Evaluating the effectiveness of different approaches to home support for people in later stage dementia:A protocol for an observational study

Background: Dementia is a major health problem with a growing number of people affected by the condition, both directly and indirectly through caring for someone with dementia. Many live at home but little is known about the range and intensity of the support they receive. Previous studies have mainly reported on discrete services within a single geographical area. This paper presents a protocol for study of different services across several sites in England. The aim is to explore the presence, effects and cost-effectiveness of approaches to home support for people in later stage dementia and their carers. Methods: This is a prospective observational study employing mixed methods. At least 300 participants (people with dementia and their carers) from geographical areas with demonstrably different ranges of services available for people with dementia will be selected. Within each area, participants will be recruited from a range of services. Participants will be interviewed on two occasions and data will be collected on: their characteristics and circumstances; quality of life; carer health and burden; and informal and formal support for the person with dementia. The structured interviews will also collect qualitative data to explore the perceptions of older people and carers. Conclusions: This national study will explore the components of appropriate and effective home support for people with late stage dementia and their carers. It aims to inform commissioners and service providers across health and social care

Person-centredness in the care of older adults: a systematic review of questionnaire-based scales and their measurement properties

Abstract Background Person-centredness is promoted as a central feature of the long-term care of older adults. Measures are needed to assist researchers, service planners and regulators in assessing this feature of quality. However, no systematic review exists to identify potential instruments and to provide a critical appraisal of their measurement properties. Method A systematic review of measures of person-centredness was undertaken. Inclusion criteria restricted references to multi-item instruments designed for older adult services, or otherwise with measurement properties tested in an older adult population. A two-stage critical appraisal was conducted. First, the methodological quality of included references was assessed using the COSMIN toolkit. Second, seven measurement properties were rated using widely-recognised thresholds of acceptability. These results were then synthesised to provide an overall appraisal of the strength of evidence for each measurement property for each instrument. Results Eleven measures tested in 22 references were included. Six instruments were designed principally for use in long-stay residential facilities, and four were for ambulatory hospital or clinic-based services. Only one measure was designed mainly for completion by users of home care services. No measure could be assessed across all seven measurement properties. Despite some instruments having promising measurement properties, this was consistently undermined by the poor methodological quality underpinning them. Testing of hypotheses to support construct validity was of particularly low quality, whilst measurement error was rarely assessed. Two measures were identified as having been the subject of the most rigorous testing. Conclusion The review is unable to unequivocally recommend any measures of person-centredness for use in older adult care. Researchers are advised to improve methodological rigour when testing instruments. Efforts may be best focused on testing a narrower range of measurement properties but to a higher standard, and ensuring that translations to new languages are resisted until strong measurement properties are demonstrated in the original tongue. Limitations of the review include inevitable semantic and conceptual challenges involved in defining ‘person-centredness’. The review protocol was registered with PROSPERO (ref: CRD42014005935)

A discrete choice experiment to explore carer preferences. Quality in Ageing and Older Adults.

© Emerald Publishing Limited. Purpose - The purpose of this paper is to describe a case study to test the applicability of the discrete choice experiment (DCE) method to assess the preferences of carers of people with dementia. The focus of enquiry was home care provision. Design/methodology/approach - A multi-method approach was adopted for this pilot study. A literature review identified key characteristics of home care for dementia. This informed consultations with lay representatives. Key attributes of home care for the DCE were identified and formed the basis for the schedule. In all, 28 carers were recruited by two voluntary organisations to complete the DCE. A multinomial logistic regression model was used to analyse the data. Findings - Seven attributes of home care for people with dementia were identified from the consultation. The use of the DCE approach permitted the identification of those most important to carers. Despite the modest sample, statistically significant findings were reported in relation to five of the attributes indicating their relevance. A lay involvement in the identification of attributes contributed to the ease of administration of the schedule and relevance of the findings. Originality/value - This study demonstrated the utility of a DCE to capture the preferences of carers of people with dementia and thereby gather information from carers to inform policy, practice and service development. Their involvement in the design of the schedule was critical to this process

