people with personal experience of care homes (n = 7), researchers (n = 15) and others (n = 9). Outcomes were eligible for inclusion if they met an a priori threshold. A consensus meeting with stakeholders resulted in agreement of the final outcome set. RESULTS: Following the Delphi and consensus meeting, twenty-four outcomes were recommended for inclusion. These are grouped across four domains of infection, severity of illness, mortality, and 'other' (intervention specific or life impact). Due to the considerable heterogeneity between care homes, residents, and interventions, the relevance and importance of outcomes may differ between trial contexts. Intervention-specific outcomes would be included only where relevant to a given trial, thus reducing the measurement burden. CONCLUSION: Using a rapid response approach, a COS for COVID-19 prevention interventions in care homes has been developed. Future work should focus on identifying instruments for measuring these outcomes, and the interpretation and application of the COS across different trial contexts. Beyond COVID-19, the outcomes identified in this COS may have relevance to other infectious diseases in care homes, and the rapid response approach may be useful as preparation for future pandemics.

Video-guided exercise after stroke: a feasibility randomised controlled trial.

BACKGROUND: Facilitating self-directed upper-limb exercise in people after a stroke whilst not in therapy sessions may increase therapy intensity and improve outcomes. Objectives: To investigate the feasibility and acceptability of video-guided exercise for facilitating upper-limb exercise after stroke. METHODS: A single-blind feasibility randomized controlled trial with embedded qualitative study in stroke wards at a large teaching hospital in the United Kingdom. Fourteen participants with stroke were randomized to either video-guided exercise intervention or a "treatment-as-usual" control group. Intervention participants received a computer tablet containing filmed individualized exercises to guide out of therapy practice. The primary outcome measure was the Motor status scale (MSS) for the upper limb, which was used to guide possible sample sizes for a future main trial. Qualitative focus group and interview data on feasibility/acceptability were collected and analyzed. RESULTS: The intervention was acceptable, but the need for motivation/support to exercise was highlighted. Based on similar assumptions to the feasibility study, circa ninety-two patients in each group would be needed to detect a difference of 5 in upper-limb motor status for a main trial. CONCLUSION: A trial of video-guided exercise is feasible, although an optimal main trial would require some relatively minor changes to design, outcome measures, eligibility, and the intervention.

Effects of computerised clinical decision support systems (CDSS) on nursing and allied health professional performance and patient outcomes: a systematic review of experimental and observational studies.

OBJECTIVE: Computerised clinical decision support systems (CDSS) are an increasingly important part of nurse and allied health professional (AHP) roles in delivering healthcare. The impact of these technologies on these health professionals' performance and patient outcomes has not been systematically reviewed. We aimed to conduct a systematic review to investigate this. MATERIALS AND METHODS: The following bibliographic databases and grey literature sources were searched by an experienced Information Professional for published and unpublished research from inception to February 2021 without language restrictions: MEDLINE (Ovid), Embase Classic+Embase (Ovid), PsycINFO (Ovid), HMIC (Ovid), AMED (Allied and Complementary Medicine) (Ovid), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), Social Sciences Citation Index Expanded (Clarivate), ProQuest Dissertations & Theses Abstracts & Index, ProQuest ASSIA (Applied Social Science Index and Abstract), Clinical Trials.gov, WHO International Clinical Trials Registry (ICTRP), Health Services Research Projects in Progress (HSRProj), OpenClinical(www.OpenClinical.org), OpenGrey (www.opengrey.eu), Health.IT.gov, Agency for Healthcare Research and Quality (www.ahrq.gov). Any comparative research studies comparing CDSS with usual care were eligible for inclusion. RESULTS: A total of 36 106 non-duplicate records were identified. Of 35 included studies: 28 were randomised trials, three controlled-before-and-after studies, three interrupted-time-series and one non-randomised trial. There were ~1318 health professionals and ~67 595 patient participants in the studies. Most studies focused on nurse decision-makers (71%) or paramedics (5.7%). CDSS as a standalone Personal Computer/LAPTOP-technology was a feature of 88.7% of the studies; only 8.6% of the studies involved 'smart' mobile/handheld-technology. DISCUSSION: CDSS impacted 38% of the outcome measures used positively. Care processes were better in 47% of the measures adopted; examples included, nurses' adherence to hand disinfection guidance, insulin dosing, on-time blood sampling and documenting care. Patient care outcomes in 40.7% of indicators were better; examples included, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity and triaging appropriateness. CONCLUSION: CDSS may have a positive impact on selected aspects of nurses' and AHPs' performance and care outcomes. However, comparative research is generally low quality, with a wide range of heterogeneous outcomes. After more than 13 years of synthesised research into CDSS in healthcare professions other than medicine, the need for better quality evaluative research remains as pressing.

COVID-19 point-of-care testing in care homes: what are the lessons for policy and practice?

