Transient conformations in the unliganded FK506 binding domain of FKBP51 correspond to two distinct inhibitor-bound states.

Members of the FK506-binding protein (FKBP) family regulate a range of important physiological processes. Unfortunately, current therapeutics such as FK506 and rapamycin exhibit only modest selectivity among these functionally distinct proteins. Recent progress in developing selective inhibitors has been reported for FKBP51 and FKBP52, which act as mutual antagonists in the regulation of steroid hormone signaling. Two structurally similar inhibitors yield distinct protein conformations at the binding site. Localized conformational transition in the binding site of the unliganded FK1 domain of FKBP51 is suppressed by a K58T mutation that also suppresses the binding of these inhibitors. Here, it is shown that the changes in amide hydrogen exchange kinetics arising from this K58T substitution are largely localized to this structural region. Accurate determination of the hydroxide-catalyzed exchange rate constants in both the wildtype and K58T variant proteins impose strong constraints upon the pattern of amide exchange reactivities within either a single or a pair of transient conformations that could give rise to the differences between these two sets of measured rate constants. Poisson-Boltzmann continuum dielectric calculations provide moderately accurate predictions of the structure-dependent hydrogen exchange reactivity for solvent-exposed protein backbone amides. Applying such calculations to the local protein conformations observed in the two inhibitor-bound FKBP51 domains demonstrated that the experimentally determined exchange rate constants for the wildtype domain are robustly predicted by a population-weighted sum of the experimental hydrogen exchange reactivity of the K58T variant and the predicted exchange reactivities in model conformations derived from the two inhibitor-bound protein structures.

Improving the quality of written communication at patient discharge: triangulation of qualitative analyses and intervention co-design.

BACKGROUND: Poor handovers between hospital and primary care threaten safe discharges, with elderly and frail patients most at risk of harm. Using Behavioural Science we explored influences and identified relevant behaviour change techniques (BCTs) to improve written handovers and safety during discharge. METHODS: We conducted two qualitative studies: (1) ethnographic observations (>80 h) collected by five researchers in five purposively sampled clinical areas of a London teaching hospital, investigating routine work and interactions of hospital staff involved in discharges; and (2) 12 semi-structured interviews with hospital staff involved in discharge exploring influences on preparations of written handovers. Written consent was sought from clinical leads for ethnographic observations and from interview participants. Ethnographic fieldnotes and interview transcripts were thematically analysed using inductive and deductive approaches, respectively. Study findings were triangulated to identify key influences, mapped onto the Theoretical Domains Framework (TDF). We identified appropriate BCTs to address observed influences within each TDF domain using the Theory and Techniques Tool. Health-care workers (n=15), patients (n=2) and carers (n=2) selected and designed an intervention to improve written handovers in two workshops. Hospital workshop participants were involved with preparing written discharge handovers. Public participants had either recently been discharged from hospital or cared for someone recently discharged, including patients from groups especially vulnerable during discharge. FINDINGS: Triangulation of study findings generated 11 key influences on preparations of written handovers within five TDF domains: knowledge (eg, lack of awareness of guidelines), skills (staff experience), social or professional role and identity (effective communication), environmental context and resources (working patterns), and social influences (lack of feedback). 14 BCTs were identified to address these influences, including behavioural rehearsal or practice, instruction on how to perform a behaviour, and social support (practical). Workshop participants selected and designed a multifaceted educational intervention to improve written handovers. INTERPRETATION: The quality of handover documentation prepared by hospital staff for primary care teams is affected by influences from multiple domains, requiring a multifaceted approach to improve handovers. Although only based on findings from one hospital, the designed intervention should be tested in clinical settings with key stakeholders, including primary care staff, to evaluate impact on quality of written handovers and patient safety. FUNDING: National Institute for Health and Care Research (NIHR) Imperial Patient Safety Translational Research Centre.

External inspection approaches and involvement of stakeholders' views in inspection following serious incidents - a qualitative mixed methods study from the perspectives of regulatory inspectors.