A list of tools is NOT enough! Professionals’ advice on how to implement a Core Outcome Set in practice

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Hubble space telescope images of SN 1987A: Evolution of the Ejecta and the Equatorial Ring from 2009 to 2022

Supernova (SN) 1987A offers a unique opportunity to study how a spatially resolved SN evolves into a young SN remnant. We present and analyze Hubble Space Telescope (HST) imaging observations of SN 1987A obtained in 2022 and compare them with HST observations from 2009 to 2021. These observations allow us to follow the evolution of the equatorial ring (ER), the rapidly expanding ejecta, and emission from the center over a wide range in wavelength from 2000 to 11,000 Å. The ER has continued to fade since it reached its maximum ∼8200 days after the explosion. In contrast, the ejecta brightened until day ∼11,000 before their emission levelled off; the west side brightened more than the east side, which we attribute to the stronger X-ray emission by the ER on that side. The asymmetric ejecta expand homologously in all filters, which are dominated by various emission lines from hydrogen, calcium, and iron. From this overall similarity, we infer the ejecta are chemically well mixed on large scales. The exception is the diffuse morphology observed in the UV filters dominated by emission from the Mg ii resonance lines that get scattered before escaping. The 2022 observations do not show any sign of the compact object that was inferred from highly ionized emission near the remnant’s center observed with JWST. We determine an upper limit on the flux from a compact central source in the [O iii] HST image. The nondetection of this line indicates that the S and Ar lines observed with JWST originate from the O free inner Si–S–Ar-rich zone and/or that the observed [O iii] flux is strongly affected by dust scattering

Components, impacts and costs of dementia home support: a research programme including the DESCANT RCT

