RESUMEN
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).
Asunto(s)
Proteínas de Caenorhabditis elegans , Discapacidad Intelectual , Animales , Humanos , Cuerpo Calloso/patología , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Discapacidad Intelectual/genética , Fenotipo , Ligasas/genética , Ubiquitinas/genética , Agenesia del Cuerpo Calloso/genética , Agenesia del Cuerpo Calloso/patología , Ubiquitina-Proteína Ligasas/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Factores de Intercambio de Guanina Nucleótido/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismoRESUMEN
The Scottish Intercollegiate Guidelines Network (SIGN) have recently published their guideline SIGN168 on 'Assessment, Diagnosis, Care, and Support for People with Dementia and their Carers'. The guideline makes evidence-based recommendations for best practice in the assessment, care and support of adults living with dementia. Topics featured in this guideline are limited to those prioritised by stakeholders, especially people with lived and living experience, and those not well covered under pre-existing guidance. We summarise the guideline recommendations related to identification and diagnosis of dementia, investigative procedures, postdiagnostic support living with dementia, including non-pharmacological approaches for distressed behaviours, using technology to support people with dementia, grief and dementia and changing needs of people with dementia. The guideline content is summarised as officially published, with additional commentary in the final section.
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Cuidadores , Demencia , Humanos , Demencia/diagnóstico , Demencia/terapia , Demencia/psicología , Cuidadores/psicología , Apoyo Social , EscociaRESUMEN
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.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/terapia , Casas de Salud , Estudios Retrospectivos , Pandemias , Web Semántica , Estudios de CohortesRESUMEN
BACKGROUND: Assessment of functional status is an integral part of older adult healthcare and research. Therefore, it is essential that tools to capture function are contextually appropriate. Many tools designed to evaluate extended Activities of Daily Living (eADLs) were developed decades ago. OBJECTIVE: Our aim was to explore which eADL tasks are commonly performed by older adults and map these tasks to popular eADL scales, seeking stakeholder perspectives to inform recommendations on scale content. DESIGN: Online survey with quantitative questions and free text followed-by semi-structured interviews. SUBJECTS: Older adults (≥60-years), carers and health, social care and voluntary/community professionals. METHODS: We extracted eADL tasks from existing scales to develop a survey on frequency of performance, with space for additional comment. The survey was disseminated via Join Dementia Research and other clinical and professional networks. Online semi-structured interviews were undertaken with thematic analysis of verbatim transcripts. RESULTS: From 2244 online survey responses, 87% came from older people and two-thirds of respondents were female. Some eADL tasks were never performed by many participants. Tasks not part of existing tools included online banking and mobile phone use. From fifteen interviews, a recurring theme was that technological and societal changes have altered daily tasks. CONCLUSIONS: Commonly used eADL scales contain obsolete tasks and omit tasks older people consider part of their everyday lives. There is a need to work collaboratively to update eADL tools to reflect the priorities and activities of older people to ensure these remain valid measures for use in practice and research. To complement this abstract, a video abstract is available online. A more detailed video-based summary of the content is also available as supplemental material.
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Actividades Cotidianas , Estado Funcional , Evaluación Geriátrica , Humanos , Femenino , Anciano , Masculino , Evaluación Geriátrica/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Encuestas y Cuestionarios , Entrevistas como Asunto , Envejecimiento/psicología , Factores de EdadRESUMEN
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.
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Unidades de Cuidado Intensivo Pediátrico , Secuenciación Completa del Genoma , Humanos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Unidades de Cuidado Intensivo Pediátrico/organización & administración , Lactante , Preescolar , Masculino , Femenino , Niño , Secuenciación Completa del Genoma/métodos , Recién Nacido , Adolescente , Estudios Prospectivos , Estudios de CohortesRESUMEN
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.
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Iduronato Sulfatasa , Mucopolisacaridosis II , Lactante , Recién Nacido , Humanos , Mucopolisacaridosis II/diagnóstico , Mucopolisacaridosis II/epidemiología , Mucopolisacaridosis II/genética , Tamizaje Neonatal , Incidencia , FamiliaRESUMEN
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.
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Disfunción Cognitiva , Demencia , Humanos , Anciano , Demencia/diagnóstico , Demencia/psicología , Revisiones Sistemáticas como Asunto , Sensibilidad y Especificidad , Disfunción Cognitiva/diagnóstico , Encuestas y CuestionariosRESUMEN
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.
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Envejecimiento , Atención a la Salud , Humanos , Anciano , Cuidadores , Comunicación , LongevidadRESUMEN
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.
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Hogares para Ancianos , Internacionalidad , Evaluación de Resultado en la Atención de Salud , Investigación , Anciano , Humanos , Práctica Clínica Basada en la Evidencia , Conjuntos de Datos como Asunto , Proyectos de InvestigaciónRESUMEN
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.