OBJECTIVE: The objective was to gain knowledge about how external inspections following serious incidents are played out in a Norwegian hospital context from the perspective of the inspectors, and whether stakeholders' views are involved in the inspection. METHODS: Based on a qualitative mixed methods design, 10 government bureaucrats and inspectors situated at the National Board of Health Supervision and three County Governors in Norway, were strategically recruited, and individual semi-structured interviews were conducted. Key official government documents were selected, collected, and thematically analyzed along with the interview data. RESULTS: Our findings overall demonstrate two overarching themes: Theme (1) Perspectives on different external inspection approaches of responding and involving stakeholders in external inspection following serious incidents, Theme (2) Inspectors' internal work practices versus external expectations. Documents and all participants reported a development towards new approaches in external inspection, with more policies and regulatory attention to sensible involvement of stakeholders. Involvement and interaction with patients and informal caregivers could potentially inform the case complexity and the inspector's decision-making process. However, stakeholder involvement was sometimes complex and challenging due to e.g., difficult communication and interaction with patients and/or informal caregivers, due to resource demands and/or the inspector's lack of experience and/or relevant competence, different perceptions of the principle of sound professional practice, quality, and safety. The inspectors considered balancing the formal objectives and expectations, with the expectations of the public and different stakeholders (i.e. hospitals, patients and/or informal caregivers) a challenging part of their job. This balance was seen as an important part of the continuous development of ensuring public trust and legitimacy in external inspection processes. CONCLUSIONS AND IMPLICATIONS: Our study suggests that the regulatory system of external inspection and its available approaches of responding to a serious incident in the Norwegian setting is currently not designed to accommodate the complexity of needs from stakeholders at the levels of hospital organizations, patients, and informal caregivers altogether. Further studies should direct attention to how the wider system of accountability structures may support the internal work practices in the regulatory system, to better algin its formal objectives with expectations of the public.

Decoding healthcare teamwork: a typology of hospital teams.

The effectiveness of healthcare depends on successful teamwork. Current understanding of teamwork in healthcare is limited due to the complexity of the context, variety of team structures, and unique demands of healthcare work. This qualitative study aimed to identify different types of healthcare teams based on their structure, membership, and function. The study used an ethnographic approach to observe five teams in an English hospital. Data were analyzed using a combined inductive-deductive approach based on the Temporal Observational Analysis of Teamwork framework. A typology was developed, consisting of five team types: structural, hybrid, satellite, responsive, and coordinating. Teams were challenged to varying degrees with staffing, membership instability, equipment shortages, and other elements of the healthcare environment. Teams varied in their ability to respond to these challenges depending on their characteristics, such as their teamworking style, location, and membership. The typology developed in this study can help healthcare organizations to better understand and design effective teams for different healthcare contexts. It can also guide future research on healthcare teams and provide a framework for comparing teams across settings. To improve teamwork, healthcare organizations should consider the unique needs of different team types and design effective training programs accordingly.

Shifts in the composition and distribution of Pacific Arctic larval fish assemblages in response to rapid ecosystem change.

The Pacific Arctic marine ecosystem has undergone rapid changes in recent years due to ocean warming, sea ice loss, and increased northward transport of Pacific-origin waters into the Arctic. These climate-mediated changes have been linked to range shifts of juvenile and adult subarctic (boreal) and Arctic fish populations, though it is unclear whether distributional changes are also occurring during the early life stages. We analyzed larval fish abundance and distribution data sampled in late summer from 2010 to 2019 in two interconnected Pacific Arctic ecosystems: the northern Bering Sea and Chukchi Sea, to determine whether recent warming and loss of sea ice has restricted habitat for Arctic species and altered larval fish assemblage composition from Arctic- to boreal-associated taxa. Multivariate analyses revealed the presence of three distinct multi-species assemblages across all years: (1) a boreal assemblage dominated by yellowfin sole (Limanda aspera), capelin (Mallotus catervarius), and walleye pollock (Gadus chalcogrammus); (2) an Arctic assemblage composed of Arctic cod (Boreogadus saida) and other common Arctic species; and (3) a mixed assemblage composed of the dominant species from the other two assemblages. We found that the wind- and current-driven northward advection of warmer, subarctic waters and the unprecedented low-ice conditions observed in the northern Bering and Chukchi seas beginning in 2017 and persisting into 2018 and 2019 have precipitated community-wide shifts, with the boreal larval fish assemblage expanding northward and offshore and the Arctic assemblage retreating poleward. We conclude that Arctic warming is most significantly driving changes in abundance at the leading and trailing edges of the Chukchi Sea larval fish community as boreal species increase in abundance and Arctic species decline. Our analyses document how quickly larval fish assemblages respond to environmental change and reveal that the impacts of Arctic borealization on fish community composition spans multiple life stages over large spatial scales.

Interventions to enhance pre-pregnancy care for women with type 2 diabetes: A systematic review of the literature.

AIMS: The aim of the study was to examine the content and impact of interventions that have been used to increase the uptake of pre-pregnancy care for women with type 2 diabetes, and their impact on maternal and fetal outcomes. METHODS: A systematic search of multiple databases was conducted in November 2021, and updated July 2022, to identify studies assessing interventions to enhance pre-pregnancy care for women with type 2 diabetes. Over 10% of articles were screened by two reviewers at title and abstract phase, after which all selected full-text articles were screened by two reviewers. Quality assessment was conducted using the Critical Appraisal Skills Programme checklist for cohort studies. Meta-analysis was not possible due to study heterogeneity; therefore, narrative synthesis was conducted. RESULTS: Four eligible cohort studies were identified. The conclusions able to be drawn by this review were limited as women with type 2 diabetes (n = 800) were in the minority in all four studies (35%-40%) and none of the interventions were exclusively tailored for them. The uptake of pre-pregnancy care was lower in women with type 2 diabetes (8%-10%) compared with other participant groups in the studies. Pregnancy preparation indicators generally improved among all groups exposed to pre-pregnancy care, with varying impact on pregnancy outcomes. CONCLUSIONS: This review demonstrates that previous interventions have had a limited impact on pre-pregnancy care uptake in women with type 2 diabetes. Future studies should focus on tailored interventions for improving pre-pregnancy care for women with type 2 diabetes, particularly those from ethnic minorities and living in poorer communities.

Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts.

Immunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink". The panel concluded there is moderate evidence that PFOS and PFOA are immunotoxic, based primarily on evidence from animal data. However, species concordance and human relevance cannot be well established due to data limitations. The panel recommended additional testing that includes longer-term exposures, evaluates both genders, includes other species of animals, tests lower dose levels, assesses more complete measures of immune responses, and elucidates the mechanism of action. Panel members agreed that the Faroe Islands cohort data should not be used as the primary basis for deriving PFAS risk assessment values. The panel agreed that vaccine antibody titer is not useful as a stand-alone metric for risk assessment. Instead, PFOA and PFOS toxicity values should rely on multiple high-quality studies, which are currently not available for immune suppression. The panel concluded that the available PFAS immune epidemiology studies suffer from weaknesses in study design that preclude their use, whereas available animal toxicity studies provide comprehensive dataset to derive points of departure (PODs) for non-immune endpoints. The panel recommends accounting for potential PFAS immunotoxicity by applying a database uncertainty factor to POD values derived from animal studies for other more robustly supported critical effects.

An integrated assessment of the 1,4-dioxane cancer mode of action and threshold response in rodents.

