No difference in effects of ‘PACE steps to success’ palliative care program for nursing home residents with and without dementia : a pre-planned subgroup analysis of the seven-country PACE trial

Background: 'PACE Steps to Success' is a multicomponent training program aiming to integrate generalist and non-disease-specific palliative care in nursing homes. This program did not improve residents' comfort in the last week of life, but it appeared to improve quality of care and dying in their last month of life. Because this program included only three dementia-specific elements, its effects might differ depending on the presence or stage of dementia. We aimed to investigate whether the program effects differ between residents with advanced, non-advanced, and no dementia. Methods: Pre-planned subgroup analysis of the PACE cluster-randomized controlled trial in 78 nursing homes in seven European countries. Participants included residents who died in the previous 4 months. The nursing home staff or general practitioner assessed the presence of dementia; severity was determined using two highly-discriminatory staff-reported instruments. Using after-death questionnaires, staff assessed comfort in the last week of life (Comfort Assessment in Dying-End-of-Life in Dementia-scale; primary outcome) and quality of care and dying in the last month of life (Quality of Dying in Long-Term Care scale; secondary outcome). Results: At baseline, we included 177 residents with advanced dementia, 126 with non-advanced dementia and 156 without dementia. Post-intervention, respectively in the control and the intervention group, we included 136 and 104 residents with advanced dementia, 167 and 110 with non-advanced dementia and 157 and 137 without dementia. We found no subgroup differences on comfort in the last week of life, comparing advanced versus without dementia (baseline-adjusted mean sub-group difference 2.1; p-value = 0.177), non-advanced versus without dementia (2.7; p = 0.092), and advanced versus non-advanced dementia (- 0.6; p = 0.698); or on quality of care and dying in the last month of life, comparing advanced and without dementia (- 0.6; p = 0.741), non-advanced and without dementia (- 1.5; p = 0.428), and advanced and non-advanced dementia (0.9; p = 0.632). Conclusions: The lack of subgroup difference suggests that while the program did not improve comfort in dying residents with or without dementia, it appeared to equally improve quality of care and dying in the last month of life for residents with dementia (regardless of the stage) and those without dementia. A generalist and non-disease-specific palliative care program, such as PACE Steps to Success, is a useful starting point for future palliative care improvement in nursing homes, but to effectively improve residents' comfort, this program needs further development

Consensus definition of advance care planning in dementia: A 33-country Delphi study.

Existing advance care planning (ACP) definitional frameworks apply to individuals with decision-making capacity. We aimed to conceptualize ACP for dementia in terms of its definition and issues that deserve particular attention. Delphi study with phases: (A) adaptation of a generic ACP framework by a task force of the European Association for Palliative Care (EAPC); (B) four online surveys by 107 experts from 33 countries, September 2021 to June 2022; (C) approval by the EAPC board. ACP in dementia was defined as a communication process adapted to the person's capacity, which includes, and is continued with, family if available. We identified pragmatic boundaries regarding participation and time (i.e., current or end-of-life care). Three interrelated issues that deserve particular attention were capacity, family, and engagement and communication. A communication and relationship-centered definitional framework of ACP in dementia evolved through international consensus supporting inclusiveness of persons with dementia and their family. This article offers a consensus definitional framework of advance care planning in dementia. The definition covers all stages of capacity and includes family caregivers. Particularly important are (1) capacity, (2) family, (3) engagement, and communication. Fluctuating capacity was visualized in relation to roles and engaging stakeholders

Force and Motion Generation of Molecular Motors: A Generic Description

We review the properties of biological motor proteins which move along linear filaments that are polar and periodic. The physics of the operation of such motors can be described by simple stochastic models which are coupled to a chemical reaction. We analyze the essential features of force and motion generation and discuss the general properties of single motors in the framework of two-state models. Systems which contain large numbers of motors such as muscles and flagella motivate the study of many interacting motors within the framework of simple models. In this case, collective effects can lead to new types of behaviors such as dynamic instabilities of the steady states and oscillatory motion.Comment: 29 pages, 9 figure

A stochastic evolutionary model generating a mixture of exponential distributions

Recent interest in human dynamics has stimulated the investigation of the stochastic processes that explain human behaviour in various contexts, such as mobile phone networks and social media. In this paper, we extend the stochastic urn-based model proposed in \cite{FENN15} so that it can generate mixture models, in particular, a mixture of exponential distributions. The model is designed to capture the dynamics of survival analysis, traditionally employed in clinical trials, reliability analysis in engineering, and more recently in the analysis of large data sets recording human dynamics. The mixture modelling approach, which is relatively simple and well understood, is very effective in capturing heterogeneity in data. We provide empirical evidence for the validity of the model, using a data set of popular search engine queries collected over a period of 114 months. We show that the survival function of these queries is closely matched by the exponential mixture solution for our model

Consensus definition of advance care planning in dementia: a 33-country Delphi study

INTRODUCTIONExisting advance care planning (ACP) definitional frameworks apply to individuals with decision-making capacity. We aimed to conceptualize ACP for dementia in terms of its definition and issues that deserve particular attention.METHODSDelphi study with phases: (A) adaptation of a generic ACP framework by a task force of the European Association for Palliative Care (EAPC); (B) four online surveys by 107 experts from 33 countries, September 2021 to June 2022; (C) approval by the EAPC board.RESULTSACP in dementia was defined as a communication process adapted to the person's capacity, which includes, and is continued with, family if available. We identified pragmatic boundaries regarding participation and time (i.e., current or end-of-life care). Three interrelated issues that deserve particular attention were capacity, family, and engagement and communication.DISCUSSIONA communication and relationship-centered definitional framework of ACP in dementia evolved through international consensus supporting inclusiveness of persons with dementia and their family.Public Health and primary careGeriatrics in primary car

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases – A multicenter cohort study

Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4e12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.Carl-Jacob Holmberg ... Brendon Coventry ... Hidde Kroon ... et al