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COVID-19 , Pandemias , Humanos , COVID-19/epidemiología , COVID-19/terapia , Aprendizaje , Investigación CualitativaRESUMEN
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) initiates a stress response mechanism to clear out the unfolded proteins by either facilitating their re-folding or inducing their degradation. When this fails, an apoptotic cascade is initiated so that the affected cell is eliminated. IRE1α is a critical sensor of the unfolded-protein response, essential for initiating the apoptotic signaling. Here, we report an infantile neurodegenerative disorder associated with enhanced activation of IRE1α and increased apoptosis. Three unrelated affected individuals with congenital microcephaly, infantile epileptic encephalopathy, and profound developmental delay were found to carry heterozygous variants (c.932T>C [p.Leu311Ser] or c.935T>C [p.Leu312Pro]) in RNF13, which codes for an IRE1α-interacting protein. Structural modeling predicted that the variants, located on the surface of the protein, would not alter overall protein folding. Accordingly, the abundance of RNF13 and IRE1α was not altered in affected individuals' cells. However, both IRE1α-mediated stress signaling and stress-induced apoptosis were increased in affected individuals' cells. These results indicate that the RNF13 variants confer gain of function to the encoded protein and thereby lead to altered signaling of the ER stress response associated with severe neurodegeneration in infancy.
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Ceguera/congénito , Ceguera/genética , Insuficiencia de Crecimiento/genética , Mutación con Ganancia de Función , Heterocigoto , Microcefalia/genética , Espasmos Infantiles/genética , Ubiquitina-Proteína Ligasas/genética , Secuencia de Aminoácidos , Apoptosis , Niño , Preescolar , Discapacidades del Desarrollo/genética , Estrés del Retículo Endoplásmico , Humanos , Lactante , Masculino , Modelos Moleculares , Espasmos Infantiles/congénito , Ubiquitina-Proteína Ligasas/química , Respuesta de Proteína DesplegadaRESUMEN
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.
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Fragilidad , Casas de Salud , Humanos , Estudios Retrospectivos , Hospitalización , Apoyo SocialRESUMEN
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.
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Fragilidad , Accidente Cerebrovascular , Anciano , Anciano Frágil , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Prevalencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapiaRESUMEN
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.
RESUMEN
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.
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Cuidados a Largo Plazo , Motivación , Anciano , HumanosRESUMEN
BACKGROUND: Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. METHODS: We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. RESULTS: From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. CONCLUSIONS: Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.
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COVID-19/epidemiología , Publicaciones Periódicas como Asunto/normas , Calidad de la Atención de Salud/normas , Investigación Biomédica , Humanos , Proyectos de Investigación/normas , Informe de InvestigaciónRESUMEN
BACKGROUND: understanding care-home outbreaks of COVID-19 is a key public health priority in the ongoing pandemic to help protect vulnerable residents. OBJECTIVE: to describe all outbreaks of COVID-19 infection in Scottish care-homes for older people between 01/03/2020 and 31/03/2020, with follow-up to 30/06/2020. DESIGN AND SETTING: National linked data cohort analysis of Scottish care-homes for older people. METHODS: data linkage was used to identify outbreaks of COVID-19 in care-homes. Care-home characteristics associated with the presence of an outbreak were examined using logistic regression. Size of outbreaks was modelled using negative binomial regression. RESULTS: 334 (41%) Scottish care-homes for older people experienced an outbreak, with heterogeneity in outbreak size (1-63 cases; median = 6) and duration (1-94 days, median = 31.5 days). Four distinct patterns of outbreak were identified: 'typical' (38% of outbreaks, mean 11.2 cases and 48 days duration), severe (11%, mean 29.7 cases and 60 days), contained (37%, mean 3.5 cases and 13 days) and late-onset (14%, mean 5.4 cases and 17 days). Risk of a COVID-19 outbreak increased with increasing care-home size (for ≥90 beds vs <20, adjusted OR = 55.4, 95% CI 15.0-251.7) and rising community prevalence (OR = 1.2 [1.0-1.4] per 100 cases/100,000 population increase). No routinely available care-home characteristic was associated with outbreak size. CONCLUSIONS: reducing community prevalence of COVID-19 infection is essential to protect those living in care-homes. More systematic national data collection to understand care-home residents and the homes in which they live is a priority in ensuring we can respond more effectively in future.
