TBK1 mutation spectrum in an extended European patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS

Service provision for Frailty in European Emergency Departments (FEED): a survey of operational characteristics

Background The observational Frailty in European Emergency Departments (FEED) study found 40% of older people attending for care to be living with frailty. Older people with frailty have poorer outcomes from emergency care. Current best practice calls for early identification of frailty and holistic multidisciplinary assessment. This survey of FEED sites explores variations in frailty-attuned service definitions and provision. Methods This cross-sectional survey included study sites across Europe identified through snowball recruitment. Site co-ordinators (healthcare professionals in emergency and geriatric care) were surveyed online using Microsoft Forms. Items covered department and hospital capacity, frailty and delirium identification methods, staffing, and frailty-focused healthcare services in the ED. Descriptive statistics were reported. Results A total of 68 sites from 17 countries participated. Emergency departments had median 30 (IQR 21–53) trolley spaces. Most defined "older people" by age 65+ (64%) or 75+ (25%). Frailty screening was used at 69% of sites and mandated at 38%. Night-time staffing was lower compared to day-time for nursing (10 [IQR 8–14] vs. 14 [IQR 10–18]) and physicians (5 [IQR 3–8] vs. 10 [IQR 7–15]). Most sites had provision for ED frailty specialist services by day, but these services were rarely available at night. Sites mostly had accessible facilities; however, hot meals were rarely available at night (18%). Conclusion This survey demonstrated variability in case definitions, screening practices, and frailty-attuned service provision. There is no unanimous definition for older age, and while the Clinical Frailty Scale was commonly used, this was rarely mandated or captured in electronic records. Frailty services were often unavailable overnight. Appreciation of the variation in frailty service models could inform operational configuration and workforce development

Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning

Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study

Summary Background Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. Methods 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15–30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). Findings Postoperative cognitive dysfunction was present in 266 (25·8% [95% CI 23·1–28·5]) of patients 1 week after surgery and in 94 (9·9% [8·1–12·0]) 3 months after surgery, compared with 3·4% and 2·8%, respectively, of UK controls (

Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study

Summary Background Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. Methods 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15–30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). Findings Postoperative cognitive dysfunction was present in 266 (25·8% [95% CI 23·1–28·5]) of patients 1 week after surgery and in 94 (9·9% [8·1–12·0]) 3 months after surgery, compared with 3·4% and 2·8%, respectively, of UK controls (

Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study

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