TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2

Background: Glioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs). Results: We found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 in TP53 mutated GSCs remained unchanged. Conclusion: Our data suggest that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored

Driving Performance in Patients With Idiopathic Cervical Dystonia; A Driving Simulator Pilot Study

Objective: To explore driving performance and driving safety in patients with cervical dystonia (CD) on a simulated lane tracking, intersections and highway ride and to compare it to healthy controls. Design: This study was performed as an explorative between groups comparison. Participants: Ten CD patients with idiopathic CD, 30 years or older, stable on botulinum toxin treatment for over a year, holding a valid driver's license and being an active driver were compared with 10 healthy controls, matched for age and gender. Main outcome measures: Driving performance and safety, measured by various outcomes from the simulator, such as the standard deviation of the lateral position on the road, rule violations, percentage of line crossings, gap distance, and number of collisions. Fatigue and driving effort were measured with the Borg CR-10 scale and self-perceived fitness to drive was assessed with Fitness to Drive Screening. Results: Except for a higher percentage of line crossings on the right side of the road by controls (median percentage 2.30, range 0.00-37.00 vs. 0.00, range 0.00-9.20, p = 0.043), no differences were found in driving performance and driving safety during the simulator rides. Fatigue levels were significantly higher in CD patients just before (p = 0.005) and after (p = 0.033) the lane tracking ride (patients median fatigue levels before 1.5 (range 0.00-6.00) and after 1.5 (range 0.00-7.00) vs. controls median fatigue levels before and after 0.00 (no range). No significant differences were found on self-perceived fitness to drive. Conclusion: In patients with CD there were no indications that driving performance or driving safety were significant different from healthy controls in a simulator. Patients reported higher levels of fatigue both before and after driving compared to controls in accordance with the non-motor symptoms known in CD

Types, aspects, and impact of relocation initiatives deployed within and between long-term care facilities:A scoping review

Relocation of residents within or between long-term care facilities occurs regularly. To mitigate potential negative consequences, supportive relocation initiatives have been developed. This scoping review addresses types, aspects, and impact of relocation initiatives developed to relocate residents between or within long-term care facilities. A total of 704 articles were identified in a systematic literature search of 11 databases between April and July 2021. Using predefined eligibility criteria, two researchers independently screened titles and abstracts, resulting in 36 articles for full-text screening. Finally, six articles were included. Analysis was performed using thematic coding. Three types of relocation initiatives were identified, namely, interventions (n = 3), guidelines (n = 2), and a plan (n = 1). These initiatives described specific aspects of relocation, namely, spatial orientation (n = 3), practical assistance (n = 3), psychological support (n = 3), staff preparation (n = 2), and client engagement (n = 2). Only three intervention studies reported the impact of relocation initiatives on residents, namely, improved mental health (n = 3), spatial orientation (n = 2), self-reliance (n = 2), and social behavior (n = 1). The scope of the found relocation initiatives was often limited as they focused on specific designs, aspects, and residents. Therefore, the complexity of relocation processes is often overlooked, and more comprehensive relocation initiatives should be developed

Pan-European Study on Functional and Medical Recovery and Geriatric Rehabilitation Services of Post-COVID-19 Patients: Protocol of the EU-COGER Study.

OBJECTIVES: There is insufficient knowledge about the functional and medical recovery of older people infected with SARS-CoV-2. This study aims to gain insight into the course of functional and medical recovery of persons who receive geriatric rehabilitation (GR) following SARS-CoV-2 infection across Europe. Special attention will be paid to the recovery of activities of daily living (ADL) and to the GR services offered to these patients. DESIGN: A multi-center observational cohort study. SETTING AND PARTICIPANTS: This study will include several European countries (EuGMS member states) each providing at least 52 comparable routine datasets (core dataset) of persons recovering from a SARS-CoV-2 infection and receiving geriatric rehabilitation. The routine data will be anonymously collected in an online CASTOR database. The ethical regulations of each participating country will be followed. PRIMARY OUTCOME: ADL functioning. SECONDARY OUTCOMES: length of stay, discharge destination, hospital readmission and mortality. Other variables that will be collected are quality of life, treatment modalities, complications, cognition, frailty, mood/anxiety, BMI, nutrition and pain. All variables will be reported at admission and compared with follow-up scores (discharge, 6 weeks and 6 months follow-up). CONCLUSION: This study will explore the effect of geriatric rehabilitation on post-COVID-19 patients, especially on ADL recovery, and the variety of geriatric rehabilitation services across Europe. Information from this study may help improve recovery of older persons infected with SARS-CoV-2 and improve geriatric rehabilitation services in the ongoing COVID-19 pandemic