COVID-19 has devastated care homes. Point-of-care tests (POCTs), mainly using lateral flow devices (LFDs), have been deployed hurriedly without much consideration of their usability or impact on care workflow. Even after the pandemic, POCTs, particularly multiplex tests, may be an important control against spread of SARS-CoV-2 and other respiratory infections in care homes by enabling identification of cases. They should not, however, replace other infection control measures such as barrier methods and quarantine. Adherence to LFDs as implemented among care home staff is suboptimal. Other tests-such as point-of-care polymerase chain reaction and automated antigen tests-would also need to be accommodated into care home workflows to improve adherence. The up-front costs of POCTs are straightforward but additional costs, including staffing preparation and reporting processes and the impacts of false positive and negative tests on absence rates and infection days, are more complex and as yet unquantified. A detailed appraisal is needed as the future of testing in care homes is considered.

Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with cerebral palsy, intellectual disability, and commonly, accumulation of cerebrospinal fluid (CSF). Histologically, IVH leads to subependymal gliosis, fibrosis, and disruption of the ependymal wall. Importantly, expression of aquaporin channels 1 and 4 (AQP1 and AQP4) regulating respectively, secretion and absorption of cerebrospinal fluids is altered with IVH and are associated with development of post hemorrhagic hydrocephalus. Human cord blood derived unrestricted somatic stem cells (USSCs), which we previously demonstrated to reduce the magnitude of hydrocephalus, as having anti-inflammatory, and beneficial behavioral effects, were injected into the cerebral ventricles of rabbit pups 18 h after glycerol-induced IVH. USSC treated IVH pups showed a reduction in ventricular size when compared to control pups at 7 and 14 days (both, P < 0.05). Histologically, USSC treatment reduced cellular infiltration and ependymal wall disruption. In the region of the choroid plexus, immuno-reactivity for AQP1 and ependymal wall AQP4 expression were suppressed after IVH but were restored following USSC administration. Effects were confirmed by analysis of mRNA from dissected choroid plexus and ependymal tissue. Transforming growth factor beta (TGF-ß) isoforms, connective tissue growth factor (CTGF) and matrix metalloprotease-9 (MMP-9) mRNA, as well as protein levels, were significantly increased following IVH and restored towards normal with USSC treatment (P < 0.05). The anti-inflammatory cytokine Interleukin-10 (IL-10) mRNA was reduced in IVH, but significantly recovered after USSC injection (P < 0.05). In conclusion, USSCs exerted anti-inflammatory effects by suppressing both TGF-ß specific isoforms, CTGF and MMP-9, recovered IL-10, restored aquaporins expression towards baseline, and reduced hydrocephalus. These results support the possibility of the use of USSCs to reduce IVH consequences in prematurity.

Is point-of-care testing feasible and safe in care homes in England? An exploratory usability and accuracy evaluation of a point-of-care polymerase chain reaction test for SARS-CoV-2.

INTRODUCTION: Reliable rapid testing for COVID-19 is needed in care homes to reduce the risk of outbreaks and enable timely care. This study aimed to examine the usability and test performance of a point of care polymerase chain reaction (PCR) test for detection of SARS-CoV-2 (POCKITTM Central) in care homes. METHODS: POCKITTM Central was evaluated in a purposeful sample of four UK care homes. Test agreement with laboratory real-time PCR and usability and used errors were assessed. RESULTS: No significant usability-related hazards emerged, and the sources of error identified were found to be amendable with minor changes in training or test workflow. POCKITTM Central has acceptable sensitivity and specificity based on RT-PCR as the reference standard, especially for symptomatic cases.Asymptomatic specimens showed 83.3% (95% confidence interval (CI): 35.9-99.6%) positive agreement and 98.7% negative agreement (95% CI: 96.2-99.7%), with overall prevalence and bias-adjusted kappa (PABAK) of 0.965 (95% CI: 0.932- 0.999). Symptomatic specimens showed 100% (95% CI: 2.5-100%) positive agreement and 100% negative agreement (95% CI: 85.8-100%), with overall PABAK of 1.Recommendations are provided to mitigate the frequency of occurrence of the residual use errors observed. Integration pathways were discussed to identify opportunities and limitations of adopting POCKIT™ Central for screening and diagnostic testing purposes. CONCLUSIONS: Point-of-care PCR testing in care homes can be considered with appropriate preparatory steps and safeguards. Further diagnostic accuracy evaluations and in-service evaluation studies should be conducted, if the test is to be implemented more widely, to build greater certainty on this initial exploratory analysis.

Understanding the staff behaviours that promote quality for older people living in long term care facilities: A realist review.

