Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

OBJECTIVES: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. DESIGN: Ambidirectional multisite cohort study. SETTING: Four tertiary children's hospitals. PATIENTS: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02). CONCLUSIONS: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

Analysis of the impact of COVID-19 on Scotland's care-homes from March 2020 to October 2021: national linked data cohort analysis.

BACKGROUND: The impact of the COVID-19 pandemic on long-term care residents remains of wide interest, but most analyses focus on the initial wave of infections. OBJECTIVE: To examine change over time in: (i) The size, duration, classification and pattern of care-home outbreaks of COVID-19 and associated mortality and (ii) characteristics associated with an outbreak. DESIGN: Retrospective observational cohort study using routinely-collected data. SETTING: All adult care-homes in Scotland (1,092 homes, 41,299 places). METHODS: Analysis was undertaken at care-home level, over three periods. Period (P)1 01/03/2020-31/08/2020; P2 01/09/2020-31/05/2021 and P3 01/06/2021-31/10/2021. Outcomes were the presence and characteristics of outbreaks and mortality within the care-home. Cluster analysis was used to compare the pattern of outbreaks. Logistic regression examined care-home characteristics associated with outbreaks. RESULTS: In total 296 (27.1%) care-homes had one outbreak, 220 (20.1%) had two, 91 (8.3%) had three, and 68 (6.2%) had four or more. There were 1,313 outbreaks involving residents: 431 outbreaks in P1, 559 in P2 and 323 in P3. The COVID-19 mortality rate per 1,000 beds fell from 45.8 in P1, to 29.3 in P2, and 3.5 in P3. Larger care-homes were much more likely to have an outbreak, but associations between size and outbreaks were weaker in later periods. CONCLUSIONS: COVID-19 mitigation measures appear to have been beneficial, although the impact on residents remained severe until early 2021. Care-home residents, staff, relatives and providers are critical groups for consideration and involvement in future pandemic planning.

De Novo Variants in RAB11B Cause Various Degrees of Global Developmental Delay and Intellectual Disability in Children.

BACKGROUND: RAB11B was described previously once with a severe form of intellectual disability. We aim at validation and delineation of the role of RAB11B in neurodevelopmental disorders. METHODS: We present seven novel individuals with disease-associated variants in RAB11B when compared with the six cases described in the literature. We performed a cross-sectional analysis to identify the clinical spectrum and the core phenotype. Additionally, structural effects of the variants were assessed by molecular modeling. RESULTS: Seven distinct de novo missense variants were identified, three of them recurrent (p.(Gly21Arg), p.(Val22Met), and p.(Ala68Thr)). Molecular modeling suggests that those variants either affect the nucleotide binding (at amino acid positions 21, 22, 33, 68) or the interaction with effector molecules (at positions 72 and 75). Our data confirmed the main manifestations as neurodevelopmental disorder with intellectual disability (85%), muscular hypotonia (83%), structural brain anomalies (77%), and visual impairment (70%). Combined analysis indicates a genotype-phenotype correlation; variants impacting the nucleotide binding cause a severe phenotype with intellectual disability, and variants outside the binding pocket lead to a milder phenotype with epilepsy. CONCLUSIONS: We confirm that disease-associated missense variants in RAB11B cause a neurodevelopmental disorder and suggest a genotype-phenotype correlation based on the impact on nucleotide binding functionality of RAB11B.

Listening and learning: a qualitative study of Scottish care home staff experiences of managing COVID-19 between March 2020-August 2022.