Prevalence, Severity and Impact of Visuospatial Neglect in Geriatric Stroke Rehabilitation, a Cross-Sectional Study

Objectives: Visuospatial neglect (VSN) is a common cognitive deficit of lateralized attention after stroke and can have a negative influence on patients’ daily activities, community participation, and caregiver burden. VSN prevalence has been investigated in several mixed-age populations, but rarely in only an older population. As the population in geriatric rehabilitation (GR) is understudied and VSN may influence rehabilitation goals in GR (return home), we examined the prevalence of VSN as well as associations between VSN (severity) and population characteristics and the impact of VSN on functioning, length of stay, and discharge destination after GR. Design: Multicenter cross-sectional study. Setting and Participants: Stroke patients admitted to GR. Methods: Three VSN tests (Star cancelation task, Line bisection task, and Catherine Bergego Scale) were administered in the first 2 weeks of GR admission. To examine VSN severity, a composite score was calculated based on scores of the 3 tests. Results: A total of 114 stroke patients were included [55.3% female; mean age 80.2 (SD 8.0) years]. VSN prevalence was 47.4%, in which allocentric and egocentric neglect were more prevalent than VSN during activities of daily living. Participants with VSN spent more days in GR compared to participants without VSN (median 68.5 vs 35.5 days) and had fewer home returns. In addition, VSN participants showed less mobility, lower cognitive functioning, and less independence during self-care compared to participants without VSN. Mobility, self-care, cognition, duration of rehabilitation, and home return were negatively associated with VSN severity. Conclusions and Implications: VSN is very prevalent in the GR stroke population. VSN severely hampers older people during daily activities and their rehabilitation process and, therefore, has a major personal and societal impact. Accordingly, systematic assessment of VSN in the early phase of geriatric rehabilitation with multiple VSN screening tests is recommended

Distancing Measures and Challenges Discussed by COVID-19 Outbreak Teams of Dutch Nursing Homes:The COVID-19 MINUTES Study

The most severe COVID-19 infections and highest mortality rates are seen among long-term care residents. To reduce the risk of infection, physical distancing is important. This study investigates what physical distancing measures were discussed by COVID-19 outbreak teams of Dutch long-term care organizations and what challenges they encountered. The COVID-19 MINUTES study is a qualitative multi-center study (n = 41) that collected minutes of COVID-19 outbreak teams from March 2020 to October 2021. Textual units about distancing measures were selected and analyzed using manifest content analysis for the first wave: early March-early May 2020; the intermediate period of 2020: mid-May-mid-September 2020; and the second wave: late September 2020-mid-June 2021. During all periods, COVID-19 outbreak teams often discussed distancing visitors from residents. Moreover, during the first wave they often discussed isolation measures, during the intermediate period they often discussed distancing staff and volunteers from residents, and during both the intermediate period and the second wave they often discussed distancing among residents. During all periods, less often admission measures were discussed. Challenges persisted and included unrest among and conflicts between visitors and staff, visitors violating measures, resident non-adherence to measures, and staffing issues. The discussed distancing measures and corresponding challenges may guide local long-term care and (inter)national policymakers during the further course of the COVID-19 pandemic, outbreaks of other infectious diseases, and long-term care innovations

COVID-19 management in nursing homes by outbreak teams (MINUTES)-study description and data characteristics:A qualitative study