BackgroundOver half of people with dementia live at home. We know little about what home support could be clinically effective or cost-effective in enabling them to live well.ObjectivesWe aimed to (1) review evidence for components of home support, identify their presence in the literature and in services in England, and develop an appropriate economic model; (2) develop and test a practical memory support package in early-stage dementia, test the clinical effectiveness and cost-effectiveness of routine home support in later-stage dementia and design a toolkit based on this evidence; and (3) elicit the preferences of staff, carers and people with dementia for home support inputs and packages, and evaluate the cost-effectiveness of these approaches in early- and later-stage dementia.DesignWe undertook (1) an evidence synthesis, national surveys on the NHS and social care and an economic review; (2) a multicentre pragmatic randomised trial [Dementia Early Stage Cognitive Aids New Trial (DESCANT)] to estimate the clinical effectiveness and cost-effectiveness of providing memory aids and guidance to people with early-stage dementia (the DESCANT intervention), alongside process evaluation and qualitative analysis, an observational study of existing care packages in later-stage dementia along with qualitative analysis, and toolkit development to summarise this evidence; and (3) consultation with experts, staff and carers to explore the balance between informal and paid home support using case vignettes, discrete choice experiments to explore the preferences of people with dementia and carers between home support packages in early- and later-stage dementia, and cost–utility analysis building on trial and observational study.SettingThe national surveys described Community Mental Health Teams, memory clinics and social care services across England. Recruitment to the trial was through memory services in nine NHS trusts in England and one health board in Wales. Recruitment to the observational study was through social services in 17 local authorities in England. Recruitment for the vignette and preference studies was through memory services, community centres and carers’ organisations.ParticipantsPeople aged > 50 years with dementia within 1 year of first attendance at a memory clinic were eligible for the trial. People aged > 60 years with later-stage dementia within 3 months of a review of care needs were eligible for the observational study. We recruited staff, carers and people with dementia for the vignette and preference studies. All participants had to give written informed consent.Main outcome measuresThe trial and observational study used the Bristol Activities of Daily Living Scale as the primary outcome and also measured quality of life, capability, cognition, general psychological health and carers’ sense of competence.MethodsOwing to the heterogeneity of interventions, methods and outcome measures, our evidence and economic reviews both used narrative synthesis. The main source of economic studies was the NHS Economic Evaluation Database. We analysed the trial and observational study by linear mixed models. We analysed the trial by ‘treatment allocated’ and used propensity scores to minimise confounding in the observational study.ResultsOur reviews and surveys identified several home support approaches of potential benefit. In early-stage dementia, the DESCANT trial had 468 randomised participants (234 intervention participants and 234 control participants), with 347 participants analysed. We found no significant effect at the primary end point of 6 months of the DESCANT intervention on any of several participant outcome measures. The primary outcome was the Bristol Activities of Daily Living Scale, for which scores range from 0 to 60, with higher scores showing greater dependence. After adjustment for differences at baseline, the mean difference was 0.38, slightly but not significantly favouring the comparator group receiving treatment as usual. The 95% confidence interval ran from –0.89 to 1.65 (p = 0.56). There was no evidence that more intensive care packages in later-stage dementia were more effective than basic care. However, formal home care appeared to help keep people at home. Staff recommended informal care that cost 88% of formal care, but for informal carers this ratio was only 62%. People with dementia preferred social and recreational activities, and carers preferred respite care and regular home care. The DESCANT intervention is probably not cost-effective in early-stage dementia, and intensive care packages are probably not cost-effective in later-stage dementia. From the perspective of the third sector, intermediate intensity packages were cheaper but less effective. Certain elements may be driving these results, notably reduced use of carers’ groups.LimitationsOur chosen outcome measures may not reflect subtle outcomes valued by people with dementia.ConclusionsSeveral approaches preferred by people with dementia and their carers have potential. However, memory aids aiming to affect daily living activities in early-stage dementia or intensive packages compared with basic care in later-stage dementia were not clinically effective or cost-effective.Future workFurther work needs to identify what people with dementia and their carers prefer and develop more sensitive outcome measures.Study registrationCurrent Controlled Trials ISRCTN12591717. The evidence synthesis is registered as PROSPERO CRD42014008890.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 6. See the NIHR Journals Library website for further project information

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

Cognitive aids for people with early stage dementia versus treatment as usual (Dementia Early Stage Cognitive Aids New Trial (DESCANT)): study protocol for a randomised controlled trial

Background: There is a growing need for an evidence-based approach to home support for people with dementia and their carers following diagnosis but research on the effectiveness and cost-effectiveness of different approaches is sparse. The Dementia Early Stage Cognitive Aids New Trial (DESCANT) will evaluate the clinical and costeffectiveness of a range of memory aids, training and support to people with mild to moderate dementia and their carers at home and compares that intervention with treatment as usual.Methods/design: This is a multi-site, pragmatic randomised trial preceded by a feasibility study and internal pilot. We aim to allocate at random 360 pairs comprising a person with mild to moderate dementia and an identified carer between the DESCANT intervention and treatment as usual. We assess participants at baseline, 13 and 26 weeks. The primary outcome measure is the Bristol Activities of Daily Living Scale; other participant outcomes include cognition, quality of life, activities of daily living and social networking; carer outcomes include quality of life, sense of competence and mental health. To enhance this quantitative evaluation we are conducting a qualitative component and a process evaluation to assess the implementation process and identify contextual factors associated with variation.Discussion: The DESCANT intervention reflects current policy to enhance the capabilities of people with dementia after diagnosis and their carers. If it is clinically and cost-effective, its modest nature and cost will enhance the likelihood of it being incorporated into mainstream practice.Trial registration: Current Controlled Trials, ISRCTN12591717. Registered on 29 July 2016.Protocol number: 31288: North West - Haydock Research Ethics Committee, 20/06/2016, ref.: 16/NW/0389

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pmed.100213