BACKGROUND: The serious outcomes of outbreaks of COVID-19 in care homes have been described internationally. The experiences of professionals working through outbreaks has received less attention, missing opportunities to acknowledge and learn lessons. Our aim was to explore the experiences of care home staff in Scotland of managing COVID-19 within their homes to help inform understanding and future practice. METHODS: From April to August 2022, 34 individual semi-structured interviews were conducted with care home staff working in homes which experienced an outbreak(s) of COVID-19. Reflexive thematic methods were used to analyse verbatim deidentified transcripts. FINDINGS: There was no singular experience of COVID-19 outbreaks within care homes. We identified four broad groupings of homes with outbreaks (significant outbreaks, managed outbreaks, outbreaks in remote/rural homes & outbreaks in homes supporting younger adults), with overlaps in timing and severity and variation in the support received and impact. The national response to the COVID-19 pandemic resulted in fundamental change to care home relationships. Staff responded by adaptation in uncertainty. However, they were challenged by emerging inequalities influencing residents' care. There were tensions between staff experience and evolving external approaches to regulation and oversight. All this change resulted in psychological impacts on staff. However, there was also widespread evidence of compassionate leadership and teamwork in their responses. Effective sources of support were underpinned by respectful relationships and continuity, tailored to individual contexts. CONCLUSIONS: The lived experiences of care home staff during the COVID-19 pandemic provide valuable insights applicable beyond the pandemic context. This includes: recognition of the specialism, complexity and diversity of care home practice; the value afforded by embedding genuine representation and involvement in planning, policy-making and research; the need for individualising to people in their contexts and the value of fostering respectful relationships across professional groups to support residents.

New horizons in the role of digital data in the healthcare of older people.

There are national and global moves to improve effective digital data design and application in healthcare. This New Horizons commentary describes the role of digital data in healthcare of the ageing population. We outline how health and social care professionals can engage in the proactive design of digital systems that appropriately serve people as they age, carers and the workforce that supports them. KEY POINTS: Healthcare improvements have resulted in increased population longevity and hence multimorbidity. Shared care records to improve communication and information continuity across care settings hold potential for older people. Data structure and coding are key considerations. A workforce with expertise in caring for older people with relevant knowledge and skills in digital healthcare is important.

Outcome measures from international older adult care home intervention research: a scoping review.

BACKGROUND: Care homes are increasingly important settings for intervention research to enhance evidence-informed care. For such research to demonstrate effectiveness, it is essential that measures are appropriate for the population, setting and practice contexts. OBJECTIVE: To identify care home intervention studies and describe the resident outcome measures used. DESIGN: Scoping review. METHODS: We reviewed international care home research published from 2015 to August 2022. We searched MEDLINE, EMBASE, CINAHL and ASSIA. We included any intervention study conducted in a care home, reporting resident outcomes. We extracted resident outcome measures, organised these using the domains of an adapted framework and described their use. RESULTS: From 7,330 records screened, we included 396 datasets reported in 436 publications. These included 12,167 care homes and 836,842 residents, with an average of 80 residents per study. The studies evaluated 859 unique resident outcomes 2,030 times using 732 outcome measures. Outcomes were evaluated between 1 and 112 times, with 75.1% of outcomes evaluated only once. Outcome measures were used 1-120 times, with 68.4% of measures used only once. Only 14 measures were used ≥20 times. Functional status, mood & behaviour and medications were the commonest outcome domains assessed. More than half of outcomes were assessed using scales, with a fifth using existing records or administrative data. CONCLUSIONS: There is significant heterogeneity in the choice and assessment of outcomes for intervention research in care homes. There is an urgent need to develop a consensus on useful and sensitive tools for care homes, working with residents, families and friends and staff.

The Guyana Program to Advance Cardiac Care: A Model for Equitable Cardiovascular Care Delivery.

Guyana is one of the poorest countries in South America, with the highest rate of cardiovascular mortality on the continent. As is the case in many low- and middle-income countries, cardiovascular care is available through the private sector but is not accessible to much of the urban and rural poor. We present the 10-year experience of the Guyana Program to Advance Cardiac Care (GPACC), an academic partnership aiming to provide high-quality, equitable cardiovascular care in Georgetown's only public hospital. We discuss the implementation of a cardiac care program using the World Health Organization Framework for Action, outlining vital components for care delivery in resource-limited settings. GPACC was able to demonstrate that targeted investment, education of clinicians, and cohesive healthcare delivery strategies can contribute to sustainable service delivery for Guyana's largest burden of disease. This structured approach may provide lessons for implementation of similar programs in other resource-limited settings. Highlights: In many LMICs, specialized cardiovascular care is available in the private, but not public, sector.The WHO Framework for Action can guide development of sustainable programs in low-resource settings.GPACC can serve as a successful and innovative model for delivery of sustainable cardiovascular care.