1,4-Dioxane is an environmental contaminant that has been shown to cause cancer in rodents after chronic high dose exposures. We reviewed and integrated information from recently published studies to update our understanding of the cancer mode of action of 1,4-dioxane. Tumor development in rodents from exposure to high doses of 1,4-dioxane is preceded by pre-neoplastic events including increased hepatic genomic signaling activity related to mitogenesis, elevation of Cyp2E1 activity and oxidative stress leading to genotoxicity and cytotoxicity. These events are followed by regenerative repair and proliferation and eventual development of tumors. Importantly, these events occur at doses that exceed the metabolic clearance of absorbed 1,4-dioxane in rats and mice resulting in elevated systemic levels of parent 1,4-dioxane. Consistent with previous reviews, we found no evidence of direct mutagenicity from exposure to 1,4-dioxane. We also found no evidence of CAR/PXR, AhR or PPARα activation resulting from exposure to 1,4-dioxane. This integrated assessment supports a cancer mode of action that is dependent on exceeding the metabolic clearance of absorbed 1,4-dioxane, direct mitogenesis, elevation of Cyp2E1 activity and oxidative stress leading to genotoxicity and cytotoxicity followed by sustained proliferation driven by regenerative repair and progression of heritable lesions to tumor development.

The impact of COVID-19 on nurses (ICON) survey: Nurses' accounts of what would have helped to improve their working lives.

AIMS: To use nurses' descriptions of what would have improved their working lives during the first peak of the COVID-19 pandemic in the UK. DESIGN: Analysis of free-text responses from a cross-sectional survey of the UK nursing and midwifery workforce. METHODS: Between 2 and 14 April 2020, 3299 nurses and midwives completed an online survey, as part of the 'Impact of COVID-19 on Nurses' (ICON) study. 2205 (67%) gave answers to a question asking for the top three things that the government or their employer could do to improve their working lives. Each participants' response was coded using thematic and content analysis. Multiple response analysis quantified the frequency of different issues and themes and examined variation by employer. RESULTS: Most (77%) were employed by the National Health Service (77%) and worked at staff or senior staff nurse levels (55%). 5938 codable responses were generated. Personal protective equipment/staff safety (60.0%), support to workforce (28.6%) and better communication (21.9%) were the most cited themes. Within 'personal protective equipment', responses focussed most on available supply. Only 2.8% stated that nothing further could be done. Patterns were similar in both NHS and non-NHS settings. CONCLUSIONS: The analysis provided valuable insight into key changes required to improve the work lives of nurses during a pandemic. Urgent improvements in provision and quality of personal protective equipment were needed for the safety of both workforce and patients. IMPACT: Failure to meet nurses needs to be safe at work appears to have damaged morale in this vital workforce. We identified key strategies that, if implemented by the Government and employers, could have improved the working lives of the nursing and midwifery workforce during the early stages of the COVID-19 pandemic and could prevent the pandemic from having a longer-term negative impact on the retention of this vital workforce. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution, due to the COVID-19 Pandemic, urgency of the work and the target population being health and social care staff.

Exploring the role of leaders in enabling adaptive capacity in hospital teams - a multiple case study.

BACKGROUND: Resilient healthcare research studies how healthcare systems and stakeholders adapt and cope with challenges and changes to enable high quality care. Team leaders are seen as central in coordinating clinical care, but research detailing their contributions in supporting adaptive capacity has been limited. This study aims to explore and describe how leaders enable adaptive capacity in hospital teams. METHODS: This article reports from a multiple embedded case study in two Norwegian hospitals. A case was defined as one hospital containing four different types of teams in a hospital setting. Data collection used triangulation of observation and interviews with leaders, followed by a qualitative content analysis. RESULTS: Leaders contribute in several ways to enhance their teams' adaptive capacity. This study identified four key enablers; (1) building sufficient competence in the teams; (2) balancing workload, risk, and staff needs; (3) relational leadership; and (4) emphasising situational understanding and awareness through timely and relevant information. CONCLUSION: Team leaders are key actors in everyday healthcare systems and facilitate organisational resilience by supporting adaptive capacity in hospital teams. We have developed a new framework of key leadership enablers that need to be integrated into leadership activities and approaches along with a strong relational and contextual understanding.

Understanding complex work using an extension of the resilience CARE model: an ethnographic study.

BACKGROUND: Resilient Healthcare research centres on understanding and improving quality and safety in healthcare. The Concepts for Applying Resilience Engineering (CARE) model highlights the relationships between demand, capacity, work-as-done, work-as-imagined, and outcomes, all of which are central aspects of Resilient Healthcare theory. However, detailed descriptions of the nature of misalignments and the mechanisms used to adapt to them are still unknown. OBJECTIVE: The objectives were to identify and classify types of misalignments between demand and capacity and types of adaptations that were made in response to misalignments. METHODS: The study involved 88.5 hours of non-participant ethnographic observations in a large, teaching hospital in central London. The wards included in the study were: two surgical wards, an older adult ward, a critical care unit, and the Acute Assessment Unit (AAU), an extension unit created to expedite patient flow out of the Emergency Department. Data were collected via observations of routine clinical work and ethnographic interviews with healthcare professionals during the observations. Field notes were transcribed and thematically analysed using a combined deductive-inductive approach based on the CARE model. RESULTS: A total of 365 instances of demand-capacity misalignment were identified across the five wards included in the study. Of these, 212 had at least one observed corresponding work adaptation. Misalignments identified include equipment, staffing, process, communication, workflow, and space. Adaptations identified include process, resource redistribution, and extra-role performance. For all misalignment types observed across the five in-patient settings, process adaptations were the most frequently used adaptations. The exception to this was for staffing misalignments, which were most frequently responded to with extra-role performance adaptations. Of the three process adaptations, hospital workers most often adapted by changing how the process was done. CONCLUSIONS: This study contributes a new version of the CARE model that includes types of misalignments and corresponding adaptations, which can be used to better understand work-as-done. This affords insight into the complexity of the system and how it might be improved by reducing misalignments via work system redesign or by enhancing adaptive capacity.

Implementation of eHealth to Support Assessment and Decision-making for Residents With Dementia in Long-term Care: Systematic Review.

BACKGROUND: As dementia progresses, symptoms and concerns increase, causing considerable distress for the person and their caregiver. The integration of care between care homes and health care services is vital to meet increasing care needs and maintain quality of life. However, care home access to high-quality health care is inequitable. eHealth can facilitate this by supporting remote specialist input on care processes, such as clinical assessment and decision-making, and streamlining care on site. How to best implement eHealth in the care home setting is unclear. OBJECTIVE: The aim of this review was to identify the key factors that influence the implementation of eHealth for people living with dementia in long-term care. METHODS: A systematic search of Embase, PsycINFO, MEDLINE, and CINAHL was conducted to identify studies published between 2000 and 2020. Studies were eligible if they focused on eHealth interventions to improve treatment and care assessment or decision-making for residents with dementia in care homes. Data were thematically analyzed and deductively mapped onto the 6 constructs of the adapted Consolidated Framework for Implementation Research (CFIR). The results are presented as a narrative synthesis. RESULTS: A total of 29 studies were included, focusing on a variety of eHealth interventions, including remote video consultations and clinical decision support tools. Key factors that influenced eHealth implementation were identified across all 6 constructs of the CFIR. Most concerned the inner setting construct on requirements for implementation in the care home, such as providing a conducive learning climate, engaged leadership, and sufficient training and resources. A total of 4 novel subconstructs were identified to inform the implementation requirements to meet resident needs and engage end users. CONCLUSIONS: Implementing eHealth in care homes for people with dementia is multifactorial and complex, involving interaction between residents, staff, and organizations. It requires an emphasis on the needs of residents and the engagement of end users in the implementation process. A novel conceptual model of the key factors was developed and translated into 18 practical recommendations on the implementation of eHealth in long-term care to guide implementers or innovators in care homes. Successful implementation of eHealth is required to maximize uptake and drive improvements in integrated health and social care.

The utility of surrogate markers in predicting HLA alleles associated with adverse drug reactions in Vietnamese.