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COVID-19 , Anciano , Estudios de Cohortes , Brotes de Enfermedades , Humanos , Casas de Salud , SARS-CoV-2 , Escocia/epidemiología , Web SemánticaRESUMEN
BACKGROUND: older people living in care-homes are particularly vulnerable to adverse effects of psychotropic and anticholinergic drugs. METHODS: anonymised dispensed prescription data from all 4,478 residents aged ≥ 60 years in 147 care-homes in two Scottish health boards were analysed. Psychotropic medicines examined were antipsychotics, antidepressants, hypnotic/anxiolytics, opioids and gabapentinoids. Anticholinergic burden was measured using the modified anticholinergic risk scale (mARS). Variation between care-homes and associations with individual and care-home characteristics were examined using multilevel logistic regression. RESULTS: 63.5% of residents were prescribed at least one psychotropic drug, and 27.0% two or more, most commonly antidepressants (41.6%), opioids (20.3%), hypnotic/anxiolytics (16.9%) and antipsychotics (16.7%). 48.1% were prescribed an anticholinergic drug, and 12.1% had high anticholinergic burden (mARS ≥ 3). Variation between care-homes was high for antipsychotics (intra-cluster correlation coefficient [ICC] 8.2%) and hypnotics/anxiolytics (ICC = 7.3%), and moderate for antidepressants (ICC = 4.7%) and anticholinergics (ICC = 2.8%). Prescribing of all drugs was lower in the oldest old. People with dementia were more likely to be prescribed antipsychotics (adjusted OR = 1.45, 95%CI 1.23-1.71) but less likely to be prescribed anticholinergics (aOR = 0.61, 95%CI 0.51-0.74). Prescribing of antipsychotics was higher in Tayside (aOR = 1.52, 95%CI 1.20-1.92), whereas prescribing of antidepressants (particularly tricyclic-related) was lower (aOR = 0.66, 95%CI 0.56-0.79). There was no association with care-home regulator quality scores. CONCLUSION: care-home residents have high psychotropic and anticholinergic burden, with considerable variation between care-homes that is not related to existing measures of quality of care. Research to better understand variation between care-homes and the interaction with local prescribing cultures is needed.
Asunto(s)
Casas de Salud , Psicotrópicos , Anciano , Anciano de 80 o más Años , Antidepresivos/efectos adversos , Antagonistas Colinérgicos/efectos adversos , Estudios Transversales , Humanos , Psicotrópicos/efectos adversosRESUMEN
BACKGROUND: COVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified. METHODS: Care-home residency was identified via a national primary care registration database linked to mortality data. Life expectancy was estimated using Makeham-Gompertz models to (i) describe yearly life expectancy from November 2015 to October 2020 (ii) compare life expectancy (during 2016-18) between care-home residents and the wider population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL). RESULTS: Among care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3 years for women and 2.3 to 1.8 years for men. Age-sex-specific life expectancy in 2016-18 in care-home residents was lower than in the Scottish population (10 and 2.5 years in those aged 70 and 90, respectively). Applying care home-specific life expectancies to COVID-19 deaths yield mean YLLs for care-home residents of 2.6 and 2.2 for women and men, respectively. In total YLL care-home residents have lost 3,560 years in women and 2,046 years in men. Approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents. CONCLUSION: COVID-19 infection has led to the loss of substantial years of life in care-home residents aged 70 years and over in Scotland. Prioritising the 5% of older adults who are care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of YLL.
Asunto(s)
COVID-19 , Esperanza de Vida , Anciano , Causas de Muerte , Femenino , Humanos , Masculino , Mortalidad , SARS-CoV-2 , Escocia/epidemiologíaRESUMEN
BACKGROUND: The diagnosis of dementia relies on the presence of new-onset cognitive impairment affecting an individual's functioning and activities of daily living. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a questionnaire instrument, completed by a suitable 'informant' who knows the patient well, designed to assess change in functional performance secondary to cognitive change; it is used as a tool for identifying those who may have dementia. In secondary care there are two specific instances where patients may be assessed for the presence of dementia. These are in the general acute hospital setting, where opportunistic screening may be undertaken, or in specialist memory services where individuals have been referred due to perceived cognitive problems. To ensure an instrument is suitable for diagnostic use in these settings, its test accuracy must be established. OBJECTIVES: To determine the accuracy of the informant-based questionnaire IQCODE for detection of dementia in a secondary care setting. SEARCH METHODS: We searched the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (Database of Abstracts of Reviews of Effects - via the Cochrane Library); HTA Database (Health Technology Assessment Database via the Cochrane Library) and ARIF (Birmingham University). We also checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on IQCODE for dementia diagnosis to try to find additional studies. We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel and included terms relating to cognitive tests, cognitive screening and dementia. We used standardised database subject headings such as MeSH terms (in MEDLINE) and other standardised headings (controlled vocabulary) in other databases, as appropriate. SELECTION CRITERIA: We selected those studies performed in secondary-care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the 'secondary care' setting we included all studies which assessed patients in hospital (e.g. acute unscheduled admissions, referrals to specialist geriatric assessment services etc.) and those referred for specialist 'memory' assessment, typically in psychogeriatric services. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of all potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool, and reporting quality using the STARD tool. MAIN RESULTS: From 72 papers describing IQCODE test accuracy, we included 13 papers, representing data from 2745 individuals (n = 1413 (51%) with dementia). Pooled analysis of all studies using data presented closest to a cut-off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity 0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to 3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22). There was a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a 'general' setting. We found no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration. There was significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalisability. There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice. AUTHORS' CONCLUSIONS: The IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment; it is useful specifically for ruling out those without evidence of cognitive decline. The language of administration did not affect test accuracy, which supports the cross-cultural use of the tool. These findings are qualified by the significant heterogeneity, the potential for bias and suboptimal reporting found in the included studies.