Newborn screening for mucopolysaccharidosis type II: Lessons learned.

We describe our experience with population-based newborn screening for mucopolysaccharidosis type II (MPS II) in 586,323 infants by measurement of iduronate-2-sulfatase activity in dried blood spots between December 12, 2017 and April 30, 2022. A total of 76 infants were referred for diagnostic testing, 0.01% of the screened population. Of these, eight cases of MPS II were diagnosed for an incidence of 1 in 73,290. At least four of the eight cases detected had an attenuated phenotype. In addition, cascade testing revealed a diagnosis in four extended family members. Fifty-three cases of pseudodeficiency were also identified, for an incidence of 1 in 11,062. Our data suggest that MPS II may be more common than previously recognized with a higher prevalence of attenuated cases.

Piloting of a minimum data set for older people living in care homes in England: protocol for a longitudinal, mixed-methods study.

INTRODUCTION: Health and care data are routinely collected about care home residents in England, yet there is no way to collate these data to inform benchmarking and improvement. The Developing research resources And minimum data set for Care Homes' Adoption and use study has developed a prototype minimum data set (MDS) for piloting. METHODS AND ANALYSIS: A mixed-methods longitudinal pilot study will be conducted in 60 care homes (approximately 960 residents) in 3 regions of England, using resident data from cloud-based digital care home records at two-time points. These will be linked to resident and care home level data held within routine National Health Service and social care data sets. Two rounds of focus groups with care home staff (n=8-10 per region) and additional interviews with external stakeholders (n=3 per region) will explore implementation and the perceived utility of the MDS. Data will be assessed for completeness and timeliness of completion. Descriptive statistics, including percentage floor and ceiling effects, will establish data quality. For validated scales, construct validity will be assessed by hypothesis testing and exploratory factor analysis will establish structural validity. Internal consistency will be established using Cronbach's alpha. Longitudinal analysis of the pilot data will demonstrate the value of the MDS to each region. Qualitative data will be analysed inductively using thematic analysis to understand the complexities of implementing an MDS in care homes for older people. ETHICS AND DISSEMINATION: The study has received ethical approval from the London Queen's Square Research Ethics Committee (22/LO/0250). Informed consent is required for participation. Findings will be disseminated to: academics working on data use and integration in social care, care sector organisations, policy makers and commissioners. Findings will be published in peer-reviewed journals. Partner NIHR Applied Research Collaborations, the National Care Forum and the British Geriatrics Society will disseminate policy briefs.

Prevalence, measurement, and implications of frailty in stroke survivors: An analysis of three global aging cohorts.

BACKGROUND: Our understanding of the relationship between frailty and stroke, beyond the acute phase of stroke, is limited. We aimed to estimate the prevalence of frailty in stroke survivors using differing methods of assessment and describe relationships with stroke outcomes. METHODS: We used data from three international population surveys (American Health and Retirement Survey/English Longitudinal Study of Ageing/Survey for Health and Retirement in Europe) of aging. Frailty status was assessed using the Fried frailty phenotype, a 40-item frailty index (FI) and the clinical frailty scale (CFS). We created estimates of frailty prevalence and assessed association of frailty with outcomes of mortality/hospital admission/recurrent stroke at 2 years follow-up using logistic regression models adjusted for age/sex. Additional analyses explored effects of adding cognitive measures to frailty assessments and of missing grip strength data. FINDINGS: Across 9617 stroke survivors, using the frailty phenotype, 23.8% (n = 2094) identified as frail; with CFS, 30.1% (n = 2906) were moderately or severely frail; using FI, 22.7% (n = 2147) had moderate frailty and 31.9% (n = 3021) had severe frailty. Frailty was associated with increased risk of mortality/hospitalization/recurrent stroke using all three measures. Adding cognitive variables to the FI produced minimal difference in prevalence of frailty. People with physical frailty (phenotype or CFS) plus cognitive impairment had a greater risk of mortality than people with an equivalent level of frailty but no cognitive impairment. Excluding people unable to provide grip strength underestimated frailty prevalence. INTERPRETATION: Frailty is common in stroke and associated with poor outcomes, regardless of measure used. Adding cognitive variables to frailty phenotype/CFS measures identified those at greater risk of poor outcomes. Physical and cognitive impairments in stroke survivors do not preclude frailty assessment.

Informant-based screening tools for dementia: an overview of systematic reviews.

BACKGROUND: Informant-based questionnaires may have utility for cognitive impairment or dementia screening. Reviews describing the accuracy of respective questionnaires are available, but their focus on individual questionnaires precludes comparisons across tools. We conducted an overview of systematic reviews to assess the comparative accuracy of informant questionnaires and identify areas where evidence is lacking. METHODS: We searched six databases to identify systematic reviews describing diagnostic test accuracy of informant questionnaires for cognitive impairment or dementia. We pooled sensitivity and specificity data for each questionnaire and used network approaches to compare accuracy estimates across the differing tests. We used grading of recommendations, assessment, development and evaluation (GRADE) to evaluate the overall certainty of evidence. Finally, we created an evidence 'heat-map', describing the availability of accurate data for individual tests in different populations and settings. RESULTS: We identified 25 reviews, consisting of 93 studies and 13 informant questionnaires. Pooled analysis (37 studies; 11 052 participants) ranked the eight-item interview to ascertain dementia (AD8) highest for sensitivity [90%; 95% credible intervals (CrI) = 82-95; 'best-test' probability = 36]; while the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was most specific (81%; 95% CrI = 66-90; 'best-test' probability = 29%). GRADE-based evaluation of evidence suggested certainty was 'low' overall. Our heat-map indicated that only AD8 and IQCODE have been extensively evaluated and most studies have been in the secondary care settings. CONCLUSIONS: AD8 and IQCODE appear to be valid questionnaires for cognitive impairment or dementia assessment. Other available informant-based cognitive screening questionnaires lack evidence to justify their use at present. Evidence on the accuracy of available tools in primary care settings and with specific populations is required.

Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2, a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions in axon development. We used CRISPR/Cas9 gene editing to introduce disease-associated variants into conserved residues in the Caenorhabditis elegans MYCBP2 orthologue, RPM-1, and evaluated functional outcomes in vivo. Consistent with variable phenotypes in patients with MYCBP2 variants, C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioural abnormalities including altered habituation. Furthermore, abnormal axonal accumulation of the autophagy marker LGG-1/LC3 occurred in variants that affect RPM-1 ubiquitin ligase activity. Functional genetic outcomes from anatomical, cell biological and behavioural readouts indicate that MYCBP2 variants are likely to result in loss of function. Collectively, our results from multiple human patients and CRISPR gene editing with an in vivo animal model support a direct link between MYCBP2 and a human neurodevelopmental spectrum disorder that we term, MYCBP2-related developmental delay with corpus callosum defects (MDCD).

Understanding Pathways into Care homes using Data (UnPiCD study): a retrospective cohort study using national linked health and social care data.

BACKGROUND: Pathways into care are poorly understood but important life events for individuals and their families. UK policy is to avoid moving-in to care homes from acute hospital settings. This assumes that moves from secondary care represent a system failure. However, those moving to care homes from community and hospital settings may be fundamentally different groups, each requiring differing care approaches. OBJECTIVE: To characterise individuals who move-in to a care home from hospital and compare with those moving-in from the community. DESIGN AND SETTING: A retrospective cohort study using cross-sectoral data linkage of care home data. METHODS: We included adults moving-in to care homes between 1/4/13 and 31/3/16, recorded in the Scottish Care Home Census. Care home data were linked to general and psychiatric hospital admissions, community prescribing and mortality records to ascertain comorbidities, significant diagnoses, hospital resource use, polypharmacy and frailty. Multivariate logistic regression identified predictors of moving-in from hospital compared to from community. RESULTS: We included 23,892 individuals moving-in to a care home, 13,564 (56.8%) from hospital and 10,328 (43.2%) from the community. High frailty risk adjusted Odds Ratio (aOR) 5.11 (95% Confidence Interval (CI): 4.60-5.68), hospital discharge with diagnosis of fracture aOR 3.91 (95%CI: 3.41-4.47) or stroke aOR 8.42 (95%CI: 6.90-10.29) were associated with moving-in from hospital. Discharge from in-patient psychiatry was also a highly significant predictor aOR 19.12 (95%CI: 16.26-22.48). CONCLUSIONS: Individuals moving-in to care homes directly from hospital are clinically distinct from those from the community. Linkage of cross-sectoral data can allow exploration of pathways into care at scale.

Engagement in research during specialist geriatric medicine training: results of a national trainee survey.

INTRODUCTION: Meaningful ageing research across the UK is dependent on a network of engaged geriatricians. The research in geriatric specialty training (RGST) survey aimed to establish current research opportunities available to geriatric medicine specialty trainees in the UK. METHODS: The RGST survey was disseminated to UK higher specialist trainees in geriatric medicine in 2019 via the Geriatric Medicine Research Collaborative network. RESULTS: Among the 36.9% (192/521) of respondents, 44% (83/188) reported previous research involvement and 7% (n=8) held a PhD or MD. Of the respondents with no research experience to date, 59.0% (n=49) reported a desire to undertake a period of research. One-third (31%) of geriatric registrars surveyed felt that they had gained sufficient research experience during their training. Perceived encouragement and support to undertake research was low (30.7%). Enablers and barriers to research engagement were identified. CONCLUSION: Research opportunity and engagement in geriatric medicine training is lacking. This could jeopardise the future workforce of research-active geriatricians in the UK and limit patient access to emerging research and innovation. Interventions to promote research engagement among geriatric medicine trainees are needed to facilitate integration of research into routine clinical practice to improve the health and care of older people.

Developing a minimum data set for older adult care homes in the UK: exploring the concept and defining early core principles.

Reforms to social care in response to the COVID-19 pandemic, in the UK and internationally, place data at the heart of proposed innovations and solutions. The principles are not well established of what constitutes core, or minimum, data to support care home residents. Often, what is included privileges data on resident health over day-to-day care priorities and quality of life. This Personal View argues for evidence-based principles on which to base the development of a UK minimum data set (MDS) for care homes. Co-produced work involving care home staff and older people working with stakeholders is required to define and agree the format, content, structure, and operationalisation of the MDS. Implementation decisions will determine the success of the MDS, affecting aspects including data quality, completeness, and usability. Care home staff who collect the data need to benefit from the MDS and see value in their contribution, and residents must derive benefit from data collection and synthesis.

Prevalence and implications of frailty in acute stroke: systematic review & meta-analysis.

BACKGROUND: frailty is common in older adults and associated with poor outcomes following illness. Although stroke is predominantly a disease of older people, our knowledge of frailty in stroke is limited. We aimed to collate the literature on acute stroke and frailty to estimate the prevalence of pre-stroke frailty and its associations with outcomes. METHODS: paired researchers searched multidisciplinary electronic databases for papers describing frailty and acute stroke. We assessed risk of bias using Newcastle-Ottawa tools appropriate to study design. We created summary estimates of pre-stroke frailty using random effects models. We collated whether studies reported significant positive associations between frailty and clinical outcomes in adjusted models. RESULTS: we included 14 studies (n = 27,210 participants). Seven studies (n = 8,840) used a frailty index approach, four studies (n = 14,924) used Hospital Frailty Risk Scores. Pooled prevalence of pre-stroke frailty was 24.6% (95% confidence interval, CI: 16.2-33.1%; low quality evidence, downgraded due to heterogeneity, bias). Combining frailty and pre-frailty (nine studies, n = 23,827), prevalence of any frailty syndrome was 66.8% (95%CI: 49.9-83.7%). Seven studies were at risk of bias, from participant selection or method of frailty assessment. Pre-stroke frailty was associated with all adverse outcomes assessed, including longer-term mortality (positive association in 6 of 6 studies reporting this outcome; odds ratio: 3.75 [95%CI: 2.41-5.70]), length of admission (3 of 4 studies) and disability (4 of 6 studies). CONCLUSIONS: despite substantial heterogeneity, whichever way it is measured, frailty is common in patients presenting with acute stroke and associated with poor outcomes. This has implications for the design of stroke services and pathways.

Contextual factors influencing complex intervention research processes in care homes: a systematic review and framework synthesis.

BACKGROUND: Care homes are complex settings to undertake intervention research. Barriers to research implementation processes can threaten studies' validity, reducing the value to residents, staff, researchers and funders. We aimed to (i) identify and categorise contextual factors that may mediate outcomes of complex intervention studies in care homes and (ii) provide recommendations to minimise the risk of expensive research implementation failures. METHODS: We conducted a systematic review using a framework synthesis approach viewed through a complex adaptive systems lens. We searched: MEDLINE, Embase, CINAHL, ASSIA databases and grey literature. We sought process evaluations of care home complex interventions published in English. Narrative data were indexed under 28 context domains. We performed an inductive thematic analysis across the context domains. RESULTS: We included 33 process evaluations conducted in high-income countries, published between 2005 and 2019. Framework synthesis identified barriers to implementation that were more common at the task and organisational level. Inductive thematic analysis identified (i) avoiding procedural drift and (ii) participatory action and learning as key priorities for research teams. Research team recommendations include advice for protocol design and care home engagement. Care home team recommendations focus on internal resources and team dynamics. Collaborative recommendations apply to care homes' individual context and the importance of maintaining positive working relationships. DISCUSSION: Researchers planning and undertaking research with care homes need a sensitive appreciation of the complex care home context. Study implementation is most effective where an intervention is co-produced, with agreed purpose and adequate resources to incorporate within existing routines and care practices.

The uptake and use of a minimum data set (MDS) for older people living and dying in care homes: a realist review.

BACKGROUND: Care homes provide long term care for older people. Countries with standardised approaches to residents' assessment, care planning and review (known as minimum data sets (MDS)) use the aggregate data to guide resource allocation, monitor quality, and for research. Less is known about how an MDS affects how staff assess, provide and review residents' everyday care. The review aimed to develop a theory-driven understanding of how care home staff can effectively implement and use MDS to plan and deliver care for residents. METHODS: The realist review was organised according to RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines. There were three overlapping stages: 1) defining the scope of the review and theory development on the use of minimum data set 2) testing and refining candidate programme theories through iterative literature searches and stakeholders' consultations as well as discussion among the research team; and 3) data synthesis from stages 1 and 2. The following databases were used MEDLINE via OVID, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ASSIA [Applied Social Sciences Citation Index and Abstracts]) and sources of grey literature. RESULTS: Fifty-one papers informed the development of three key interlinked theoretical propositions: motivation (mandates and incentives for Minimum Data Set completion); frontline staff monitoring (when Minimum Data Set completion is built into the working practices of the care home); and embedded recording systems (Minimum Data Set recording system is integral to collecting residents' data). By valuing the contributions of staff and building on existing ways of working, the uptake and use of an MDS could enable all staff to learn with and from each other about what is important for residents' care CONCLUSIONS: Minimum Data Sets provides commissioners service providers and researchers with standardised information useful for commissioning planning and analysis. For it to be equally useful for care home staff it requires key activities that address the staff experiences of care, their work with others and the use of digital technology. REGISTRATION: PROSPERO registration number CRD42020171323.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