BACKGROUND: Screening for HLA-A*31:01/HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01 is recommended in selected populations for prevention of carbamazepine, abacavir, and allopurinol-induced severe cutaneous adverse reactions (SCARs). Compared to conventional methods for detection of HLA alleles, PCR using a tag single nucleotide polymorphism (SNP) can be cost-effective, particularly where the surrogate marker SNP is in absolute linkage disequilibrium with the relevant HLA allele. OBJECTIVE: To determine guidelines for prevention of SCARs though predictive screening for the Australian Vietnamese population, the prevalence of four HLA alleles (HLA-A*31:01, HLA-B*15:02, HLA-B*57:01 and HLA-B*58:01) was examined. The utility of surrogate markers, rs2395029 and rs9263726, was investigated to predict for the presence of HLA-B*57:01 and HLA-B*58:01, respectively. METHODS: Genotyping for specific HLA alleles was performed in 152 healthy Vietnamese living in Sydney using validated and established PCR-based methods. SNP genotyping was conducted using restriction-fragment-length-polymorphism analysis. RESULTS: rs2395029 and rs9263726 strongly correlated with HLA-B*57:01 (κ = 1, p < 0.001) and HLA-B*58:01 (Κ = 0.9, p < 0.001) with 100% sensitivity and 100% negative predictive value for predicting the HLA-B*57:01 and HLA-B*58:01 carriers, respectively. A high prevalence of carriers of HLA-A*31:01 (3.29%), HLA-B*15:02 (14.47%), HLA-B*57:01 (6.58%) and HLA-B*58:01 (9.21%) was revealed. Conclusions: Screening is recommended for these alleles in Australian Vietnamese prior to introducing relevant therapies. SNPs, rs2395029 and rs9263726, can be successfully used as surrogate markers for HLA-B*57:01 and HLA-B*58:01 in this population.

The role of transactive memory systems, psychological safety and interpersonal conflict in hospital team performance.

Safe patient care in hospitals relies on teamwork. Transactive Memory Systems (TMS), are shared cognitive systems that have been linked to team performance in other domains, but have received limited attention in healthcare. This study investigated the role of TMS, psychological safety and interpersonal conflict in predicting team performance in hospital ward teams where team membership is dynamic and often loosely defined. Hospital staff (n = 106) in four wards completed a battery of instruments assessing team performance, TMS, psychological safety and interpersonal conflict. TMS was a weak predictor of team performance, but the relationship was mediated by psychological safety. Overall, team performance was predicted by high psychological safety, low interpersonal conflict and low reliance on team members' knowledge (i.e. TMS credibility). These findings suggest that, in hospital teams, TMS is not a strong predictor of team performance but team culture is critical to ensure the quality and safety of patient care. Practitioner summary: This study investigated the role of Transactive Memory Systems (TMS) and cultural factors in hospital team performance. Team performance was predicted by psychological safety, low interpersonal conflict and low reliance on team members' untested knowledge. This highlights the importance of a supportive and psychologically safe team culture for safe care in hospitals. Abbreviations: TMS: transactive memory systems; HCA: health care assistant.

Responses of ichthyoplankton assemblages to the recent marine heatwave and previous climate fluctuations in several Northeast Pacific marine ecosystems.

The effects of climate warming on ecosystem dynamics are widespread throughout the world's oceans. In the Northeast Pacific, large-scale climate patterns such as the El Niño/Southern Oscillation and Pacific Decadal Oscillation, and recently unprecedented warm ocean conditions from 2014 to 2016, referred to as a marine heatwave (MHW), resulted in large-scale ecosystem changes. Larval fishes quickly respond to environmental variability and are sensitive indicators of ecosystem change. Categorizing ichthyoplankton dynamics across marine ecosystem in the Northeast Pacific can help elucidate the magnitude of assemblage shifts, and whether responses are synchronous or alternatively governed by local responses to regional oceanographic conditions. We analyzed time-series data of ichthyoplankton abundances from four ecoregions in the Northeast Pacific ranging from subarctic to subtropical: the Gulf of Alaska (1981-2017), British Columbia (2001-2017), Oregon (1998-2017), and the southern California Current (1981-2017). We assessed the impact of the recent (2014-2016) MHW and how ichthyoplankton assemblages responded to past major climate perturbations since 1981 in these ecosystems. Our results indicate that the MHW caused widespread changes in the ichthyoplankton fauna along the coast of the Northeast Pacific Ocean, but impacts differed between marine ecosystems. For example, abundances for most dominant taxa were at all-time lows since the beginning of sampling in the Gulf of Alaska and British Columbia, while in Oregon and the southern California Current species richness increased as did abundances of species associated with warmer waters. Lastly, species associated with cold waters also increased in abundances close to shore in southern California during the MHW, a pattern that was distinctly different from previous El Niño events. We also found several large-scale, synchronized ichthyoplankton assemblage composition shifts during past major climate events. Current climate projections suggest that MHWs will become more intense and thus our findings can help project future changes in larval dynamics, allowing for improved ecosystem management decisions.

Priorities and opportunities for palliative and end of life care in United Kingdom health policies: a national documentary analysis.

BACKGROUND: Access to high-quality palliative care is inadequate for most people living and dying with serious illness. Policies aimed at optimising delivery of palliative and end of life care are an important mechanism to improve quality of care for the dying. The extent to which palliative care is included in national health policies is unknown. We aimed to identify priorities and opportunities for palliative and end of life care in national health policies in the UK. METHODS: Documentary analysis consisting of 1) summative content analysis to describe the extent to which palliative and end of life care is referred to and/or prioritised in national health and social care policies, and 2) thematic analysis to explore health policy priorities that are opportunities to widen access to palliative and end of life care for people with serious illness. Relevant national policy documents were identified through web searches of key government and other organisations, and through expert consultation. Documents included were UK-wide or devolved (i.e. England, Scotland, Northern Ireland, Wales), health and social care government strategies published from 2010 onwards. RESULTS: Fifteen policy documents were included in the final analysis. Twelve referred to palliative or end of life care, but details about what should improve, or mechanisms to achieve this, were sparse. Policy priorities that are opportunities to widen palliative and end of life care access comprised three inter-related themes: (1) integrated care - conceptualised as reorganisation of services as a way to enable improvement; (2) personalised care - conceptualised as allowing people to shape and manage their own care; and (3) support for unpaid carers - conceptualised as enabling unpaid carers to live a more independent lifestyle and balance caring with their own needs. CONCLUSIONS: Although information on palliative and end of life care in UK health and social care policies was sparse, improving palliative care may provide an evidence-based approach to achieve the stated policy priorities of integrated care, personalised care, and support for unpaid carers. Aligning existing evidence of the benefits of palliative care with the three priorities identified may be an effective mechanism to both strengthen policy and improve care for people who are dying.

Empowering Better End-of-Life Dementia Care (EMBED-Care): A mixed methods protocol to achieve integrated person-centred care across settings.

OBJECTIVES: Globally, the number of people with dementia who have palliative care needs will increase fourfold over the next 40 years. The Empowering Better End-of-Life Dementia Care (EMBED-Care) Programme aims to deliver a step change in care through a large sequential study, spanning multiple work streams. METHODS: We will use mixed methods across settings where people with dementia live and die: their own homes, care homes, and hospitals. Beginning with policy syntheses and reviews of interventions, we will develop a conceptual framework and underpinning theory of change. We will use linked data sets to explore current service use, care transitions, and inequalities and predict future need for end-of-life dementia care. Longitudinal cohort studies of people with dementia (including young onset and prion dementias) and their carers will describe care transitions, quality of life, symptoms, formal and informal care provision, and costs. Data will be synthesised, underpinned by the Knowledge-to-Action Implementation Framework, to design a novel complex intervention to support assessment, decision making, and communication between patients, carers, and inter-professional teams. This will be feasibility and pilot tested in UK settings. Patient and public involvement and engagement, innovative work with artists, policymakers, and third sector organisations are embedded to drive impact. We will build research capacity and develop an international network for excellence in dementia palliative care. CONCLUSIONS: EMBED-Care will help us understand current and future need, develop novel cost-effective care innovations, build research capacity, and promote international collaborations in research and practice to ensure people live and die well with dementia.

Experience of mobile nursing workforce from Portugal to the NHS in UK: influence of institutions and actors at the system, organization and individual levels.

In UK, since 2010 shortages of nurses and policy changes led many health service providers to become more active in recruiting nurses from the European Union Member States. This article analyses the experience of Portuguese nurses working in the English NHS considering the individual and organizational factors that affect the quality and duration of nurses' migration experience, future career plans and expectations. Twenty-seven semi-structured interviews were conducted at the individual, organizational and policy levels in UK with Portuguese nurses and NHS healthcare staff in 2015-16. The results demonstrate that organizational settings, conditions, actors' attitudes and level of support influence nurses' level of commitment to their employer and their overall mobility experience. Professional achievements, professional and personal sources of support made these nurses evaluate their overall mobility experience as positive, even overcoming personal challenges such as homesickness. The results reveal that migration is accomplished through constant interaction between institutions and individual actors at different levels. Understanding the influencing factors as well as the complex and dynamic nature of a professional's decision-making can design more effective retention responses.

Defining the boundaries and operational concepts of resilience in the resilience in healthcare research program.

BACKGROUND: Understanding the resilience of healthcare is critically important. A resilient healthcare system might be expected to consistently deliver high quality care, withstand disruptive events and continually adapt, learn and improve. However, there are many different theories, models and definitions of resilience and most are contested and debated in the literature. Clear and unambiguous conceptual definitions are important for both theoretical and practical considerations of any phenomenon, and resilience is no exception. A large international research programme on Resilience in Healthcare (RiH) is seeking to address these issues in a 5-year study across Norway, England, the Netherlands, Australia, Japan, and Switzerland (2018-2023). The aims of this debate paper are: 1) to identify and select core operational concepts of resilience from the literature in order to consider their contributions, implications, and boundaries for researching resilience in healthcare; and 2) to propose a working definition of healthcare resilience that underpins the international RiH research programme. MAIN TEXT: To fulfil these aims, first an overview of three core perspectives or metaphors that underpin theories of resilience are introduced from ecology, engineering and psychology. Second, we present a brief overview of key definitions and approaches to resilience applicable in healthcare. We position our research program with collaborative learning and user involvement as vital prerequisite pillars in our conceptualisation and operationalisation of resilience for maintaining quality of healthcare services. Third, our analysis addresses four core questions that studies of resilience in healthcare need to consider when defining and operationalising resilience. These are: resilience 'for what', 'to what', 'of what', and 'through what'? Finally, we present our operational definition of resilience. CONCLUSION: The RiH research program is exploring resilience as a multi-level phenomenon and considers adaptive capacity to change as a foundation for high quality care. We, therefore, define healthcare resilience as: the capacity to adapt to challenges and changes at different system levels, to maintain high quality care. This working definition of resilience is intended to be comprehensible and applicable regardless of the level of analysis or type of system component under investigation.

Using Safety-II and resilient healthcare principles to learn from Never Events.

OBJECTIVES: Conduct a secondary analysis of root cause analysis (RCA) reports of Never Events to determine whether and how Safety-II/resilient healthcare principles could contribute to improving the quality of investigation reports and therefore preventing future Never Events. DESIGN: Qualitative and quantitative retrospective analysis of RCA reports. SETTING: A large acute healthcare Trust in London. PARTICIPANTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Quality of RCA reports, robustness of actions proposed. RESULTS: RCA reports had low-to-moderate effectiveness ratings and low resilience ratings. Reports identified many system vulnerabilities that were not addressed in the actions proposed. Using a Safety-II/resilient healthcare lens to examine work-as-done and misalignments between demand and capacity would strengthen analysis of Never Events. CONCLUSION: Safety-II/Resilient Healthcare concepts can increase the quality of RCA reports and focus attention on prospectively strengthening systems. Recommendations for incorporating Safety-II concepts into RCA processes are provided.