BACKGROUND: Little is known about how the workforce influences quality in long term care facilities for older people. Staff numbers are important but do not fully explain this relationship. OBJECTIVES: To develop theoretical explanations for the relationship between long-term care facility staffing and quality of care as experienced by residents. DESIGN: A realist evidence synthesis to understand staff behaviours that promote quality of care for older people living in long-term care facilities. SETTING: Long-term residential care facilities PARTICIPANTS: Long-term care facility staff, residents, and relatives METHODS: The realist review, (i) was co-developed with stakeholders to determine initial programme theories, (ii) systematically searched the evidence to test and develop theoretical propositions, and (iii) validated and refined emergent theory with stakeholder groups. RESULTS: 66 research papers were included in the review. Three key findings explain the relationship between staffing and quality: (i) quality is influenced by staff behaviours; (ii) behaviours are contingent on relationships nurtured by long-term care facility environment and culture; and (iii) leadership has an important influence on how organisational resources (sufficient staff effectively deployed, with the knowledge, expertise and skills required to meet residents' needs) are used to generate and sustain quality-promoting relationships. Six theoretical propositions explain these findings. CONCLUSION: Leaders (at all levels) through their role-modelling behaviours can use organisational resources to endorse and encourage relationships (at all levels) between staff, residents, co-workers and family (relationship centred care) that constitute learning opportunities for staff, and encourage quality as experienced by residents and families.

Synthesis, antibacterial action, and ribosome inhibition of deoxyspectinomycins.

Spectinomycin, an aminocyclitol antibiotic, is subject to inactivation by aminoglycoside modifying enzymes (AMEs) through adenylylation or phosphorylation of the 6-hydroxy group position. In this study, the effects of deoxygenation of the 2- and 6-hydroxy group positions on the spectinomycin actinamine ring are probed to evaluate their relationship to ribosomal binding and the antimicrobial activities of spectinomycin, semisynthetic aminomethyl spectinomycins (amSPCs), and spectinamides. To generate these analogs, an improved synthesis of 6-deoxyspectinomycin was developed using the Barton deoxygenation reaction. 6-Dehydrospectinamide was also synthesized from spectinamide 4 to evaluate the H-bond acceptor character on the C-6 position. All the synthesized analogs were tested for antibacterial activity against a panel of Gram (+) and Gram (-) pathogens, plus Mycobacterium tuberculosis. The molecular contribution of the 2- and 6-hydroxy group and the aryl functionalities of all analogs were examined by measuring inhibition of ribosomal translation and molecular dynamics experiments with MM/GBSA analysis. The results of this work indicate that the 6-hydroxy group, which is the primary target of AMEs, is a required motif for antimicrobial activity in current analogs. Removal of the 6-hydroxy group could be partially rescued by offsetting ribosomal binding contributions made by the aryl side chains found in the spectinamide and amSPCs. This study builds on the knowledge of the structure-activity relationships of spectinomycin analogs and is being used to aid the design of next-generation spectinomycins.

SEeking AnsweRs for Care Homes during the COVID-19 pandemic (COVID SEARCH).

The care and support of older people residing in long-term care facilities during the COVID-19 pandemic has created new and unanticipated uncertainties for staff. In this short report, we present our analyses of the uncertainties of care home managers and staff expressed in a self-formed closed WhatsApp™ discussion group during the first stages of the pandemic in the UK. We categorised their wide-ranging questions to understand what information would address these uncertainties and provide support. We have been able to demonstrate that almost one-third of these uncertainties could have been tackled immediately through timely, responsive and unambiguous fact-based guidance. The other uncertainties require appraisal, synthesis and summary of existing evidence, commissioning or provision of a sector- informed research agenda for medium to long term. The questions represent wider internationally relevant care home pandemic-related uncertainties.

Assessment of interprofessional competence in undergraduate health professions education: protocol for a systematic review of self-report instruments.

BACKGROUND: Health practitioners from different professions, and with differing competencies, need to collaborate to provide quality care. Competencies in interprofessional working need developing in undergraduate educational preparation. This paper reports the protocol for a systematic review of self-report instruments to assess interprofessional learning in undergraduate health professionals' education. METHODS: We will search PubMed, Web of Science, CINAHL and ERIC from January 2010 onwards. A combination of search terms for interprofessional learning, health professions, psychometric properties, assessment of learning and assessment tools will be used. Two reviewers will independently screen all titles, abstracts and full-texts. Potential conflicts will be resolved through discussion. Quantitative and mixed-methods studies evaluating interprofessional learning in undergraduate health professions education (e.g. medicine, nursing, occupational and physical therapy, pharmacy and psychology) will be included. Methodological quality of each reported instrument, underpinning theoretical frameworks, and the effects of reported interventions will be assessed. The overall outcome will be the effectiveness of instruments used to assess interprofessional competence. Primary outcomes will be the psychometric properties (e.g. reliability, discriminant and internal validity) of instruments used. Secondary outcomes will include time from intervention to assessment, how items relate to specific performance/competencies (or general abstract constructs) and how scores are used (e.g. to grade students, to improve courses or research purposes). Quantitative summaries in tabular format and a narrative synthesis will allow recommendations to be made on the use of self-report instruments in practice. DISCUSSION: Many studies use self-report questionnaires as tools for developing meaningful interprofessional education activities and assessing students' interprofessional competence. This systematic review will evaluate both the benefits and limitations of reported instruments and help educators and researchers (i) choose the most appropriate existing self-report instruments to assess interprofessional competence and (ii) inform the design and conduct of interprofessional competency assessment using self-report instruments. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework [https://osf.io/vrfjn].