BACKGROUND: Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious adverse outcomes. Treatment options for established delirium are limited and so prevention of delirium is desirable. Non-pharmacological interventions are thought to be important in delirium prevention.  OBJECTIVES: To assess the effectiveness of non-pharmacological interventions designed to prevent delirium in hospitalised patients outside intensive care units (ICU). SEARCH METHODS: We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP to 16 September 2020. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of single and multicomponent non-pharmacological interventions for preventing delirium in hospitalised adults cared for outside intensive care or high dependency settings. We only included non-pharmacological interventions which were designed and implemented to prevent delirium.  DATA COLLECTION AND ANALYSIS: Two review authors independently examined titles and abstracts identified by the search for eligibility and extracted data from full-text articles. Any disagreements on eligibility and inclusion were resolved by consensus. We used standard Cochrane methodological procedures. The primary outcomes were: incidence of delirium; inpatient and later mortality; and new diagnosis of dementia. We included secondary and adverse outcomes as pre-specified in the review protocol. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes and between-group mean differences for continuous outcomes. The certainty of the evidence was assessed using GRADE. A complementary exploratory analysis was undertaker using a Bayesian component network meta-analysis fixed-effect model to evaluate the comparative effectiveness of the individual components of multicomponent interventions and describe which components were most strongly associated with reducing the incidence of delirium. MAIN RESULTS: We included 22 RCTs that recruited a total of 5718 adult participants. Fourteen trials compared a multicomponent delirium prevention intervention with usual care. Two trials compared liberal and restrictive blood transfusion thresholds. The remaining six trials each investigated a different non-pharmacological intervention. Incidence of delirium was reported in all studies.  Using the Cochrane risk of bias tool, we identified risks of bias in all included trials. All were at high risk of performance bias as participants and personnel were not blinded to the interventions. Nine trials were at high risk of detection bias due to lack of blinding of outcome assessors and three more were at unclear risk in this domain.  Pooled data showed that multi-component non-pharmacological interventions probably reduce the incidence of delirium compared to usual care (10.5% incidence in the intervention group, compared to 18.4% in the control group, risk ratio (RR) 0.57, 95% confidence interval (CI) 0.46 to 0.71, I2 = 39%; 14 studies; 3693 participants; moderate-certainty evidence, downgraded due to risk of bias).  There may be little or no effect of multicomponent interventions on inpatient mortality compared to usual care (5.2% in the intervention group, compared to 4.5% in the control group, RR 1.17, 95% CI 0.79 to 1.74, I2 = 15%; 10 studies; 2640 participants; low-certainty evidence downgraded due to inconsistency and imprecision).  No studies of multicomponent interventions reported data on new diagnoses of dementia.  Multicomponent interventions may result in a small reduction of around a day in the duration of a delirium episode (mean difference (MD) -0.93, 95% CI -2.01 to 0.14 days, I2 = 65%; 351 participants; low-certainty evidence downgraded due to risk of bias and imprecision). The evidence is very uncertain about the effect of multicomponent interventions on delirium severity (standardised mean difference (SMD) -0.49, 95% CI -1.13 to 0.14, I2=64%; 147 participants; very low-certainty evidence downgraded due to risk of bias and serious imprecision). Multicomponent interventions may result in a reduction in hospital length of stay compared to usual care (MD -1.30 days, 95% CI -2.56 to -0.04 days, I2=91%; 3351 participants; low-certainty evidence downgraded due to risk of bias and inconsistency), but little to no difference in new care home admission at the time of hospital discharge (RR 0.77, 95% CI 0.55 to 1.07; 536 participants; low-certainty evidence downgraded due to risk of bias and imprecision). Reporting of other adverse outcomes was limited.  Our exploratory component network meta-analysis found that re-orientation (including use of familiar objects), cognitive stimulation and sleep hygiene were associated with reduced risk of incident delirium. Attention to nutrition and hydration, oxygenation, medication review, assessment of mood and bowel and bladder care were probably associated with a reduction in incident delirium but estimates included the possibility of no benefit or harm.  Reducing sensory deprivation, identification of infection, mobilisation and pain control all had summary estimates that suggested potential increases in delirium incidence, but the uncertainty in the estimates was substantial.  Evidence from two trials suggests that use of a liberal transfusion threshold over a restrictive transfusion threshold probably results in little to no difference in incident delirium (RR 0.92, 95% CI 0.62 to 1.36; I2 = 9%; 294 participants; moderate-certainty evidence downgraded due to risk of bias).  Six other interventions were examined, but evidence for each was limited to single studies and we identified no evidence of delirium prevention.  AUTHORS' CONCLUSIONS: There is moderate-certainty evidence regarding the benefit of multicomponent non-pharmacological interventions for the prevention of delirium in hospitalised adults, estimated to reduce incidence by 43% compared to usual care. We found no evidence of an effect on mortality. There is emerging evidence that these interventions may reduce hospital length of stay, with a trend towards reduced delirium duration, although the effect on delirium severity remains uncertain. Further research should focus on implementation and detailed analysis of the components of the interventions to support more effective, tailored practice recommendations.