OBJECTIVES: Nursing homes are hit relatively hard by the COVID-19 pandemic. Dutch long-term care (LTC) organisations installed outbreak teams (OTs) to coordinate COVID-19 infection prevention and control. LTC organisations and relevant national policy organisations expressed the need to share experiences from these OTs that can be applied directly in COVID-19 policy. The aim of the ‘COVID-19 management in nursing homes by outbreak teams’ (MINUTES) study is to describe the challenges, responses and the impact of the COVID-19 pandemic in Dutch nursing homes. In this first article, we describe the MINUTES Study and present data characteristics. DESIGN: This large-scale multicentre study has a qualitative design using manifest content analysis. The participating organisations shared their OT minutes and other meeting documents on a weekly basis. Data from week 16 (April) to week 53 (December) 2020 included the first two waves of COVID-19. SETTING: National study with 41 large Dutch LTC organisations. PARTICIPANTS: The LTC organisations represented 563 nursing home locations and almost 43 000 residents. RESULTS: At least 36 of the 41 organisations had one or more SARS-CoV-2 infections among their residents. Most OTs were composed of management, medical staff, support services staff, policy advisors and communication specialists. Topics that emerged from the documents were: crisis management, isolation of residents, personal protective equipment and hygiene, staff, residents’ well-being, visitor policies, testing and vaccination. CONCLUSIONS: OT meeting minutes are a valuable data source to monitor the impact of and responses to COVID-19 in nursing homes. Depending on the course of the COVID-19 pandemic, data collection and analysis will continue until November 2021. The results are used directly in national and organisational COVID-19 policy

Aging affects attunement in perceiving length by dynamic touch

Earlier studies have revealed age-dependent differences in perception by dynamic touch. In the present study, we examined whether the capacity to learn deteriorates with aging. Adopting an ecological approach to learning, the authors examined the process of attunement—that is, the changes in what informational variable is exploited. Young and elderly adults were trained to perceive the lengths of unseen, handheld rods. It was found that the capacity to attune declines with aging: Contrary to the young adults, the elderly proved unsuccessful in learning to detect the specifying informational variables. The fact that aging affects the capacity to attune sets a new line of research in the study of perception and perceptual-motor skills of elderly. The authors discuss the implications of their findings for the ongoing discussions on the ecological approach to learning

Post-COVID-19 recovery and geriatric rehabilitation care: a European inter-country comparative study.

PURPOSE: There is variation in organization of geriatric rehabilitation across Europe. The purpose of this study was to describe the selection criteria for referral to geriatric rehabilitation, care provided, and recovery trajectories of post-COVID-19 patients referred to geriatric rehabilitation in Europe. METHODS: This observational cohort study included 723 patients in 59 care facilities for geriatric rehabilitation across 10 countries. Patient data were collected from medical records on admission to geriatric rehabilitation (between September 2020 and October 2021), discharge, 6 weeks and 6 months follow-up. The primary and secondary outcomes were recovery in daily functioning (Barthel Index) and Quality of Life (EQ-5D-5L) from admission to discharge. These were examined using linear mixed models with two levels (measurements nested in patients) and country as an independent variable. Random intercept and random linear slope parameters were added when they improved model fit. A survey about organization of geriatric rehabilitation for post-COVID-19 patients was filled out by country coordinators and data were analyzed using descriptive statistics and inductive coding of answers to open questions. RESULTS: Patients had a mean age of 75.7 years old and 52.4% were male. Many countries used various combinations of the selection criteria, such as functional status, age, frailty, Comprehensive Geriatric Assessment, comorbidities, and cognitive impairments. Most patients received physiotherapy (88.8%) and occupational therapy (69.7%), but there was substantial variance between countries in the percentages of patients that received protein or calorie enriched diets, oxygen therapy, and other treatment components. In all countries, patients showed recovery in daily functioning and quality of life, although there was variation in between countries in rate of recovery. Daily functioning seemed to increase most rapidly in the Czech Republic, Germany, and Russia. The steepest increases in quality of life were seen in the Czech Republic, Germany, and Spain. CONCLUSION: Post-COVID-19 patients showed recovery during geriatric rehabilitation, albeit at variable rates. The observed variation may be explained by the heterogeneity in selection criteria and care provided. This study highlights the need for harmonization of measurements in geriatric rehabilitation order to perform explanatory research and optimize geriatric rehabilitation throughout Europe to ensure optimal patient recovery

Post-COVID-19 patients in geriatric rehabilitation substantially recover in daily functioning and quality of life.

BACKGROUND: After an acute infection, older persons may benefit from geriatric rehabilitation (GR). OBJECTIVES: This study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery. DESIGN: Multicentre prospective cohort study. SETTING: 59 GR facilities in 10 European countries. PARTICIPANTS: Post-COVID-19 patients admitted to GR between October 2020 and October 2021. METHODS: Patients' characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL. RESULTS: 723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0-7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: -0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: -0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients. CONCLUSIONS: Post-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR